13 Episode results for "Protease Inhibitor"

Ep. 18: Speed vs. Safety: Rapid Approvals from the FDA

Sounds of Science

15:46 min | 1 year ago

Ep. 18: Speed vs. Safety: Rapid Approvals from the FDA

"I'm Mary Parker and welcome to this. Episode of Rico Sounds of scientists It is well known that most drugs can spend years development before making it to market to satisfy the FDA every drug that is approved for treatment must pass rigorous safety and efficacy testing before it reaches consumers production of drug and pretrial safety safety. Testing can easily take one to five years but what happens with drugs that are only intended for one patient and what if that patients need is so severe. That delayed access access to a drug. Is the difference between life and death to discuss this issue. I'm joined by Dr Loren black distinguished scientists with scientific advisory services at Charles River. Welcome Lauren thanks for having me on Mary thanks for being here. I understand you've done biotech consulting a long time but how did you start your career in research and can you tell me a bit. What about your background with the FDA sure thing I was opposed talk at Nih and I was doing molecular pharmacology on neurons in Nineteen ninety-one on the basic research took this huge downturn at the time and so I took a job at FDA thinking it would be nice steady science work But they had posted a job opportunity at the Age Group at FDA called Bannon Barrel Drugs Group Division. And and I had really had my head in the laboratory and I wasn't aware of how bad the AIDS crisis was And it was actually a very depressing time. Because the we were really weren't addressing the actual viral Lyra load The toxicity of the drugs was terrible. Act Up was protesting and very rightly so and before Internet. If you you think about it they were passing out pamphlets. They were educating themselves on the nature of virology and the difficulties of the immune system. And they we're being extremely effective in getting FDA NIH is attention by that time and so the antivirals group was actually invented to be very. Are you proactive group to embrace. Those patients needs and to speed up. The approval look drugs so I actually cut my teeth in the process of public health the crisis on high risk disease. And I've never left field. I've always felt very strongly that patients had an unmet medical need needed to get the fastest Access to drugs after seeing upfront personal with the what they were up against so why is the FDA's rigorous testing so necessary. Well I I think you're aware that a lot of drugs fail From safety concerns we all know about getting sleepy with antihistamines. Or you know that's the actual aside side effect that comes from the action of the drug on the brain. That's at the senior centers that we would like to counteract allergy. So that's what we call pharmacologic based aced toxicity. It's an effect actually on the target. But it's in a way that we don't want it to act GOTCHA. So as we're working on very new drugs we often don't understand like where there's receptors are in God or the brain or the immune system. There's a lot of things we don't understand about the basic mechanisms of action of disease and there's lot of things that we don't understand sometimes about where the receptors are in the buddy. I mean it seems great. Yeah but that's why. I'm kind of glad if my original training and classic Comic Anthology Because you have to ask questions okay. where else is the receptor? Who else could hit end so? FDA trained to think about those nightmare scenarios of what it could do that. You don't want it to do right and ask those hard questions to make sure that we have the checks and balances right a lot of the early drugs That were used in AIDS. Patients Cause Peripheral neuropathy and that wasn't shown very well in the animal models models but it caused intense pain in the patients at the same doses that was needed for the virus. It wasn't until later that we got the protease inhibitors that really counteracted the road. And that's the basis of the lifesaving therapies that we have today I was really fortunate to be. FDA during that time when the protease inhibitor came through so switching gears a little bit what is personalized medicine. When it comes to patients like for example adjacent armstead and meal Amac? I understand that Jaycee is a twenty five year old with Lou GEHRIG's disease while meal is a young girl with batons disease who have both recently benefited from personalized medicine. He I think we have come to the place in drug development where we understand a lot more about genetics of disease so so yes switching away from viruses and into genetic Madison we have a lot of inborn errors when we learned that there is an inborn Gene that was missing in a patient has always been there born like that and as soon as we can diagnose them and with that replacement gene product or the enzyme of interest interest. We can save their lives so. LS has also been learned to be a whole series of different mutations responsible for LS Um and so you have to look at those different subsets according to their genetic diagnosis. But we also know that Batten's disease is a specific mutation and there's also something like fourteen different forms of Batten's disease that are mutations in same pathway that result in the same type of phenotype of neurological article degeneration some earlier some younger and some an older kids or adults in the case of Mula. She has two mutations that are different on both of the wheels that caused the dysfunction of a particular protein. Batten's disease six seven and there's only a handful or double handful of kids worldwide. They're known to have that particular subtitled batons and Jaycees case she has a very aggressive form of al it lasts called F s mutation and it has a particularly bad course people with F.. US typically sadly succumbed LS typically approximately a year. Because it's so aggressive. It's very hard to intervene soon enough. And there has never been a medication that could actually address the fundamental gene problems in these two cases so we need to design whole new the truck when we find the particular mutation and it turns out depending on the molecular biology and that control mechanisms around them. A tation some all of them are amenable to go nuclear type therapy and both of these girls have been their particular. Genetics have been amenable to A strategy she of using nuclear tight enter equally sadly we did not know that. JC had this particularly bad ale ass us until she was twenty five. Her family had lost her twin sister at the age of seventeen and Alex add add. Actually he contracted the symptoms of L. S. at age eleven so the two girls were identical. They had the same mutation but one got symptoms at eleven on the other at twenty five. JC I guess Through some grace right. Her symptoms arose during time in which a drug was already available in unaccompanied show that happened to be appropriate for her. So I understand and that in this case she got lucky. Well in a way because the drug already existed otherwise we couldn't have intervened quickly enough. Yeah it was an act of considerable effort on the part of the patient advocacy group project. LS The head of Columbia University's LS LS center. Dr Neil Snider in the company who originated the drug and all of us that were helping around the sides trying to support like an exoskeleton including Charles forever and I was helping with the regulatory strategy and also trying to make sure that the drug that was chosen was actually appropriate to the most expedient animal model so as a result of that we were able to put together a very lean and mean I N D for JC and get her approved through the FDA. I have to say. FDA was understandably cautious but when they heard her situation detail and how she'd lost her twin sister the understood of course about a few and they made a lot of exceptions to the usual toxicology regulations. Well I know that she had been she and her family. They had been advocating pretty publicly for a while up until it was approved. I if I'd been in her mom shoes I would have done the same thing called. She lower local congressman. The Stephen King and there was actually quite a response. In Congress. There is a bill that was put forward to ask. FDA to move expediently for JC. I don't know that that had specific impact but just to say that they got some considerable public discussion. And how Camilla's case different in her case Tim you At Boston Children's Hospital recognized that her condition was suitable for an exon skipping being drug very similar to Isis Been Raza and he was able to use a similar backbone and design a drug from scratch within several months it was quite remarkable global. We've done the testing for it and then we've Were able to get started with just a acute data and then I designed a type of a program in which we would update the FDA very regularly on the progress of the toxicology studies so that we could extend her dosing and again. FDA's group group that does an enzyme replacement was wonderful. In working with us to customize that I approach how do you envision cases like these being handled in the future after all not everyone. Everyone has a congressman. That's willing to go to bat for them. Like Jaycee did not. Everybody should take one. There's definitely a sea-change coming is really exciting. And it goes back to the changes brought about by the AIDS patients who identified that they were an extreme unmet medical. Need we see the finalization of the L. S. guidance. We see a lot of guidances have come out on rare disease from the agency in the past twenty four months. And I'm very excited about this because we're really getting to the place where we custom tailor the amount of upfront non clinical research. That has to proceed to human trials customize. That the patient's situation well do you think that each was going to require its own uniquely designed non clinical research at will or will there kind of. Okay you're not gonna be able to have like a standard version that works for most Aso's typically called platform toxicology in kind of a dream. Right now when you look across all a good nuclear tides you find out remember. I mentioned early in this talk about the pharmacologically driven toxicity. Let's say there's another place in the genome that has has a similar sequence. We end up having the drug acting by its intended action bit at the wrong place which is an off what we call an on target but unwanted toxicity existed that could arise by modulating genome which is a little scary right to put something into the spine or once. You invoke gene therapy. What's done is done so you need to have really careful toxicology evaluations that look at the animal as if it were a miniature clinical trial? And you know you're basically siklie handling the animals has patients and so we get as much information as we can vary from each particular experiment and try to make sure that Ed's translation Lee accurate for predicting patient risk. We need the parents to know that right. If if you were me. Resigning are up to our child. An an in-and-out shoes you have to. You have to feel as if you've done the best job possible to make the you don't make something worse. It was unintended that. That's what I was going to mention A. I would understand that the pretrial stuff for this would be a lot more complicated and a lot more involved when it comes to nonlethal genetic mutations nations right I think angel men syndromes a great example of that. Alison Barrington. Genetics and fast work together with us to work. Ghana therapy for Angelman Syndrome. And these children again can be diagnosed as young as allison's daughter Quincy but but these kids are very happy. They live long and normal links lives but like a severe autism. There's many things that they can't do and require constant oversight site for their entire lives much as a toddler so the caretaking responsibilities are huge if an intervention could make these children able to to participate in fuller lives to be especially to come verbal and communicate with their parents. Prime thing is we wish we knew what they were thinking and they they are thinking all kinds of things. They're shooting into what's around them very much there's intelligence and an interaction and socialization there. They can't talk. We need to make sure that we cultivate an appropriate risk-benefit approach to each one of these patients groups absolutely so I think what you're saying is that there needs to be a balance absolutely so again. This is part of the patient driven medicine initiative. Each patient subgroup has to be looked at in terms of the context of their disease natural history the availability of other medications to treat them for these kinds of diseases. I'm talking about people that have completely unmet. Medical need that have never been able to have intervention mentioned before. And that's what's so exciting. As for the first time in history I guess starting with the advent of gene therapy in the early early ninety s we started to see the ability to for instance fix skid severe combined immunodeficiency and so it's been slow progress progress boat were. I think we're here now. I think so too and it looks to me. Like regulation is doing. Its best to keep pace with science and we're part of the MIX and trying to help cultivate that. What would you call it an unbiased? And and stakeholder collaboration that's required to bring these about quickly absolutely well thank you for taking the time to talk with me about these complex issues. I'm delighted to have a chance to and I'm so enthusiastic together. Chance to get this word it out and to make sure that people know that. There's there's hope for patients on today that before didn't have an opportunity absolutely well. Thank you

FDA congressman Jaycee Mary Parker Nih Dr Loren black severe combined immunodeficien protease inhibitor Charles River Batten Rico Lauren Peripheral neuropathy Bannon Barrel Drugs Group Divi Lou GEHRIG Dr Neil Snider AIDS LS LS center Ghana
Mild or Moderate Covid-19

NEJM This Week - Audio Summaries

27:20 min | 9 months ago

Mild or Moderate Covid-19

"Welcome this is the New England Journal of Medicine. I'm Dr Lisa Johnson. This audio program provides the full text of mild or moderate Kovic nineteen a clinical practice article by Reject Gandhi from Massachusetts General Hospital. Boston John Lynch from the University of Washington School of Medicine. Seattle and Carlos del Rio from emory university school of Medicine Atlanta. This article was published in the New England Journal of Medicine on April. Twenty Fourth Twenty Twenty mild or moderate co vid nineteen seventy three year old man with hypertension and chronic obstructive pulmonary disease calls to report that he has had a fever maximal temperature thirty eight point three degrees Celsius and a dry cough for the past two days. He notes that his shortness of breath has worsened. His medications include low Sutton and inhaled glucocorticoid. 's He lives alone. How should he be evaluated if he has Corona Virus Disease Twenty Nineteen Cove in nineteen the disease caused by Severe Acute Respiratory Syndrome Corona virus? To SARS covy to then how should he be treated the clinical problem corona virus typically? 'cause common cold symptoms but a two. Beta corona viruses SARS covy one and Middle East Respiratory Syndrome CORONA VIRUS. Merce covy can cause severe pneumonia respiratory failure and death in late twenty nineteen infection with Evil Beta corona virus subsequently named SARS covy to was reported in people who had been exposed to a seafood market in Wuhan live animals were sold since then there has been rapid spread of the virus leading to a global pandemic of Kovic nine team. We discussed the presentation and management of Cova Nineteen in patients with mild or moderate illness as well as prevention and control of the infection discussion of covert nineteen that occurs in children and during pregnancy and of severe disease is beyond the scope of this article strategies and Evidence Corona viruses are. Rna viruses that are divided into four. Genera- Alpha Corona viruses and Beta corona viruses are known to infect humans SARS v two is related to Bat Corona viruses and to SARS. Covy won the virus that causes. Severe Acute Respiratory Syndrome SARS similar to stars. Covy one SARS covy to enters human cells through the NGO tencent converting enzyme. Two eight two receptor. Soroush covy to has ornate depended RNA polymerase and prices which are targets of drugs under investigation. Transmission SARS covy to is primarily spread from person to person through respiratory droplets which are typically released when an infected person coughs or sneezes because droplets usually fall within a few meters. The likelihood of transmission is decreased if people remain at least two meters apart. Transmission is thought not normally occur through the inhalation of aerosols variance suspended in air but there are concerns that the virus may be aerosolize during certain activities such as singing or procedures such as interbay. Shen or the use of nebulizers and that it may linger in aerosols for more than three hours. Sars covy to are a has been detected in blood and stool although fecal oral spread has not been documented. Sars covy to May persist on cardboard plastic and stainless steel for days as a result contamination of inanimate surfaces may play a role in transmission a major challenge to containing the spread of SARS covy to is that pre symptomatic people are infectious. Recent reports suggest that patients may be infectious one to three days before symptom onset and that up to forty to fifty percent of cases may be attributable to transmission from ASEM dramatic or pre-symptomatic people just before or soon after symptom onset patients have high nasal for initial viral levels which then fall over the course of approximately one week patients with severe disease. May shed the virus for longer periods. Although the duration of infectious viral shedding is unclear clinical manifestations the median incubation period from exposure to symptom onset is approximately four to five days and ninety seven point five percent of patients who are symptomatic. We'll have symptoms with in eleven point. Five days after infection symptoms may include fever cough sore throat. Malays and my Aljaz. Some patients have gastrointestinal symptoms including anorexia nausea and diarrhea and Osmania and Agouza have also been reported in some series of hospitalized patients. Shortness of breath developed a median of five to eight days. After initial symptom onset its occurrence is suggestive of worsening disease risk factors for complications of Covert Nineteen. Include older age. For example older than sixty five years cardiovascular disease chronic lung disease hypertension diabetes and obesity. It is unclear whether certain other conditions kidney disease immunosuppression cancer and uncontrolled. Hiv infection confer an increased risk of complications. But because these conditions may be associated with worse outcomes after infection with other respiratory pathogens close monitoring of patients with Kovic nineteen. Who have these conditions is warranted established and potential risk factors for Severe Kovic? Nineteen are summarized in Table One laboratory findings in hospitalized. Patients may include lymph. Oh Pina and elevated levels of Di di Mer lactate dehydrogenation c reactive protein and Farrington at presentation. The pro calcitonin level is typically normal findings associated with poor outcomes in some series include an increasing white cell count with lymph opini. A- A- prolonged pro thrombin time and elevated levels of liver enzymes lactate dehydrogenation deamer interleukin six C reactive protein and pro calcitonin when abnormalities are present on imaging. The typical findings are ground glass. Oh pacification or consolidation diagnosis the diagnosis of cove nineteen is usually based on the detection of SARS covy to by means of polymerase chain reaction. Pcr Assay soon. After symptom onset the sensitivity of C are testing of nasal swabs appears to be high but false negatives may occur with certain frequency if a person is suspected to have covered nineteen but has negative testing of a nasal torrential swab repeat. Testing is prudent especially if that person lives in an area with active community transmission the type of specimen that is collected depends on which specimens have been validated for use with the specific. Pcr test most PC are essays used in the United States contested nasal for NGOs swaps. A video demonstrating how to obtain a nasal fringe. Swab specimen is available at any J. M. Dot Org however laboratories are increasingly able to test sputum and lower respiratory tract specimens sputum samples or Endo tracheal aspirants from intimated patients may be easier to obtain in some settings and testing of sputum may be more sensitive than testing a nasal swab sputum induction is contra indicated because of concerns about Aristotle Ization there are limited data regarding the use of oral fringe. Ill swaps in one. Study testing of these swabs was less sensitive than testing of nasal for NGOs swabs particularly later in the disease. Course if a nays over Angel Swab cannot be obtained for example because of supply shortages the Centers for Disease Control and Prevention. Cdc recommends the use of an oral for NGO SWAB THE FOOD and Drug Administration. Fda recently recognized onsite self collection of an anterior nary specimen as an acceptable method of collection. This option may facilitate home based testing and reduce exposures for healthcare workers evaluation evaluation and management of covert nineteen is guided by the severity of the illness. According to initial data China eighty one percent of people with Kovac Nineteen had mild or moderate disease including people without pneumonia and people with mild pneumonia. Fourteen percent had severe disease and five percent had critical illness. Patients who have mild signs and symptoms generally do not need additional evaluation and depending on the risk profile they may not even need to undergo covert nineteen testing since the infection will usually resolve however some patients who have mild symptoms initially will subsequently have precipitous clinical deterioration that occurs approximately one week after symptom onset in patients who have risk factors for severe disease close monitoring for clinical progression is warranted with a low threshold for additional evaluation if new or worsening symptoms such as dystopia develop in patients with initially mild illness. Additional evaluation is warranted. A physical examination should be performed to assess for to Kip Neha Samia and abnormal lung findings. In addition testing for other pathogens such as influenza virus depending on the season and other respiratory viruses should be performed. If available and chest imaging should be considered if findings on the initial assessment are suggestive of moderate or severe illness. Hospitalization is generally warranted. Patients with moderate disease may have disc Nia but the blood oxygen saturation is usually at ninety. Four percent while the patient is breathing ambient air indicators of severe disease are marked to Kip Nia respiratory rate greater than or to thirty breaths per minute hypoc Sima Oxygen Saturation. Ninety three percent or less ratio of partial pressure of arterial Jn to fraction of inspired oxygen. Less than three hundred and lung infiltrates greater than fifty percent of the lung field. Involved within twenty four to forty eight hours laboratory testing in hospitalized patients should include a complete blood count and a comprehensive metabolic panel in most instances and especially if a medication that affects the corrected Cutie Cutie see interval is considered a baseline electrocardiogram should be obtained chest. Radiography is usually the initial imaging method. Some centers also use lung ultrasonography. The American College of Radiology recommends against the use of computed Tomography C. T. as a screening or initial imaging study diagnose Kovic nineteen urging that. It should be used sparingly and only in hospitalized patients when there are specific indications additional tests. That are sometimes performed include coagulation studies such as Di Diamond Measurement and tests for inflammatory markers such as c reactive protein and Ferret then lactate dehydrogenation creatine kinase and pro calcitonin. The prognostic value and clinical utility of the results of these and other tests remain uncertain management of mild or moderate. Kovic nineteen took patients who have mild illness usually recover at home with supportive care and isolation in accordance with guidelines. It may be useful for people who are at high risk for complications to have a pulse similar to self monitor the oxygen saturation patients who have moderate or severe disease are usually monitored in the hospital if there is clinical evidence of bacterial pneumonia empirical antibacterial. Therapy is a reasonable option but should be stopped as soon as possible. Empirical Treatment for influenza may be considered during the period when seasonal influenza transmission is occurring until results of specific testing are known there are no approved treatments for Kovac Nineteen thus people with covert nineteen should be referred to clinical trials. Several agents have been touted as treatments for cove. Nineteen but at this point. The data are insufficient to inform recommendation for or against the use of these agents. Outside of clinical trials. Well conducted randomized. Trials will be critical. In determining how Kovic nineteen should be treated hydroxy chloroquine and chloroquine with or without a Zithromax sin chloroquine and hydroxy chloroquine have in vitro activity against SARS covy to perhaps by blocking and will transport hydroxy chloroquine also has anti inflammatory effects. Chloroquine is recommended in China for the treatment of Kovic nineteen but high quality data are lacking to show whether it or hydroxy. Chloroquine is safe and effective for this indication. A small open label. Non randomized study from France showed a higher rate of SARS covy to clearance by day six in fourteen patients who were treated with hydroxy chloroquine then in patients who declined to participate in the study or were at a different clinic. The effects appear to be greater in the six patients who are receiving chloroquine combined with Zithromax in six patients. In the hydroxy chloroquine group were excluded from the analysis of factor that potentially biases the results a case series showed high rates of viral clearance and clinical improvement in patients treated with hydroxy. Chloroquine plus Zithromax Jason However both studies had substantial methodological limitations including a lack of adequate comparison groups. A small randomized trial showed no significant difference in SARS covy to clearance or the disease course between the hydroxy chloroquine group and the Control Group results from additional studies are currently available as non peer reviewed. Prince one small trial for which important details are not yet available. Showed a modest improvement. In the group that received hydroxy chloroquine as compared with a control group whereas other studies did not show increased viral clearance or clinical benefit with hydroxy chloroquine steady limitations preclude definitive conclusions safety concerns with hydroxy chloroquine and as three mice include the potential for q t C. prolongation which is greater when both agents are used together a study in which patients received high dose. Corcoran was stopped because of a trend toward excessively high mortality determination of the role of hydroxy chloroquine with or without as throw mice in for the treatment of cove nineteen hinges on the results of well conducted clinical trials the FDA has issued an emergency use authorization easy way for the use of chloroquine and hydroxy chloroquine from the strategic national stockpile for the treatment of hospitalized adults with Kovic national team but this action does not constitute FDA approval of these rights for this indication the EU way encourages the conduct of and participation in randomized control trials to provide evidence for the effectiveness of these drugs for the treatment of Kovic. Low Pin. Aveer Retana Vir Lapenne Aveer Ritonavir an HIV. One protease inhibitor has been proposed as a treatment but it is not known whether drug levels adequate to inhibit the stars covy to produce as can be reliably achieved in people with Kovac nineteen. Who received this medication? In an open label randomized trial involving one hundred ninety nine hospitalized patients the addition of Lopin of your return of air to standard care did not result in faster clinical improvement or brisker drops in SARS covy to are in a levels at this time. Most experts advise against the use of low of your return of year or any other HIV one protease inhibitor for the treatment of covert nineteen outside of clinical trials in addition people with HIV. One should be discouraged from changing their antiretroviral regimen to one that includes an HIV one protease inhibitor given the lack of data supporting the use of such drugs for the treatment or prevention of Cova Nineteen. Remm DEZ Aveer Rendez Aveer an inhibitor of RNA. Dependent aren a polymerase has had activity against SARS covy to in vitro and against other corona viruses in several animal models in a case series involving patients with Severe Cova. Now who received Rendez Aveer through a compassionate use program? The majority of patients had a decrease in the need for oxygen support but there was no comparison group results of ongoing phase. Three randomized controlled. Trials are anticipated Immuno modulation because of concerns. That a hyper inflammatory. State may drive. Many of the severe manifestations of covert nineteen several immunomodulating therapies including glucocorticoid convalescent. Plasma and anti cytokine therapy are under investigation largely in patients with severe disease. Discussion of these agents is beyond the scope of this article use of concomitant medications in people with Kovic teen because SARS covy to enters human cells through the two receptor questions have been raised regarding whether the use of ace inhibitors or NGO tencent receptor blockers a bees which may increase ace two levels might increase the acquisition of SARS two or the severity of Kovic nineteen however given the absence of definitive clinical data. The current recommendation is that patients who are receiving ace inhibitors or a RV's for another indication such as hypertension or heart failure should not stop taking these agents routinely even if they have cove nineteen. Some reports have suggested a possible deleterious effect of Non Steroidal anti inflammatory drugs on the course of Kovic nineteen but several authoritative organizations have noted the absence of clinical data to support. This concern. Concerns have also been raised about the use of glucocorticoid and some guidelines suggest that they should not be used in patients with Cove Nineteen. Monja the use of systemic or inhaled. Glucocorticoid should not be stopped in patients. Who are taking them. For other indications infection control and prevention healthcare workers must be protected from acquiring SARS covy to providing clinical care using telehealth when possible reducing the number of healthcare workers who interact with infected patients and performing healthcare. Environmental cleaning are critical personal protective equipment. Pp should include at a minimum an isolation gown gloves a face mask and eye protection goggles or a face. Shield the use of droplet contact precautions again. Gloves face mask and protection for the routine care of patients with Kovic. Nineteen is consistent with guidelines from other countries and the World Health Organization. Who the CDC prefers? The use of a respirator usually an end ninety five filtering face. Peace respirator a powered. Air Purifying respirator. Pa PR unit or a contained. Air Purifying Respirator C. Apr Unit instead of a face mask however in the context of supply shortages the CDC regards the use of face masks as an acceptable alternative the CDC and the WHO both recommend the use of enhanced protection for Aerosol generating procedures including the use of a respirator and airborne infection isolation room at sites where enhanced protection is not available the use of Nebulizers and other aerosol generating procedures should be avoided when possible recent studies indicating that transmission occurs before symptom onset may support unit droplet contact precautions for all initial patient encounters strategies to facilitate infection prevention and control are needed for people with unstable housing. And people who live in congregate settings where physical distancing is inconsistent or impossible such as dormitories jails prisons detention centers long term care facilities and behavioral health facilities in Table. Two SARS covy to transmission. According to the stage of infection is shown areas of uncertainty numerous uncertainties remain in our understanding of the spread of Cova and its management the contribution of transmission from a symptomatic and pre-symptomatic people to the community and knows a call meal spread of SARS covy to and the extent to which foam lights and aerosols those not generated by medical procedures. Contribute to transmission are unclear data to inform treatment remain limited trials are in progress to assess the effects of various medications such as hydroxy chloroquine with without Zithromax in Rendez Aveer and fava's pure of year which has anti-influenza vity on the disease course in patients with different severity of as well as to evaluate hydroxy chloroquine as prophylaxis in high risk or exposed people studies are underway to develop ineffective back him? It is unknown whether infection confers partial or unity and if so for how long and weather results of serologic testing can be used to inform when healthcare workers and others can safely return to work guidelines in a rapidly changing pandemic many professional organizations have developed interim guidelines for the management and prevention of Kovic Nineteen guidelines from the Infectious Diseases Society of America and the National Institutes of health highlight the fact that there are no proven therapies for Cova nineteen and that randomized trials are critical conclusions and recommendations. The patient in the Vignette is at high risk for having Cova nineteen with potential complications given his disk NIA and risk factors for severe illness. The authors of this Review Doctors Rajesh Gandhi John Lynch and Carlos del Rio would refer him for. Pcr testing of nays. Oh for NGO SWAB FOR SARS. Covy to along with an examination and chest radiography. He should be advised to wear a mask on route. After arrival at a healthcare facility he would be given a surgical mask and promptly escorted to an examination room. Admission would be warranted for close monitoring given his disk Nia and increased risk on the basis of the limited available data doctors. Gandhi Lynch and Del. Rio would continue his RB and inhaled glucocorticoid. It's in the absence of high quality data to support any covert nineteen specific therapy doctors. Gandhi Lynch and del Rio would recommend enrollment in a randomized clinical trial. If possible when the patient's condition improved sufficiently for discharge. He should be advised to remain isolated. The minimum of seven days after symptom onset and for at least three days after resolution of fever and improvement in respiratory symptoms there may be additional local guidance regarding the duration of isolation. This concludes the reading of mild or moderate Kovic nineteen a clinical practice article by Doctors Rajesh Gandhi John Lynch and Carlos del Rio to see the complete text with references and complete web addresses as well as accompanying tables figures. Disclosure statements acknowledgments supplementary material or subsequently publish corrections. Please visit any. Am Dot Org. Any comments or suggestions may be sent to audio at any J. M. Dot Org. Thank you for listening.

chloroquine Kovic Kovic Nineteen Cove glucocorticoid SARS Merce covy Cova fever Gandhi Lynch Cova Nineteen Kovac New England Journal of Medicin Cdc pneumonia Hiv infection Fda Fourth Twenty Twenty
Tony Fauci, the nation's top infectious disease doctor

POLITICO's Pulse Check

33:35 min | 1 year ago

Tony Fauci, the nation's top infectious disease doctor

"I was presented by our incredible CDC director, Dr Bob Redfield, and Tony falcon who runs our nationals of allergy and infectious disease, saying, you know, what mister secretary we have the data that tells us where we have to focus. We have the tools we have the leadership. Now, this is an historic opportunity, and I was immediately captivated that we could solve one of the greatest public health challenges of our time. I'm Dan diamond this pulse. Check. And that was h secretary Alexander discussing on NPR by the Trump administration is pursuing its issue strategy as the secretary mentioned one person helping set the strategy is twenty thousand the nation's top infectious disease, doctor in the legendary figure for his five decade career as a government health physician. You may have seen him on TV during recent outbreaks of flu and a Bulla he someone I wanted to get on this podcast for a long time. And you'll hear us talk about his path the new HIV strategy and more before that reminder that if you like politico balls, Jack you can help us by rating or reviewing the show if you're interested in the HIV strategy, we discuss check out a podcast for a few weeks ago with Jen Cates. The Kaiser family foundation, we got more into detail about why the nation's HIV problem has persisted. And what the current strategy would do. With that. Let's get to Dr Tony thoug-, Dr Tony thoug-. Welcome to politico. Pulse. Check. Thank you. It's good to be with you. You've been at an ex for fifty years. Fifty one years a fifty years, right? You've run the National Institute of allergy and infectious disease for thirty four and a half years you've been doing this work longer than many listeners have have been alive. Why? Well, first of all, I think it's very it's an important issue. The issue of of health particularly in the arena of infectious diseases, I trained after I had a full training in internal medicine. I did a fellowship combined in infectious diseases and immunology and got fascinated by elements of the interaction of the interface between the body's ability to fight infection and the actual microbe itself. And what's happened over the years as it's evolved. The reason I still feel as refreshed than is excited about. What I do is that it's an ever changing challenge. I mean, the first really big challenge that I was confronted with as a science and science administrator was when I began became involved in HIV back in nineteen Eighty-one and HIV is is kind of the the the the Pitta me of an emerging infectious disease that can transform societies. And at the time known even knew it was well, no, I mean, it was an extraordinary period of my life. I had been working in the interface between immunology and infectious diseases following my medical training. I did that for about eight or nine years. And then when I I noticed the first cases of curiously gay men from L A who presented with the strange Numa Misys pneumonia that I was very well familiar with because I was an infectious disease expert as it were. But that only occurred in people had very compromise. Immune systems. I had no idea. What it was? That was an MSW war that appeared in June of nineteen Eighty-one MMWR morbidity and mortality weekly report, which is the CDC's kind of alert publication about what's new in infectious disease. What's going on? I didn't make much of it. I thought it was a fluke and then one month later in July of nineteen Eighty-one. There was a second report in that journal now of twenty six curiously all game in not only from way. But from San Francisco and New York who presented with these bizarre infections and captures Oklahoma. And that day that I read that I I would say without personally really changed my life, my professional career in my life because I decided that this was something brand new and it was scary. And it was going to be huge. So I changed the direction of my research from doing things in fundamental -nology and autoimmune diseases to decide that I was going to start bringing in. These young men who at the time role gay men and study them to see if we could figure out what it was. So that was in the summer of nineteen Eighty-one, and I have been doing my own research and HIV since then, but in one thousand nine hundred four when I was offered the job as the director of the infectious disease institute, I'd never wanted to get into science administration. I'd been fundamentally clinician and scientist, but I felt that that was something I needed to do to call attention, not only to HIV, which was phenomenal example of the incredible impact of infectious diseases, but all infectious diseases, and it's been a changing landscape over the years. It's just changed Ebola Zeka things like that. Well, since you bring up HIV, let's just park there for a second. And my understanding Dr is that in the nineteen eighty s there's a lot of frustration toward the federal government in terms of its response around HIV and aids whether they're going to be enough funds. Whether the Reagan administration was going to be a friend to. LGBT community. What position to that? Put you in. Well, I mean, I it put me in a position of some discomfort. But I try to remedy it. And I think slowly were we were able to erode that profound stigma and sometimes even nonchalant approach towards something that was exploding into a play the problem with the early years of the Reagan administration is that he could've used the bully pulpit of the presidency to call attention to what I have been saying in a couple of my colleagues were saying this is going to be really big we've got to do something about it. Now. In fact, I wrote an article in nineteen eighty one that wasn't published till eighty two saying anybody with thinks this is going to stay confined to a relatively small group really doesn't know what they're talking about. And it wasn't until the second term of Reagan that even mentioned the word. Word aids. Which was really unfortunate. The good news started when George H W Bush when he was vice president decided he really wanted to learn a little bit about HIV and came to the H. And that's when I developed a very close relationship with him. So that when he became president. Although many would say still didn't do enough. He really got the ball rolling in in getting the funding for HIV up there where it should be when his son George W Bush ended up expanding HIV aids work around the globe with pepper involve. Yeah. Well, I, you know, George W Bush, regardless of with anybody feels about any other aspect of his presidency is historic in what he did with pep far. I mean, he did it because of all the right reasons because I can remember very clearly called me into his office at the White House at a meeting and said that he feels strongly that as a rich nation. We have the moral responsibility now to make sure that people. Who live in a different part of the world. Don't die of something that we could treat them with mealy because of where they live who they are. And how poor their country is in the spring of two thousand and two he sent me to Africa with the group to do a fact-finding. Can we do something? And remember by two thousand and two we already had the triple combination that were really transforming HIV in the United States, the triple combination of anti retroviral drugs. That's when the protease inhibitor kicked it off. We even have better drugs in the protease inhibitor now, but back then as we will giving people the triple combination people who otherwise looking at a death sentence. We're actually going back to relatively normal life, and he was struck by that that we have it here in the United States. Can we be doing something for the people in the developing world, and he asked me to put together the program. And that's how we got that far. I'm struck doctor you've worked with multiple presidents administrations. Over over your time. You have personally appealed to the leader. Of the nation to make things a priority. What is the most effective way to sway a president? Is it about this is an immediate problem? This is a legacy issue. This is in the best interest of America something else. No. It's it's a combination of things. And and I think. Any success? I had was in being over the years viewed as an honest broker who tells the president things that he or she may not even want to hear an and I learned that lesson a long time ago, if you wanna be able to keeping coming back to the White House, two different presidents, you've got to get a reputation that you're not self serving in that you're coming with some facts about some important things. So right now, and I've done it with every president since Reagan was to to tell them the truth about what we need to do. You know, you someone told me, and it's important lesson whenever you walk into the White House. Just make sure that you realized that this may be the last time you have a walk in because you may have to tell the president something he doesn't like, and then they don't wanna talk to you anymore. However, the good side of that is that if you do it with honesty and with basing on evidence and facts, it turns the other way. And you gain a reputation that they do want to talk to you even this administration. Well, you know, I haven't had personal interactions with the President Trump, but though the interactions with the department of health and human services, particularly with the secretary as who I knew back in the George W Bush years because he was the general counsel at HHS, and then became deputy secretary. So he was there when we put pep fought together. So he knows what a strong administration can do. My understanding is that you've were you've worked with something like seventeen different HHS secretaries, even counting the acting ones where where to secretary as our rank, you know, I think he ranks right up there as somebody who gets it who clearly has an understanding of what positive impact the department of health and human services through NIH through FDA through CDC. These are all components of HHS. This administration has tried to cut some of those programs. And funding over the past. That is true. We're in a very tough situation here where we have, you know, the the the coal from the from Owen be to be making dramatic cuts at the same time that the congress keeps bailing us out and helping us I mean for us at NIH, it has been that way for the last couple of years, you know, the original budget that was proposed for the h was a dramatic cut. But thanks to a bipartisan support in the house in the Senate when the house and the Senate were both Republican. It was interesting that they not only rejected the budget that the president put out but actually gave us a couple of billion dollars extra. I wanna go back to President Trump and the HIV plan that he announced at the state of the union to effectively 'em HIV transmission plan, the you helped devise with big focus on prevention. I broke that story. So I got to see the reaction from advocates right away. And they're. Was deep skepticism there, there were folks were even worried about what it could mean for LGBT patients given other administration policies do understand that skepticism. Oh, I absolutely understand the skepticism. And and you know, my response to it is that the program was driven. You know by people who have a deep commitment to working with the appropriate communities to get this done including and specifically the Q community. So when you feel you talk about how this occurred, you know, I have been trying and it was it's been going back a couple administrations saying we now have the tools to end the epidemic. You treat. Somebody you get the viral load to below detectable level, they will not transmit to a sexual partner. You give somebody prep who's at high risk decreased by ninety seven percent prep. Prepping drug from Gilead exposure prophylaxis in this case Trotta will working on other types of drugs. But right now, it's it's Travolta you could decrease by ninety seven. In percent. The likelihood that an individual will acquire infection. So when we had the tools the question is why don't we try and implement them in a very aggressive fashion at that time Bob Redfield who became the CDC director and his background like mine, very similar was steeped in HIV aids. So we started talking to saying maybe we should see if we could put together an initiative, so we bought it with the people from her. So we partnered with the people from Indian health service, and we had Breteuil who's the assistant secretary bought into it. He said this might be a good idea. Let's bring it to Alex as Aw. So we brought it to secretary as oh. And and as I would have predicted he thought this was terrific idea. Let's do it. And it was it was secretary Azores idea to bring it to the president and say, okay, can we make this a presidential initiative? And that's when the president announced that at the state of the union address on February fifth you met. Mentioned prepping and Travolta the drug company Gilead polls, the patent on that which is very expensive. Jennifer cates. From Kaiser family foundation, who I think, you know, she was on this podcast a few weeks ago talking about distraction can only go so far right given how expensive the drug is if we really want to prevent HIV that drug needs be cheaper. Yes. Has Gilead sent any signal that they are willing to cut the price of this. You know, I haven't been dealing with them in that regard. But I can confirm you that clearly prep will have to be very important part of this ending the HIV epidemic in the United States plan that we've put forth to decrease by ninety percent of new infections in ten years and seventy five percent in five years prep is going to be critical to that. And you're absolutely right. We have to figure out some way, I hope that we can to get the price of that drug dramatically lower than it is right now we have to do that. Otherwise, we're not going to be. To do the plan. One more V questioned the US government spends tens of billions of dollars on HIV and aids domestically abroad, some of that's through mandatory program. Some is in research. My understanding is you're quite involved in research about how much of the three billion dollars spent on aids research goes to vaccines and how much goes to antivirals show. Oh, I could tell you that since that's part of that's part of my budget. So we spend now if you look at all of the aids money right now, we spend about thirty to forty percent of it. Now on vaccines. We used to spend forty to fifty percent on any retrovirals. But because we have so many good anti retrovirals right now that it isn't that? We'll pulling back on it. But we're not emphasizing as much as HIV vaccine HIV prevention monoclonal antibodies that you could passively transfer. If you put all that together, it's not quite half. But it's getting there. How close are we? HIV vaccine that that's a very good question. And it's not an easy answer. Because I can tell you that we are not going to have a measles like vaccine for HIV. We're not gonna have something that's ninety seven percent effective when we know that because of the very peculiar nature of HIV that the body does not regularly make a very good response. So we almost have to do better than what natural infection does. So what my vision and the vision of many of my colleagues are is that if we could combine treatment as prevention with pre exposure prophylaxis with circumcision mostly in the developing world together with the vaccine that's about fifty to sixty percent affective. I think we could turn around the dynamics of the pandemic both domestically and globally. I really do believe we have we don't need. Well, I wish we had it. But we don't really need a ninety eight percent effective vaccine because we have combinations of prevention that we can use. Here's you're seeing it as a. Tool in the toolbox. Many tools in combination toolbox. You mentioned measles who maybe this is a good opportunity to pivot to some of the other public health challenges that come across your desk. How much does it hurt your heart to see the resurgence of vaccine? Preventable. Diseases like measles. It really troubles me. A lot, you know, as an infectious disease person who's devoted my professional life to preventing and treating infectious diseases to see turning victory into defeat is very troubling. I it's it's it's ironic and paradoxical that with measles. We have one of the most contagious viruses known to man, it is so easily transmittable if you had measles in this room that were recording in and left the room. And I came later it's possible that I could get it. You're not immune there'd be a ninety percent chance that you would get. It's really that Trump whereas in other infections like flu and colds, there's a five to ten to fifteen to twenty percent. But it is a very transmissible virus on the other hand, the measles vaccine is one of the most effective vaccines known to man. So you have the tool in your hand to not only control, but to eliminated an even if we needed to eradicate it and to have people for reasons many of which are just not valid in based on false information decide they don't want to vaccinate children. Then you get the kinds of outbreaks that a causing the crises we're seeing right now in New York City and the Williamsburg section or in Rockland county, or in the state of Washington that should never happen. This is entirely avoidable. New York City had to issue an emergency alert calling for mandatory vaccination exact, and this is the orthodox Jewish community. And in New York City, exactly. So do you see these vaccine preventable diseases coming back because of either misinformation around vaccines, or or is it just deeper stigma and fear in some of these isolated communities like the orthodox Jew? You know, I think there are a lot of factors that are that are involved with measles. It was a lot of misinformation. For example, the incorrect and false information saying that there was a relationship between measles vaccine and autism, which is completely not true. But in general in addition to this anti vacs of feeling and movement that there is not only in the United States, but in many countries throughout the world. It's a combination of full information that people cling to as well as kind of anti-scientific anti-government libertarian approach that we don't want anybody telling us what we need to do with ourselves. Even though what we don't have. Because if you turn back the clock decades and decades at a time when diseases were rampant and. Children and otherwise healthy adults would dying vaccine preventable. Diseases people were fighting and struggling to get vaccines to use them. Now, we're almost a victim of our success because got people about what it's like to have diseases like diphtheria, and measles and polio and things like that. So, unfortunately, we're having a resurgence of this. I hope that we don't have to get to. I told you so situation where we have the resurgence of these diseases, and then people will say, oh, I guess, you're right. We should have been vaccinating people. You're the nation's top infectious disease. Doctor what disease scares you the most right now well disease that has not yet occurred. What what I think can have the most profound devastation in society is if we get a brand new influenza, that's a pandemic flu of which individuals don't have underlying cross reacting immunity. The too, and we have the repeat of what we saw in that icon ick year of nineteen eighteen when we had that so-called Spanish flu, which wasn't really a Spanish flu. But it kills fifty to one hundred million people I've actually seen there is a museum that has an exhibit on on the fluids up in Maryland. I can't remember which healthy agency runs in. But I went to this museum few months ago. And the suggestion was it wasn't a Spanish flu may have come out of a military camp in the United States, it likely did I mean, we don't know exactly where it came from. But the one thing that we know it didn't come from with Spain. And the reason why they call it the Spanish flu is that emerged during the first World War and Spain was one of the noncombatant countries during the first World War. So when they had this big outbreak. They were not reticent to say, hey, we're having this this horrible outbreak of a flu whereas all the other countries because they didn't want to appeal a week to the rest of the world never really admitted until it was Peyton the obvious. So they said, well, this must be the Spanish flow because the. Manish talking about it. Yes. There was a story. Just this week in the New York Times on a fungus right that that is under the radar and starting to infect patients in hospitals is is that a top concern is that stole a concern that is more suited for worrying about in in the papers of in the pages of newspapers, but not present for doctors around the country. Well, the the situation that he was speaking about is a fungus called Candida Auras, which is a fungus that has now emerged in a very disturbing way. It falls under the broader category of antimicrobial resistance, pathogens microbes, the reason this is disturbing is that really is brand new because Candida as a species generally eminently treatable by a variety of drugs that we have you know, you have Thrush in the mouth and vaginal candidiasis, you generally think of it except for an immunise oppressed person which. You could really be a problem, which you can also treat all of a sudden I recognized in two thousand and nine in Japan comes this fungus, that's from common family called Candida, which is spreading rapidly. It's very difficult to remove from surfaces in the hospital the way it was described in the New York Times. But the people who are particularly vulnerable people who are immune to suppress cancer patients people on immunosuppressive therapy for variety of reasons. People who have underlying him into the press diseases. Those are the ones that are truly at a high risk. So this is something that is more than just a trivial curiosity. We really have to keep ROY out on this given the threat of these diseases where were these microbes that are resistant? Have you urged any administration to make this more of a priority? Yes, yes. We urge them, but we didn't really have to because they were already over at the CDC is very concerned about this and back in the Obama admit. Ministration? We spoke a lot about the importance of cooling attention to this and President Obama put out an executive order to create a interagency one government approach involving the CDC the department of agriculture, the NIH the food and Drug administration in a variety of things ranging from surveillance to looking at agriculture use of it appropriately to research that we do at NIH. So the specific answer to your question is yes, we've dealt directly with the ministrations. And we now have a carryover of that in micro resistant initiative right now up to the present day secretaries or has has spoken about go back to something you said earlier, doctor, you said that when you go into the White House, you have to be prepared for it to be the last time, and that that is in some ways freeing because then you have to give the advice that you think the president needs in your time. Was there ever a moment when you walked into the White House and thought what I just hold the president? That's it for me that I've I've said the most. Correct thing. I could and my career might be over now. Yes, it wasn't. It turned out to be something very very positive because it led to a really strong and warm relationship and friendship between me and president George H W Bush because when I went into the White House and sat down with him because he had asked me when he was vice president that he wanted to learn a little bit more about this disease HIV that he knew I was connected with and I remember at a meeting in the White House in the Oval Office when he asked me about how we were doing. And I said Mr President, we are not doing very, well, we really need to do more. And you know, if you your legacy is going to be hurt if we do not pay more attention to this. So we could have looked at me and says oh to hell with you get out of here, and I wanna see it. But he didn't he didn't he listened? He says we'll tell me more about it. And I did and I sat down and spoke to him about it. And then as the months and years went by it got better and better you've been doing this work longer than than I've been alive. So I wanted to run a theory by you in that that theory. Is that all the new fights are actually old fights just with new actors new details, but the same script coverage expansion funding for research new diseases is is that true? It is it is. I mean things just keep recycling in different ways on the different circumstances with different people. But I mean things like universal healthcare people not having insurance. This is in decades and decades of that all responsibility for global health. I mean, what what is the issue what kind of responsibility that we have when we partnering with the country. Should we be helping to build healthcare infrastructure health systems that a sustainable these arguments have been going on for forever? Really? If there was one fight that you wish we would never have to have again. What would it be? I think it gets back to the early years of HIV and getting people to really appreciate that the disease. Is the problem because we would dealing with such. It's a me painful of manifestations of stigma against the LGBT community, which is something that I hope we never ever have that kind of thing in this country again before we wrap up at a lightning round list of questions. I hope it's okay by you. I've heard that you've turned down the job of NIH director four times. Yes, that's true. It is why. Well, I just felt that what I wanted to do with my life. And where I felt I would have the most impact would be to focus on a certain set of diseases that I thought were profoundly important and those were the infectious diseases that we have just been discussing right now. And I felt that if I took the responsibility as NIH director, I would be responsible for many many important things, diabetes, heart disease cancer, all of which are important. But I didn't have a passion for them. I had a passion for h. Aids and other emerging infectious diseases, and I thought if I stepped into that is on Ariffin is that would be it was not really what I wanted to do. And is there a risk just being more involved in the political fights when you're up another level? Yeah. Political fights that I don't really feel like I wanna I wanna lay it on the line, whereas all be happy to slug it out with you. When you're talking about HIV aids. And other things I'm not interested in fighting with you. Like in good shape. And your command of the faxes is better than mine. I've been doing this podcast three years. I think you may be the first person to appear who's pulled the full Ginsburg think you've you've been pulled the full Ginsburg Royce twice. And that's where where someone appears on all the Sunday morning shows ABC CBS NBC, Fox News CNN CNN. How do you prepare for something? Like that. You know, there isn't any real preparation because the reasons that I was on those shows was to talk about something that I was doing every single day into the middle of the night worrying about it concerned about it. So when I got on the show, I mean, for example, when Chuck Todd would ask me a question. There was no way that he was going to ask me a question that I know that I know the answer do because I have been living with it throughout that entire time. Yeah. And just to be clear, you're doing all these shows the same morning the same day, you know, it was really interesting, and I have to say to a tipping of the hat to the. The communication staff at the White House because they arranged in a car to get me to every single studio on time. Some I did live some I did taped. But at the end of the day we had done all five shows for two Sundays in a row. It was like amazing. I could have never done it alone. That was the Abol that was evil. Yeah. Right. Do you know who the full Ginsburg is named for? Yes. Ginsburg was the lawyer for Monica Lewinsky. That's exactly right. I hear from tipsters that you ride the DC metro as an infectious disease expert. Do you have any tips on how to keep safe while riding public transportation? Whether that's a good question because I'm going to be getting on the metro right after we finished here to get back to the age. You know, what I try and do and tough sometimes when it's crowded, but if you see somebody that's sneezing and coughing all over the place to the best of your ability to try and sort of move a little bit away at least three and a half to five feet away. The other thing is is to wash hands. You know, we always talk about infectious disease, doc say wash hands. Is frequently as you can. And that's what I do. But other than that, you know, I I don't worry about and a lot of people don't wash their hands long enough as my understand twenty seconds with soap and water twenty seconds. A long time. It is you think it's short. But it's twenty seconds is a long time. There is a new head of FDA. Yeah. Acting head Dr Charles who I think you've worked with. Yes. I have you. You've seen agency heads come and go over the years. What's your advice to running an agency? Well, you know, I actually did have the opportunity to sit down with Ned who's a good good person, and a friend, and we developed a good friendship over the last year and a half since he's been the NCI director is that as a leader. You've got to be consistent in what you do and not change how you respond to something depending on the circumstances. And you've got to lead, by example, which which he did very well at the NCI. And I think he's going to do a great job at FDA in my job. I have to read the healthcare news every day. I'm. Curious. What do you read? What are you reading these days? Well, I try to keep up as best as I can with with the top medical journals that just give me the information that I need. I have a very very good staff of people who summarize the news items that relate either in policy or a scientific standpoint to what I'm interested in and every day at the end of the day. I get a stack about an inch and a half to two inches thick of papers with yellow highlighting about what I need to be. So I that's what I do a lot of reading, and I read the scientific literature. Very avidly. I have to do that have to keep up have to know what's going on. What's your favorite book about healthcare? I don't read about. I try to read books that are not related to help to to to sort of distract me. What are you reading right now right now, actually, I just finished a book by Sally field? Call in pieces, which is very troubling book about a very difficult childhood that she went through some sexual abuse. And and insecurities and things it was kind of a troubling book. So I alternate between a book about real things, particularly I love, you know, political scenes in Washington, I like that and biographies with pure fiction spy type thing. So right now, I'm reading one of many Michael Conway books about the Harry Bosch series. You gotta read that. If you haven't doing really good, I haven't. But I think they turned it into a TV. She did. And it's excellent. It's excellent. Yeah. Well, an endorsement from the nation's top infectious disease, doc for the Harry Bosch series and. We will let you get back on the metro, and I expect but travel safely several feet away from anyone who might is. Thanks very much. It's nice being with you. Nice to be with you to Dr. That's it for pulse. Check this week. My thanks to Dr Tony thou- Chee and his team at NIH and Mikhail Rodriguez. And the folks at politico for producing the show if you like politico pulse. Check you can help us rate review this podcast on your favorite podcast player. If you have suggestions for upcoming episodes. Find me I'm indeed island at politico dot com by Email, and you can find a new episode, politico pulse. Check in your podcast player next week.

HIV infectious disease disease vice president CDC White House director United States NIH secretary flu president MMWR morbidity and mortality Trump Kaiser family foundation George W Bush FDA New York City
Multiple Myeloma, Bicycles, and Working Toward a Cure

Healthcare Triage Podcast

33:49 min | 1 year ago

Multiple Myeloma, Bicycles, and Working Toward a Cure

"Looking back to the healthcare triage podcast? This healthcare Trieste podcast is sponsored by Indiana University school of medicine whose mission is to advance health and the state of Indiana beyond by promoting innovation and excellence and education, research and patient care. I you school of medicine is leading Indiana university's first grand challenge. The precision health initiative with bold goals to cure, multiple myeloma, triple negative, breast cancer, and childhood sarcoma and prevent type two diabetes and Alzheimer's disease. And that's perfect because today we're going to be talking about multiple myeloma our guest this week is rough it up norm. Who's the director of the mile Oma program at Indiana University school of medicine, we're going to be talking today about multiple myeloma? And where the cutting edge research is what people are doing what people are thinking where we might be going. So welcome. Thank you for joining us. Thank you for having me. Could we start a little bit? I've we're always interested in hearing about the backgrounds of our guests. How did you get to this position? How did you get interested in your research? How did you get here? So I started one. To become a transplant surgeon. But then I ended up doing just hematology followership and boomer transplant and I did my research on plasma cells. These are the cells that cause multiple myeloma. And then I started doing, gene therapy. And gene therapy was an exciting and dangerous. I needed to focus on something. So I knew plasma cells and I loved myeloma patients. So I decided to focus on that. So let's say what are plasma cells. So plasma cells are the cells that make antibodies to help us fight infection. We need them. That's how we survive, you know, one hundred years seventy years, whatever so one what happened is at one of these plasma cells become malignant and start reproducing itself and causing harm to the patient. So so there type of white blood cell. Yes, sir. Okay. Where they made. Well, they actually start in the lymph nodes, and then they migrate to the bone marrow where they reside. You know? So you get your first encounter was for example is a Tatton us or, you know, Newman. Yeah. Bacteria in the blood, and then the these cells much sure become plasma cells produce memory antibodies to help us fight infections, as you know, when we get exposed into the new Monia, and they reside in the moment when we need them. You know, they got out they make more new antibodies to help us fight infection. So can you talk a little bit more about how they work when they're working, right? How exactly do they help us fight infection? Well, they produce a specific antibodies. So we have a repertoire of plasma cells that capable of recognizing different pathogens, you know, from the mums to the measles to influenza to the new Monja and. And so every time we get exposed to one of these pathogens these plasma cells proliferate and produce more antibodies to fight the infection. So what happens when they produce the antibodies? What happens next? Well, the antibodies bite to the pathogens, and you just neutralize it or, you know, help other cells gobble it up. Okay. So what happens when things go wrong? Well, when things goes wrong is that one of these plasma cells start accumulating in the bone marrow. So you initially have for example, maybe five percent of normal plasma cells in the boom marrow. They don't cause any harm. We call that condition. Magas monoclonal Gama thief, undetermined significance just have a monoclonal protein doesn't cause harm to the patient. But what happened next is that tons of these cells stock, you know, accumulating in the bone marrow. They have like ten twenty percent, but it's still not causing harm. So we call that condition smoldering myeloma. And then eventually what happened is that these. Plasma cells can affect the patients in different ways. One is that it can weaken the bund so about seventy percent of patient was myeloma will have either osteoporosis holes in the bones or the star breaking bones. So they have you know, they just tried to lift a bag, you know, and then they break a bone in their back or something like that. So myeloma can affect the bones can cause a Nimia can cause very high calcium level because you lesion calcium out of the bone. So the patient become enable to think and may go into a coma or they can actually get kidney damage, so we call these of the crab criteria for diagnosing myeloma, the c is for high calcium, the are renal or kidney failure AMA or bone disease. So you have a lot of these abnormal cells in the and you have one of these criteria. Then we you know that patient has. Multiple myeloma. What makes the plasma cells? Go bad what what goes wrong? So we actually a lot of research going on in term of environmental exposures and just this week got big settlement against roundout because they when patients develop multiple myeloma from using them. So we think there is a toxic exposures farming communities. There's increased risk of multiple myeloma near factories, and you're mining communities, for example, I have patients in your a mine in south west, Indiana, where multiple people who worked in that minds developed multiple myeloma, you know, and the questions of what did they dumped into the water? These people are drinking water. And so I think we think chemical exposure plays a role in making these plasma cells so are become malignant, and multiply, and and you know, 'cause. Harman cosies. Okay. So once somebody is once we have a concern, they've met their the crab criteria. What what happens next to help make the diagnosis? So we do several things number one. Obviously, we need to do blood tests this anemic, they have high calcium or they have kidney failure. The the second thing is that we look for this abnormal protein because myeloma start from one plasma cells the protein, they produce is unique we call it mono clone protein. So we do a specific blood test to check for the monoclonal protein and find it we have to find a monoclonal protein or we find an abnormal part of that protein. Raise recall, it the free light chain. So we check that the second thing that we have to look and see what they have in the bone marrow. So we do a bone marrow biopsy to see the number of these abnormal cells, and what type of cells we do genetic analysis on those cells to see. What they do. Because my my Aloma patients some of them do very well, some of them, do okay. And some of them do poorly and the genetic makeup of the mile Oma can help you distinguish these three groups. So that was actually going to be my next question is sort of all cases of multiple myeloma the same or they already different or do. They fall into a bunch of category. Yeah. I mean, I think that term multiple may not be really because of multiple lesions was in the patients things multiple presentation of the disease. Okay. So I have patients who do very, well, they get one kind of tweet -ment and go on and stay in remission forever. And then we have patients who was in a year or two they relapse and they actually don't do. Well. And then so that's about twenty percent for each group. And then the rest the sixty percent those patients, you know, have multiple relapses, but you can control the disease the can live long life. So what is the treatment for the most part? Yeah. So the treatment has evolved that used to be more chemo. Arab your traditional drugs that cause hair loss or blood counts. Abnormalities? But now, we have these recall them, so our novel drugs, they work on things that influence the proliferation of the cells or the interaction was the neighborhood where they live. So these cells can't, you know, not really find hospitable environment was in the boomer to grow. So these new drugs that in combination have produced amazing results, we still consider high dose chemotherapy and stem cell transplant as part of the tweet -ment to improve the outcome. And some patient may need Menton therapy after you do the stem cell transplant. So for the most part, though, it's it's drugs. Yes is drugs. And so what's the typical course if of treatment? So most patients will require what we call induction treatment, you know, which is trying to control the disease trying to improve the symptoms and. That will take three to four cycles the psychos about four weeks after that, you do the stem cell transplant, which is two components wants collecting this themselves that support the use of high dose chemotherapy, then you give this big dose chemotherapy, which tells everything in the bone marrow. But you have the patient stem cells that make blood cells stored. So the next day you give it to the patients, and these cells will grow and make healthy cells. This is when you're doing a stem cell transplant transplant in the patient cells back into their own body. Yes, how does that work? So what you do is you collect the patient own stem cells I and these cells live in the bone marrow. So what you do is you give specific hormone that stimulates these cells to grow every day for four days on the fifth day. They're blood is full of these stem cells. What you do is you take the blood out, and you do a process like Dallas as a process called a freezes. So you collect the only the stem cells, and you store them you give the blood back to the patients, and you do this in the outpatient and a bloodbath. Four hours five hours a day. Sometimes in one day, you get all the stem cells you need sometimes you need to three days. How do you be sure that you're not collecting bad cells or that those won't turn into bed? So yeah. So we have looked actually we did research on that. So what we looking for is specific marker on the surface of these cells makes them stem cells called CD thirty four, and we look to see if we collect any Milena cells, and we did very sensitive essay and two things. One is the myeloma cells don't mobilize, you know, that effectively and the second things that they don't freeze. Well, so basically the products we give back to the patients, very unlikely to contain any Milena cells knowing that the stem cells could then are you assured that the stem cells won't then develop into cells, which will turn back into my or is that just you just have to take this stem cells are the cells that make white cells red blood cells on platelet, right? And the process of developing multiple myeloma doesn't really start at the stems. Okay. Stems stock to probably around, you know, when they sort of mature to white cells, and before they divide into lymphocytes or neutrophils different part of the white cells. It's the lymphocytes level when you know, they become B cells of the B cells become plasma cells. So maybe it's between the B cells and the plasma cells. So I guess I'm reading this question. Maybe totally naive given that we know that whatever was in this person to that such that their cells could develop into myeloma cells would they be better off with someone else's stem cells that dose sales are less likely or is that just too hard to do. Well, it's very hard to do. So we have done what we call allogeneic transplant donor stem cell transplant. The problem is that most patients in was multiple myeloma are in their late sixties. So I'll genyk transplant is very risky. We actually lose large number of these patients and despite doing an allogeneic transplant some patients have relapsed. So it's not really a route. Eighteen Lee us approach maybe in the young patients, and you may concern allergenic transplant. The issue was allergenic transplant is the risk of a graph versus house disease that immune cells from donor. Do not like that where the living in the new in the patients, so you get damage to the skin liver and the intestine, but the other thing is that the advantage of allergenic transplant used to be the graft versus disease and fortunately, the myeloma cells tend to hide from the immune system. And we don't get very good graft versus myeloma affect when allogeneic transplant. Okay. So patients get around of drugs and then stem cell therapy. And how what what's the usual course after that? So after three months later, they recover from the stem cell transplant, then some patients are considered for Menton insz therapy. So two things one we give him medicine to keep their bone from breaking down. We do that as an infusion or injection once a month, and then sometimes. We give pills of these novel chemotherapy drugs that will help maintain the, you know, the response, I think that research should be focusing on what to do after transplant when the patient have minimal residual disease. How can we improve the patient immune response to radically the residual disease is that the chemo pill, or is it some other strategies that we try actually to explore here? How many different types of drugs are available. I mean is it did everybody gets sorta the same octave of drugs or is it individualized? So when I started working on multiple myeloma, we had only this traditional chemotherapy in two thousand and three the first in class drug was approved which is a protease inhibitor and protease inhibitor is just thinking about it like a, you know, you have a garbage disposal, and you just clogging then you just accumulation of toxic stuff, and you know. The cells start dying. So that's how it works. And these are amazing. I mean, these drugs have changed the course of the disease now there are three drugs in that class available and in two thousand six we got a class of drugs approved called the immunomodulators drugs. So and the first in class was the drug thalidomide drug that cause a birth defect. When it was used in the fifties for motion sickness and nauseous associated with pregnancy and this drug we didn't understand how it works for a long time. But so and that but the problem was using thalidomide for a long time it can cause nerve damage. Okay. So the company that makes drug start developing next generation of that drugs that caused less neuropathy. We actually have to drugs in that class now. So we have three immunomodulating drugs three inhibitor. And then more recently the FDA approved drugs. We call him monoclonal antibody. So these are drugs that recognize the surface of myeloma cells, and sort of, you know, help eradicate these myeloma Celso protein that bind to the myeloma and bring immune cells to try to radically them Saturday decide which of those to us. Well, that's a great things. That's why we do clinical trial and in clinical trials, we find the best combination. So first of all we now know that one drug is not enough you have to use a cocktail of drugs. And so we just you know, the good things for patient today is that you have different cocktails so based on their medical condition, you can find the right combination therapy. So when you say their condition, what specific example, if somebody has significant nerve damage, you went to avoid drugs that cause further nerve damage if somebody have advanced kidney failure you and avoid the drugs that can be too toxic. If you have kidney failure. So that's a good news for the patient is that we can tailor. The therapy to were there conditions, and they're actually desire. I mean, some people would like only oral regimen. They don't wanna go to envision the can really go twice, you know, week to the clinic to get chemotherapy, we have oral regimens for them. So when you say they're cocktails a multiple drugs in a class or you're picking drugs from each different class. Exactly we pick drugs from different class. So basically what we do is synergy was at overlapping. Toxicity. Okay. And so what does the usual course, you have your dream Indra maintenance how to most patients too. So most people as I told you, you know, they really do. Well, they stay in remission for a long time. You know, now the average, you know, time in remission, maybe five to seven years, but unfortunately, we have these about twenty percent of patients who relapse was in the first two years, we call these are high risk risk of what risk of shorter remission shorter survival. That's where really a lot of research going on to try to improve the. Outcome of these patients. Do treat them again. Yes. Which read them again, we tried to find novel combinations. We tried to find clinical trials for these patients. We trying to employ some newer strategy. For example, one of the nearest strategy will be what we call Carty cells, which is basically taking the patient own immune cells expand them, genetically modify them to make sure that they can recognize myeloma and kill it. So we put to Sheen's one to recognize my Loma and one killer jeans. So that's why we call it kind Merrick receptor Antillean T-cells Carty cells. So these cells are I mean, these kind of therapy is now used and clinical trial in relapsed patients, but we may be able now to use it in a clinical trials for the higher spacious affront before they get to you know, relapse and have a horrible disease that how to control how hard is it to do that. So first of all you have to collect the patient and. T cells lymphocytes that become the killer cells. So basically, it's like we collect the stem cells. We do a free says we take the blood out separate the white cells from the rest of the blood. And then when you take these to the lab, I mean to the processing manufacturing facility, you separate the specific cells, we call them T cells. And then you incubate them was a virus that get two genes inside the cells after you expand these cells, and then you bring them back into getting back to the patient. So it's very expensive process. And you know, the FDA as, you know, approved to Carty saws one for lymphoma in one for leukemia that are very expensive. But there's a lot of different companies are working on it. We at Indiana University school of medicine put together grants, and we have a center the Brown center for immunotherapy. We almost ready to recruit the director. Of that. And our goal is to try to improve on the safety of these products, the specificity of these products and improve the sort of sustainability. I mean, unfortunately, if you look at some of the clinical trials the cells lasted about a year that's not good enough. Because if they start relapsing a year and you give them very expensive therapy. So our goal is to try to make Carty sells more specific safe and maybe less expensive house pensive visit. Well, I mean for the commercial products is almost four hundred thousand dollars charge for that. If we produce it locally, and may cost us probably forty thousand dollars, you know. But that's why our goal is to see if we can start making your own cartoons. What what's the usual prognosis for for a patient of developmental model? Really has improved significantly. If you look at patients when they were diagnosed fifteen years ago twenty years ago, he uses say you can live on average to three years now. Think if you look at patients depends on their station, you know, so if you have stage one disease, you know, you would think the spacious should live at least fifteen twenty years, you tell us what stage one is. So sage one is the we look at certain things we look at the chromosomes and the side of the bone marrow. The are they good chromosome backrooms? And we look at something called L D H is of you know, enzymes in the blood. We look at albumin. So if these are normal and there's another protein, we look at the blood called beta to micro glob, and so these are normal and the signings. Good one that's a stage one and these patients, you know, if you look at their five year survival more than ninety three percent of a life at five year. So the statement, you know, influence chirp how long they live, but we are seeing more patients living was myeloma and starting to die from something else. Compared to what we did ten fifteen years ago. What did the other stages so sage two and three? So three is the high risk where you have high beta to micro gloveman, high L D H. Hi, low albumin and bad cytogenetics in the bone marrow. Okay. So it it's more about the state like the actual chromosomes, and what the cells look like then how quickly you caught it or how much I'm obviously metastasized surely different. Meaning. Well, yeah, I mean myeloma is always sorta detected, you know, at a advance or all over the body. You know, so, you know, unlike you know, other tumors assist, always systemic disease. But it's you know, if you detected early stage before you have a lot of Milo, my you have a lot of bone destruction. I think you're gonna do. Well, now the trick is what we're doing is that a lot of research going on is first of all as I told you my only go is preceded by two conditions mug us and smoldering myeloma. So why don't we treat all smoldering myeloma treatment can have? Side effect. And we don't know if you'll really can cure patients, if we have a curative regimen, then we can use it early on and take some risk. So only specific group of smoldering myeloma, which we call him high-risk for progressing in a half of them will rely progress to my Aloma was in two years. We doing clinical trials on them and are to kind of clinical trials one use the combination chemotherapy that we have the novel, Asians, you know, the monoclonal antibodies that proteome inhibitor we put them together. And what we trying to do was in two years to see how many patients are we putting in really solid remission with the hope to cure, these shrines the other approach to the higher swelled among multiple myeloma is that can we actually make this myeloma cells visible to that mean system can we make that new system recognized myeloma? And so what we're trying to do is actually generate vaccine from these myeloma cells, and then inoculate. The patients was this vaccine was the hope that they develop immunity that will eradicate the myeloma. So the vaccine battalion individually each patient or just kind of vaccine for everybody. Yeah. So we take the myeloma cells generate a vaccine from their Milo myself. So it was that the kind of thing that's just going to have to be you think will be commercially like Dobie a company that does that. Or is that we're just you need to go somewhere. That's doing it in a lab, I think we should be commercially available. That's the hope is that you can generate a vaccine that for each patient's unique just send the cells, and they process it, and they send new vaccine, what do you think the most exciting works being done right now. Or what what is the most? What area I'm not saying we're in the country. I mean what area? Do you think is the most exciting for me? For example. I am actually looking at trying to figure out can we prevent the development of multiple myeloma. So I'm doing clinical trial in patient was monoclonal Gamaa, a thief undetermined significance, and I'm trying to see if we can actually prove, you know, prevent him from developing multiple. Milo moment. So let me tell you the background of that. So in my practice. I see a lot of monitoring gum with even determine significance. And I have seen patients who lost the mock Logam up at the so how did it disappear? So in the six to eight patients I have seen the lost weight and by weight loss, they lost the monoclonal gum up. Really? So we think obesity is an inflammatory state can stimulate plasma cells. So what we doing? Actually, we putting a trial together we start accruing here. We're gonna look at patients who undergoing weight reduction surgery, and what we're gonna do is screen them for Magus. And then those are positive for the monoclonal mafi. We're gonna follow them after the surgery and look at the group that lose weight versus the group doesn't lose weight. Sure. Are they going to lose the mug us or not? So if we can prove that they hit LA. Lost this abnormal protein. That's a good things. And we're gonna try to explore and see why is it you know, because they lost certain inflammatory proteins when they lost the weight or not. And so that will be a crate advances. And so basically a known risk factor for myeloma. Yes, if patient who are appea-, let me tell you if somebody has monoclonal Gama Pathy, and if you know, and they are obese they have four and a half a chance of developing multiple myeloma compared to non Opie obese patients. Yeah. So this is a big study that was done at Saint Louis VA hospital because they have records on patients who developed myeloma, and they have, you know, they know their weight, and they know if they had manga so not so that will be four and a half time just type two diabetes tied up in that too. Or is it just the obesity? I think just the obesity. I haven't looked at. I'm not familiar with any day down diabetes. But so besides the prevention what else is so prevention, I think the other thing is that we really need to screen. I mean, we need to see in this area that we talk about the higher scary near farming community near mining community near factories that was dumping a lot of these chemicals. Can we understand how many? People do have these premium conditions will be interesting to understand that. I mean, because then we will source study the impact of you know, this environment on these preconditions. And then what we would like to see is predisposing factor. In addition to the chemicals, if you have certain gene, will you get myeloma when you're exposed to certain pathogens. So I think that's exciting to us. And then finally can we find a way to deal with high risk Milo. My thing that's really the most frustrating. You know condition we deal with and Michael is to really understand the immune makeup of these patients and try to understand how we can enhance it to help us radical the disease Howard. I mean, just because clearly we live locally how are patients doing here. Locally. And what are we doing? What kind of studies are we doing locally to to try to help? So that's a great questions as you know, Indiana University issued this gr- gr-. Grand challenge. Grant, trying to really cure three diseases and cancers in Indiana and multiple myeloma was selected as one of these diseases. And so one of the proposal that we have is that we want to understand how myeloma patients do in Indiana. We want to understand their diagnosis their treatment their outcome their side effect. In addition, we want to understand their genetic makeup and also understand the myeloma genetic makeup and environment. So we putting together what we call a cohort of patients. We want to analyze one thousand patient was myeloma and Premio on condition in Indiana. We started actually accruing patients in November. And we have more than one hundred seventy patients thus far enrolled. So what we do is we looking at their sort of baseline genetic in formations. You know, we take saliva. We take a blood, and when we do a Blencoe biopsy. We take the mile cells and the neighborhood where they live inside the mirror cells. And we tried to analyze them. And the goal is to try to understand do. They have a predisposition to certain things what is their immune profile? Was there ability to metabolize certain drugs or not, and then sort of correlate the natural history of the disease was their genetic makeup, the myeloma genetic makeup and the micro environment was in the Bom omega. Are you looking at their broader environment as well where they live might be exposed to exactly. So we are doing that in collaboration with group down in Bloomington because you know, by zip code, you can figure out what they live what they exposed to and things like that. And we have sort of a that we ask the patients to help us understand, you know, their occupation. Whether they grew up things like that. So how long do you think that'll have to take to to get all the patients you want? So as you see I mean since November, you know, that's about four four months. Five months. We have one hundred. Seventy patients. So I'm hopefully, we can accrue all these patients was in two two and a half years. There's all new diagnoses or picking up pay our patients, you know, fr newly diagnosed relapse stations how common is myeloma to begin with. So my is about one and a half percent of all cancers, and we trying to figure out the exact incidents in Indiana's probably about twelve hundred new patients diagnosed a year, clearly the NIH has to you know, give money to this. But how else do you put money together? Dacians how else does myeloma research kit done as an avid runners, you know, I of about fifteen years ago, we were sitting with patients and trying to figure out how we can you know, sort of support myeloma research at Indiana University. So one of my patients said why do we just do five K for myeloma? And I said, well, everybody has a five K for mile on how about we do something different. You guys come to me from all over Indiana for a second of. Opinion, why go to your community and spread sort of word about the disease? And they said, wow, that's exciting. So how you know? But I'm not going to be writing a car to go there. I'm just gonna run, you know. And I year, you know, I wanted to go run to Fort Wayne. Okay. That was a huge far away twenty. Not really, you know. So what do we did is we saw in the first four years? We split it. You know, one day of frightening and one day of cycling, tell me about fifty miles off reading in the rest of cycling. So that's how miles for myeloma started. And then because the distance are getting like two hundred two hundred and fifty miles is just two days or three days of cycling. Okay. So we have, you know, come from Saint Louis, Indianapolis from Columbus, Ohio to Indianapolis miles for my we've raised almost five million dollars. But the most exciting thing about the whole thing is that we have patients who ride with us. It's organized by family of patients that do that. And so the thing about it is that makes me really excited to see you. My Loma patience writing. And I still remember one day because you know, you get these guys who wants to write was you. And they very really amazing cyclists. And they just you know, this is not a race. This is a group of people trying to write together to support each other and spray. Adored about my lowest. So if you have somebody already in Indianapolis, and the the other person's still in Tara hold is not fun now, it's hard. So I remember one time it was like I want to tame the group down a little bit. So I stopped everybody. And I said, do you know why we're doing this because of my Aloma? What we going to do about it? You know, we're going to spread the word we're going to try to raise awareness. We wanted to make sure that everybody understand this disease need to be cured. So I said how many of you writing was myeloma today, and there were two people. And I said how many a few writing, you know, was myeloma and still on treatment for myeloma one guy. I said, okay. So this guy is going to lead us and everybody has to follow him. Right. Do not pass this. So I was kind of probably doing it because I was tired when it's slow the pace down a little bit. So this guy grab a bottle of water? Pour it over his head, and we actually stopped at the bottom of a hill. And this guy was climbing so fast. I was like working hard to stay was when they say, oh my gosh. Why did I say that? But it was amazing to see how excited he was how aggressive he was climbing that hill, and it just makes me know that, you know, today myeloma patient can live a normal life. They is not, you know, a disease that stop you from living your life, and that's what we need to tailor therapies, so they can live healthy quality life, and hopefully, we can find a combination that cure them. So they're gonna stay on treatment forever. This healthcare podcast is sponsored by Indiana University school of medicine whose mission is to advance health and the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care. I you school of medicine is leading Indiana university's first grand challenged precision health initiative with bold goals to cure, multiple myeloma, triple negative, breast cancer, and childhood sarcoma and prevent type two diabetes and Alzheimer's disease. Thanks again to our guest raff avenue. Our for our discussion of multiple myeloma. What causes it doing about it where things might be going in the future? Listen to the healthcare trash podcast each and every month for information about health health policy health research, we'll see next month.

multiple myeloma Indiana Indiana University school of m Indiana university director obesity Alzheimer's disease Gama Pathy FDA bone disease Menton sarcoma Newman osteoporosis
Warren Buffett on Banks, Boards, & Scandal; Coronavirus Fears Hit Wall Street

Squawk Pod

34:41 min | 11 months ago

Warren Buffett on Banks, Boards, & Scandal; Coronavirus Fears Hit Wall Street

"Today's uncertainty may cause you to question your investment strategy but with the right perspective and investment solutions. We think it's possible to stay on track toward long-term goals with Janice. Henderson abandon your doubts. Not your financial goals bring in show musically squawk pod daily podcast brought to you by the team behind squawk box and why CNBC control to CNBC's essential morning show every day. Get the best stories. Debate and analysis from the biggest names in business and politics are coming to a next today on Squawk pod the US has reported its first Kovic nineteen case of unknown origin. Dr Scott Gottlieb. Who USED TO RUN THE? Fda explains what's next for the United States. An epidemic isn't inevitable but we need to start taking concerted actions right now and more from the Oracle of Omaha Warren Buffett's insight on boards banks and avoiding corporate disaster prevention worth a ton of cure. Plus how the world's most famous investor finds those Cinderella stories. It can take a lot longer than you think but eventually you get to midnight and everything turns to Pumpkin and mice all that and a few small changes. That could make a big difference in your health. Shaking hands is a barbaric thing to do barbaric. I'm CICI producer Katie Kramer. It's Thursday February twenty seventh twenty. Twenty squad pod begins right now in three good morning everyone welcome to squawk box here on. Cnbc we're live from the Nasdaq market site in Times Square. I'm becky quick along with Joe. Kernan and Andrew Ross Sorkin cove nineteen or the corona virus has taken over nearly every news outlets coverage this week including here at CNBC last night. The CDC confirmed the first US Corona virus case of unknown origin a northern California patient with no known travel history to affected areas or contact with another case. This could be the first instance of so-called community transmission in the United States. The news broke on the same day. That Germany's health minister warned. That country is at the beginning of an epidemic with chains of transmission that can no longer be traced. The virus has now spread to at least forty seven countries in the world. Health Organization confirmed that new cases outside of China have surpassed those inside China in Japan. All schools will be closed through March as cases approach two hundred in Iran with two hundred forty five infected and twenty six dead. Friday prayers have been cancelled in South Korea. Case numbers are over seventeen hundred. Here's Joe with Becky. Andrew and our guest host this morning Barry Nap of ironsides economics president trump as you probably have heard by now held a news conference last night to reassure the American public and Wall Street That the US government is prepared to respond to an outbreak of the Varsity is appointing Vice President Mike Pence as a point person for the US response and Aiming Jabar's joins us now with more What are you got yeah? We'll look this appointment of Mike Pence by the president of the United States. The White House has gone back and forth about whether or not they were going to appoint a czar. The president insists. This is not a czar position. But Mike Pence's appointment here does. Elevate the administration's response and the president was in sort of a delicate position. Yesterday he was trying to reassure the public that the United States government is fully prepared for this but even as his health and medical advisors were suggesting to Americans that they'd better brace for more cases of Corona virus inside the United States. The president had this to say about whether or not the virus is going to spread. I don't think it's inevitable. I think that we're doing a really good job in terms of maintaining borders and turning terms of letting people in in terms of checking people and also. That's one of the reasons I'm here today. Getting the word out so people can till no they're GONNA now no. I don't think it's I don't think it's inevitable. I think that there's a chance that it could get worse. As a chance he could get fairly substantially worse but nothing's inevitable and Joe. The president also reached for other explanations for that two thousand plus point Dow Jones. Dropped that we've seen in the market this week. Here's my exchange with him on that pretty clear. The Dow Jones dropped more than two thousand points. This week suggesting that was overblown. Our financial markets overreacting. Here I think financial markets are very upset when they look at the Democrat candidate standing on that stage making fools out of themselves and they said we have to have a president like this and always a possibility. It's an election. You know who knows what happens now. Joe When I pressed the president he did acknowledge that the virus played some role in the two thousand point. Selloff that we've seen here but this is the president who clearly is looking for other explanations for that stock market. Sell off. Not Happy with what you've seen both in the stock market in terms of the response by some of the people on his own medical and health team the president sort of walking that fine line here between reassuring the public that everything is under control and try not to really set off any kind of panic either in the public generally or in financial markets too. Yep and you heard all the SCUTTLEBUTT and in in media sort of Even before the President spoke about there are times in a president's tenure with defining moments. And you know we don't need to go over the list now. But and the reaction of the administration to those defining moments can mean a lot for the look back at the tenure of president. So I'm sure there's a lot of sensitivity to that as well and it is a fine line and even if you know love trumps hate trump. Any president put in that position yesterday probably would have been a strain to walk that same. Fine Line between trying to reassure the country but not trying to sugarcoat it too much top tough position to be in yet. And you talk about the look back to the president's tenure. These kinds of events can affect the length of the presidential election. Coming up right is not lost on him and his aides in the White House that this sparks any kind of economic ripple effect. If they're accusations that they've dropped the ball or mishandled. This allowed Americans to get sicker than the otherwise recipient a global slowdown or recession in the stock market. Break that it's worse than your garden variety. Correction there's a lot of a lot of the enormous amount at stake for the White House. All right Even for more on the president's response to Corona virus fears. Let's bring in our guest. Dr Scott Gottlieb he is the former FDA commissioner and CNBC contributor. He also serves on both visor and a luminous boards and got. It's really good to have here today. Thank you How should we be looking at this? How are you looking at this? Well I think we're entering a new face. I think we're going to have community transmission. The states already do this probably cases in major cities dozens maybe hundreds not thousands at this point and we'd be seeing that but the California case demonstrates the transmission and epidemic isn't inevitable but we need to start taking concerted actions right now. We need to crash development of Therapeutics and a vaccine we need to dramatically broadened screening and people need to start getting prudent. Simple changes in behavior can have a very big impact when distributed over large population handwashing. Staying home when you sick workplaces changing practices we might need to start engaging in broader mitigation steps to engage in social distancing. Another things like that. You say workplaces changing changing What do they need to do? I think you need to start thinking about flexibility for employees employees. Sick how they can stay home how you can support employees with things like daycare and other things that can keep them out of the workplace. If they're sick we need to start thinking about if we're going to have to change practices to to limit social contact cancel large meetings limit travel. We're not there yet. But those are the kinds of things that you would need to do to prevent an epidemic spread. We will have outbreaks here in the United States. It's inevitable but we do not need to have an epidemic here. We can't avoid that when you sat down at the table you pull pure l. out of your pocket and actually did this year hands. What what. What does that do in terms of improving your chances of getting sick? Well look I think a lot of the transfer people worry about Aerosol and there's a certain amount of things that we can do to prevent that I think a lot of the transfer this probably touching and in touching your face So if you're on a plane it's not the air on a plane it's somewhat passing out cups on the plane to all the all the airline passengers but I thought that parral didn't kill viruses. It kills the virus virus. It appears that this viruses. It lives on services for a period of time. But it's not a hearty virus so alkali away. Shaking hands is barry barbaric thing to do. Are you shaking hands with anybody or trying to avoid it? You don't agree on. I don't agree with using the word barbaric. I think that at a point like it's a good idea not to but I think if you weren't worried about it it's it's a human thing to do to look someone in the eye and I don't think Nancy Barrick Barrett Dakotas that there was a study that showed that fist bear transferred by ninety percent. Yeah all right. What about the fist bump? Because there's no germs here. It can cut your seriousness. I think the backstop that we have to prepare that this is not something that's going to start and stop. This could become something that we have to live with. What's going to inevitably be backstop against? It's going to be a therapeutic vaccine. We need to invest very heavily therapeutic already. Theoretically we're not GONNA have a vaccine for at least off so why not. Why not focus on on something that lessens the severity and Rendez severe looks promising? And it could be here. That's Gilead and also an antibody based prophylaxis regenerates working on those things could be near term opportunities. Something we maybe even could have in the late fall or early winter. What about a protease inhibitor? We have stuff already that might classifications in the in the in vitro studies. We haven't done good clinical size yet. But I think we need a moonshot approach right now. We have the ability to conquer this with science sciences. There it's available for general and was able to develop prophylactic antibodies to Ebola and they had one in the lab from these things are obtainable. Isn't it. It's not a year and a half as mountain faced with H. One N One. The swine flu in two thousand nine. The first case was identified. I think April fifteen thousand nine by September. We had a vaccine. Okay this possible. And that's what we had time. How much money that. I think we should put billions of dollars not a time to be a fiscal conservative. Where where are you on the question of The the weather the time of year whether this is out when we this summer sh this summer should be a backstop but it might not stop transfer entirely because very novel virus. We don't have crushing unit. Should be a backstop so you could see this dissipating summer in combat in the fall but by the fall will have a therapeutical. I know I've seen lots of questions on either side but Dr Gotlib WanNa thank you for being with. The outbreak is also taking a toll on companies. Hp's bottom line. We'll take a hit this quarter because of the virus CEO. Enrico Loris Tying Jim Cramer last night. That the impact will be felt most in the company's manufacturing business today majority of the factories open but the production is not handed percents eleven from a demand perspective. We don't see any impact. He sold us. We play chain driven impacts. We calculated and we have estimated audio cue to these will have an ancient impacting. Eps and a related story. Microsoft says that it does not expect made its quarterly revenue guidance for the segment that includes windows. It's blaming a slower return to normal after corona virus supply disruptions. Microsoft generates most of its windows revenue by selling licenses device makers including HP who sales have been disrupted by the outbreak and then shares of new tonics are plummeting. The cloud storage and networking software. Company cited the Cronin virus as one reason for lowering its twenty. Twenty outlook is taking a more cautious view on the Asia Pacific and Japan region where it generates more than twenty percent of its revenue. Let's see through the thick green tie. AIRBNB is out with a statement on the outbreak saying that extenuating circumstances its policy allows guests and hosts to cancel reservations with no penalties. It's reminding people of this policy. The company says it is working to support. The hosts and guests employs communities. It believes that the travel industry will bounce back in the long run. Jet Blue became the first. Us carried a cut fees for changing or canceling flights for passengers concerned about the outbreak. I have a question you have a question. Yeah when AIRBNB says we can do it without fees. Who Does that point? I mean it's it's the homeowners who are the ones taking that on the Chin right because the fees would be paid to them. I would assume if you cancel. Maybe I'm wrong. But if you cancel the fees get partially shared with the homeowner who you cancelled on. Who will get the Revenue Dave Dave Evans points at at my ear the homeowners can also cancelled? Forget it. I don't want somebody coming into my house. That's possible too in there and therefore I don't know does a fee go to the. Us just dig into that area. Nap is here Berry watching some of these moves you can get a little bit of whiplash. Yeah it's been a fascinating week. But the thing that struck me as I was driving in listening to dominic and your headlines that this is the worst week since October of Financial Crisis. And you know when it got me thinking about first of all had a front row seat for that as managing director at Lehman Brothers. But this when you think you almost caused it but yeah okay. We have a long talk about that one kidding but yeah but it's just funny when you said a front row seat at Lehman Bros. It's like yeah you did. I did for sure but but the thing that started to occur to me I was hearing more discussion about Central Bank. Reaction Functions easing policy in the. Like if you recall during going into the global financial crisis household debt was at its highest levels ever recorded in this country and the mechanism by which you resolve. That is largely household. Refinancing mortgage refinancing. That's the single biggest financial obligation that most households have and rates are record lows. Would you couldn't do it. There was actually no mortgage credit available. And that's why fed policy was so ineffective during the crisis because that mortgage credit channel was called. But this is different. It's not close. It's far from clogged right. We're already running. Revise it one hundred and sixty percent above of where they were a year ago before we even had this last thirty basis point leg lower in mortgage rates and by the way household obligations as percent of disposable income or at their all time low. That's GONNA go down even further so the household sector is going to be absolutely flushed. Ben De Leveraging through this whole business cycle. It's only the second cycle since World War. Two where that happened. It happened in the sixties as well so getting reaction you can get a confident shock in the household sector to be sure you've seen some indication of that for morning. Console does great Confidence Work it did finally take a hit this week but it is likely to be temporary and then if you think about the business confidence channel and just compare it to what happened a year ago going into the trade wars business. Confidence was at multi decade highs because of the tax cuts and jobs act the impact on business confidence and production was pretty profound from the trade war. Now it's at it's at its lowest level since two thousand sixteen so that Delta Change that is likely to be much smaller. Furthermore from a supply chain disruption perspective is suspect that this will be less disruptive than the Great East Japan Earthquake Tsunami e that shut down the auto industry for four months and then was quickly followed by the floods that shut down parts of the semiconductor and electronics industry. For another couple of months interesting thing that was also warning shot to companies your interview with Honeywell's CEO at Davos this year. He said we locally source right. We produce where final demand is eleven was the inflection point for that the trade war further. Push that agenda so I just don't see the supply chain disruption is likely to be as big as those. The confidence channel doesn't look as vulnerable. So yeah this is clearly going to have a hit but if you think about them the knock on effects from what happened during the financial crisis the second order effects. I don't see them as likely to be anything like that. So we should we should stable keys will be coming up. Warren Buffett insight and ideas when Berkshire Hathaway Chairman and CEO on corporate leadership from the boardroom. To Times of scandal you absolutely have to pack problem assume as it occurs. Then you know about an ad that that had happened. Well furniture older squash pod. We'll be right back. Today's uncertainty may cause you to question your investment strategy but with the right perspective and investment solutions. We think it's possible to stay on track toward long-term goals with Janice Henderson abandoned your doubts. Not your financial goals Alpha. You're listening to Squawk pod from CNBC. Berkshire Hathaway Chairman and CEO Warren Buffett. The Oracle of Omaha joined squawk box earlier this week for a three hour special. We call ask Warren. You can find a special hour long episode as well as more great content from that interview in your feed for this podcast among the topics covered in this vast. But really fascinating. Conversation was corporate board diversity which was also a topic featured in Berkshire hathaway's annual shareholder letter. Buffet said that women. Having a voice in the boardroom continues to be a work in progress. Here's Andrew Ross Sorkin. I read the letter like everybody else over the weekend. It was fascinated by so many of your comments. Warren specifically I wanted to ask you you talk about diversity on boards in this letter and of the things I wanted you to weigh in on if you could. I don't know if you saw but David Salomon the CEO of Goldman Sachs on. Our Air actually announced a couple of weeks ago that he won't be taking any companies public. Goldman won't in less. They have at least one diverse board member and they're likely GONNA push that to to come from a position of my own experience why look at the Goldman Sachs Board with four women out of eleven we have Blackley director at I really value the diverse perspectives. I'm getting which are helping me on. The company is starting on July first in the US and Europe. We're not going to take a company public unless there's at least one diverse board candidate with a focus on women and we're going to move toward 2021 requesting to and we realize that this is a small step but it's a step in the direction of saying you know what we think this is right. We think it's the right advice. You know. In the state of California they put a law into place saying that you needed to have a female board member and I'm curious what you think of Not just the push towards more diversity on boards but the requirement because I also note in your letter that you have very specific thoughts about what it means to be a board member what it means to be independent board member. How wealth is involved in all of that. What are your thoughts well at Berkshire for decades we've given the three factors in addition to integrity but For Board membership and and we want people who are business savvy We want them to have a A strong personal interests in Berkshire itself. And we've we. We've got directors who really Represent shareholders basically at Berkshire. And I think they do a great job now. That doesn't mean that they don't think that we should delight our customers that we should treat associates. Well we should be behave well in our community both local and national but but our directors represent the shareholders so warrants. It just just a follow up on it though. What's your thoughts about both the requirement that maybe banks and others investors are going to force companies to have a diverse candidates on their board laws. As I mentioned in California. Yeah I actually there. There may be. There's been sent to us a proposal which most withdrawn. We'll be on our proxy. I can't tell you precisely what it says. But the relations issue and we will get our shareholders view on it I I personally. I want shareholders I want directors that represent the shareholders in in terms of my estate You know with with maybe currently eighty billion dollars worth of to give the philanthropy. I hope that we have a we do have directors that I think will be very conscious of doing the right thing. The reason asked the question is because the other point you made which I think is a very smart one and is often miss construed and the corporate governance land is that an independent director. These days isn't always independent. Enlarge part and you make the point that those that don't come to the table with some form of wealth often need the job. They need the money they want the money and therefore that makes them less independent and the reason I ask. This is one of the things we've been trying to get more diverse candidates on boards. More Women on boards as you know there there are fewer. Ceo's fewer people who've made enormous amounts of money and people therefore they can question their independence. It becomes a very tricky issue. And that's what I was hoping you might weigh in on Andrew. I bet on twenty-one publicly owned boards of publicly owned companies and I've seen them an operation and I would say that the people that I've often seen and that's perfectly understandable. I have often seen. People are classified as independent directors. And they're getting three hundred thousand dollars a year for a job that takes them A couple of days maybe six times a year maybe four times a year and The company flies him to their office. And it's very enjoyable and the company's good and and who wouldn't want a job like that I mean it's an incredible job and people I get calls from. I get calls from head honors. I get calls from CEOS and they ask you know who I think would make a quote. Good an quote director and what they are asking is not going to cause too much trouble. And who is going to reflect who their name is going to reflect credit on the institution and they are not looking for somebody that that That I would regard as really independent and I don't blame them. I mean if it if I had spent my life being a teacher or whatever it might be my cue is just as high as the average or higher than the people on the boards and all that but on the other hand I want to get on board. I mean three hundred thousand bucks. A year would look terrific and you don't even have to retire. Probably in most cases sixty fiber anything short sort of call them. Independent is ridiculous and If you're if you're on one board like that you want to really go on another one. That makes six hundred thousand a year and you are not going to do things that irritate your presidency. And here she gets a call and says this guy make a good director that the answer is no. It's it's it's just ridiculous to ignore the the factor of compensation with board members. A lot of people had questions about the banks about what's happening with the banks. You've changed with some of your Investments OVER TIME JASON. Goldberg writes and he says please ask Martin about his views on the bank stocks in general and on Wells Fargo in particular over the last two quarters. He sold almost a quarter of his long-standing Wells Fargo steak also in the fourth quarter. He dumped a third of his. Goldman Stock Goldman Sachs shares. Although he still owns every seventy five billion dollars in bank equity banking is a good business. If you don't do dumb things on the asset side I mean basically I it. It's a business that The bags we own EARN BETWEEN THE COMMERCIAL BANKS. Earn between twelve percent and sixteen percent or so on tangent net tangible assets. That's good business. It's a fantastic business against the long-term bond that you know a two percent EPA choice between the two percent instrument and twelve percents cement which one's GonNa win over time so so if you ask me whether I think Banks are going to get our. They only earn three or four percent on tangible assets. I don't think that'll happen questions really whether they do something massively dumb. I mean which periodically a number of banks of Donna. And I I feel very good about the banks we own I. They're they're very attractive. Compared to most other securities I see an ad. Most of them are buying bank of America's buying a lot of stock every year so our older ship of the Bank of America. This year probably will go up seven or eight percent without a spending time. I I'd like to eighty business any good business. Where MY OWNERSHIP STAKES? Who's up seven or eight percent every year without me spending any money on on top of it. I get it. They're very they're very attractive. Both against interest rates at against a against bonds and against other stocks in my bill. You say occasionally they did. Some things Maybe you're talking about wells. Fargo with the scandal that it had just settled on Friday with a number of the regulatory institutions. That were kind of looking into the investigations that were taking place for three billion dollars. Does this mean that they have kind of finally gotten through that and can move forward. I don't know the answer to that. I know that they billion dollars. I don't know what else is outstanding but wells Fargo's classic in in terms of one lesson by partner. Charlie Munger you ISA's whenever we have a problem you attack the mmediately so as an announcer prevention is worth a ton of cure. And we've seen that time after time and the interesting thing I I don't know the details at all but the original thing was a bunch of whole bunch of phony accounts now. I don't know how if you opened up a couple of million phony accounts you make any money on it at all. I don't the shareholders. Didn't make money people say well. The sentence structure was set up. So that some of the system you can and as soon as you learn you can devise incentives systems. We've got ourselves. I mean you can. You can cause people to do the wrong thing because they will do. What their incentive to do ad they had obviously a very dumb incentive system people's are playing at various ways and the big thing is they ignored nor when they found out about it. I mean you see you. You're GONNA do dumb things in business and we do them every day you know but the the absolutely have to attack a problem assume as it occurs and and you know about let me ask you a broader question that comes in just on interest rates impact. That might have as well ruin John. Jane writes on Facebook Hi I'm a huge fan and student Mr Buffet. Please ask him. What impact does zero interest rate environment across places like Japan and Europe have on their banks whether the business is still good and does the prolonged low interest rate regime in the United States? Her hurt the prospects of American banks like J. P. Morgan etc. Generally speaking with a lot but a lot of other variables too but the banks are going to make more money. If there's a higher rates with a with a steeper curve the curve makes is more important than words the tenure versus short term rates may make more efforts in the APP absolutely level but America banks have made very good money with very low interest rates around the world You look in the UK or Europe Japan Even lower rates amid pretty tough for banks the returns on equity or not as high and they have to use more leverage To even get the same returns that I don't like that as well. You made a point in the letter of saying that you don't know how long these interest rates were last. You Charlie never trying to figure these things out but we did have saint. Louis Fed President Jim Bullard on the program last week and he said that he expects to see these low interest rates for a long time to come. We Watch Financial stability issues and bubble type issues. very carefully. I think that conventional wisdom is that valuations loci but not at this level of interest rates and so to the extent you think this level of interest rates is probably the future which I've been arguing. I think we're okay for now. That does raise a lot of questions if that happens about what this means for the stock market what that means for banks what that means for insurance companies which you touched on in the letter to Bradford insurance companies but it it. It's good for stocks Bad for insurance companies and what happens to insurance companies as a result are they getting more benefit ones. That really get hurt on are are either life. Annuity companies that have promised return. The property casualty. Business doesn't promise returned so holds money so it hurts them. But if you promise somebody an annuity that's paying them three or four percent and now you find that you're reinvesting your money at one percenters something you know you're gonNA disappear are insurance companies being forced to make riskier and riskier beds. Well they shouldn't. I mean the answer if if you need to get three percent and you're only getting one percent. The answer is to quit giving three percent. It's not try and get the one up to three and do more dangerous thing. They should always adapt your consumption to your income. You shouldn't try and adjust your income to your consumption. That's a basic principle for individuals businesses and everything else and reaching for yield is really stupid. But it's very humid. I mean I understand it And people say well I save all this money on my life and I can only get one percent i. What do I do the answers you learn to live on one percent unfortunately and and You don't go and listen to some salesman come along until you. I've got some magic way to get your five percent. Do you think though that that's what should be happening. Do you think that there is more risk taking place in the insurance market? And you'd see that and you'll see that in like all leverage loans and weaker covenants at all people are reaching for yielded. No question about that and that stupid and it it has consequences over time but it's very human consequences that could have a big market impact. Fargo's yeah yeah it's the it's it's something that the things that get building slowly people going crazy and tech companies in the late nine thousand nine hundred. It can take a lot longer than you think. But eventually you get to midnight and everything turns to Pumpkins and mice chip crook right sending out and says it was reported. The Boeing was looking for a large cash loan where you ever approached about Berkshire loaning the money kind of like the Goldman Sachs deal from years executives from your. I think I think Boeing's raised about thirteen billion but that's bank type money words. I my memory is maybe one percent male. And they're looking for. They'RE LOOKING FOR TRADITIONAL BANK LOANS. And we don't make traditional bank loans. You also talked in the letter about how Berkshire Hathaway has Berkshire hathaway energy. I should say has the ability and the talent to manage big investments. One hundred billion dollars more. I think you wrote we stand ready willing and able on such opportunities. California Governor Gavin Newsom Asked you at one point to bid on. Pg Is that such an opportunity PGA we. Obviously we worked with them for decades and been familiar with them But but that doesn't that doesn't fit Berkshire if there were a hundred billion transmission lines or whatever it might be. Burke can do it. I mean we would love it That happens to be a very tough thing to do. Because you're across all these states and everybody says not in my backyard and all that but but There can be huge. Intelligent investment made in the utility enter get area and no one is better equipped to do it than Berkshire in both Taliban resources why does pgn enough at that bill? It's too tough. I don't I don't know the answer to it. I mean rearranging that utility know governor newsom. I think he's very very very smart. Guy and and in terms of solving this problem. It's just not easy you've got so many constituencies they're at each other's throats and there's lots of money involving I don't want to be. I don't know all that. Thank you for listening to squad. Tomorrow we wrap up our special week of comcast segments with Warren Buffett. The wisdom of the Oracle of Omaha certainly can't predict the market by reading the daily newspaper. That is for sure. And you really have certainly listening to me. Box is hosted by Joe. Kernan Becky an Andrew. Ross sorkin tune in weekday mornings on. Cnbc at six am eastern to get the smartest takes and analysis from our TV. Show right into your ears. Subscribe to Squawk Pot. We are available for free wherever you listen to podcasts. And if you have a minute leave us a rating or review on Apple podcasts or your platform of choice that helps other listeners find squad. We'll be back here tomorrow. You guys I'm Kelly Evans host of CNBC's the exchange which is now a podcast subscribe. Today it's your one stop shop for the top business stories. Plus listen in for lots of original reporting in depth conversation and some of the best of CNBC's award winning investigative work. Subscribe to the Exchange for free and you can always catch the exchange live weekdays at one. Pm Eastern only on CNBC. So you then.

president United States CNBC California Warren Buffett Japan Goldman Sachs Joe CNBC director CEO Berkshire hathaway Dr Scott Gottlieb Andrew Ross Sorkin Berkshire Janice Henderson Fda AIRBNB managing director
330: Science-Backed Practical Strategies for Immunity & Decreased Viral Threat With Dr. Ken Brown

The Healthy Moms Podcast

1:13:44 hr | 9 months ago

330: Science-Backed Practical Strategies for Immunity & Decreased Viral Threat With Dr. Ken Brown

"My Bobby podcast. This episode is sponsored by up. Spring baby a company making innovative science batch products for MOMS and babies and I wanna tell you about one of their products in particular because even though I'm not even currently pregnant or have tiny babies. It's been really helpful to me. I really liked their stomachs. Settle Nausea relief drops which are great for any kind of stomach upset from motion sickness which get in the couple of my daughters. Get to morning sickness which I think we do not have right now because I'm not pregnant but any kind of bloating or digestive upset at all. I love to keep these on hand and my kids like them too. They help relieve Nausea Motion. Sickness gas bloating in any kind of digestive upset. In fact I keep these in my car and I kind of like emergency kit in each of my cars also in my purchase to have on hand because you can be a thing when out on the go there. Lemon GINGER HONEY. 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Eyewear Company you've probably seen pictures of me on social media wearing orange glasses of various types at night and here's why in nature we aren't exposed to certain types of light after dark specifically blue light because that type of light signal is the body that it's daytime that intern suppresses. Melatonin and can interfere with sleep. This is the reason that are really dramatic. Study found that camping for seven days straight with no artificial light at all could actually completely reset and he'll circadian rhythm and help a lot of light related problems seasonal affective disorder. This is also the reason that I wear orange glasses after dark to block these types of light and protect my sleep which I am adamant about protecting. I also wear a certain types of yellow glasses. An anti fatigue glasses during the day if I want a computer to reduce fatigue. Blue blocks has orange glasses and yellow glasses. Their orange glasses for nighttime wear are designed to block a hundred percent of the wavelengths between four hundred meters and five hundred fifty nanometers. Which are the ones that are studied to interfere sleep and told him production and Circadian Rhythm? My kids also these kinds of glasses at night and I noticed a difference in their sleep as well which is a huge win for a mom. This is especially important when we're watching a family movie at night or looking at any kind of screen. As artificial light there is a source of blue light and can interfere with sleep. You can learn more. They have a ton of educational content and check out all of their innovative protective glasses by going to blocks dot com over slash wellness. Mama and using the Code Wellness Mama to save fifteen percent so again. That's blue blocks DOT COM B. L. U. B. L. O. X. dot com for Josh Wellness Mama and the Code Wellness Mama All one word and all lower case to save fifteen percent. Hello welcome to the Wellness Mama podcast. I'm Katie from wellness. Mama Dot Com and wellness DOT COM. That's wellness with an e. On the end and this special timely episode is about things that we can all do in a very practical way to help support me in health and to possibly fortified the body against viruses in general and the quote that I love from this episode and that this up so definitely gave me. Is that calm is contagious. And I'm here with Dr Ken Brown. Who is a highly respected and award winning board certified gastroenterologist who is on the front lines of this right now both in research and in medicine and we know right now that the virus does have a gastrointestinal aspect and his research he shares some things in this episode that. I have not heard or read or seen anywhere else and I think that are extremely practical impertinent and might help not only all of us individually right now but also might help us with the trajectory of this virus in general so his research began with traditional pharmaceutical drug development and then he branched out into using very specific polyphenol polyphenyls which we talk about today further effects on health. And what we're finding in the studies explains Indebtedness episode is that the same polyphenols may have an action against not just viruses bacteria. That often goes along with that. Might be the real cause up some severe respiratory distress tuned into this episode for. He's GonNa share all of his science back techniques and the substances that he's using to keep himself and his family and other healthcare workers that he works with safe and healthy as well so without further ado. I want to jump straight into this episode with Dr. Ken Brown Dr Brown Welcome. Thanks for being here. Oh Katie thank you so much for having me on your show. This is really exciting. I think it's been a few years since I've done this. So it has and it's always a pleasure to chat with you and I love that. We can record this one and share with the listeners. Today I think you have such a wide amount of knowledge and on some really fascinating topics especially got health which I am huge. I love researching. I think it's one of the most important things that we can look at when it comes to overall health and I think from there. There's a lot of stuff we can talk about today. obviously we all heard that gut health impacts the health of the whole body. But I think that's even more pertinent important right now to jump in there. What what are you thinking in the midst of all of this right now? I mean I I hope that you and your family are doing great. And you guys were tolerating this whole process. Well I know with the kids. You gotTa keep a very excited attitude while still entertain them and figure out how the you know. You're gonNA continue with your life for the most important thing is making sure that your family's good so first of all I hope you and south and the kids are doing fantastic are you. We are going a little. Stir crazy Obviously and having to adapt our normal lives as I think everybody listening is but I'm very grateful that we all are in good health for the extra family time right now and just trying to adapt day by day. Yeah definitely I love hearing that and I just want to let you know that I cannot tell you how excited I am to be doing this particular show because I loved your podcast with Tina Anderson. You and her covered so much cool stuff that. I'm exactly online with her. It's your jut and your immune system. They go hand in hand. If you do not have a healthy gut you not have a healthy immune system. I thought that I would come on here. And talk about all that she did the heavy lifting and you and her covered that and so now I am so excited to share some stuff that I don't think anybody else's talking about and I'm hoping that this will blow your mind. I can't wait I. Yeah that's a cliffhanger. Let's jump right in. Well all right so everything that we're going to be talking about. I just want you to realize this is a lot of it is going to be related to cove in nineteen pandemic. It's almost impossible not to not talk about that. But more importantly everything that we're GonNa talk about can be used afterwards because once we get through this cycle the data that I've been looking at the things I've been evaluating. It's not just for the Kobe. Nineteen this could be extrapolated to other things other infectious cycles that I can't believe it's imprint and people are not talking about it so this is not a one and done in fact. I kind of feel like we're going to end up having some sort of cyclical version of this SARS cub to borderline influenza type. So it's not to make everybody nervous about this but I think that the more that we start preparing this is it. Let's just hunker down and talk about this one thing because the reality is is that I think we're going to keep seeing more things. Maybe new viruses. There's the potential that this could actually cycle back like the flu. I've heard some biologists talk like that so there's a lot going on a lot that we don't really understand so the one thing is that calm is contagious so when this thing started happening. I started getting anxious like everybody else and when I do that I start looking for answers in evidence based medicine that way. I can at least take some control and that is what I want to do. Today is share some calmness through science A. Yeah okay with that. I love that quote. I think That we could all use a little bit more calm right now and I think that's perfectly start. Yeah so in two thousand seventeen. I did your podcast and we discussed how the polyphenyls in our Toronto help in irritable Bowel Syndrome Simone and gut health. If you recall we talked about polyphenyls being the molecules that fruits and vegetables their color and now they are thought to be the anti-ageing anti inflammatory molecules that make the Mediterranean Diet so beneficial. But since then we have been learning more and more about how these polyphenyls can do some amazing things you and Tina discussed pro out. Exim prebiotics now. I WANNA throw a whole new field of study at you. And that is something that scientists are calling host -biotics. Have you ever discussed post by at all with anybody? I have not not on here. I've heard that term but I don't have really any knowledge about it so explain it to us. It's a super cool field because what we're learning is is that our molecules like polyphenyls and prebiotics. They functioned to feed our own bacteria. Now scientists are realizing that the bacteria can break them down into very beneficial anti-inflammatory type molecules called post -biotics so now a lot of science is looking into okay. If we give this and you have a good microbiome then you will be able to produce these different molecules that can then do x Y and Z. So it's this whole new field of study but it ties into gut health the microbiome and all that stuff and so knowing that I have always been trying to stay up with the latest science but in a very weird twist of fate. This lockdown has actually allowed me the time to dig really deep into studies which are coming out daily during the SARS cub to pandemic now. I'm extremely fortunate to work closely with a wonderful Dietitian. Aren graduate student named Angie and she has access to all kinds of literature and be able to download it preprinted stuff things waiting for publication things waiting for Peer Review. And I want to call her. Basically my scientific Sherlock Holmes of finding scientific data to make connections what I mean by. That is the data's out there who has the time to look at something from two thousand three tied into an article. Two thousand seventeen and go. Oh this ties to this study. That's going on in two thousand twenty. Well since I'm not working right now the governor won't let me do my real job. It's almost a twist of fate that I have just been obsessed with this and it has just been this incredible thing. Thanks to this lockdown. I'm not doing the usual job. But I feel like I've been working harder than ever. And we've uncovered some pretty cool things so everything that I'm going to talk about is based on scientific studies either in the lab animals or human studies. What I WanNa let all your listeners know is that we're in the process of building a a reference page on our website. So that everything that gets talked about you can just click on and you can just see the article so that you can read it on your own and interpret it the way that you would like to interpret it but this is so that we want to have a repository of these different articles. We don't have that up yet but that's what we're working on as you know time money all that stuff to you know to keep that kind of stuff going so. I'm just really excited to share this with you and I think that you and your audience are the perfect place to get this at least some information out there whether it's what I think it is or whether it's it can be disproved is irrelevant at this point because we can only go with what we know right now so with your help and with your audience because you're always trying to better yourself you're always doing scientific research. I think that we can make your audience calm. I think that is a spectacular goal. Let's start there. Calmness is contagious so for every mother. That's out there listening when your calm? That can actually be contagious. So keep that in mind. I always practice that in fact if my staff and my kids are listening. They're probably like what so? I try but all right so super brief. I know that everybody's been talking about this. But whenever I talked to any of my patients I get one question. I'm just really confused about all these turns at everybody's throwing around so super brief remember that cove in nineteen hundred talks about SARS Cov- to is the virus. Which has a similar structure like ninety five percents similar? To SARS of two thousand three the media will tend to confuse people. And they'll say this is the Corona Virus. Have you been exposed to the virus? Had he been exposed SARS? Cov To have you been exposed to Kobe. Nineteen these are all different terms. Think of it. This way SARS coved to is much like having HIV in the sense that it's a virus when you develop aids that's like having Kobe nineteen so everybody keeps talking about the virus and then covered nineteen. That is one way to sort of distinguish the two we do know that the virus binds to receptor called ACE two which is located in your digestive track and your lungs. People keep forgetting about the digestive track now. Recent studies have shown that close to fifty percent of people who have cove nineteen. Or who developed the disease? Actually start with gastrointestinal issues. They tend to have worse outcomes. They go to the hospital later by the time they show up there. Sicker and interestingly around thirty percent will present with just mild diarrhea. Eighty five percent will present with anorexia not wanting to eat and many of these people. You've probably been seeing. Have you been seen on the news at all about the lack of smell? Katie I have been thinking about that. Where do you? What does that stemming from Wiltz really interesting because when we were looking at eighty five percent of the people just decide that they're not hungry some ear-nose-and-throat doctors were saying you know. We're seeing a lot of people that have lack of smell and taste has changed and that seems to proceed a lot of the other symptoms and that's one of the diagnoses or one of the symptoms that we're probably missing like as a screening tool. You had a cough. Have you had a fever? Well I'm asking my patients is. Are you smelling things normally? Do you still like to eat? And do you have any loose stools? Those are the things because they tend to present earlier. So it's something that we're learning but it's really interesting now. This is a really change. A paradigm shift and whatever's been saying new studies have come out that shows that you can shed the virus in your stool for five weeks after you quit shedding it in your lungs and I only bring that up because that is something super important to think about when we're talking about the possibility of virus lingering and coming back study came out yesterday in the Netherlands that they're actually finding viral proteins in the sewer system once it hit the Netherlands. That wasn't there before once it hit and now they're finding so very clearly in the stool this can actually affect people in that way. So it's one of those things that were probably not paying that close attention to and people need to start looking at the GI tract more. Some people have even been testing negative in their throat drops in the. That's called peace job where they do the throats rods but they're positive in stool so doctors are saying. Hey look this person looks like Kobe. Nineteen their negative check their stool so everything comes down to gut health. And that's why I was so excited when you had teen on and you guys were talking about that so that's where I'm starting with this. Don't forget about the gut wise a gastroenterologist talking about Kobe nineteen because I think that were very important to helping people get over this pandemic. So that's why I was so excited to hear you and talk about that okay so knowing that I had a little time on my hands and got this incredible scientific detective with me. We basically spent countless hours looking at hundreds and hundreds of studies and then trying to link these from two thousand eight hundred eighty two thousand three before before that what we've been finding as I mentioned. I consider somewhat extraordinary but I'm a huge nerd and I want to do the spoiler alert for any of your listeners. Because if they're sitting around going well I don't know if I really want to hear this guy talk for this long. I'm just GonNa give you the nuts and bolts of what we've been finding and then you and I can decide how deep wanna go into each one of these things and the science of it but once again we're going to put all these studies up on our website so that you can follow it basically going through. Does that sound fair? Yeah sounds great all right so I brought up the polyphenyls in the beginning because it appears that these polyphenols are actually mother. Nature's secret weapon in fighting this disease and I've got a one two three four five six steps that I think we can make a difference in people's lives so step number one polyphenyls and saplings have been shown to actually kill the SARS virus. Step number two. They have been shown to block the viruses ability to bind to ourselves. Meaning they have to bind to be able to infect it step number three. They appear to block the ability of the virus to replicate if it makes it into the cell so if the virus can infect sell then it'll block its ability to replicate quick side. Note the way that works. The virus gets into a cell hijacks it and makes the sell produce more virus. The cell dies start causing inflammatory process. step number. Four people seem to be dying of a bacterial infection that runs with SARS Cov- to called Preval Tele. Something new that the news is not talking about yet and prone to sign it in which are large polyphenyls have been shown to kill Trevor Tele companies since the SARS Cov virus in two thousand and three have realized the potential of this and they are now. Developing polly feel coated masks and wipes for their antiviral. Activity couldn't be more relevant right now since all this Protective Equipment for a healthcare workers is running low so I need to find out what happened with. The companies are actually trying to do that. That was like back in two thousand fourteen looking at this. A German company was realizing that the potential these polyphenyls can bind to the SARS. Cov Virus so tight that they have developed a quick rapid and inexpensive test where they take the human fluid and then they soak it in a mixture of some polyphenyls course attended Lucille. And in this case and if the polyphenols bind to the virus then they know that that is a clumping and they can see through some filters that that's positive so in the beginning we know that we need to kill the virus. You need to not let the virus into your cell if it does get in there trying not let it replicate try not to sit there and get an infection by bacteria that runs with this has been known since two thousand three. So companies have tried to non-exploitative but try to take advantage of that. One is trying to put this into wipes and masks and another company is using it as a rapid diagnostic test instead of using the antibody test. So that is the cliff notes of the rest of the stuff that we're gonNA talk about. I hope I didn't just lose everybody but we've got a lot more to talk about. I'M GONNA leave it with that with. Uk whoa what are your thoughts on talking about the steps of the virus that we have in natural science based possible adjunct. At least let's call it an adjunct related to these viral processes. I think that's fascinating and I wonder because it seems like we're seeing kind of two very different case scenarios when it comes to this virus there are people who they're saying are completely asymptomatic or it's so mild that people don't even necessarily know they have it like people could present with just like Oh. My stomach was upset for a little while or I had a headache for a day. Look very mild symptoms and then we have people obviously in respiratory failure at the the other very extreme end So I'm wondering are these doctors that are maybe coming into play as far as how expressing In the human body. That's that'd be one of my questions and also you mentioned ace to and I'd love to just have a little bit more of an explanation on what that is and if there are factors that we can do to optimize that in the long to kind of keep our long strong. Yes Oh the receptor. This is what they have determined that the virus binds to ace two is on the surface of cells primarily in the gut and in the long. So what the virus does is it will come in and it has to have an enzyme called protease enzyme that allows it to bind to this h two receptor it uses a cholesterol knows as Super Geeky here. But just follow me for a second because we'll back up and talk about some different things that we can do in life so the two receptor binds or it uses this price the proteas allows it to attach and then cholesterol is used to form a lipid raft to let it slide now. Couple fix the ACE. Two RECEPTOR CAN BE UP. Regulated and down regulated. We know that the people that tend to have worse outcomes are those with hypertension diabetes. Obesity are the big ones so just realizing that if you smoke. Oh and smokers armed soldiers. If smoke you actually up regulate aced to receptors in your lungs which means if you get infection you have more receptors to come on buddy right over here and they just wave them in. We don't know what vaping does but we do know that thirty percent of these people that get this now have pretty serious disease. And they're between the ages of twenty five and forty five and everybody's trying to figure out why why is it. These people have signed storms. They have these different things. Some people are theorising when you to tease out. The data is it vaping. We don't know that yet so another thing is is that hypertension. Actually and there's a whole schematic of how this works. But when you have high blood pressure you will actually up regulate your ace two receptors. So Smoking High Blood Pressure and obesity with the cholesterol and that putting it together possibly will up regulate so if we can control those three things you can down regulate that now. This is a moving target because every day I get on and I'm saying articles been published. I mean literally daily because it's coming from all over the world so this is probably going to change and people are looking at ace. Inhibitors or ACE. Two receptor blockers there. There's a lot of debate on that. They're looking at Different ways to try and attack that receptor itself. But you need a protease to allow it to attach starters one of the things that super interesting is that as we age and you have bad dentition. I think you've got a really cool toothpaste on you. We do. Yeah we actually like we use I drop the appetite which is clinically studied to support the the AMMO and so so check us out. We're now remember. This is like every time I wake up. There's a study where somebody and this is what we did. I'd read go. What the heck. I'm like. Wait a minute I saw something on this and then you go back to. What so now people are doing that now. And somebody had published recently the age effects in oral bacteria if you have poor dentition if you have ginger vitus and as we age people tend to have more ginger virus. You will grow more prevalent Hella in your gums and in the back of your throat. Then just keep that in mind. We're GONNA talk about this premise l. Coming up then. People that tend to have gastrointestinal issues including CBO small intestinal bacterial overgrowth and other issues. They tend to have more prevalent. Hello and then. Finally Right Up Tina's alley if you have despite meaning that the bacteria in your colon are not really diverse. And you have a narrow amount of your own microbiome. That is being linked to hypertension. Somebody read that. And then they analyze the stool and they show that. There's more private tele so looking back. Your question was how do we protect ourselves? Well your microbiome it all begins and ends in the Gut because I'm a gastroenterologist. That's what I always say but looking at this there could. This could be totally true because if the virus needs this bacteria called pro tele. It's like a Bonnie and Clyde situation where they both go together the virus hops into the bacteria and then hides and then the bacteria become the bacterial pneumonia which is why so many er doctors are like man. They were fine three hours ago. And now they're just we put Endo tracheal tube in and there's frothy stuff coming so it's it's so interesting that we have this group of people with this death rate and so many people like I might have had this already. So the antibody thing is like like what you're talking about a super important so proper oral healthcare proper gut. Health Care May actually lead to cropper blood pressure and we now know that narrow microbiome. Ken predisposes you to. Ob as well so all those things actually can kind of play into it. Does that make sense kind of moving all over the map here trying to play in a bunch of different studies that have been reading. Yeah that does make a lot of sense and you're right. I think there's so much information coming from all sources and everybody's trying to make sense of it right now but I I think you're absolutely right with starting with gut health because at the end of the day like you said this is one virus. That could very much come back. And if it doesn't we're still going to see other viruses and there's every year there's new viruses in. There's the common cold the flu so supporting the immune system is always a good idea. And I think that maybe a silver lining of this as we've now got all of this new data and research and focus on ways that we can improve the immune system because as of right now there is not even a conventional medical treatment for this virus so truly our immune system is our first line of Defense and I. I'm fascinated with the gut side too because I know when I when we first started hearing about this it was just upper respiratory and then we found out there is gut aspect as well so it makes sense that if we can start and support the gut from the very beginning that that might actually change the trajectory of the virus in the body one hundred percent so just saying that. Now let's go ahead and look at some stuff that we could possibly do related to the the points that I said. So this is the I'm unexplained a little bit more about spoiler alert that I just That I started with okay. Let's look at the antiviral capacity as it. Turns OUT HORSE? Chestnut and polyphenols have been studied extensively in this horse. Chestnut extract is known as Ace Callas Hippo Cast-iron Numb muck along word. But what that is. That's our horse chestnut extract. Which is why I know a lot about this. Because that's in Toronto. So once I started going down the horse chestnut path and went holy cow. They are looking at this. This is absolutely crazy there. Scientists coming out with that. He's our in vitro studies. Meaning these are labs after the SARS COV infection in two thousand and four or in two thousand three. These guys looked at over ten thousand compounds as an academic institution in China including two hundred drugs. Five hundred protease inhibitors. Meaning the drugs that president trump is talking about right now in over a thousand natural Chinese herbs what they determined was two compounds. Had the most Vera seidel effect meaning the ability to kill the SARS Cov virus was blood pressure. Medicine called recipient and the other is done throughout horse chestnut extract. Imagine reading an article where you've been dealing with this for the last ten years and you've been using it for a totally different reason and these scientists said. Hey Y- molecule that you're familiar with is better than ten thousand other compounds that we test it like. Oh my gosh well. That's lucky I guess so. Then I started diving further into it me. Angie started diving further into other studies. So another group saw that study in. W- let's look at the the antiviral effect of Horse Chestnut in killing R. S. V. Respiratory. Whatever virus that usually. It's a virus that's not Cov- but it is. Rsv So it's a mouse. This is it shows that it has the ability to do certain things. The reason why this one was so cool was that day infected mice with RSV and they demonstrated that the Horse Chestnut extract decreased. Inflammatory markers specifically one called. I'll six that's relevant Katie. Because a study just came out where they now are looking at when somebody shows up to the hospital if they check their. I'll six level. That is a prognostic sign on whether the patient will need an ICU. Bed or they're going to do good. That particular inflammatory. Marker seems to be something that sets off the side of kind store some reading an article that was done now. These articles that are done in two thousand four two thousand fourteen. These are these are lab articles showing this. I'm like Oh my gosh. It's makes total sense so if you block. I'll if you don't allow the body to overreact then you're attenuating this cytokine storm which killing young people then fun to other studies where they're looking at other viruses like HIV. Dang gay and the activity of the extract. These people were trying to determine because of the other through studies. Are we able to make a drug on this so they wanted to pull out the Beta ason portion of it just meaning like all things we see this all the time in traditional medicine? If there's something that works naturally then somebody's going to try and figure out. How do we extract that molecule and mass produce a molecule so that we can get a patent because it's very hard to patent mother nature so they compared the whole chestnut extract versus? Just what was supposed to be a drug? And they determined that when they gave pneumonia to mice. And I'm sorry I know there's probably animal lovers out here but this is a lot of the studies that we get unfortunately but when they gave him only two mice they showed that the whole chestnut extract the chest x Ray did much better in decreasing the inflammatory markers in the mice had much better clinical outcomes so trying to just take one little thing out and go. Oh I'M GONNA I'm GonNa make this and just move on so just the straight up. Antiviral effect is pretty impressive at least in the lab and so that was the first step. Which is we're GONNA have antiviral effect for you. I mentioned or you said the as two inhibitor. I explained that the way that the virus actually gets attached to the as two receptor is through a proteinase. So right now there are tons of studies will on over thirty five when I last checked looking at protease inhibitors to try and help the SARS Cov to virus so protease inhibitors is what president trump is getting on TV. And talking and goes we're GONNA talk about hydroxy chloroquine and a secular and there's great studies going on with all these protease inhibitors because that's what we that's what was developed for age to treat AIDS so there's two different studies looking at the anti protease effect of polly females polyphenyls have been shown to block the SARS Cov- twos ability. So in the first part I'm referencing SARS cubs two thousand three now and talking about the virus that causes Kobe. Nineteen two different studies looked at the anti protease effect. One looked at three antivirals and eleven. Different polyphenols in different classes. This show that the polyphenyls as effective as the antivirals in being a protease inhibitor. So then a group out of Turkey and Pakistan Red Dot and their lab published a comparison where they're looking at the binding strength of one commercial protease inhibitor. Compared to twenty-six polyphenyls the conclusion was twenty four polyphenyls out of mother. Nature outperformed the Commercial Nelfinavir. Which is used an AIDS treatment so I loved what happened here. One Academic Institution said we read the data from two thousand four. We're GONNA now do a study on SARS come to and then another one said we wanNA know if binds harder to or not as much in it outperformed the antiviral that was there the commercial antiviral have. I lost you completely yet no I mean that's really astounding. I'm not surprised that Mother Nature can outperform. But that's incredible to know we have those tools. It's pretty wild isn't it? I mean imagine being somebody who's studied these molecules for ten years and I'm just like uncovering one after another going now no and I'm like rubbing my eyes I'm like am I. Am I delusional my in an ICU? Bed Right now intimated and this is how. I'm trying to cope with this that. I'm seeing that I can help this so now. Let's talk about so the first one was it's it's it has the possibility of killing the virus. The second one that has the possibility of not allowing the virus. Attach the third one that I mentioned is. Don't allow the virus to actually replicate in your cells. What we do know is that zinc is critical to this. But you can't just take tons of zinc you have to get the zinc into the cell intracellular. Zinc is the key to this. Because we figured out that if zinc's to sell it will block let's call the Arna polymerase of SARS of two so when this virus infiltrate sell it hijacks it it goes up to the ARNA preliminaries and says I need you to replicate me a billion times and the Arne polymerase normally as well if you're in the cell. Oh that makes sense all right so they tell the ribe zome everybody we gotta start replicating this now and then the virus gets replicated so zinc comes in there and says now wait a minute let me see your let me see your security pass so to speak and zinc blocks that from happening but you have to zinc into the cell and what you need there is called a zinc ion afor so a zinc ion afford drives zinc into the cell. Guess what hydroxy chloroquine is we've all been talking about the antiviral effects of Hydroxy Chloroquine. Pla- Quinnell plus a cycle of beer. But hydroxy chloroquine is here. That's one of the methods that some of these virologist feel that it's killing the virus or helping some people driving zinc into the cell so we found an article in two thousand fourteen which showed that polyphenyls like Carson in an SEC act as zinc ion fears meaning. They drive zinc into the cell. So it pushes it in there. We're looking at doing a mass drug hydroxy chloroquine which new data coming out that it may have a toxic effect on anybody on a diabetic medication called foreman. And there's reasons for that and it can cause some prolongation in in college can run out of the drug and all these other things and some researchers showed. Hey Do you know that these polyphenyls Mother Nature gave us can actually drive zinc into the cell? Nobody is talking about this and we. I've been joking around with my team. I'll say something and people will blow it off and then a month later the news will be like we don't to. They'll say something that I've been talking about because you know to make it into the news. I don't know what what you have to do or do something but I'm over here going okay. So this is all like okay. Now wait a minute. There's no there's no way Katya Times I feel like this time off and when I've been doing this it was either divine intervention or Kismet. Or whatever it is that fate but it's just like one step is leading to the next so now so we've talked about that so now I want to talk about this. Whole thing about this predatory bacteria. Nobody's talking about it yet. But I've been looking a lot of the data a lot of the research coming out of China. A lot of doctors like we don't understand how some crash and burn so fast. New evidence is showing that SARS Cov- to virus may have this accomplice called Prep Attala which is why it can be so infectious and people can have really legal rapid pneumonia crash and burn an hours and two studies out of China have demonstrated that SARS Cov to the causes covered. Nineteen has the ability to integrate with this bacteria. Called prevot. Hella. The virus can actually has a way to get into the bacterial species. And then it can hide so when you test for it but it can get the Potala to start replicating itself. One of the theories of these. These different studies coming out. Preval is found in the gut and many patients that are dying of pneumonia are being cultured with prepa Tele Bacteria as 'cause here's what's wild. Two thousand. Seventeen study in cattle looked at giving Cabrera show to cattle to see if that helps them gain. Weight have better milk production and things like that well. The conclusion was that it actually made the Kennel much healthier and like an afterthought I never would've seen this article after thought it was. The only interesting conclusion was after checking the bacterial content of these cattle. And they just like aspirated the stomach. The unique factor was privy. Tele species were drastically decreased adding to the fact that private. Alec and actually cause problems in cattle so they viewed it as a positive thing so tobacco can actually get rid or at least in. This study has been shown to be bacteria. Sidled to Preval Tele. Cabrillo was the molecule that we studied that I that I always call the workhorse of until but because it's a large polly phenolic compound that can help get rid of different gases and things like that and it appears that it's bacterial. Seidel to maybe co accomplice of SARS Cov to imagine you're going to be hearing more about this in the near future as it starts making mainstream media right now. It's all over the academic literature where people are like that makes sense makes sense so backup step zinc ion affairs. Zinc doesn't allow to replicate and the bacteria that it runs. It looks like can at least be killed naturally in cattle in that case am I getting too nerdy here. No not at all. I'm just sitting here taking notes. That's so fascinating and it makes sense because that would explain why we're seeing these drastically different outcomes and potentially gives us hope for testing and treatment that lets us let people out eventually exactly so studies are showing that polyphenyls act as potent antivirals. So there's a company that is looking at infusing polyphenyls wipes and polyphenol mass to kill the virus and their studies showed that viral. Not just SARS cub to the antiviral properties of the polyphenyls embedded into wipes and masks actually are potent anti viral. So if you're breathing it in it's like hitting a bug Zapper. That's that's the way I was thinking about it. It's like they're coming in. They're running at it and they just go in there debt so that is really cool because as we run out of equipment this alternatives. A German company saw that on. And that's the one that they saw and in two thousand and twenty they said okay. We have all this evidence that these polyphenyls can do this and they can bind to the viruses and do this. We should make a rapid SARS COV to test so this is a twenty twenty tasks that these guys are trying to mass produce and put out there looking which are large polyphenols and what they showed is that they can label those polyphenyls. They can put a patient sample. And that has SARS come to and if the polyphenols jump on like dog pilot it'll clump up. And then they view these clumps as the way that it actually binds to it and so the assumption is that you have SARS Cov to the only other way to do it is to use an antibody against SARS COV to which is very expensive so their theory is look we got a rapid test. We have this dirt cheap. You know thing that's out here called Polyphenols and we can actually show it. In a cheap fast way in knocked us out so that to me is some pretty compelling evidence. What are your thoughts on that and that is incredible and I think. Hopefully you're like you said COM can be contagious. That's also I think a glimmer of hope for a lot of us that I know there's a lot of feelings of just kind of helplessness and feeling like there are no tools against this so to know that there are actual studies that show some things that we can have access to. That might actually really help in that. Also support the body in various other ways. I think it's just a huge glimmer of hope right now so I'm my wife for the last several weeks he'll just find me or just articles and articles. I've never worked this hard to make zero money and I've never been this excited about not making any money in working really really hard. She's like she was like a madman. Just walked around. You like wait a minute zinc and she's like you're mumbling stuff like zinc proteases and this and that and then you run back to your computer and then you get an email and then all of a sudden there it is so she's like you're you're you're crazy. She was like you just need to just chill out. Well that enthusiasm is because I keep thinking I'm GonNa find something that'll just pull the rug out from under me and as of yet. I haven't found that and Katie even if this does not translate to a large double blind placebo controlled trial. We don't have time for that right now. And quite honestly if I can save one life either through improving their gut health or possibly taken out the virus then I have a moral obligation to share this and I feel so strongly about this that I've met with my team and we are building a platform that we're going to give away to frontline healthcare workers who are the current heroes. Hundreds of doctors and nurses have died taking care of people and we can theorize on that as to wire so many young people in healthcare workers dying now compared to that it should be a very benign disease and eighty percent of the people. And I think it's related to the viral load. I think it's related to the work that they're still doing wall. There're probably exposed meaning. They're wearing their immune system now and I think it could also be that the ones that are in the hospital may have a slightly more virulent strain so they're self selecting themselves to be targets currently because of the way the way we are in the hospital. I don't spend a whole lot of time in the hospital but in New York. They're doing medical drafts. They're calling doctors out of retirement. They're taking specialists like myself. And they're saying we need your help in the ICU. Eric and I just did a show where I specifically asked him I. Let's do a show where basically you're giving me a refresher on lung physiology and how to run event and all these other things because if I get called in I want to be prepared and I wanNA share that that show with all health co workers who are in that same situation so we feel so strongly about this that we're going to give our Toronto to frontline healthcare workers at least a few hospitals that I have connections with around here Katie. The way I see the worst case scenario is that they have less bloating. And they're they have better gut health best case scenario we would be able to show epidemiologic changes in infection rates in zonal area. And if we can do that with hundreds of doctors and nurses in two locations then that would really park everybody's ears up and maybe we're onto something. If if we can do that then this could be something much cheaper than what other people are doing out there and maybe can be part of hospital formularies. The risk is low. I mean we. We've been in business for five years. Hundreds and hundreds and hundreds of thousands of people have taken the product and knock on wood. We've not seen any real bad side effects so we know that this is mother nature stuff. We're not altering it. These are full large polyphenyls so the way I see it. The risk is low. The potential for helping is might be high and the cost is only to us when we launched ultra ntil. I was totally scared that it wouldn't work and that the science that we had discovered would blow up in my face. I'm very happy to say that it did work now. I'm scared again but we have nothing to lose but money. I feel obligated to do this. And I WANNA thank you for allowing me to share this for the first time and hopefully if this could actually end up being something that we would be part of the solution and I'm really proud of my team. I'm really proud of all the frontline healthcare workers and the first responders. Because we don't know where this is going to go but it would be nice to at least give some advice on how to protect your gut to help your immune system and possibly help if you were to ever be exposed. Yeah I think that's an important point is just to reiterate that these are beneficial things to do anyway And the other caller the question I would have is. What if any are the risks or downsides of trying this approach because I also I get frustrated in medicine I understand wanting to have a double blind clinical study about everything? But like you said when time is of the essence. You can't always do that. And so I tried to evaluate if this is something that could work with relatively low Cost and relatively low chance of anything. Negative happening then with the risk benefit analysis. It seems like a thing you would want to try and just see if it works. But are there any like risk or downsides that you can see trying this approach will the only downside that I would say is that we don't really know how this would interact with certain narrow therapy drug so what I've told all my patients are if you're on an anti rejection drugs. I don't know what it's GonNa do. I don't want your body rejecting anything if you're on a blood thinner we don't really know what's going to do and that's strictly because it has been studied so the reason why it's works it's so convenient and I think beneficial to do the to do the people on the front line. The nurses and doctors taking care of people. Is that number one. It's their choice. They have an option to do it or not many times. The reason why they always say double blind randomized placebo control is because a doctor saying. Take this to a patient and many times. The patient usually not many times almost always vision will be like okay. You're the doctor. And they take it here it is. This is a reference page. This is why we think it will help prove to us that you are affiliated with an institution that we're at and we're just GonNa send it to you. You can throw it away if you want or not but my suggestion is to take it. At least fairly. We have not quite figured out that I personally am telling people that have asked me this. Because there's you know worked a lot of nurses and stuff and they're all like you know. Hey we heard this podcast that you did and I. I want some of that. How should I take it? And I'm like I think we should take it one capsule three times a day. Because if you're exposed we just on the mechanisms that I was talking about. Do you want to kill it when it's in there? Do you WANNA zapped bacteria that it's hiding in. Do you want to prevent it from attaching to the cell and just in case it gets in you want to make sure that you get that zinc waiting there check and badges to make sure nobody snitch. Through so I'm suggesting may possibly and this is not. This is based on my experience with this with just trying to you. Know it's more frequency so at least three times a day and by doing one bottle each one of these healthcare workers will get a full month. And that's imagine and you know how it is. I mean you have a business. Imagine sitting with your with your team and they're looking at you like you want to give the stuff away and like yes. I want to give this stuff away because if we can then look back and have somebody say. Hey Look. We saw a little pocket. North Dallas and the healthcare workers exposed. I'm at one of the hospitals where they're funneling people too because we've got all the proper equipment all that stuff so we're they're gonNA be at high risk and if we can eventually say look. I get that it's a moving target. But if we can eventually say they chose to do they had an option they signed up. They were not coerced. There's the studies and it and it works. Well now we've offered some you know like I said I feel like I have a moral obligation if I end up with a in my face and it's completely wrong. Well I at least tried. You know I mean it's the whole I don't know I've got a poster in my room with that Theodore Roosevelt famous quotes and I just want to paraphrase. That you've heard it's a long one but I always think about. It is not the critic who counts the credit belongs to the man who is actually in the arena and if he fails at least fails while daring greatly so. I'm convincing a lot of people that we need to go this route and if if we fail it's just my money that's the way. I view it so our frontline. Healthcare workers are currently the people in the arena. As far as I'm concerned and I'm one of them and I'm making sure that I'm taking it and I'm making sure that my family takes it next thing. I want to talk about a couple of things not related to our Tronto. But I'm also taking and you antena talked about some of that but I got a couple I got. I got a couple of other things that I think you can add to. What you guys talked about also awesome. We'll end before we move onto that. I love that Cardi Roosevelt quote so much have in my office actually And I think I also just want to speak to all the parents listening because your parent as well and I feel like a lot of the parents are also on the front lines of this in the arenas now being teachers and managing everything. They would normally managing trying to maintain that calm that. I'm hoping is contagious. Through this episode. And so I just wanted to give a shot all the parents who are working extra hard right now to and And I think we as parents have a unique ability to also hopefully Not to the degree that medical professionals do but to affect the outcome as well by keeping our families safe and so. That's why it was so important for me to have you on stay in to talk about. Some science backed ways that we can do that with our own families So let's talk about the things using conjunction with this and I love to hear specifically like what are you doing as a parent? What are you doing? What is your daily protocol? Look like right now. What is your kids? Daily Protocol look like right now so as parent. I'm trying to isolate myself because I still have to get exposed a little bit. I'm on call every once in a while and I have to do it so every time I do that. I really try sleeping different bedroom. I'm trying to do the the best. I can to do. Decontamination Protocol. When I walk through the House I'm trying to do most of my telemedicine and things like that at at our studio so that I'm not sitting around the house all day because I feel like I would be the vector right now and I'm really trying to do that and so the kids and the protocol. I'm taking it serious of I'M GONNA ask other people to do it. I'm doing also so I have not hugged or kissed my wife and kids in several weeks. Because you know I'm talking to people and I realized that well what happened in calm is contagious. Not trying to do anything but I you know you wake up in the middle of the night and you just go if I brought this home and there's a potential that I that my kids could lose their mother that stats the part. That always gets me to stop wash my hands longer. Instead of our nature is to be social. Our nature is to hug somebody when you see him and I love what you WanNa talk about that you don't you just because it's it's social distancing it is not social isolation so you can be socially connected to people while being isolated and so. I'm doing a lot zooms with friends and family. I celebrated a birthday with my childhood friends. Were all over the country and we all port a cocktail and told stories about two hours and that was a great social engagement when everybody's on lockdown in La Florida Panama. And all these other things. So what I'm doing. I'm doing my part and my wife is doing a great job of. I've very huge tennis family. And so you know. It's all about tennis and so as long as they're not touching anybody or doing anything. They're still doing their workouts. My son he's fifteen and he gets a daily workout from the US. Training Center in Florida. And I did it with him yesterday. And I'm like Dang hard a workout for an elite level. Tennis player is really hard and it was. It was pretty funny so we're still working out. We're going outside. Words getting walks lots of parts. I'm reading a ton and my wife is doing a really good job of cooking everything at home so that we're not risking any of that either so it's one big supermarket. Ron and then we just go through all that food. So that's what we're doing on a day to day level. What I'm giving my family's a little bit something that I think that we should talk about. Are you cool talking about what I'm looking at that? I have no financial bond or anything like that but looking at the science. I feel like that everybody should risk low benefit might be really big kind of thing. Are you okay talking about other stuff absolutely and I'm right there with you on wanting to just try to protect our families? And then we can. So I've been taking notes the whole time you're talking to make sure I can put links and as to. The study is in the products. We're talking about in the show notes but absolutely dive in okay so one of my favorite things that I've been using a ton of over the last several months and having tremendous success. I started doing it because they contacted me. And we're talking about the association with Gut and all that stuff is a product called Broccoli. And you've probably heard of it like I'm Rhonda. Patrick always lectures about sulfurophane. Have you ever heard that before of? Oh Yeah I I Take Broccoli and actually grow still Broccoli sprouts because they love them but yeah she's the Best I've ever heard on so forth and then the compounds Glue Carafe nanomedicine as in how those all work together but basically yeah explained to us what so far fain is and why it's helpful right now. Yeah totally so you can get it. Johns Hopkins discovered this molecule. That is found in Broccoli sprouts and when a sprout when a Broccoli sprouts up or all cruciferous vegetables they actually have today high concentration of this molecule that they actually discovered which is a Raffin it and then when you masticate or you chew on a Broccoli Sprout Morosini converts that to Sulfurophane. So I've been playing around with this for years trying to grow my own spouts. Forgetting my house smells like weird stuff for the garage and smell. I was not very good at that. Because I'm always my times are always way off. So then I get contacted by the CEO of Broccoli it was actually set up through Mike Luggage and I sat with his PhD. And we were going through. And I'm like holy cow. The biggest problem with this is that it's it's almost impossible to make sulfurophane stable and these guys. I may be speaking out of line here but I believe they're the only stable sulfurophane supplement if you go on Amazon and look. There's two thousand different Broccoli sprout supplements but it's usually some version Messina's plus squeaker Raffin. And do you know of another one? You're going to say something I know. It's the only one I've ever found as well because it's such a complicated process and I've talked to the founder as well. It's extremely involved thing. And it took a whole lot of research to be able to that and even like you mentioned. I mean Broccoli. Sprouts can be a pain to grow. I have a tutorial anyone who wants to But then there's a whole process actually activate the sulfurophane. Make sure that you're getting it because you can eat a lot of Broccoli sprouts and still not actually get the sulfurophane if you don't have the right temperature if you don't chew it there's all these factors that come into play. So this is the first supplement I've ever found. That actually has results and test. Data backing up that it's bioavailable yes so these it was such a great zoom call because the PhD clearly was like I need to give out to the lab. Yes I was like. Well how do you know that it's audio? It's available like we checked NRF2 levels. You know what I'm just like. So what happens is sulfur turns on a pathway called NRF2 now interrupt to Rhonda. Patrick goes into great detail about how it is actually a potent anti inflammatory and it's also a potent anti cancer. That's cool and Johns Hopkins is looking or they St- they started a a study where they're looking at. How when you turn on the energy of two pathway or Sulfurophane can actually cross the blood brain barrier? So they're looking at it for autism and things like that. There's a study but they're not looking. They're not using Broccoli to do that. There's a different one so I've been using it in my clinical practice. Since you know since the day I found out about him and I can't keep the stuff in my office and so it's I use it for gut health and it's a great combination with our Toronto because as their scientists explained Y- Polyphenols in it. Actually help it to be absorbed. So you're like okay great so you like it well. Here's what's once again. What the heck so we discovered. There's data to show that sulfurophane turns into pathway which actually hits a different surface pro. Da's which is activated by something Trans searing produce too so they get really science on this but basically it can actually down regulate the expression to prevent the virus from binding. So I explained to you that there's studies to show that polyphenols will bind the proteas. It appears that sulfurophane turns gene on where they just start closing the doors or they start decreasing the amount. That's there earlier you said. How do we protect ourselves? I said well. If you smoke you're going to up regulate those receptors here you're down regulating those receptors. So that's one way. And then they actually determined that there's something called S. l. p. one witch when it's expressed what it does and when. Eric I did the show. He explained how when you get an infection in your lung you go through this inflammatory cascade and a neutral phil will come in. And that's good and bad it'll help kill but sometimes it breaks down the tissue around it. And that's how we these massive pulmonary things by turning on sap one it actually decreases the pulmonary damage by sort of controlling the amount of damage being done by that. So I went only cow. I'm so my kids are on that and then clearly. It's like when you start looking at the stuff. I'm a huge fan. Cbd BEEN INTO CD for years and years and years. And I don't have all the science on that because I just started looking into the last couple of days because I want. Is there any possibility of that? I tell all my patients. Hey these are anxious. Times CD helps with my anxiety. And then Angie sent me several articles this morning which I haven't gotten too I was like Hey. I'm going on Wellness Mama. Do you think that there's anything CD? And then she already sent me some stuff where it's like it. Attenuates the inflammatory response specifically. I'll sex and I'm like cool our own endo cannabinoid. Cbd specifically increases that and then the final thing would be Melatonin. So I take Melatonin every night. Yes it helps you sleep. But it also shows that it'll decrease I'll six now so I'll sexist the inflammatory mediators so hopefully if God forbid if I were to ever get any type of infection. I'm locked and loaded and who you know with these different things. So that's that's my little combination. There are Tron -Til Broccoli Melatonin and CBD is what I had my family on all my patients so yeah we're on a very similar protocol. I am. Oh I'm sorry in vitamin D Vitamin C. Jacket with Tina. Talk about I was GONNA say. I am giving them vitamin C. Vitamin D and. I know it's controversial but I am making sure that we are all outside in our own yard but in the sunshine for like a moderate amount of time not ever sunburn but for sure that's also like light. Signaling is an important thing for immune health and also vitamin D is so important and several of us have vitamin D MUTATION. So we don't absorb it. Well be a supplements. I'm also making sure we're spending time outside but exactly the same as you and I will actually right out that protocol that we took a treadmill anyway but now making sure to be very regular about it in light of all. This is pretty wild. Yeah Eric and I did a whole show why we think these supplements based on science with references and stuff like that so I will have all of those resources linked in the show notes and Wellness Mama Dot FM. I know many people listen to podcasts. While they're exercising or driving so if you are doing that don't worry about writing it down. You can find everything in the show. Notes there including links to a transient. I love that. You guys are also using this as a way to get this in the hands of medical professionals. Because I think you're delivering on your promise about calm and hope being contagious. Because you're right if we can start showing an effect in medical professionals in certain areas and bubbles that actually gives us data to hopefully like improve this and all of us get out of our houses eventually. So you guys are taking the front lines like that totally. This episode is sponsored by up. Spring baby a company making innovative science batch products for MOMS and babies and I wanna tell you about one of their products in particular because even though I'm not even currently pregnant or have teeny babies. It's been really helpful to me. I really liked their stomach. Settle Nausea relief drops which are great for any kind of stomach upset from motion sickness. Which I get in a couple of my daughters get to morning sickness which I think do not have right now because I'm not pregnant but any kind of bloating or digestive upset at all. I love to keep these on hand and my kids like them too. They help relieve Nausea Motion. Sickness gas bloating in any kind of digestive upset. In fact I keep these in my car and my kind of emergency kid and each of my cars also in my purse just to have on hand because to me it's can be a thing when out and on the go there. Lemon ginger honey. Flavored stomach settled drops contain not just one but three natural remedies or digestive upset. Ginger spearmint and lemon plus. They contain vitamin B. Six to help relieve occasional nausea motion sickness gas and bloating. Their ingredients are micronized. Meaning that they provide faster acting relief and they've been really helpful like I said especially for motion sickness. They're individually wrapped. Great for on the go and I was able to negotiate a discount just for you. You can check this out at up spring baby dot com forward slash pages forward slash wellness. Mama and the code wellness. Ten saves you ten percent so that's up S. P. R. I. N. G. B. B. Y. dot com forward slash pages forward slash. Mama all one word and use the code wellness all lower case wellness ten to save ten percent. This podcast is sponsored by blue blocks that's B. L. U. E. L. which is an advanced light filtering. Eyewear Company you've probably seen pictures of me on social media wearing orange glasses of various types at night and here's why in nature we aren't exposed to certain types of light after dark specifically blue light because that type of light signals the body that it's daytime that intern suppresses. Melatonin and can interfere with sleep. This is the reason that are really dramatic. Study found that camping for seven days straight with no artificial light at all could actually completely reset and he'll circadian rhythm and help a lot of light related problems like seasonal affective disorder. This is also the reason that I wear orange glasses after dark to block these types of light and protect my sleep which I am adamant about protecting. I also wear a certain types of yellow glasses. An anti fatigue glasses during the day on a computer to reduce fatigue. Blue blocks has orange glasses and yellow glasses. Their orange glasses for nighttime designed to block one hundred percent of the wave links between four hundred nanometers and five hundred fifty nanometers which are the ones that are studied to interfere with sleep and told him production and Circadian Rhythm. My kids also wear these kinds of glasses at night and I noticed a difference in their sleep as well which is a huge win for a month. This is especially important when we're watching the family movie at night or looking at any kind of screen as the artificial light there is a source of blue light and can interfere with sleep. You can learn more. They have a ton of educational content and check out all of their innovative protective glasses by going to blue blocks dot com over lash wellness. Mama and using the Code Wellness. Mama to save fifteen percent so again that's blue-blocker dot com B. L. U. B. L. O. X. dot com for slash wellness Mama and the code wellness. Mama all one word and all lower case to save fifteen percent. Hey super-quick not interrupt but Republican a little. Over the normally do but your. Your team sent me three questions. Yes doesn't want. I usually wrap up with. Are you up for those now? I'm up for those okay. The first being what are a few things about your area of expertise that most people don't understand okay so I'm a gastroenterologist? Most people don't realize that your gut can affect just about everything and so because of that. When I'm in clinic I really do have to play detective and ask questions and people wonder why I'm asking you about their skin or why I'm asking about their sleep. But because that helps me determine is there underlying gastrointestinal? 'cause or if you're not healthy is that causing your psoriasis. And things like that and the thing that people don't realize is there like why would you like to be a gastroenterologist number one? I do that. I get to play detective and I have to keep sharp and a lot of things but number two. I basically get play video games in people's digestive system and save their lives by taking out polyps and stuff like that so that's a gastroenterologist and people are like simply a horrible job on my gets the best of world that's awesome. Yeah I think like things like this. It just illustrate more and more that the gut is so so important to all aspects of health. What was what was the second question. The second is is there a book or a number of books that have had a really dramatic impact on your life and if so what are they and why so this is this is the one I was. I stared at and I the the the normal thing when you talked about Viktor Frankl. Menial life I'd read that one in high school and had to do a report on that and I was like that was a good book and then I started thinking. I'm like what affected my life so when I was in sixth grade I went to a Catholic grade school and we were assigned to go into the library and check out a Pulitzer Prize winning book and I chose and I'm not. I was not a good student up until college. I was really bad student and I was lazy and I said Oh. I found a children's book written in Nineteen Thirties. There was a Pulitzer Prize winning and it was called the capital into heaven and I thought it would just be like sweet. I pulled one over on them and then I did this whole book. Report which ended up being massive huge. I get called in with all these nuns. And they're like why did you do this? I'm like I thought it'd be easy but I wrote a really long book report as it turns out. That book is All about Buddhism in acceptance and expanding your mind and things but you have to really read between the lines and then unsaid. I think this book chose you and that kind of started south super super super. You know Catholic and didn't see anybody else's view and that was the first time I went The book chose me and that's kind of that's the basis of the book and so a Children's book changed my reference of the world when I was in sixth grade and since then I've just been on a journey to sort of accept and be open. Wow that is definitely a new and that's fascinating And lastly any advice that you WANNA leave with our listeners as parting advice today for everyone listening just realize that I see a lot of people's insides I look at a lot of Colin's old young professional models people that are struggling with their weight. Any race you can name it. And here's something that you can always just rest on if you see somebody that's bothering you. Whatever your insides look exactly like their insides so take everything with a grain of salt. I Love Humor in perspective to end. I think that's perfect and I really appreciate you and all of the work. You're putting in right now in research and also on the front lines of medicine and it's just so grateful for you for having these products available to us and also to medical professionals. I am also really hopeful that we will hopefully find some strategies and CNN to all of this soon and that we can hopefully help a lot of people in spreading this information. But thank you for your expertise for your time today. Thank you just. It's just amazing what you're doing out there and I know that your audience really leans on you and you take the time to try and find proper gassed. You take the time to do your own research so thank you for everything that you do. I WanNa thank you as always thanks to all of you for listening and for sharing one of your most valuable resources. Your time with both of us were so grateful that you did today and I hope that you will join me again on the next episode of the Wellness Mama podcast. If you're enjoying these interviews would you please take two minutes to leave a rating or review on I tunes for me? Doing this helps more people to find the podcast which means even more moms and families can benefit from the information. I really appreciate your time and thanks as always for listening.

SARS Katie I bloating Toronto flu chloroquine Kobe AIDS Nausea Mother Nature respiratory distress China Preval pneumonia Angie
Governors outraged by more Trump admin vaccine supply lies

MSNBC Rachel Maddow (audio)

48:07 min | 23 hrs ago

Governors outraged by more Trump admin vaccine supply lies

"The show we did nine eastern on. Msnbc it is friday president trump's last friday night in office. Some people drink on friday nights after a long week some people get high or have a movie night or whatever our president. He likes to spend a friday night issuing scandalous pardons and commutations too. Well known criminals. Who helped him cover up his own potential crimes or to whom he owes other potentially criminal favors. So it's friday night. We are on. Pardon watch tgif congresswoman alexandria ocasio. Cortez is going to join us. Live tonight in just a moment We're also going to be joined live tonight by the man who president-elect biden just announced will be in charge of the country's vaccination efforts against covid nineteen scientists and researchers of course did there. They moved heaven and earth really did the impossible by developing safe and effective coronavirus vaccines as quickly as they did. But then the government it. The government did not come up with any sort of national plan at all to get the vaccines. These scientists had made actually distributed at scale and administered to people with any sort of efficiency and so even though those vaccines were developed and approved and produced with such alacrity. All that got us is the situation. We're in tonight. Where millions of doses of the vaccine or just sitting in freezers while every single passing day. Another two hundred thousand. Plus americans get infected just today state governments all over. The country are reeling once again after trump health secretary. Alex are told states they were gonna get a whole bunch of vaccine doses next week that they are actually going to get. This is at least the second time that the trump administration has told the states that there were doses shipping out to them. This is that didn't actually exist. Which is just frying. These already fragile cobbled together systems and all the states as the states have had to try to figure out vaccine distribution programs on their own with no national plan to help them do it. So we're gonna have much more on that tonight and more importantly we're going to have the first national interview with the man who soon to be president. Joe biden just named as the person who will be tasked with fixing this mess and setting up a national vaccination plan for the first time under president biden. Dr david kessler. We'll be overseeing a whole new multibillion dollar effort that among other things will put the national guard and fema in the field at new mass vaccination sites in every state in the country. The proverbial cavalry is coming on vaccines. Dr david kessler will be leading. It he is our guest here tonight in just a moment in washington tonight as we prepare for the biden harris inauguration on wednesday. The secret service is now in charge of security preparations. They have now literally announced that they're forming a green zone in washington to include a huge area of downtown dc around the capital. Yes a green zone like the one. We've all reported from baghdad during the iraq war within the green zone there will be a restricted red zone. Where nobody's allowed to be the national mall will be closed more than a dozen metro stations. Which is the dc subway stations subway system. More than a dozen metro stations will be closed. Trains will be stopped private bus companies. That run bus routes into dc from other cities. They're stopping those bus. Runs into dc airbnb last minute hotel room. Booking sites are not only not taking new bookings for people travelling into dc anymore. They are cancelling bookings that already exist. There was due to be a rehearsal for the biden harris inauguration. This weekend that will now be postponed for security reasons. They'll try to do it next week. But each passing day now brings more arrests of the radicalized. Trump supporters violently attacked the capital to try to stop the counting of the vote in the election and each new public indictment reveals more lurid descriptions of what these people did what they intended to do. One man charged tonight a forty three year old man from rochester. New york told people that Have they got their hands on nancy pelosi inside capitol. They would have killed her and also vice president. Mike pence he told people had they been able to find him inside the capitol complex. They would have killed him to. There has been back and forth sort of unbecoming of the justice department today about what it means that federal prosecutors in texas and arizona told judges an individual defendants cases that the aim of these attackers was to physically restrain and potentially assassinate lawmakers inside the chamber the new yorker today reports that members of the mob that attacked the capital were armed with guns and tasers and baseball bats and truncheons. At least one person carried a news with them into the capital which puts a fine point on the fact that so much of the crowd was yelling. Hang mike pence. Cnn interviewed one of the dc. Police officers dragged down the capitol steps and beaten and tased by the trump mob. I was trying to fight as best. I could I remember like guys were stripped. Me and my gear these riders pulling my badge off my chest They ripped my radio off of off. My vest start pulling like amunition magazines from their holder on my belt and then some guy started getting a hold of my gun and they were screaming out. Kill him with his own gun At that point you know. Just like self-preservation wash survive this situation. And i thought about using deadly four thought about shooting people and then i. I just came to the conclusion that you know if i was to do that. Yeah might get a few. But i'm not going to take everybody and they'll probably take my gun away from me and that would definitely give him the justification that they looking for to kill me if they already didn't have made that open their minds so they'll option. I thought of was you know. Try to appeal to somebody's humanity. And i i just remember yellen out that i have kids and it seemed to work. Some people in the crowd started to encircle me and try to offer me some level protection and they gave you know that provided me with enough time or or other officers specifically my partner jimmy albright enough time to get to me and get me the hell out of there and back into the west front of the capitol Lot of people have asked me. You know my thoughts on the individuals and the crowd that you know that helped me or try to offer some assistance. And i think kind of conclusion i've come to is like you know. Thank you for being there. That's officer michael. Phenomena the dc metropolitan police He doesn't describe it there in that interview. He was repeatedly shot with a stun gun with taser by the attackers post reporting late. Last night that that officer suffered a mild taste also that he drifted in and out of consciousness while he was being beaten the inauguration on wednesday the justice department today released a bulletin saying commercial airlines have tracked an increase in passengers checking in guns on their ways to on their way to airports in the washington area. Dc of course itself has strict gun laws but reagan national and dulles. Airport are both in virginia. Where of course the gun. Laws are super lax and the airlines. Say lots of people are checking guns on their flights into those airports denote that we've heard nothing from the f. b. i. or the justice department about any apprehension of whoever it was who placed the operational not fake pipebombs outside the headquarters of both the republican and democratic parties near the capital on the day of the attack at the capitol. Whoever did that whoever place those pipebombs is apparently still at large despite a huge effort by the fbi to find that person and a big reward posted for information leading person's arrest and capture national guard. Units are being warned that improvised explosive devices. That bombs may be used in an attack around the inauguration. Today we're also hearing from the justice department and from open source reporting in the in the new yorker and elsewhere about military style tactics and coordination among the trump mob attackers including this tidy. Corden of single file men in full military gear marching single file through the crowd in a disciplined way. See how they're each holding onto the caller or the shoulder of the man in front of them. That's what the ap describes as ranger file formation pieces quotas as president donald trump's supporters massed outside the capitol last week and sang the national anthem. A line of men wearing olive drab helmets and body armor trudged purposefully the marble stairs in a single file. Line each man holding the jacket. Caller of the one head that formation known as ranger file is standard operating procedure for a combat team that stacking up to breach a building. Its instantly recognizable to any us soldier or marine. Who served in iraq and afghanistan. It was a chilling sign that many at the vanguard of the mob that stormed the seat of american democracy either had military training or we're trained by those who did if those kinds of us military tactics were brought to bear against congress in the capital attack this past week. It's imaginable that even organized force like that would be deterred by the more than twenty one thousand arms national guards men and women who will be stationed in. Dc in advance of the inauguration to protect it but they can't be everywhere and this weekend the expectation is that the armed trump mobs are not necessarily to do due to turn up in dc. This weekend there do this weekend. Turn up at state capitals around the country over this weekend and into monday. And you know if they're intent on waging military style potentially military trained arms terrorist assaults on multiple state capitals. Well all the troops in dc aren't going to make a difference to that that's part of what is so unsettling about tonight's heading into this weekend knowing what we have come to learn about the attack on congress the attack on the capital by the president's supporters we've now got this huge fortification of dc. But there's this worry still about what might happen in dc on top of all that and more mmediately warnings about what's planned well outside of dc by armed pro-trump mobs state capitals. Are anybody anywhere else. They might want to show force or continue advancing their violent campaign against the democracy. And then there's the inside question. The question of whether members of congress have been complicit did members of congress help pro-trump rioters basically case the joint by bringing them into the capitol the day before the attack. Show them around orient them to the inside space. That possibility now under investigation by the capitol police did members of congress. Betray the location of people who would have been targets of the mop in other words. Did they help house speaker. Nancy pelosi today announcing that that prospect that some republican members of congress may have essentially helped in the insurrection attempt that is under investigation. She says any members found to be complicit in the attacks should expect to face not only potential expulsion from congress but also criminal prosecution if in fact it is found members of congress were accomplices to this insurrection. If they aided and abetted the crime the may have to be actions taken beyond the congress and in terms of prosecution for that suplicy addressing the fact that that is now under investigation by the us capitol police and reportedly by the general accounting office The gao that's also been asked to look into what happened. Specifically including the question of whether or not any members of congress or congressional. Staffers may have effectively aided and abetted in the attack on the capitol building in on the congress. One of the first members of congress to raise this prospect was firebrand now second term new york congresswoman. Alexandria ocasio cortez. There's a secure extraction point And a secure room that you may have heard a lot of people you know members give interviews from the minute secure location on a secure location. You know republican members of congress. Don't wear masks. They refuse to wear masks in that enclosed secure location and now we are on you know just in the last twenty four forty eight hours. Our third member of a democratic member of congress who tested positive for cove it because they were sheltering in that place. I myself did not even feel safe going to be that extraction. Point because there were cunanan and white supremacists sympathizers and frankly white supremacists members of congress in that extraction point who i know and who i have felt would disclose my location and allow me to Would create opportunities to allow me to be hurt kidnapped etc. And so i didn't feel safe around other members of congress as for myself i had a pretty traumatizing. Event happened to me. And i do not know if i can even disclose the full details of that event due to security concerns. But i can tell you that. I had in very close encounter where i thought i was going to die and you have all of those thoughts. Where at the end of your life and all of these thoughts come rushing to you. And that's what happened to a lot of us on wednesday. And i thought i i did not think i did not know if i was going to make it to the end of that day life and not just in a general sense but also in a fear riveria specific sense when it was an extremely traumatizing event. And it is not an exaggeration to say that many many members of the house where nearly assassinated. It's just not an exaggeration to say that at all we were very lucky. That things happened within certain minutes that allowed members to escape the cap but the the house floor unharmed congresswoman ocasio. Cortez made those statements on tuesday and because the conservative media is obsessed with absolutely everything she says and does and thinks they have since attacked her for those comments saying oh nothing serious happened at all. She's just making it up today. The washington post is reporting that justice. The congressman says it was actually a matter of seconds between the mob and their targets inside the capitol who they explicitly said. They wanted to kill the post. Reporting that vice president mike pence was rushed into a hideaway outside the senate chamber less than one hundred feet from where a huge pro-trump mob chased capital police officer. This was part of the crowd demanding. Where are they counting the votes and hang mike pence from the post quote rioters loudly denouncing the vice president as a traitor began to pour into the capital secret service. Officers spirited the vice president to a room off the senate floor with his wife and daughter about one. Minute after pence was hustled out. A group of mobs a group a group of the rioters. Excuse me charged up the stairs to a second floor landing pence and his family had just ducked into a hideaway office less than one hundred feet from that lending if the trump mob had arrived seconds earlier. The attackers would have been an eyesight of the vice president as he was rushed into that hideaway office congresswoman ocasio cortez was right about the dire and very near threat to members of congress who are inside that day and it turns out to the vice president as well and now of course. There's the threat of the this weekend and the week ahead joining us now is congresswoman alexandria. Ocasio cortez of new york congresswoman. I really appreciate you being here. I know you have lots of options. And i appreciate you coming here to talk about this or thank you for having me so you and your colleagues have been through ordeal. You made those public remarks on tuesday. About how specifically scary and dangerous was the situation that you were in and you send at the time that for security reasons. He didn't feel like you could say more about the direct threat that you experience that caused you to go through all those things that people worry about when they worry that their life is in danger. Can you either tell us more about that event or tell us more about why you can't in terms of how you've been advised about your own security here. Yeah you know. I think one of the reasons we hesitate to share more details is because of frankly the security lapses that exist and that existed that day and date to reveal locations and and what actually happened. In order to not reveal other other. Lapses in vulnerabilities. Potentially but you know. I think one of the things that was so scary that day not just for myself but for many other members and i think even for people at home watching on television was these acts of great heroism. I'm you know even within capital police and within congressional staff etcetera that were juxtaposed with acts of great betrayal by people in those same ranks. And what's so scary in a situation like that is that you don't know even if a person is in uniform whether they are there to hurt or to help and and it goes without saying that this is what a lot of communities have experienced but to be not is extremely scary and just as you pointed out are where it seems as though and it it seems as though some of the arrests have either been military ex-military or trained by military and police officers to police officers have been to virginia. Police officers have been arrested and charged that that is extremely unsettling when you have that kind of breach of trust and And it can be very scary to especially when you're in the actual midst of an emergency situation. Let's talk about that in terms of members of congress and congressional staff as well you saying that you didn't feel safe going to that extraction point because you believed from knowing them that. There were members of congress. You didn't trust not to betray your location. Put you in danger in that way. Can you just talk a little bit more about that. About why you why you believed that if if it's if what you believed about that what you know about that is something that ought to be part of the investigation or is it. Part of the investigation. That's been announced into whether or not members of congress are complicit. Here right well i mean. We can't know. I can't speak as to what is currently under investigation specifically or not but But we but there are members of congress who have made public comments comments like that. Muslim americans should not hold public office. They've made public comments. That are quite closely aligned with the beliefs of white supremacists and white supremacy sympathizer organizations Am these were all public record. And you know people of color are not safe around any individual who frankly sympathizes with a white supremacist. 'cause it doesn't matter if you've been elected to congress or not. It is a complete abdication of any responsibility that we all have to protect and defend and be there for each other as human beings as certainly has americans and so You know it wasn't safe. I'm the implications of that are quite dire to not be in a secure location Because being in the insecure location seems like a safer bet than being in a secure location. I mean it's it's pretty scary. And i can also say that i was not the only member of congress That felt that way you know not. Every member was not secure room and even from members who were in that secure room. We have now seen several. Who have come down with covid and you know this is a big day So members of congress who had just been sworn in three days prior had spouses with them children with them Young staffers with them. And we're responsible for their safety to and On the flip side members who didn't wear their masks endangered. Those families to and those numbers are on video as well. I mean they bear full responsibility For india the lives of the people around them for and also for what a conspiracy theory a political point. It's truly it's not just a betrayal but it's also just simply embarrassing that you have members that don't even have scientific competency writing policy and responsible for the lives of other people one of the things that we've started to report out a little bit Is this newfound interest in the third clause of the fourteenth amendment which says if you participated in direction of rebellion against the united states. You're barred from holding office ever again. And that's obviously come up in the context of the impeachment article that you voted for and the majority of your colleagues voted for against against the president. But we've started to realize that it's being discussed now as far as we can tell in terms of potentially invoking that against members of congress so this is being investigated we know from Nets plus the house speaker talking about that today. the gao the us capitol police and others are reportedly looking into members of congress and congressional staff potentially being part of this thing but in order to expel people potentially from congress and ban them for life from holding public office for having been part of something like this congress would have to act as far as we can tell pass some sort of legislation in order to do it. I wonder if if you feel like that might be ahead. I mean it's it would be a it would be has stork thing for congress to take those steps because of worries about members in its midst. Do you think that's possible. And that's been worked on. Well you know. I don't think the fact. It is absolutely historic but this insurrection was historic for infamous. Violent reasons as well we have never had a breach of our capital. In this respect we have never had the confederate flag. Make get to into our nation's capital not even during the civil war and frankly you know to see that. There were members of congress. Cheering them on calling them. You know. they're people their constituents It is you know there is a resolution that has already been drafted. And i'm a proud co-sponsor of it. This is representative corey bush's resolution to investigate and to essentially sanction and expel members of congress. That have been found by investigation to be essentially working with with the folks who flew a confederate flag in our nation's capital. And i don't know how many of my colleagues need to be reminded of this but the confederacy were a band of enemies and traitors to the united states and insurrectionists themselves and they are not part of the united states have never been part of the united states and we'll never be part of the united states and frankly you know if they find more sympathy with them than perhaps they shouldn't be serving in united states congress and frankly they should my belief is that if they believe the investigate any investigations particularly law enforcement. Investigations will find them complicit or perhaps even assisting in such an attack at they should resign before they are removed But you know with these investigations. They the the facts will bear out in in due course congresswoman alexandria ocasio cortez of new york again. I know you have lots of options for where to come. Talk about these things. I appreciate you being here and Although i had nothing to do with it. I am very sorry for what you and your staff. And your colleagues have been through it is heartrending above all the other things that it is and i'm sorry of course thank you so much. We'll get through this all right Okay the doctor who president-elect biden just put in charge of overseeing the new national effort to vaccinate americans against covid nineteen is going to join us ahead tonight. Stay with us. Hi everyone steve kornacki here you may remember. I hosted an nbc news. Podcast called article two inside impeachment that followed the developments of president. Donald trump's first impeachment last winter the article. Two podcast is back with a special episode bringing you the latest on the second impeachment of donald trump. I'm joined by. Nbc news capitol. Hill correspondent leeann caldwell who was in the capital on the day of the riots to break down the house. Vote and what i said. Trial could look like search for article two inside impeachment wherever. You're listening right now. To subscribe for free not here the curse the document we. I had a light a candle. I'm chuck rosenberg on my podcast. The oath i talked with people who served with integrity and honor men and women who liked the way this week former. Fbi assistant director. Frank figliuzzi if you're all about harsh rigorous aggressive rules enforcement. You're not going to last very long as an organization because people will hate you for it. Your system won't have credibility. They won't report misconduct and they won't cooperate with the core values. You're trying to maintain so with any disciplinary system with any attempt in your family. Your team your community. Your company to enforce compliance enforce as you better have compassion along with consequences. Join me for season for the oath and msnbc podcasts. Search for the oath wherever you're listening right now and subscribe new episodes every wednesday earlier this week. The trump administration announced what was extensively a big change in the way. It was distributing the coronavirus vaccine. They said that instead of holding back sechin doses of the vaccine for people who had already gotten their first shot they were gonna release all the doses now to get the first dose of the vaccine into more people more quickly. All those doses. They've been holding in reserve. Those would be released to the states so the states could vaccinate more people so states plan accordingly turns out all those vaccine doses in reserve the trump administration talked about the ones. They said they. Now send out to the states turns out. They're not actually real. They're not they're jaw-dropping lead from the washington post today quote when health and human services secretary alex as our announced this week that the federal government would begin releasing coronavirus vaccine doses held in reserve for second shots no such reserve existed and governors. Today are apoplectic about this. You and you can see why he told us we were getting lots more vaccine we've been planning on that and signing people up for appointments and expanding our state eligibility requirements because now we thought that more people would be able to get the vaccine all in the basis of what you said you were sending us now. You're not sending it to us. Really oregon's governor. Kate brown said today. She is shocked and appalled. I'm shocked and appalled that they've set an expectation on which they could not deliver with such grave consequences. This is deception on a national scale oregon. Seniors teachers all of us. We were depending on the promise of oregon share of the federal reserve of vaccines being released to us. Minnesota's governor says the trump administration just straight up lied to the state of minnesota about. This lied to them. I mean it's it's astonishing it's also the second time. The trump administration has done this the second time in the space of a month that the trump administration has suddenly at the last minute the states. They were getting way. Fewer vaccine doses. They said they were then. They said they were going to get way. Fewer than the number of doses. The states had been told they were getting that they plan for that. They built their vaccination strategy around sorry last minute they're actually not coming fury. Aiding it'd be it's one thing to think about like ges and the need to like ramp up the manufacturing. You know the difficult work of getting the vaccines made at approved and tested and produced. That's one thing. We understand those sort of physical constraints but we don't know what we've got and we're promising you things. That aren't there infuriating. Don't take my word for it. Ask the governor's. They are infuriated. Wall street journal reporting today. That leaders at operation warp speed. The trump administration's unfortunately named vaccine. They waited months to approve any kind of vaccine distribution plan. They left states virtually no time to implement their own plans. This fall when the trump administration announced at the very last minute that it would be the state's one former government vaccine official telling the journal quote. They didn't plan for the last inch of the last mile. The part that matters most how you how you're going to actually vaccinate that many people quickly. They didn't try to come up with a plan for it. There was no national plan for implementing vaccine distribution and in addition to not having a plan and repeatedly telling states. Were getting phantom doses. That don't really exist. The trump administration has also not been doing a transition on this stuff with the incoming biden folks the washington post reporting this afternoon that the trump administration has refused to share information about its or sats. Vaccine roll out. With the biden transition biden officials shut out of operation warp speed meetings until this week which has caused biden transition officials to try to glean information. They can about the vaccine situation from like their contacts at pharmaceutical companies or from career government. Staffers who have been communicating with the biden transition on their personal email accounts during their downtime. Because they weren't allowed to do that work at work under the trump administration. It's bad it's very bad. I mean with two hundred thousand. Plus americans getting infected every day now while millions of vaccine doses sit in freezers unused with three and four thousand americans dying every day. It is very very bad that we are failing. This badly getting people vaccinated. The scientist did their work. The government failed but today president-elect biden laid out his plan for how to fix it starting when he takes office next week for one thing there will be a national plan forgetting people vaccinated which is a good start. Part of that federal plan will be for central community testing community based testing sites. All over the country in places like school gyms sports stadiums community centers. They wanna use fema and the national guard set up and staff those facilities and get vaccines into arms at scale as quickly as possible. And here's something. They're going to try to bill. Basically a medical corps one hundred thousand americans they want hire nationwide to do contact tracing and to accede follow up which is like simultaneously an economic stimulus slash jobs program slash thing. We need really bad to tackle covert. And then there's the other part of biden's new vaccination plan the other big part of it is that he is hiring this guy to run it. His name is dr david kessler. He's a former head of the food and drug administration with expertise in particular in getting therapeutics to market quickly. He has been the co chair of biden's covid nineteen task force for months. He's going to lead the biden administration's vaccine operation. We learned today. We're also told they're not going to call it operation warp speed anymore which is probably why if they want to get people to trust what they're doing but whatever they name it. It's david kessler. Who's going to be in. Charge of vaccine manufacturing vaccine distribution and continued development the safety and efficacy of both vaccines and also treatments treatments. Which is something that has been making me crazy that there hasn't been more focus on effective therapeutics for people who have already become infected with covid nineteen and are already sick. That is also one of dr kessler's priorities. Keep americans from getting it. But for americans who do get it keep them alive. That is the plan that joe biden intends to put into motion. Just a few days from now. Dr david kessler's manny's chosen to run it. Dr joins us live here next. Hey it's chris hayes. This week on my podcast. Wise is happening. I'll be talking with ton hussy coats about the precarious nature of america's experiment in multiracial democracy. This picture and we paint of ourselves this oldest democracy hallowed institutions etc. You know it really doesn't match if you understand that if you understand that. This isn't the first attempted coup in american history. Why is this shocking. The ability to picture frankly a group of white people over running. The capital is a lack of acquaintance with american history in and of itself. That's this week on wise is happening. Search for wise is happening. Wherever you're listening right now and subscribe should be one of the most challenging operational efforts we ever undertaken as a nation. We'll have to move heaven and earth to get more people vaccinated create more places for them to get vaccinated to mobilize more medical teams to get shots and people's arms to increase vaccine supply to get it out the door as fast as possible. The man who soon to be president biden has chosen to helm that task to move in biden's words to move heaven and earth Joins us now. Dr david kessler co chairs. The biden cove nineteen advisory. Boards is former fda commissioner. And next week he will take the lead of america's krona virus vaccination program dr kessler. It's a real honor to have you here tonight sir. Thank you from me rich. What should we understand as country about the new plan That you will be leading that the biden administration is going to be pursuing to turn this vaccination effort around. This is a national emergency and we need to treat it like one on. This is gonna require a twenty four seven operation. We need more vaccination sites. We need to harness the full resources of the federal government setup with the state's community vaccination centres with federal support. We will need to mobilise. Thousands of clinical and non clinical professionals will need to launch a new partnership with community health centers. We're going to fully activate pharmacies and a president elect of the united states who is fully As he said today we will manage the hell out of this operation. How much of what you are planning to do that. Complex operation that you're talking about needs support from congress and how much of it is stuff that you can start implementing start putting into place on day one with executive action It's a combination of both. There are things we're ready to do our transparency with the state's letting them know what kind of supply they will get on a consistent basis of but is the president-elect today there is a request in a very important requests for the resources to stand up these center and term of standing up those centers. It's been reported. it's been described that it's possible that fema the national guard could be used in terms of setting up those kind of centers particularly large scale centers. Like that is that something that that we should expect. You think that's the right kind of personnel. The right kind of logistics operators who would make sense for that kind of an operation. I think they can be very helpful in certain aspects of the logistics but at the end of the day you want a health professional. You want people in your community. I'm gonna give you the vaccine of we need to do this with the state's the this has to have the full resources of the federal government of but this has to be done with the state's in true partnership. Do you have a handle yet on. Why states have repeatedly been told. They're getting doses that they don't get. We have seen a couple of what appear to federal government failures in terms of promising states. That something was coming the state's planning accordingly and then being told the last minute that those doses weren't weren't going to be there that of course you know these are fragile systems in the states. They're setting them up. They're trying to build those airplanes while they're flying as well It seems to have been a devastating frustration for the states. Do you have a handle on why that's happened and how to stop that from happening again. Ritual I need a favor for more days We need to get in there We need to roll up our sleeves. we really need to get to the bottom Of these questions and we will be up front and give you the answers look. Madonna has ship some fourteen million. Vaccines visors some fifteen million vaccines Total of about thirty million that have been shipped. we only have about twelve point. Three people vaccinated to mitch a vaccine in freezers. We have to get them in arms and we got to be able to bring both the resources and the transparency to the problem. Dr kessler. i could ask you to stick with us while we take a quick break. There's another element of your remit part of what you're going to be responsible for. Is the leader of this effort. That i Am excited about and really glad that you're working on. I'd like to ask you about that after a quick break. If you don't mind mercosur. Dr david kestler incoming chief scientific officer the biden administration's cove response. Be back with us again right after this. Stay with us. We're back with dr david kessler. President-elect biden has chosen to lead the nations corona virus vaccination effort dr kessler in a previous life. I was an aids activist. When you were the fda commissioner a million years ago and as the head of the fda at the time you you really moved. Mountains to get pioneering complex drugs called protease inhibitors approved into doctor's offices to treat people with hiv and those drugs and the speed at which you were able to move. Save the lives of a lot of people that i knew And so you're burned into my mind from that time in american history because of that. I was really interested to see that. Part of your remit now part of what president elect biden is tasked you with is not just keeping americans from getting covert by getting vaccinated but also developing treatment options to keep people alive if they do get infected and they do get sick. I feel like we've heard so little about that. Comparatively what should we understand about that effort. I just a little additive. i can rachel. We accelerated the approval process on. It was really a team a team. was part of the aids community. Late larry kramer great gonzalves. Everybody worked together and one of the things you just need to know is that president-elect has put together really incredible team here. This isn't about me at all. This is dr. Walinsky is not to share disaster o'connor jeff zion's any slavic was named today. Absolutely brilliant is a real team and that's what it takes but but to your question you remember you know nineteen ninety-one we got there with drug for hiv. It was easy. Tina didn't work very well and people were dying and there was an intense focus. We set out the policy on together. Who called accelerated approval gave the pharmaceutical industry road. Matheny we sat there in nineteen ninety six When the protease inhibitor data came there was small molecules in the change. The course of that epidemic and the important lesson. It wasn't just one antiviral. it was combinations. You have to get companies to work together They will be the president-elect in the plan has a effort for national antiviral program. It's absolutely essential of people will they will be People with the Indus- innate there will be some cases we know it's ninety five percent effective. That sounds great but one out of twenty people will still be at risk. There are people who may be. Immunosuppressed is going to be other viruses down the road. We know that so we have to have a major antiviral program and we need to do together what we did for. Hi the You know we didn't do it overnight. There it took time but we changed the cost of that epidemic. And it's another very important tool in in our momentum. Dr david kessler the co-chair of president-elect biden's cove advisory board the incoming chief scientific officer of the covid response for the nation. Good luck to you godspeed. And don't take any time away from your work to come back here but if you have time to come back here and keep a surprise. We'll put you on tv anytime you have something to tell the country during do so much. Good luck thank you. We'll be right back this weekend. South carolina and utah will be closing their state capitals. Virginia's closing the whole area around the state capital oklahoma's activating its national guard to protect its state capitol. Wisconsin has boarded up at state capital of at least a half dozen other states that have put up new fencing around their capitals for this weekend. It's all because groups of trump's supporters are pledging to force this weekend in the states and we will see if that comes to pass. Well also see a for ready for them this time. But that's gonna do it for us at least for now the show. We did nine stern on. Msnbc hi it's msnbc's haze brown know these days. There's just so much news to wrap your head around. It's challenging to get a deeper understanding of things so every morning go beyond the headlines with msnbc daily it features britain perspectives from people. You know when. Trust including tremaine. Lee mehdi hassan list. Plank and frank victim seep. They'll take you inside the most important issues of our times issues like systemic racism domestic terrorism. And how we can bridge our political divide plus get a fresh take every morning from me start your day with msnbc daily at msnbc dot com.

congress Dr david kessler Mike pence elect biden biden harris justice department dc us capitol police president biden biden united states president trump alexandria ocasio yellen donald trump jimmy albright Cortez dc metropolitan police Nancy pelosi
Ep56: Tim Springer

The Long Run

1:05:00 hr | 1 year ago

Ep56: Tim Springer

"Welcome to the long run. This is a podcast for biotech. Adventurers your host Luke Timmerman. Today's guest is Tim Springer. Tomb wears many hats. First and foremost. He's a scientist an immunologist to be specific at Harvard Medical School. He's best known for his discovery of immigrants a class of Trans Membrane receptors. Now in his seventies Tim recently won the Gairdner award sometimes called the Canadian Nobel. The prize committee cited Tim for his quote discovery of the First Immune system adhesion molecules elucidation of their roles in antigen recognition and leukocyte homing and translation of these discoveries into therapeutics for autoimmune disease. Science end quote scientists out there. Are You thinking the same thing? I'm thinking that's big. Integrators have longed analyzed drug developer's ever since some of these properties became better understood biogen's nationalism AB marketed. As is one very effective drug for multiple sclerosis aimed at immigrant target Takeda's vandalism Ab marketed as Antirio is another immigrant directed antibody that took many years to blossom but is now a billion dollar blockbuster for ulcerative colitis and groans disease. Tim Is more than a trailblazing scientist. He's also an entrepreneur. He made a fortune in one thousand nine hundred ninety s from his founder shares in Leukocyte a company acquired by Millennium Pharmaceuticals more recently. He's CO founded a pair of Boston area startups. That have gone public scholar rock and more therapeutic almost as an afterthought he even made a shrewd early investment in Moderna. The Messenger Arna therapy company. Lastly Tim founded a nonprofit venture the Institute for Protein Innovation. He hopes this open. Biology entity will advance the field of protein science which often lags behind the world of nucleic acid by the aren- in terms of fame and funding. Tim's also Iraq. Lecter if you listen toward the end he explains. Tim Really doesn't go out and seek a lot of attention for himself so I'm really happy. He agreed to sit down and share his story with me now before we start the episode a couple of quick things. Today's sponsor is PD biotech as your drug development program advances it's critical to select the right. Cro Partner for your innovative therapy with a full set of development services and global reach PDD biotech offers teams. That are dedicated to biotech and small to mid sized Pharma. Biotech knows that every milestone every project update every change in direction is important. Committed to close alignment and the right cultural fit. Pd Biotech works as an extension of your team. Every step of the way to innovative solutions that. Get Your treatment to the clinic. Faster learn more about PD biotech visit www dot PD biotech dot com. Are you a marquee service provider eager to get your name out in front of the biotech leaders? Listen to this show. Ask My new business representative Stephanie Barnes About Sponsorship Opportunities? You can reach out to her by looking at the contact page on Timmerman report DOT COM. The other thing you can do to support quality. Journalism is to purchase a subscription to Timmermann report one hundred and forty nine dollars a year for an individual subscriber companies and universities with multiple readers can purchase a group sharing license. You'll get two to three in-depth articles per week without being subjected to any advertising specifically you'll be able to glean insights from the talented crew of contributing writers. Who I edit and they are Stacey Lawrence Asher Millard. Alex harding and Laura Chef. And oh by the way. I just added another outstanding contributor to team David Shea wits formerly of Forbes Watch out for his new astounding health tech column on Timmerman report go to Tehran report DOT COM slash. Subscribe to get yours today now. Please join me Tim Springer on the long run Tim Springer. Welcome to the long run. Thanks well Tim. I'm really excited to have you on the show today as you are. A man of many hats A scientist first and foremost but also an entrepreneur and investor. I guess you could say. Science philanthropist with this institute for Protein Innovation. Yes ask you about later also like your exotic rock collector. Maybe sneaking question about that but for our listeners who who may not be super familiar tim. You just received the gairdner award. Which is the Canadian Nobel so to speak so congratulations? Thank you thought about your career. What makes you an interesting person on the show? You've had one of these scientific careers. That's a little bit unusual so I guess you know. There are a lot of people who make a big discovery in their twenties or thirties and they get known for one big thing and maybe that he can kinda rest on their laurels the rest of their career or they're always known for that yours is one of those careers where some of your early work has really accumulated and become. It's become more apparent about its value to biology in pharmaceuticals in particular later on so the one example that I want to mention to the listeners is federalism ab the Alpha Four Beta seven antibody. Which was you worked on? Leukocyte in the one thousand nine hundred ninety s it only one. Fda approval fifteen years after the sale of leukocyte in the hands of Takeda Pharmaceuticals Long. After you had let it go but even now this year I mean this is now a multibillion dollar product for ulcerative colitis and Crohn's disease. It just ran a head to head study against Takeda did against Abbey's Humira and proved superior so now this is a true multi billion dollar product. The Alpha Four Beta seven Immigrant inhibitor. This goes all the way back to your earliest research into the discovery of immigrants so very important drug. And it's certainly not the one only so it's really interesting stuff. And I want to like kind of rewind a little bit and bring our listeners along to how we got there. So Tim can you just kinda start off as I often do with this show Where were you born and raised? How did you get started on this path in science? I was born in Fort. Benning Georgia when my dad was briefly down there you know for Army Reserve Training and four years in Michigan rest of my life in California just grew up in Sacramento California boy and you went to public schools. Is that right correct? How about your family brothers and sisters? I have four sisters and one brother I happen to be the oldest uh-huh uh-huh so were you the typical oldest sibling the responsible one getting good grades working hard. Maybe I think I felt most under the gun. My parents did you know incentivizes or they expected us not now that we got too many incentives but they just expected. Us TO BE SMART. That's what they said said the display springer's have to be smart now. I think there's no we had no monopoly on that whatsoever. But just the expectation of it seemed to to help now. Your Dad was a physician. Is that right. Yes yes what. What kind of medicine. The reason I went to California. Is You want third intern. Any already had three children and a wife to take care of when he was finishing an internship and another one that was going to be on the way. Soon and my My Mom said Look Buck you know you have to earn some money now. We can afford any further training so he became a family physician but he also back in those days when you could do this also did general surgery and Obgyn and he retired before he reached sixty five and But he also you know continued in the National Guard and he wanted to make colonel so He became the commanding officer at a National Guard. Evacuation Hospital in San Francisco. And you know it was very very proud to retire. Bird colonel. So he's a military man a physician as well. There's sounds like a strong culture of service to others. Yeah Yup Yup. You're the oldest son Baby Boom Generation. I think you say born. Nineteen Forty Eight So like a lot of people you go off to college in the sixties you went to Yale straightaway right right now. Tell me about that experience. That first year I had been a A straight A student in high school and I had never visited You know Connecticut or Massachusetts I visited my dad. Dad's farm where he where he grown up in Pennsylvania. When I was a young kid that was it and So these costs was a surprise and You know and I was at an all male school for the first time in my life. Last year the ill is an all male school and And you know as with all these very well prepared on prep school kids and and I'd sign up for this Very intensive program. I had the idea that I didn't WanNa do science. Although I knew I was good at it but I wanted to study humanities because My disillusionment aware technocrats had gotten this You know like injured more. This has been middle nineteen sixties right as Ramda's at Yale nineteen sixty six to sixty seven really the height of the Vietnam War. You know a lot of my high school classmates were going over there. And you know a good number didn't come back and I was certainly wondering what this was all about. You became somewhat disillusioned with science that that scientists had made some horrible things. Possible like napalm and orange right exactly exactly and so you begin to wonder like well. What purpose what I want to do with my life classic undergraduate question right. Yeah that's right right right. It happened to be the my my biggest rebellious year. And you know You know so. I wound up not studying well. hitchhiked across the US during One of one of the brakes and find myself in Haight Ashbury which was happening in just over a break and I had a girlfriend you know from the air. Come visit me at Yale and so and also I got infectious mononucleosis and that really landed me in bed for like three at the student. Infirmary as a result. I didn't do that well and I also got in trouble with the Dean because they suspected that I was smoking marijuana which was true and I got hall to the Dean's Office for that and so anyhow. During that year some recruiters from Vista Came on campus. And you know this was the volunteers and surface to America that was Lyndon Johnson's continuation of what JFK had started with the Peace Corps. But it was just for one year and so I signed up for that. Will I applied to it? I didn't know if I'd gotten in yet but I applied vista is sort of thought of in those years as a domestic peace corps. Yes yes and he signed you applied. Yeah I applied. And where did you go with that? Well So I I I went back to Sacramento and I found out that yes I have been accepted and They would if I could have gone back to Yale but there was one course I had just never studied for which is ironic because it was LINEAR Algebra. And it I just never studied for it and so I- flunked out of course and And it's just what I really needed to be successful. Well full fallout structural biologist with Matrix transformations. I'm probably not not too bad at this point. You hadn't decided to become a structural biologist. Yeah yeah that was a long time to come in the future but I could've liked taken. One class met my junior college. You know and then gone back to Yale for my sophomore year but The volunteer application was accepted and I was invited to go out to Colorado and go in training there with the department at the University of Colorado on training in Denver and so I accepted that and you then went to an Indian reservation in Nevada for a year right. Yes yes the combustion shiny reservation. That was a really great experience for a nineteen year old kid I was thrust into community development which you know I knew almost nothing about but gladly was doing. I got to write tribal resolutions For the tribal council that were sent off to senators and Actually one of them resulted in a hearing. A Senate hearing you know where they called in some bureau of Indian officials to testify which you know government agencies. Don't like to have happened them. It's always pretty good incentive to string things out and we got a we work through the county to get a food commodities setup on the tribe to tribal chairman and I went to to county highway hearings and Explained to Governor pollock salt at the time that On kids who are going to a one room schoolhouse for grades. Kindergarten through eight could not go to high school unless they lived away from home. Because there was an unpaved road over a mountain pass That was impassable in winter to get to the local high school so Had the governor really perked up at that particularly when other people were saying. Oh you know if we had a paved road to here I could get my were out for one sentence cheaper whereas if you actually put a road in here you can send kids to school. And that's going that's GonNa propel them on a whole different life trajectory. Yeah it wouldn't. It wouldn't cost that much money. You could do it if there was the will and the determination and so you worked on you worked on this sort of thing and for a year that sounds pretty pretty satisfying like gosh. You know you can actually make a difference. Yeah and it was a blast to I mean. The Indians assigned me a horse. I had to buy an saddle. That was you know my only means of transportation for a while. I got to work with kids putting in neighborhood Well in a neighborhood. Youth Corps Program Iran. You know that was a blast so it was really a wonderful experience. Luke okay so you have this experience with this but then how do you come back to science? Gradually a lot of my buddies were at the University of California and so I got accepted to Berkeley and And then I thought okay this was. I really had a great time on the reservation. I really WANNA be a cultural anthropologist so I took a course in anthropology do that and then I had to do some field work. I interviewed some people about their. You know that was an experience and then said No. That's not gonNA work. Maybe I'll do. Sociology took a sociology class. Now not not quite so and then I took psychology and I said okay. I'm going to. I'm going to become a major in physiological psychology and sign up for that and then I I took physics and I loved physics. I took five well. I took four physics courses for the first one I took was a more general physics course and then after that I switched the one for me. I think the same thing happened to me with organic. Chemistry I ordered. Chemistry was sort of general one for Pre meds And then I really loved it and I took the regular one for chemistry majors. I loved I loved those So then I decided okay. I switched my major biochemistry which luckily had very few off course requirements and so I I was assigned biochemistry adviser. Daniel cautioned. You know who was very famous then and later and Sisa can I do this? She said she you can So you know and for biochemistry really only needed to take You know a year long course for majors and I did that my senior year and I took the laboratory. Course which is a separate course was also a great course. It's the best laboratory course I've ever had And so you know. My course was set after that this would have been right around. Nineteen seventy seventy seventy one or graduated. Okay and this adviser. He was already interested in confirmational states of writings and how they change. Now now. This is a through line throughout your career. Your remain very interested in it today. Was it about that set of questions. Then that captivated you will enzymes were regulated to turn off biochemical pathways Depending on how much of a substrate was available like if e. Coli you know had galactosyl around they would turn on on the lack. Upper Onto metabolize glucose gladys on lactose And and you know that was beginning to be understood at the time and involve some fascinating. Alistair changes in enzymes. And there's also cooperatively all of hemoglobin was known at the time And so I thought that was really cool stuff and Yeah I wanted to work on that so I went to graduate school and lineup going to to Harvard. And who was the adviser there? At Harvard Jack Straw injure famous individual still around. I believe right and science. Yes he is ninety. Four years old he on the You know still goes in laboratory daily But Hari said at Harvard. You have the greatest faculty benefits and one of them is a bus. That can pick him up. You know. He can't drive a car anymore. That can take him to wear needs to go okay but so you. You're coming back now. Your Senate set on science. This is what you're GONNA do. You're going to Harvard Jack. Stroman shares lab. What was the the interesting question in front of you? Then was it was really protein biochemistry at these very basic building block levels or were you thinking about like downstream applications with immunology then both so a lot of my colleagues there. I mean we have Jim Watson Awhile Gilbert there a lot of my fellow graduate student colleagues. We're going into nucleic acid protein interactions. But I was When I was still at Berkeley. I'd Purified some antibodies As an undergraduate and Alan Wilson you is down the hall who is the first by chemist who is studying evolution through Studying license from different Birds and determining how closely related birds were one to another through cross reactivity of their lives. Azzam's with on antibodies And so you know Allen Real Sea Interesting Guy Alan Wilson and So I you know I was sort of predisposed to be interested in immunology and Jack's Rominger had done a lot of work on penicillin and cell wall bio synthesis in bacteria annual switching to working with cell surface proteins of Mammalian cells in the immune system. So that was very interesting to me. Cell surface proteins not allow was known about them or Trans Membrane receptors. You know what are the components in which parts are hydrophobic versus hydrophobic? There was a lot to to ask an answer here. Yes yes. It was a totally a new field. Just beginning to be broken open and Yeah my Pse workers on the compatibility engines. Which on are the barriers to transplantation and were very polymorphic. But nobody knew why But we intuited. They must do something very important. Variable from one person to another and In terms of what was known You know there's only one protein beforehand Gleich a foreign That you know had been sequenced in shown to have a large bit outside the cell and then short segment in the membrane and other short segment inside the cell and the Molecule. I worked on. Each layer was only the such protein. You know to have that sort of thing characterized. This is a pretty cool problem. I mean because even then people would have you know there. Was this obvious problem with a organ transplant. Rejection you know. And but working out the molecular biology down there at the major histocompatibility complex the H. L. A. Antigens. What was different. What was causing some of that rejection. Potentially you had to work out a lot of basic biology. T T even begin to answer that. Yeah we did. We did purifying the proteins from intact. White blood cells was very challenging on. I had to learn about silencing proteins with detergents from colleagues who've been working on that in a lab on cell wall by since bacteria and Ended it also taught me that These things were so difficult to purify. It would be good to have some other immunological techniques to use and Law. We are working there. There was an antibody to One of the sub units of the Hoa Antigens called Bittu Micro Globulin and one of my colleagues started. Purifying that using that to affinity. Purify the antigens And so that was. That was pretty striking. You did this. This manual process Yara Fi. All these antibodies from from cells. But this is before colour and Milstein came up monoclonal. 's that's right which became very useful tool obviously sure You ended up going to work for Milstein actually for a while right Was very fortunate. Yeah I was in England. Another project was on. Didn't work out and I you know started working with him and I just had six more months there before I had to come back to Harvard Medical School but but Cesar and You know And Giovanni Golfer who was working with him personally showed me how to do Fusions to make monoclonal antibodies on I started characterizing narrow and then took them back with me to the states to characterize them further and I was really the first one. I was lucky I was one of the first people. Learn how to do this for your learning one of the most powerful techniques in biology even today. Yes yeah so so how you ended up coming back to Harvard. Was this right away for a faculty gig like were you on the fast track at this point yes because I was already hired. By Ruben. Ashraf the chairman of Zoology Department to start at the medical school while I was a PhD student he wanted me to come immediately after my PhD. But I said I'm sorry. I've already signed pasta and you know I really really want to do this. So reluctantly you know. Let me do that before I started with him. Usually that's not how it goes like you know somebody offers you a faculty GIG when when can I start okay so so you came back to Harvard Medical School on the faculty. What year was this? Nineteen seventy seven. Okay so you have been just shy of thirty and okay. So you're nineteen seventy seven. You know algae historians. There's so much going on here. Monoclonal antibodies have just been discovered. We're beginning to get the the manual. Dna sequencing as you say said earlier. The the nucleic acids and protein connections. So you got a lot of tools to work with. And now you're beginning to focus in on immunology or was it more basic still than that like your was this where you're immigrant work began. Yes but actually. They both started at the same time so there was the great thing about being at Harvard. Medical School was that there were people who knew a lot about Cellular phenomena that I wasn't exposed to in the Biochemistry Department I can apply my techniques to Cellular problems and at that time. Antibodies of which were produced by these cells. Were very well understood. But almost nothing was known about how G-L-A-C besides recognize Foreign Antigen which required on a direct contact between and the target cell. And you could see that direct contact under the microscope and The had been stage. So you could allow the t cells to adhere to the target cells. And then you You and then you could suspend those cells So no further contacts could occur. And then you could wait to see whether the target cell Scott Leist and they. They did And there were no molecules. That were Certainly known to participate in those prophecy. The only thing that was known was at the adhesion step. The conjugate was would it required and lethal had required. Calcium and these conjugates were visualized on the lighter the ultra microscope near Billy beautiful. The T. cells seem to form the suction like attachment to the T. Cell and between them between the two cells. As what would now be called in immunological synapse but that you know that name was far off in and actually the molecule that I discovered next elephant one was later shown to be light right at the forming their rims around the Suction Cup and really tightening the contact. And so what I did. Was I collaborated with Eric Marts? Who had this killer? T. Cell say well under hand and You know and I got to cells from mice or rats and And then isolated antibodies but instead of just looking for any old antibody would react with any old Protein on the cell surface like I had done with Cesar I focus the say in too only Choose antibodies that would would block to killing step so antibodies recognize proteins were required for the functional outcome and identified one called Elephant. One I in the mouse and then a little later. I did a similar experiment. With human t cells in identified three different molecules One of elephant one elevate to elevate three. Today's sponsor is PB biotech as your drug development program advances. It's critical to select the right. Cro Partner for your innovative therapy they full center development services global reach PD biotech offers teams. That are dedicated to biotech and small to mid sized Pharma. Pd biotechno- is that every milestone every project update every change in direction is important. Committed to close alignment and the right cultural fit. Ppd Biotech works as an extension of your team every step of the way to find innovative solutions. That get your treatment with the clinic faster to learn more about PD biotech visit. Www dot p. p. d. biotech dot com another way to support quality independent reporting on biotech is to support the Timmerman report. You can individual subscription for a company. Licensed that comes with sharing rights. Go Tim Report Dot Com and hit the green button. That says subscribe. This is interesting. I mean you're getting lots of publications. Now we're talking in the nineteen eighties. You've got this nice. Academic career going on a fast forward a bit eventually become in the early nineties and entrepreneur. Starting a company called Leukocyte. What was what we're trying to accomplish there. Will I'd moved on and we'd discover the integrations You know the elephant one AMAC. One were founding members of and we'd Discovered some why Ganz for elephant one called I cam and And then we discovered that the The elephant one of the Mac one were missing in an inherited disease The patients had plenty of white blood cells in their circulation but they couldn't leave the bloodstream to form pus And then we discovered that there were Three molecule three molecular steps. There was a weak adhesion on step on these are the steps that leukocyte to required us the bloodstream into a side of inflammation and we so we found one set of molecules and the first step a different set of molecules in a second step and a third set of molecules in step three all of which were required for this process to be completed And it was like we had the area code. You know a series of three digits That required and And then I realize wow we can block the area code for the skin without interfering with the area code the gut or we and you know and we can block the area code for one kind of white blood cell like neutrophils without blocking the area code for another kind the lymphocytes so we we could come up with much. More effective and more selective on treatments for autoimmune diseases and this area is too broad for my laboratory to really be competitive in and It's a whole new area for more biological discovery as well as drug development the only way that we can make progress on this as if I started the company. And so that's when I started leukocyte. Okay so this is. This is kind of a crossroads. I guess for just about every basic biologist. You can always move from one basic question to another get your publications and stay in your lane but here you decided you know. Actually they're they're all these applied questions which are actually interesting to me as well and potentially impactful down the road. So how do you go about Ike mustering the resources the money and the people to start leukocyte will? I didn't know many people at all. I mean I'd had some exposure to the farm industry through research support from my laboratory so I just sort of climbed up on venture capitalists Then finally A friend of mine bill. Hazeltine you know was the side of good visor to Healthcare ventures and. So you know I just. You know called on him and showed him my business plan And he said it seems really cool and he presented to them and Bill. Hazeltine in those days was he was a harvard. Professor later became CEO of Human Genome Sciences. One of the Big Jail Gogo genomics. Yes they liked what I was doing. thought. I was really crazy. Scientists than they wanted to fund the company And I did Mashreq negotiated. Good on you know sheriff. Stock is that founder and hired some great people like Chris Mirabella as CEO. And we got off to a very quick start. Okay so this is nineteen ninety three. I think you've got started. And then this is when you started working on applying some of this work that I alluded to at the very beginning of the show right. The Alpha Four Beta seven antibody Voted Lezama by Antirio is what it's marketed. As this was one of your progress. Yes and was you know was very similar to a elephant? One in the sense that on it was another Anagram Bound to an IT super family ligon feeling just like elephant one. Discover the paradigm for this but not that particular example And so look aside. Licensed the antibody Ashley from some other colleagues Within the past at Mass General Hospital in started working on it very early on it we started the company. Nineteen ninety-three in a nineteen ninety five. We published on one of our first papers. Showing that this antibody would a-block ulcerative colitis in a cotton. Top marmoset model system at the New England primate center. Yeah and a lot of people probably at at the time. Didn't Kinda Shrug you well. No they didn't exactly shrug. I mean they thought it was pretty cool. I think the problem though the reason it took so long was maybe some mistakes made along the way both scientifically and businesswise term development of of this Drug at a company. Well okay so the short history than a leukocyte I mean. This is the nineteen nineties. It's the boom time going on in biotech ended up acquiring proscriptive which was a company that had board later known as Belkaid so now. Leukocyte takes on a whole different profile in the late nineties. With this first of its kind protease. Inhibitor ends up. Getting acquired by Millennium and Millennium was. You know the big Gogo Genomics Company on the East Coast doing all this functional genomics like. We've got the code now on our desktop. We're going to understand what all these genes and their protein do and it's going to lead us to the Promised Land of of drugs targeted drug discovery and development didn't really pan out but they did have one gem of an asset that became apparent quite early with felt for multiple myeloma. Now this was important. So how does Tim Springer fit into this? I mean you're the founder of leukocyte and leukocyte suddenly becomes very valuable to millennium. It gets acquired for six hundred million. This makes you personally wealthy. Nine hundred ninety nine right. Yeah you're founder shares. Get cashed out as something like one hundred million dollars. Yeah that's That's what I get for them when I saw half of them. And so this is. This is a big moment right. I mean you could decide to you. Don't need to work anymore. You could do whatever you want. How did this change the way you thought about Your science or your life. Well I thought about it for a few months. What am I going to do and And I thought maybe I want to start another company but I know I'm never going to do as well if SORTA company What do I what do I like doing well? I decided I really liked doing science. So I just kept on at it in my lab and I learn some new techniques I learned on social biology and started making determining crystal structures of proteins and studying confirmation changes centerpiece in my laboratory. I Did some rather interesting. New Things was single molecule biophysics Let's back up here. Tim y the x Ray crystallography and in the deeper study of confirmational change. Why did that rise to the top of your priority list? Well it's as you know it's what what I was interested in ever since I was an undergraduate And also in nineteen eighty nine Mike Dustin. I reported that elephant. One Got Activated by antigen receptor signaling And when Elephant One got activated to mediate fusion. There was no increase in the number of elephant one molecules per cell so we thought that there might be a conformation change in elephant Explained the increase in Houston and I should point out that also was The reason why elevator one could function as a cell recognition molecule without negating antigen specific recognition. Okay now for those unfamiliar when you say confirmational change that is like a different shape that the protein folds into so you've got the same basic gene sequence the amino acid like it provides the code for that protein but but it it falls into a different shade. That's distinct an provides. It presents all kinds of different it has different properties when it's in that different state there's different potential pockets that one might bind with that are presented when it's in that different shape so like if you don't have that. Kinda Three D. view of the protein. Not just from a snapshot that you might be able to take with your given technology but maybe a series of views like that protein changes in a different confirmational state. That's the information you really want. Yes yes and it was the key to understanding how they function. We've we've now found that the affinity for the Ligon increases four thousand full for one integral and seven hundred. Fold for another immigrant after that confirmational change. It's like a completely different protein. Almost almost yeah. But as you say there's no change in its structure and the cool thing about that is it can be reversal to very rapidly. Reversible which is one thing I'm working on now okay so you went to. These became a focus areas of your lab at Harvard. You're working on this. Throughout the throughout the two thousands the the the arts and then like in rapid succession. You get a few more ideas. That are the genesis for companies scholar rock. There's more fiqh I guess. Could you talk a little bit about each one? In what what? What made those ideas erling accompany around? Sure so first of all I got back into in well. I got into investing to start with Through putting up part of the B ran for selective biosciences and then meeting some friends on the board Amir in his shot who I sort of Call my biotech because You know he you know we became friends and you know he simulated me a lot and asked me to join a polaris as an adviser and Ed One of their offsite advisory meetings. I teamed up with Catrine Bosley To to lead a discussion And I came up with the idea for scholar. Rock which involves trapping confirmation of Growth factors like Tgif Beta when they're inactive with antibodies and sort of built off what I learned with immigrants But it was a new way of flocking on Tgif Beta activation not with an antibiotic growth factor but with an antibody that kept the growth factor bound and inactive when it was bound to its programming so so that was cool And actually even before that I'd helped start on Edita's medicine and a Madonna and then I also just in my laboratory MODERNA. That would have been twenty ten twenty eleven timeframe right Derek Rossi. At Harvard Stem Cell Institute was looking for in an and you like the science. You had some money to invest in. You made a rather early. And in retrospect Cagey Investment on that one now market value. Whatever five six billion dollars but okay? So there's moderna there's Selecta there scholar rock maybe very briefly here. The scholar rock. This is kind of an unusual name for a company. And it's inspired by your your your interest in these exotic rocks. Could you just briefly what the inspiration is there? It's a Chinese ascetic tradition that days to the Tang Dynasty about five hundred. Ad in which natural objects from nature are collected and They should have bizarre shapes They should be hollowed out. By natural forces like water on or or wind in you know coming unusual shapes and it was just at a point when Chinese. A painting was being transformed from figurative. Painting like we have In the west of the human body to emphasize brushstrokes So basically. It's IT'S A. It's Chinese got to abstract art way before the West did and This is sort of another form of abstract art. That really They love and to a Western person. These look like sculptures But they're actually formed by natural forces and to me day on they reveal the inner strength of the Rock on and that's actually how we sort of came to the scholar. Rock Ning I determine a crystal structure of Tgif Beta surrounded by its pro to Maine and as a whole right through the middle of it. this structure and I have rocked. That Has a whole warned by the water right through the middle of and these rocks were often from metamorphised rock Which has been you know. Sedimentary to begin with and then heated up inside the earth an end metamorphasized and the The water wears away the the week. Rock and leaves The stronger denser rock behind and so it it reveals the inner strength of the Rock and it's and they can sort of look like three dimensional structures of proteins. And you actually collect some of these rocks. I know and if you ever Go to the Cape or out by me like the Oregon or Washington coast and you can see the forces of nature and how they act on these rocks it's it does make your imagination wander a bit. The perhaps about what happens down deep down at our molecular levels With molecules so okay scholar rock it's born and with some ideas on how to interact with Tgif Beta in a way that might be therapeutically relevant companies now publicly traded the other one more fiqh came a little bit later now. What was it about That idea that that made that one worth spinning out another company inhibitors To immigrants had been around a long time and they were used transparently during treatment but when when companies started developing them as aural antagonists to be chronic. They failed and in fact they made patients worse. They gave them more heart attacks. Rather than fewer okay so inter- integrated inherit back to immigrants. I mean you're yeah I who discovered the Trans Membrane sceptres in the first place. One of the best known integral hitters is the antibody from biogen nationalism appetite. Samri for Multiple Sclerosis. It's a body that binds to a target specifically expressed on the surface of cells very effective for MS also has that severe side effect. Pml which we've had to figure out how to manage later on but you're talking about is small molecule drug discovery. People have wondered. Can we make small molecules that bind with integrants and that's been more challenging? Yes yes problem. Is that the small molecules when they bind the immigrant induced this high affinity active conformation and it may be that when they dissociate than they briefly. Leave the current in that configuration in has untoward effects. you know so they Bureau some evidence even from clinical studies that this small molecules can act is not pure antagonist but as partial agonists and you can see that in the structure because when they bind to the protein they will induce the active conformation. We've we've seen a lot of that in papers. We've published But a Some some Postdoctoral fellows on my laboratory discovered a type of molecule that did not induce the active. Conformation Day Stabilize the low affinity confirmation and with APP this and then we A fellow Albert Lin discovered what the chemical basis for that was and and restarted company and Albert could become an assistant professor somewhere or you know become like the scientists that the company and every time I asked that question a gave him the choice he said I WanNa do the company And you know it's it's now very successful and one of the one of the drugs. Developing actually is a follow on for For Entire Bureau for all sorts of Gladys and then. Beta seven direct. Ya for Alpha Four Beta seven. Yes okay but now let's back up. So it's interesting that you kind of went from a mindset of trying to develop antagonise to inhibit just about everything that's something pharmaceutical companies tend to do tend to think about instead you're gonNA think about partial agonised like a completely different way of thinking about the problem but it starts even further back than that right with the the crystallography. The views the structural biology itself like the actual like and it's a series of images watching that protein. Go through its confirmational states school doing from A to B to c That gives you the extra level of insight to say. Gee maybe we could do a partial agonists right. No sorry we don't WanNa do the partial agonists. That was the problem read. What we wanted to do was a pure antagonists. I'll okay I see I see but there's another there's another spot to bind. Let's not say exactly how it works but it's a different way of binding. Okay so this. Is THE GENESIS FOR MORE THERAPEUTIC. Another company that's going public. I guess just this year on the Nasdaq. So that one's often running another one of your companies. The last thing I want to come to Tim is that this big thing. That's occupied a lot of your time in. The last few years has been this institute for Protein Innovation. So you're you're you're at this later stage of your career you've been very successful both with your science and with companies. But now you're thinking about well what can I do something more for the whole field? What what was your thinking around this guy. Will I got very excited. About a new type of antibody Lewis displayed on yeast and my colleague Mitee In winthrop had pioneered this approach of displaying things on yeast and doing selections on them and it's been established at Accompany Outta map and you know other companies But this is not a not in an academic nonprofit setting and It has huge potential beyond just making new therapeutics because this is a new type of antibody compared to what I did was Cesar. Cesar Zana bodies to Mouse or human were all by immunizing one species with proteins from another species so they could only be directed to amino acid differences between proteins. But what I'm really interested in with. Ip is making antibodies to the things that are the same there are conserved from one species. Starter those were the functionally important binding sites in proteins like enterance And there's some proteins that are entirely identical between mouse and human Particularly in the nervous system and in developmental pathway molecules like the winds and Those have defied defied recognition with antibodies to date and made Particularly neurobiology a very difficult field to work in And so We are making these. Antibodies with Really many types of applications and another Thing we want to overcome is The trade secrets That accompanies keep in Sometimes you know poor validation Where it's up to the investigator to see whether the antibody works or not And I'm so we're when we Are Antibodies to the public We will reveal their acid sequence so they are entirely reproducible If somebody wants to publish a paper a million years from now using the same paper using the same the same Antibody they will be able to get the sequence of that body from a database and and make it easily. This is open source biology. This is open source biology and yum. And and it's it's intended so that researchers don't have to run the same set of failed experiments over and over again you can actually learn from somebody else's successes and failures of which really do in a proprietary world. You're right right or even improved them coming back quickly to what you said there about the The conserved regions and identical antibodies. Between animal. And human I mean if that's the case some of these antibodies if you're able to then test them in animal models shouldn't those animal models of certain neuroscience conditions. Be More predictive of what we could expect in the in the human. Yes so we can use the same antibody to do Experiment Animals to see if you know diseases can be treated in animal models and then put those same antibodies into human clinical trial. So it's potentially a much faster way to go from the laboratory to the bedside. How long has this been up and running the Ip just two and a half years okay? So what what do you think that this ought to be able to accomplish in the next five? I think that we're going to have Antibodies to complete sets of whole interacting proteins exercise of signaling pathways. I call these Signals. So you will often have a receptor that binds ally gant the coal receptor and there are antagonists in those facilitators and we will be making antibodies to all components of one of those Signal oems at once so we can not only make the antibodies but we can select for the ones that recognized. Functionally important determinants will make those available to people in the biological community To make new discoveries with and then we hope that you know some subset of those will have interesting properties that will enable them to be developed into therapeutics. So maybe a few more Antonio's could come out of this set of of antibodies and there will be no royalties coming back to tim or the IPAI. Yeah there may be or there might not be. I mean so. People will be able to develop therapeutics with just the tool compounds. We have But we also will We we think that we can do both do the open source and we can. We can Sell antibodies to the public With really great biological activities Open source but then we can use other. Antibodies for therapeutic development or least. Because we'll be exploring so many new biological pathways We could partner with certain drug companies and tell them hey. This is a really good on target. You should go for that. And that's that's very valuable for them to have that insight really. This could provide a lot of data out there. That's that's Kinda missing you know we. We put a lot of emphasis on the the underlying code the genome and But there's a lot less visibility into these. These downstream you know The proteins structures their states and that kind of information were to become more widely available to you know everybody in academia or industrial scientists. I mean Gosh. That should be pretty useful shouldn't it? It's hugely valuable. So we you know we can touch the genes right now with nucleic acid pros but we can't touch the product. Sevilla's gene and the products. The proteins are you know what drugs are made of or what. Small molecule drugs are directed to. We need those proteins to develop drugs and so our mission is to realize the promise genomics by four gene protein tools and repeated to bridge the gap between genomics and and we also want to strengthen protein science which so essential to drug development. My colleagues in the pharmaceutical and bio communities are in Cambridge in Boston. Tell me really need better protein. Just don't have enough and I think there is a story in the NIH funding VAT Sort of cooperate with the fact that if you're using molecular biology is much more rapid to discoveries proteins which require much more time and effort and that is made most By medical science in academe focus away from onto DNA in Ra. But I think that Working scientists have our central for successful drug development. So that's one of our missions to strengthen this very important area I agree. I think that's true. Tim But it's also true. That win we have really good biological underlying hypothesis. Like say Canine. When you can see? Okay inhibiting this thing will be as likely to give you a big result. We can move very quickly with protein science that antibodies getting that underlying hypothesis right. That's hard there. Aren't that many targets that are that present themselves quite like that and this is something where you know. You've got some work that that could could bear fruit for a lot of people here so very interesting and important set of questions and answers in front of you tim. Thanks so much for joining me today on the long run push thanks for listening to the long run production of German report Peter. Rosado of EPA media was the sound editor use. It comes from. Da Wallich. See you next episode.

Tim Springer Harvard scientist Luke Timmerman ulcerative colitis Pd Biotech Partner Cesar Zana Protein Innovation autoimmune disease Multiple Sclerosis Senate Harvard Medical School Boston founder Moderna Sacramento Yale Takeda
Coronavirus update: How can we cope with COVID-19 anxiety?

Next Question with Katie Couric

1:18:56 hr | 10 months ago

Coronavirus update: How can we cope with COVID-19 anxiety?

"The third love knows there's a perfect proffer everyone that's why they use the measurements of millions of real women to create their eighty bra sizes, including their signature half-cup sizes I love the mission of third love so much. It's inclusive philosophy that I decided to invest in the company. Third Love believes every woman deserves a comfortable well fitting BRA. So right now they're offering fifteen percent off your first order. Just go to third love dot. COM SLASH NEX now to find your perfect fitting Bra and you'll get fifteen percent off your first purchase. That's third love dot com slash next for fifteen percent off today. To his week. We need to rebuild. The epic fiction podcast Tuman. Bay Returns. Before? Oh yes. You have no choice. It has to be done. What have you done from Los Twentieth on the iheartradio, APP, apple, podcasts or wherever you get your podcasts. I everyone I'm Katie couric and welcome to next question. It's a new day for us here at next question is I'm sure it is for all of you. The rampant spread of the corona virus across this country let alone. The rest of the world has forced most of us in doors for unknown period of time. The level of restrictions on where you can go and what you can do. The closure of schools restaurants nightlife the cancelling of sports and entertainment is largely unprecedented, but it's necessary for the health and safety of this country, so if you're not social distancing yet lease do. But it's a lot to deal with, and I know right now. It's all consuming for all of us is what we're reading about and what we're worried about, but I'd really like to help to settle into this new reality and perhaps understand what all of this means for us, which is why we're dedicating the rest of this season of next question, which means four more episodes every week, and perhaps even more to the corona virus pandemic. For Day to day news on this ever changing story, I do recommend you continue to search your local government, the CDC and the World Health Organization for the most up to date information I'm also providing updates on my instagram feed. As for me well I'm hold up in my house, which means I might sound a little different to you. Social distancing means I'm not going into our usual studio and speaking of fancy microphone right now I'm sitting in my Home Office and I'm recording myself on my phone. And instead of speaking to my guests in person. We're connecting over our. So bear with US everyone, but please keep listening for this critically important information so today my next question. How do we manage this new normal and Corona virus anxiety? To answer that I called up my friend, Lori Gottlieb Lori Hi. Lori Gottlieb is like Oh therapist with a private practice in Los Angeles, but she's also a bestselling author journalist, and soon a podcast or two, but today we're focused on the issue at hand. So I'm. Let's talk about why people you know. I think with good reason. People are feeling a lot of anxiety, but I think it's getting that. The unpredictability of all of this Lori is the perfect recipe for high anxiety. Can you explain that? Yeah. It makes sense that we have anxiety and I think there are two kinds of anxiety. There's productive anxiety and there's unproductive anxiety and productive anxiety is the kind of anxiety that helps you to take action, so that's why we're washing our hands all the time. That's why we're social distancing if we if we were in denial if we said Oh this is no big deal, we wouldn't be protecting ourselves and other people, so that's that's good anxiety. The kind of anxiety that gets us into trouble as unproductive anxiety, which is when we start just ruminating, and we start catastrophes in future is saying Blake. Thoughts of Oh my. I'M GONNA. Get this and I'm going to die or someone I love is going to get this and they're gonNa die, and you know just all the stories that were kind of spinning in our heads, and that doesn't help us in any way well, what makes us go as human beings to that dark place? I know that in therapy a year. You know this better than I, but sometimes people do say to patients. What's the worst that could happen as a way for them to help kind of conquer their fears But you believe in this case. That's not super helpful. I don't think that that's helpful. I, think that one of the things that can really help ground us is instead of thinking about what might happen in the future because it hasn't happened yet is distinct grounded in the present, so one of the things that I think happens is that when something extraordinary happens? We long for the ordinary we want. We want our routines back. We want all those things that we complained about. You know when we didn't have something. We weren't in a heightened state like this. We want it back and yet. It's still right in front of us so. I like to talk about the concept of both am which is yes. Something horrible is happening, and we can also enjoy certain things like the ordinary. We can enjoy the time that we're having connecting with people that we normally don't really pay attention to in our daily lives. We can enjoy cooking together. We can you know in our own isolated family units? We can enjoy having the time to read a book or to think our own thoughts or to. Actually facetime time with someone and actually. Listen when you ask. How are you I? Think one of the one of the Nice things to come out of a horrible experience like this. Is that people? are very kind. Kindness comes out there sort of a resurgence of kindness in this world, where civility has been lost, and so I think that both ad both can exist and if we can focus on. Holding our fear and feeling our feelings, not being in denial of our anxiety, and not being in denial of what's going on around us, but also really trying to stay present in what's happening in that moment we have so many questions, but before we get to some questions from people who follow me or listen to the podcast Laurie, I'm a fairly normal person in in that I don't have huge anxiety, but I'm finding. I'm feeling a little neurotic about my health, if I have a little bit of a sore throat when I wake up in the morning, or if I cough then I start thinking Oh my God. Am I sick and I'm sure I'm not alone in that because it's part of Catastrophe ising I'm sure What what is that about? How can we kind of come ourselves down? Well I. Think the first step is just realizing that it's human nature to do that so I remember. When I was in medical school, we talked about sort of medical school disease, which was every disease that we were reading about? We all thought we had all of a sudden. They felt the symptoms of it. You know it was like Oh by God I have this now, because my my gland feels inflamed or whatever. That now that we're reading all the time about the symptoms of Corona virus. It's almost like the power of of Into your suggestion right so so I think just realize that the power of suggestion is very powerful, and and so when you notice that, of course, be aware if you are having symptoms, but also take a breath. Part of part of the problem is that we're reading about it. Twenty four seven and I always tell people that. Yes. You need to get daily updates, but you don't really need more than that. I think that the more that we're just. kind of it's kind of like. Were Binge Binge watching a television show? But it's kind of like binge. Eating junk food that the more you sit there and click from this article to that article to the other article. It makes you sick. It does not fill you up. It does not help you at actually makes you psychologically ill. How do you talk to kids about this? I'm sure that a lot of parents you know. My children are older. Your son is in high school now, right? He's in Middle School Matt School so he's he's at home. Is He expressing concern? And how do you suggest people talk to their kids about this? I think that the way that we model our response to this is going to impact the way that our kids handle their anxiety around it, so it's kind of like I. Think you know when you're on an airplane. They always say put on your oxygen mask. First before you put on your child's but I think it goes beyond that it's. How does the pilot handle it when there's a problem and the pilot doesn't say Oh my God. We're all GonNa die, you know. Know if there's something, the pilots says very calmly. Hey, we're GONNA experienced some turbulence coming up. We want all of you to fasten your seatbelts and please don't walk in the aisles right now. And I think that's very calming and I think that for our kids. We need to say yes. Here are the rules. Here are the boundaries. You can't go and play basketball. Say this to my kid. You can't go play basketball with your friends right now because we're social distancing. And we're going to do this instead. And just to kind of you know under help them understand I, think giving them a sense of purpose to around this which is, we're not just doing this for ourselves doing this for our community. We're doing this for our neighbors for the elderly people that we know. We're doing this for people with compromised immune systems, and I think the kids really engage in that when they realize that it's bigger than them. It's not just Oh, this is a bummer I'm stuck here and I can't play with my friends and I can't do the normal things I'd like to do. There's something about being connected to the larger community that really resonates with with tweens and teens. Well let's play dear therapists Lori, because we've got so many questions I don't WanNa. Be Sir, a pig, about just asking my own, Rosanna, says, how much information should we deal with on an everyday basis, especially with the situation changing by the hour or day? Do you have any? Suggestions for what is a healthy media diet. Yeah I do think once a day is plenty and I think that's because we all know what we're supposed to be doing. Regardless of how many new cases are reported regardless of whether they're saying you can't go here. You can't cut that. We know we're supposed to be social isolating. We know we're supposed to be washing. Our hands constantly We know that we're supposed to be cleaning. The all the handles in and. Doorknobs and things like that in our homes, and all the sort of high touch surfaces. We know what we're supposed to be doing. Nothing is changing in that regard so and we also know if you're having symptoms what you're supposed to do so. There's no information that's going to happen during the day. That's going to change the basic facts of what we need to do in our lives, and we really need to protect our psychological immune systems as much as we're protecting our physical immune systems, and that means not overloading ourselves with information. Here's another question. What are some tools, new moms or expectant MOMS like me? She said can use to get through this uncertain time. Bringing a new baby home is tough enough, but limiting the village from visiting and helping will put a strain on many thanks to you. Yeah, I think that it's really important for parents to kind of trade off time so that they get a break so i. think that when you've got a baby and you don't have your village around you a lot of times. You need each other as adults as a couple, but sometimes you're going to have to say you know what it's your turn and I'm going to go. Take a bath or I need to go just. I need to go take a walk. Whatever it is and hand off to the other parents and you really have to work as a team so I think that's really important. If you're living in a multi generational household and you have. Other people to help. That's great. I think it's also important that you you connect again for your own mental health that you connect with your friends through technology, and you take breaks, and you laugh about how hard it is, and you laugh about the dirty diapers and you laugh about the naps that are not being taken, and all of those things 'cause you need someone to vent to. Yeah, definitely and laughter is really helpful. Here's a question. Jay, he asked. I'm an addict. In recovery are twelve step, groups and meetings are shutting down. What is the best advice to stay out of your monkey and stay connected even at a time of much-needed social distancing. So if you have a sponsor that you can connect with virtually, that would be really helpful. If you have other people from that, you know from the group that you can connect with. That would be helpful. There are also so many online resources. That you can listen to podcasts. I was going to say there's groups online where you can write in in real time and connect like that so I would really search the Internet. I think the Internet is our friend right now, not in the sense of getting an overload of of covert information, but in a sense of how we can get creative around connecting with other people when we need it most. Vivian says. How can I stop obsessing and stockpiling groceries I? Think that's such an interesting sort of primitive instinct. People are going and kind of sometimes hoarding food. They're so worried that the grocery stores are going to close and that they're gonNA. Starve to death. You saw that with the toilet paper shortage. It's fascinating thing to observe just from a human behavior standpoint What advice could you give Vivian and other people who are feeling that way? There's a difference between being prepared and obsessing, and that line is going to shift the more that you think about Oh. What's going to happen in the future? I think being prepared means that yeah, you have some provisions in the house and you. You have things that that you're going to need, but you know when you start getting to the point where you've already gotten the provisions, and then you think. Think. Oh, I, need more and then I need more, and they need more That's when you need to step back and say you know what I am prepared. I will be able to get more later, but have enough I've done my preparations and I've done with the recommendations are and then you really have to let go, and that's again. We're staying in the present house. Where instead of thinking about? Do I have enough in and spending your emotional real estate on that do something else, and I know that sounds like I'm trivializing this, but I'm not Go do a puzzle. Go get those art art supplies out. Go read a book. Take a walk. Go call a friend. You have to take breaks. You have to let go. And you have to stay active I think even though you know the it seems an. With the idea of staying home, their ways to stay active at home, clean out your closet. Get rid of all the clothes or put them aside that you can give her dress to dress for success or to the goodwill. A good time to do some serious spring cleaning open the windows, and and get the winter winter out of your house out of your things, and maybe downsize the little bit and es. I have a friend who suffers from anxiety. This is kind of an obvious question, but it's a good one. How can I best support them during this time? How can you support people who you know? What can you do for them? One of the things that happens with anxiety is logic doesn't help, so you can't really talk somebody out of their anxiety and try to tell them that things are going to be okay. What you can do is you can connect with them, and that's that naturally sues people. So why didn't you say hey, let's do. Let's have a virtual dinner together. Hey. Let's watch a movie together virtually. Whatever it is that you can do you know some people are exercising together on virtually. Which is fine. So just moving your body helped so much with anxiety, so if you can somehow get your friend to. Move around, and you can do it with that person. Virtually you can support the person through actions as opposed to your words will not really helps up. By your actions will. Abby ass how to focus on work while acknowledging that we're all scared. No I think. You and I know that when you are worried or stressed out, it's hard to concentrate actually. From when my husband was sick, I would read the same paragraph over and over again in a book, and I could not for the life of me concentrate. So how can you? How can you fight that? Is there anything you can do I guess reducing the stress. We'll help you concentrate more. There's also something you can do with your body. which is that sometimes when we kind of leave the present, we need to physically ground ourselves. So what you do is you close your eyes, and you start with your feet, and you say I feel my feet on the floor, and you feel that, and then you move up, and you say okay I feel put your knees together I feel my knees, and you move Pat, and you just keep you feel your breath, and you feel your diaphragm, and you feel the different parts of your body, and it brings you back to the present moment, and the take some breaths, and then you move on with your work. Kristen wants to know. How do you cope with the idea that we don't know how if when this is going to end, I think that's an in addition to the unpredictability of this. This kind of not knowing when life full resume I think adds to people's stress levels right? I mean not just am I. GonNa get this. What's going to happen? But how long is this going to have to be the new normal? So how do you cope with that? I think we have to acknowledge that humans don't do well with uncertainty, and so this is a good opportunity for us to build up some resilience around uncertainty, which means that we just instead of trying to figure it out. This news report says that or this physician says that to just say we don't know and to try to get comfortable with that and say. What can I do in the meantime to have as? As normal of routine that I can possibly have under these circumstances. You know I don't WanNa, let you go before asking you. If someone is having real trouble, you know if the anxiety reaches a point where it's untenable, or it's affecting someone's physical health health you know I don't want to trivialize the seriousness of this. So what can people do if they really feel there at the break their breaking Point Laurie? They should absolutely reach out to a therapist, and so therapists are doing online sessions specifically right now for this, and they should reach out, and this is not a time for shame or stigma. You know my problems. Aren't that bad minimizing our problems? Everybody else's going through this. So why? Why? Why should I get help you know all those things we say to ourselves that prevent us from reaching out. This is the time to say I need to prioritize my emotional health. Just as I'm prioritizing physical health, and if you need to talk to someone, you do not need to be in a crisis, you can just be having a moment. You can be feeling kind of free floating. Anxiety depression whatever it is or you just want to connect with someone because you feel like preventively to kind of preserve your emotional health, please please please reach out you can find. You can do a quick Google search, and you will find somebody who is available to do that for you. We'll stay safe and Kami and maybe we'll have a virtual lasts of wine together cup of tea. I don't WanNa. Encourage people to drink during this time, but a glass of wine isn't going to hurt right. That's right. That's right. Thank you so much. Katie Okay Filori. All right take care of they say. Bory got leads. Latest book is called. Maybe you should talk to someone. Also coming out with a podcast called appropriately, dear therapist co hosted by another therapist Guy Wench. It's due to come out from IHEART hopefully this summer. Are really like what Lori said. Earlier about how kindness tends to emerge out of times of crisis, people are kinder to one another. They want to help and I'd like to know the large or small. Always you're seeing kindness or promoting it in your own community. If you want to share your story, please call and leave your name and a detailed message for us. At next question. The number is eight, four, four, four, seven, nine, seven, eight, eight, three. That number once again is eight, four, four, four, seven, nine, seven, eight, eight three. You can also email me a voice memo written note at Info at Katie couric dot com just put next question, kindness and the subject line, and you might hear your story right here on next question. Coming now we're going to be checking in with a doctor WHO's a friend of mine and one of the smartest people I know to get a better sense of how the corona virus affects our bodies, and also our healthcare system. You WanNa. Feel better about what you eat right, but sometimes it's hard to prepare healthy meals that also taste good especially. If you're working and you come home exhausted, don't feel like going to the grocery store Yada Yada Yada but with Sakari you can reach your health goals without sacrificing taste. Sakari is a nutrition company that focuses on overall wellness, starting with what you eat, their organic ready to eat meals or made with powerful plant based ingredients, and they're designed to boost your energy. Improve Your digestion and get your skin glowing along with delicious meals. Meals by the way so car also has daily wellness essentials like supplements and tease to support your nutrition to boost results tried the best selling metabolism, super powder, an all natural remedy for bloating weight gain fatigue. Hey, how do they know my problems and right now cars offering our listeners twenty percent off their first order, when they go to SAFERCAR DOT com slash Katie or enter the code Katie at checkout that's Sikora. S. A. K. A. R. A. DOT COM Slash Katie to get twenty percents off your first order Sikora. Dot Com Slash Katie the. Support for today show comes from a company very close to my heart I mean literally because I'm wearing a third love Bra right now, TMI! I know I I noticed third love after reading a letter in the New York. Times written by co founder and co CEO. Heidi Zach Heidi wrote about how third love is a different kind of broad company. It's inclusive. It's salutes. Women of all shapes sizes, ages, ethnicities gender identities and sexual orientations it's. It's a company for everyone in other words, I mean I don't know about you, but who wants to look at Bras and feel bad about themselves. We have enough stuff out in society. Making us feel bad about ourselves. Am I right ladies, so go to third love dot com slash next now to find your perfect fitting Bra and get fifteen percent off your first purchase. That's third love dot com slash next for fifteen percent off today. Dr Peter. Is a Stanford and Johns. Hopkins trained physician living in San Diego. His clinical focus has been on longevity how to better and longer, but since break of Krona virus or covid nineteen, he shifted gears focusing his research toward understanding the current situation what we can do to protect ourselves and potentially the implication of what's to come. And now he's here to share some of that with us. So where are we now? Understanding this story seems to change on an hourly, if not minute by minute basis. If you had to assess the situation right now for our listeners, what would you say well, you know I think of these things through the lens of Is The rate at which we are seeing infections, growing or shrinking, so you can think of being on one side or another of that peak, so for example if we look at mainland, China we know that there are now on the tail end of this response again. There's always possibilities that there's another outbreak as they go back to work and begin to mobilize. Mobilize Society again, but notwithstanding that it's clear that they're on the right side of that curve both you know right and correct We're still on the left side of that curve, which means each and every day it appears that we are seeing more and more people get infected or the rate at which the infections are increasing is be is still increasing. Now the million dollar question for which a lot of people really smart people epidemiologists in such are trying to project his. Where is that peak because the peak is sort of what gives us a sense of that maximum rate of infection and that is once you know what that looks like. Then you kind of have a sense of what the overall number of infected people will be, and then you can extrapolate hopefully from the data we see in other countries with the impact is going to be on the healthcare system, and of course, the things that really matter like how many people are going to potentially die or otherwise be debilitated by this. Why was Italy so overrun with this virus? What was the perfect storm that made it go through that country like wildfire so I think we can speculate on a couple of things. First of all I. Think part of it is bad luck I. Mean it's it's important to understand that if let's just make the math simple and say, let's let's pretend. There were a hundred infected people in China as as where the epicenter was, and that you know ten of them on a plane and happened to travel and go someplace well, the ten place is that they land are going to have head start in terms of where this virus is going to spread, and if one of the places they landed, was Italy and one of the places they landed was on in. Those places are going to have a bit of a head start so. I think there's just a little bit of a component which is probably got an early start on the virus, reaching their other factors that seem to matter seem to be. The age of the population to Italy has a relatively old population compared to other countries in Europe, and relative to the United States meaning they have more people who are in that higher risk category based on age alone. Furthermore there seems to be a slightly higher prevalence of smoking and smoking is definitely one of the major risk factors for people who if they're infected are more likely to get ill. And then I think the other component is you know some of the sort of just societal things about the proximity that people are to each other so in other words. If you look at a place like Wyoming. If someone had landed if one of the first people infected had landed in Wyoming, it still would have likely spread slower than landing in a place like Italy northern Italy where the population density is such that there's more contact with an infected person to another, and then I think finally just at the policy level. They were probably a little bit later to realize what was happening and institute the measures necessary to slow the rate of spread. You have said it Italy taught us that it is the morbidity rate, not the mortality rate of the disease that is grave for us, non doctors in who may be listening including myself. What is the difference? So mortality is kind of a binary variable. It's to live or to die, and there's a lot of attention that is appropriately being placed on the mortality rate. It's often described through a case fatality rate, which is another way of saying how many people die for a given number of people who have this infection, and obviously that's very important, but morbidity is more about the long term impact on quality of life and illness that is suffered. That does not ultimately result in death and I was reading a paper this morning. that did a ten year follow up on people who were infected with the first SARS virus that we talk about SARS, covy one. This was the two thousand and three epidemic. This was a pretty lethal virus, certainly appeared more lethal than the current virus about ten percent of people infected with this virus died. So that's a staggering amount. But with this paper followed up on was what were the long term consequences of the people who were infected, but survived and it was quite. Disheartening frankly that you saw much higher incidence of cardiovascular disease in those people. Are Incidents of lung disease in those people as so, they didn't die from the disease, they were still somewhat debilitated by it and I think that that's something that we're going to see a lot more of an I think. The the consequences of that you know economically will be significant. There are going to be people. I I suspect who won't be able to go back to work in the same capacity a year from now when all is said and done and the people. People who are most susceptible to that are obviously the people who come in with the greatest amount of pre existing medical conditions, so for example diabetes. Why is diabetes a risk for this? I don't think we know entirely, but one thing we know is that people with diabetes might already have some underlying degree of insult to their kidneys to their heart, and it might be that they are less likely to recover from this even if they're fortunate enough to not succumb to it. Yeah, I was interested in the diabetes angle because I would understand smoking, because correct me if I'm wrong, Peter, but this virus does create some kind of fibrosis in the lungs. Is that right? Eventually yes, it. This is a virus that has kind of unique pathology relative to influenza, for example, which would be a cousin of it. The virus gets every virus has to replicate by getting into a cell within our body. So it's you know. Maybe we're taking a step back to understand what the heck virus is. A virus is not like bacteria. A bacteria is totally self sufficient meaning it has all of the equipment inside of itself to fully replicate on its own outside of the body. That doesn't mean it won't infect. But a virus is different. Virus doesn't actually have much to it. It's a much much simpler. Piece of you know biologic. Entity! It has in this case just some Aren A. And that's about it, and so for it to replicate survive, it must get inside of a host, and in this case we have now become the host prior to this. Of course, animals were the host and uses our DNA replicating machinery to replicate itself. So if you were going to think about this sort of teleological e, the virus really has no intention of hurting us. That's just an unintended consequence what it wants. Wants to do is replicate from an evolutionary perspective and the most successful viruses by the way the ones that can go on forever and ever don't hurt their host at all. It's the viruses that destroy their host that don't really survive much like Ebola. Ebola didn't spread very much because it was so devastating to its host. So when this virus comes in, it has to pick a cell, but it targets and. That just happens to come down to sort of the molecular biology of how this virus works in the sell it targets most commonly is a cell in the lung called Numa site because of a certain receptor that that cell has that allows this virus to enter when it gets into that sell it basically hijacks it. It takes over and uses the cells ability to replicate and says hey. I'M GONNA. Take this over for myself and replicate myself. And it does that and it ends up destroying that cell and it turns out that in this case. That's a really bad cell to lose. Because that cell called a type to Numa. Site makes a chemical called surfactant. And you heard of surfactant. It's like a detergent that allows the. Air Sacs in our lungs to not collapse on themselves because of the surface tension. And so when we lose enough of those, the lungs begin to collapse, and we aren't able to exchange air, and ultimately that results in a type of New Orleans or really something more severe than ammonia, an acute respiratory distress syndrome where a person can't exchange gas, and ultimately that will result in potentially fibrosis of the lung. It turns out by the way that that sell that that the virus can also gain access to muscle cells of the heart, and and so we believe that we're going to see sort of fibrosis of the heart going forward, in fact, thirty or forty percent of patients on autopsy, people who have already died from his virus or showing injury to their heart. This sounds very very bleak, but that's one of the reasons. Smokers are particularly. Susceptible because they already have some of the some damage to the cells that you were discussing. Europe and they just have less what we would call pulmonary reserve. They have less lung capacity in excess. So you know someone like you Katie. WHO's really healthy? You know you're not utilizing your full lung capacity when you're sitting here at rest right now. You're using a fraction of it but let's say that you're using twenty percent of your lung. Capacity will imagine somebody who smoked for. For a long period of time for them sitting at rest, they might be relying on sixty percent of their lung capacity, so they just have less of a buffer. You know you can think of it as like how much to someone having their savings account will the person who has lessen their savings account is going to be more likely to suffer the shock of not having a job. Before, we talk about being better prepared and I know that you watch the Bill Gates tedtalk which I thought was. PRESCIENT in its message, but let's talk just briefly because I think people are desperate for this kind of information to Peter and you have access to to the latest most accurate information in terms of protecting yourself Tell me what you're doing in your home with your kids and your wife. Well we sort of probably came across as a little bit crazy at the outset. In mid February? I sorta woke up to what was happening I. I had been largely in denial. through January and I think had naively assumed that this would be much more like the first SARS outbreak, or like the murs outbreak accept less deadly and less likely to spread in other words. I hadn't fully dug into the properties of this virus that make it a little more troublesome, which is namely its capacity for spread. But in mid February when I woke up to this. I started to think about well. What what could we do if we wanted to buy more time? And so that basically came down to much greater social distancing and that meant you know canceling all travel plans, and then eventually just came down to making a decision that was difficult to make not a decision that everybody has the luxury of making. Because many people don't have the luxury of working from home, but it was a decision to basically quarantine ourselves and so that meant that you know we don't leave the house and people don't come to us in the house and the thinking that after two to three weeks of that period of a quarantine absent, having an accurate test to measure. If you are infected, if you're completely matic, you know temperature, changes or anything like that the likelihood that you're infected is low, and now at least you're in sort of a safe spot while you wait for time to play this out in time does a lot of things right time allows us to potentially develop a vaccine. Although I think that's a longer term. Term Strategy than most people think it certainly allows us to repurpose existing drugs, and that's something. I'm really excited about, so we're gonNA talk about optimism. I actually am quite optimistic that there are suite of drugs that already exist. We're now learning. How can be re purposed for this? And most importantly, it's giving the hospital system and the healthcare system a chance to slowly. Band to meet the needs that are necessary because again to your point about Italy. The the real problem in Italy is not the total number of people that are infected. It's the speed at which those people needed medical care, and so you can you've heard the term flattening the curve wire? People saying that it's like saying if one hundred thousand people are going to require hospitalization, it's a big difference if they required in one month or one year, and so it's not clear that we're going to reduce the number of people that are ultimately going to be infected, but we want to spread it out as much as possible so on a personal level, my view is what can I do to make sure I? Don't need healthcare resources anytime soon. I talked to the director of an urgent. Care Center Peter and He said, do not go to the doctors, do not you know? Try to seek medical care unless it gets bad I wondered. Is there an inflection point because I think people are so paranoid every time I cough. I get neurotic. And and when is that point? Where you should seek medical care, or at least talk to a healthcare provider because we don't want to clog the system listeners I'm sure agree with this, but we also don't want to ignore an illness. That could worsen if we don't get if we don't get the proper attention. The such an important question, and truthfully it's one for which I think, the answer is not entirely clear We probably do need to think a little bit about how to strategy, so I would agree with the advice that your colleague and friend gave you which is. We certainly don't want everyone who. Thinks that they have a little sniffle, sneeze or a sore throat to then expose themselves to infection by going out and seeking medical care especially when we don't have testing readily available yet, that's the important thing to understand is what is it going to accomplish to go and put yourself in harm's way if we don't even have test yet? That's viable or going to offer as much so I. Think we have to stratified patients, so you know the way we are looking at. At it in our practice is, we're taking the patients who we think are at highest risk, so these are people who are you know? Sort of in their sixties and older people who have existing conditions like high blood, pressure or heart disease, atrial fibrillation, these sorts of things and we're saying we're going to have a lower threshold for getting them tested or getting them into. See someone. If we have any concern, you know my wife yesterday was called by friend of hers. Who Lives in Colorado now and she has a lot of underlying medical conditions. And you know it was really difficult to spend the time on the phone with real estate and triage, what I couldn't fully understand was either panic attack or legitimately illness and you know we had to make a call. In the end we saw we decided after an hour. She probably did need to go into the emergency room and get checked out because I just couldn't be comfortable that this was just anxiety and I and she has so many underlying medical conditions that I was actually concerned that you know she's the type of person who. Who if infected could very precipitously fall off that proverbial cliff and what happened You know she Aren't there I? It's it's still unclear. Because of course, the testing takes days to get back, so but now she is at least you know. Her blood pressure normalized her. Oxygen levels are normalized the thing we are most sensitive to is shortness of breath that seems to be the biggest single predictor of people who do versus do not need medical attention, so people who do not develop shortness of breath at any point in time are generally going to recover in what we call a self limited way. I hate to ask you this Dr. a t. f. What is how do you know if you have shortness of breath? I know that probably sounds like a dumb question, but it's there something you can do to figure out. Is Walking upstairs I. Mean I get sometimes shortness of breath? If I try to run a mile I mean when when can you tell you have that? Actually Katie bad is not a stupid question at all, and we've actually tried to explain that exactly to our patients so I'm glad you asked. We, think one of the best litmus tests for litmus tests for shortness of breath is air hunger while speaking in long sentences so when someone who could normally rattled off. The minutes talking with just the simple breath in between all of a sudden has to take longer pauses to take breaths in between speaking to me. That's true shortness of breath. You use an example of walking up a flight of stairs. I think if somebody knows what their. Normal exercise tolerances when that dramatically decreases, so if a person lives in an apartment where they have to go up and down a flight of stairs, and normally that poses no risk to them, and all of a sudden now they think oh my God. Like I'm really winded walking up this flight of stairs that that might also constitute shortness of breath the other thing to keep in mind is shortness of breath by itself probably doesn't show up without some other symptoms such as you know a fever, which is the single most common symptom we see and people who are infected, but of course it's important. Important to understand. People can develop fevers for any sort of you know common, cold or anything like that, so are right absolutely, and and so all of this I think points to something which is you know, do as much as you can by phone right? Call your doctor walk through all of these things, and and let you let your doctor help you decide. If you actually need to take the next step of getting tested which again we're currently in a testing environment that is not adequate, so the CDC guidelines on testing are actually quite stringent compared to what I think, they should be due to these limitations. So. That that does raise the question. Who should be tested in who shouldn't and. sort of thinking about the common good, and not just yourself in these situations, but gosh you know we're talking about in some cases, life or death Peter and so people. I. Think you know they have this primal survival instinct so? in terms of testing you have to rely on your healthcare provider, but. They're making some tough decisions in Italy about who who gets medical attention and who doesn't because. Of the crowded conditions of hospitals etc, I mean it's. It really feels like the makings of a of a scifi movie. Yeah, the they are making these decisions in Europe. Already and. It's not clear if we're not going to be in the same position in the next two to three weeks, As far as testing goes at the top at right this moment, Katie the CDC guidelines are the testing should be reserved for people who are symptomatic only. Now. Why do I think that that's insufficient? I think it. If you really want to control the rate of spread, you should also be testing people with known exposure, even if they ace symptomatic because this virus has such a long latency period. Let's assume that you know you were around. Somebody who then went on to test positive or frankly even went on to be symptomatic in an ideal world, if we had a sufficient number of tests, sufficient infrastructure for. For testing, it would actually be important to know that you were negative before you know we told you pay. It's you know the fact that you're not symptomatic means. You're not a risk in other words, the thing that makes this virus so particularly troublesome is that people who have no symptoms can spread the virus, and they can use for a long period of time for fourteen days right I mean. Isn't that the incubation period and the fact that some people? Can Be vectors and yet ever symptomatic that makes it really freaky right? Yeah, that's the. That's the superpower of this virus. So if you were GONNA like create A. List of all the things that make this virus sort of troubling that that would be superpower is that it has this ability to? Very subtly get you know. Get from one person to another usually without that person knowing it, but then again we'll use ebola as a stark contrast right? Why was he bowl and not really a big issue once it got into the United States because people were so sick when they got it that there is no ambiguity about whether that person had it, and it was only during that period of extreme sickness that they could go on and shed the virus. If in fact, people are practicing social distancing now. All these cities are closing down. I guess you know San Francisco is the shelter in place city, other cities as well. Is that going to ameliorate or mitigate some of the conditions that will be prime for spreading this virus around or have? We missed that window of Opportunity Peter. It will absolutely have an impact I mean in an ideal circumstance. If we had a time machine I think we would have done this. We would have taken these precautions a month sooner but I'm actually still optimistic and you know we have. A team of analysts that are building forecast models reviewing every piece of. Data that's available. An including data that aren't publicly available by you know re speaking with people on the front lines to pressure test assumptions I. I don't think that it's a foregone conclusion how this ends so? It I can't even sit here and project. How many people are going to be infected in the United States although there were lots of estimates and some of them are quite scary. You Know Mark Lips at the Harvard School of Public Health. Projects that you know more than fifty percent of the US population will ultimately be infected by this, and at the mortality rates were seeing those are staggering numbers that that the implication of by the way to put it in some numbers is more people would die from this virus in a year in the next year. Then die of all other things combined. And that that's a staggering statistic. Do I think that? That is set in stone yet that that is our fate I? Don't and I do think that the more aggressively we can socially distance ourselves the more aggressively we can implement testing which will enable this stratification of distancing between people and the more readily available. We can be pressure testing existing drugs to then bring on treatments that can reduce the mortality and morbidity I think we still have a chance to bend the curve of this thing. We're going to take a break, but we'll be right back with more critically important information from Dr Peter Attiyah. Hey, I'm Joe Levy, and on the latest episode of inside the Studio I sat down with one of the all-time great singer Songwriters James Taylor. We talked about his new album. Where is music comes from and how telling his life story through his songs has helped him. Music saved my life, but I was lucky also to survive. I did some very stupid some some years that were. Just really high risk unnecessarily so in a lot of people around. US died. So join me Joe. Editor at large at billboard for this and other in-depth conversations with the biggest artists in music was an on the iheartradio, APP apple podcasts or wherever you get cast. Hi Everyone I'm so happy we were able to get in. With Dr, Peter Attiyah and he was able to spend a good hour talking to us about this scary pandemic, because I think his knowledge, his experience and his connections are really unparalleled, so let's get back to that important conversation. Let's say someone goes to the hospital. Peter and they have covid nineteen. I know that ventilators and respirators to help with lung capacity, but. Are there any medicines that these people are getting, or are they just going to the hospital and? I mean Howard. Our doctors fighting it right now. It's varying by hospital so myself and my team. We have enough friends in hospitals that we're hearing. You know we're finding out in this hospital in Boston is using this protocol. This hospital in new. York is doing this etc.. So right now. I would say Katie. It's not standardized, but shot racy. On. That seems insane to me that it's not that it isn't standard is that it's sort of kind of a piecemeal approach we'll the primary approach as you said is supportive care so the single most important thing for a person. Once they're in the hospital is maintaining sufficient respiration, because that's the thing that's going to put a person in the hospital, so the the most common thing that people are presenting with his respiratory failure as opposed to say cardiac failure, renal failure or other organ failure, so the first, second and Third Line of Defense is through. And Supplemental Respiratory Care Hopefully, not requiring mechanical ventilation, but obviously at some point that's happening for enough people that's that's the sort of supportive side of things. And, I think we're seeing more and more patients being treated with. Chloroquine and then, of course, if the doctors treating the patient have reason to believe that they're now developing secondary infections, then things like antibiotics are coming on board, and they're also if it turns into pneumonia exactly if it's pneumonia that they believe is an actual bacterial pneumonia versus sort of a viral pneumonia, for which the antibiotics wouldn't provide any benefit. There's also HIV drugs. There's a drug. That is a protease inhibitor that I think is sort of. Weekly? Potentially. It's still too soon to say the risk of using. It seems relatively low, so it's. It's also being tested one drug that I think two three weeks ago, we thought might be valuable is looking less valuable as the common anti flu. Drug called Tamiflu so I I I think most hospitals are moving away from that now, but again it is unfortunately not a fully standardized protocol, because even though the CDC will have a recommendation. Ultimately, the physicians are the ones at the bedside that are going to be able to make the decisions. Can Uber Verse. Let's say someone goes to the hospital. They're having respiratory failure. Can those individuals with you know breathing assistance with the ventilator respirator? Can they then get the virus that as you said was sort of taking over the cells in their lungs, can they? How do they get that? How do they get it out of their lungs? I know this sounds sort of elementary, but I'm just trying to figure out you know. Is that kind of support enough to a radical this virus? No it's actually not an elementary question at all. It's very important question. What's actually happening is there's a war going on between the virus and the immune system and the whole purpose of supportive care, such as ventilation is to buy time for the immune system to win that fight. Now it becomes a bit complicated because the immune system in its best effort to win, that fight can also cause a lot of damage to the host. So you think of it like a war going on in a country, you have the good guys. The bad guys at the risk of oversimplifying it well, both of those entities when engaging in war caused collateral damage right. Immunotherapy and cancer at becomes to revved up and that can create all kinds of auto immune issues correct absolutely so the you know the checkpoint inhibitors, which are probably the most exciting thing in all of Immuno oncology right now, exactly have that as a side effect, which is auto immunity. The immune system goes a little too far now in in this type of response to the immune system. It's not. Not so much auto immunity that seeing is the problem, but it's the sort of what's called, systemic? Inflammatory Response Syndrome or this site of kind storm that is sort of you know wreaking havoc both to kill the viruses, but it's also the thing that can you know 'cause capillary leaking in the lungs that can lead to other things like Dima and it can damage other parts of the body. So basically what you're saying is that it's a delicate balance between the immune system which can cause inflammation and damage if it's overly compensating for the virus and sort of keeping the virus in check. Your in we use supportive measures like ventilation to basically by time to to augment what the lung needs to do to to create that amount of time and space necessary for the immune system to ultimately win that fight, but winning the fight means that the virus has gone. Winning the fight means that the number of actual copies of that virus goes down to some insignificant level and you know. To contrast that with other things like when you look at the Spanish flu, the Nineteen Eighteen H, one N, one pandemic that was kind of a different animal that was an animal, where so much of the damage actually came from the hyperactive immune response, and then this immune paralysis that followed it that led to these secondary infections, so Y- paradoxically the people that were most vulnerable to that flew where people that had the most robust immune system and therefore the strongest immune response. We're not seeing that here which suggests again. It's just a suggestion. That hyperactive immune response is less of a problem than the actual damage. The viruses causing to cells. That's fascinating That raises a couple of questions about ventilators and respirators. I don't even know the difference. Maybe you can explain that, but. there's a real shortage of medical equipment. How serious a problem will it be if there is a lack of ventilators respirators to by the time these patients need and what is being done about that, too. It's a huge problem. Let me answer your first question. So respirators are noninvasive so For example you've probably visited somebody the hospital in you see like a little oxygen masks that they have on or even something called a nasal Kanye where there's a little device that goes under their noses, just passively blowing oxygen at them. So you can, you can provide a person with supplemental oxygen. In, that sort of passive manner, but when a person becomes really dependent on oxygen, they are something called mechanical ventilation and to do that. You have to undergo a procedure called intimation, which anybody who's had surgery has has under general anaesthetic has had that, but that's where a tube actually placed into the main airway called the trachea, so it's called an Endo tracheal tube when a person is. Is Intimated. They also have to be paralyzed and sedated. It's not a comfortable thing you. You couldn't be wide awake. Sitting there intimated so you have to be sedating the patients and paralyzing them and the reason you have to do that. Is that their own voluntary muscular movements can't fight the ventilator, so you actually have to basically shut them down to let the machine do the breathing. And you're absolutely right that these ventilators are very very specific and specialized pieces of medical equipment, and at some point we will run out of them. In fact I was just speaking to someone today at a small hospital outside of New York City and they are now. They have just used their last ventilator, and they are now what's called double venting patients, which means using one ventilator to treat to? To patients, which you would normally never do because of the contamination, those two patients are now fully sharing all their respiratory pathogens, but of course you know desperate times call for desperate measures, and if these patients both have the same virus, and they are both suffering from the covid nineteen disease than we do what we have to do, and technically a ventilator can probably be split up to four ways. But at some point soon, and it could be within two to three weeks. this could become an enormous problem, and so can can we are manufacturers kind of? Speeding up the the production of these pieces of equipment as They are, but there is still another bottleneck in the one thing that we can't make more of is doctors, nurses and respiratory therapists, and so these pieces of equipment can't work on their own. You know a doctor is necessary to put the tracheal Tube in nurses and respiratory therapists are necessary to actually run the ventilators and manage the medications on a minute to minute basis and so. It it can't be overstated that a really fundamental break point in this system could occur when the healthcare system through its workers is so overwhelmed that we can't actually have people on the front lines that are doing this work. So How do they protect themselves because? Obviously, we need them desperately to be treating patients. We probably need to and I know that a lot of retired medical professionals are being called in are. Are they getting sick? I know that some Har. What should I mean? How worried are you about that? I'm actually quite worried about it. Because of some data that we're seeing from around the world including China in Italy which is that when healthcare workers get it, they seem to get a worse version of it, suggesting at least preliminarily that there might be something about the amount of virus or the manner in which they're exposed to it, that is otherwise making it worse than if they just acquired this virus out in the community. So that's the first thing that has somewhat concerns. How do you think they're getting it? Probably just through a greater concentration of respiratory droplets given the. Proximity that they have to people who are sick, and obviously, if someone is sick, and they're in respiratory distress in your intimidating them, you're leaning over a person and you're just being exposed to a much greater amount of virus than say if you bumped into somebody at the supermarket. The other thing that is in short supply is p. it's the protective equipment that the doctors nurses respiratory therapists, all the people in the hospital need to protect themselves against this virus, and so in as much as we need to be making more ventilators. We also need to really be ramping up on the production of all of the protective equipment in the countries that have done this well. I mean China did this very well in the second wave so in this second wave? Wave after Wuhan, very few of the healthcare workers became infected so once they dialed in on how to protect their healthcare workers They were able to do this in a much safer way, so you know if I could wave a magic wand. We'd be making more ventilators. We'd have more actual beds and spaces in the hospital. We'd have more protective equipment for the healthcare workers, and obviously we'd have more testing available so that we could more quickly identify stratified patients at risk. Speaking of that I know that a a one thousand bed naval hospital ship is being dispatched to new. York harbor, we may be seen some of these medical ships that are often used in times of war being. Deployed in specific ports all around the country. It's. It's sort of. To believe. How much has happened in one week? and and it's it speaks to the nature of non linear exponential growth, and again you know the irony of it. Is that which we're talking about today in a week or two weeks, we'll seem pedestrian in terms of what we will know. Because of how quickly things are changing including, you know the rate at which hospitals are running out of layers. We should. Mention one thing and that is a failure to comply with CDC. Guidelines I hope we're not seen as many kids in bars and not just kids, you know my neighbor in New York City who lives on the upper east side, said the bar was packed for Saint Patrick's Day, and it's so infuriating, but not only young people I read an article this morning about children of baby boomers trying to get their parents in their seventies to not travel to not go to casinos I. It seems insane to me that people are. Are Being so stupid and in some cases so selfish about this or that. What is that about? It's so interesting you say that because I have noticed two extremes and again these these are anecdotes so I can't speak to this from sort of real aggregate data, but you're absolutely right I have noticed far more concerned from my patients about their parents than their kids. I for starters, so the be I could rattle off ten stories about you know. People who are in their seventies who have decided? Yep, we're going to. We're going to the casino this weekend and we're GONNA. Do this and we're GonNa, go and do that and none of this stuff matters, and we're going out and doing things and. Again I I have no idea what it is. I could speculate and say look. People at that age have been through a lot and they've decided. Hey, if it hasn't got me now, it's not going to. There's sort of a false sense of confidence. Potentially I think. The SARS outbreak and they've been there done that. Yeah, there's a little bit of that We certainly saw a little bit of that. mccheese Mo in New York two weeks ago. which I haven't seen. I've seen it damned down a bit. which was hey look? We survived nine eleven. This thing's not gonNA. Get US Obviously that's apples and oranges, nonsensical comparison but I do share your concern with the number of people who aren't respecting these quarantines. In fact, our nanny who's in college. of her classmates was an exchange student in Italy, so he had to come back from Italy, and he tested positive upon arrival, and so he was placed in quarantine which he violated. So. He was seen out on social media three days after testing positive and being forced into a quarantine out of the party. And so you know that kind of stuff is really upsetting and I think it is a bit of communication breakdown because I don't think that these people. Would really be doing this if they understood the significance of what they're doing, I just don't think people are that selfish or that evil. If they really understand the significance, which is hey, you can feel fine. You Know You College Student Who's twenty years old? Who tested positive? Who has a little bit of a sore throat? It's not about you getting worse. It's about what you could do to somebody who could then go into it to somebody else, right? It's like you infect another kid at that party. They go home and infect their grandmother or something like that, so you know my hope is that. We're just going to educate people a lot more about why the stakes are high, and how we all kind of have a responsibility here to not just protect ourselves, but to then protect others through that protection I don't WanNa. Play the blame game, but was critical. Time lost when this wasn't taken seriously by the administration, and frankly by some in the news media how? How much damage was done by that two or three week period where it just wasn't treated as a serious threat to public health? Alluded to the the Ted talk by Bill Gates, which is now five years old, and he sort of predicted. in pretty frightening You know reality. What was potentially going to come if I were going to? You know really say if I could go back in time and change one thing in last three months. What would it be? It's the following. On January tenth twenty twenty. The genome of this novel Corona viruns was sequenced and it was made public. In other words Chinese, you got so the Chinese immediately figured out what this was immediately confirmed. It was a novel brand new never before seen corona virus and put that information out to the world. And some companies immediately ran and developed PCR. Kits and one of those companies in China has basically gone onto a million tests already and have incredible data with specificity and sensitivity. They can do a four hour turnaround. In fact, they've already built fifty laboratories in China each one capable of doing fifty thousand to one hundred thousand tests per day. What we did in my opinion was the biggest mistake which was basically ignoring that information, and then when push came to shove sort of doing a botched job, the C. D. C. Sort of put together. Its Own set of primers that ended up not working very well, and then eventually we got around to potentially doing something with a company, called Roche, and where we are right now at the time of this discussion is we still don't really have any viable means testing? Probably just a little bit over fifty thousand people have been tested in the United States which. which is you know to log orders below where we need to be so you can just use the testing that's being used in other places like South Korea, the one that was developed by the W. H. O. did the CDC simply think that test was inadequate. It seems to me that was insane. At least use them while we develop a more specific test. That is absolutely correct, so we are now in a situation called emergency use authorization where I think the CDC has finally realized that they're not going to be the ones to solve this problem and they're basically saying. You know so the secretary of HSS. Secretary of Health and human has has has basically said you know you can go and do this test on your own, so I think right now. What we're going to see is states making their own decision on what to do, and in fact, we're with one st right now to try to help them to actually just get that test from China directly, because in my opinion not does that not seem insane to you I mean. Does that not seem a massive failure of the federal government. Yeah again. I'm not the conspiracy guy so i. attribute these things more to just you know negligence than anything nefarious, and I've certainly heard people speculating that the you know there's sort of you know an anti-china bias and all of these things, but I have to be honest, I think China has been very forthcoming here and I think this demonization of China either. Either either covert or you know or sort of explicit or implicit has really hurt us. I think I think China has been very forthcoming with their data, and for some reason, our decision to not utilize exactly what they offered us. As far as testing has set us back, put us on our heels, and my hope is that in the next week the bell gets. Gets Rung Pretty Loud on that and we you know we. We take on these tests because again. It's not an economic question. The United States is very fortunate. We can afford to do the testing It's really a question of deployment and other things you know you ask questions about running out of things well. We don't even have enough swabs right now, so we're not. Not just having to buy the PC our tests gets. We actually have to make sure we have enough reagents to use them enough swabs to. Actually you know, test them on the people, and that's the stuff that really we should be stockpiling that stuff right, and and and we certainly in early. January should have been preparing for this to spread and and again i. I think Bill Gates spoke to all of those things five years ago at the tail end of the the abol outbreak when he said look, it's not a question of if but when this happens again. And yet the group responsible for a pandemic response are the pandemic response team was disbanded in two thousand eighteen. Yeah, I mean Michael Lewis is book. The fifth risk I think does a great job of explaining all the non sexy parts of government that we tend to forget about until disaster hits and it's funny I. Read that book when it came out so i. don't even remember if in the book Michael Lewis talked about this particular side of the government. But you're absolutely right, this is. Is. This is a part of government that when things are good, it's easy to forget about. It's easy to say. Hey, we can we can. We can cut costs by getting rid of them but but you know you think of this like you think of insurance, right? You don't buy insurance for your home after it burns down. You have the insurance place before there's a fire. Before we go one one last question, even though I could talk to you for hours. Peter and that is. Is there any evidence that once you get the this pathogen or this virus? You build some immunity to getting a second time, or is that just a complete unknown? I think it's an unknown right now Katie. There are two issues at hand. The I is, is this going to be like influenza? Where if you get it in a given season? You're not likely to get it again, but you'll always be susceptible to it in subsequent seasons, because it has enough genetic migration or drift year upon year upon year. Or. Is it something like you know the measles or polio? Where once you're vaccinated against it once you know it doesn't. The the virus is not moving around genetically very much, and you know either getting vaccinated against it or in this case, if you acquire the virus and recover, you're fine. We certainly think in the short term. There is immunity, and that's one of the other, really exciting. Potential therapies right now is something called convalescent serum where you actually take blood from a person who has recovered you identify the you know. The. The sort of the antigens and things that are in the blood, and you can then infuse them into people who are sick as a form of therapy at high doses, low doses to impart short-term immunity on people so given that we're seeing. reasonable. Evidence of the efficacy of convalescent serum that tells us that there must be at least some immunity that's acquired from this Peter Thank you very much for spending some time with US talking about this very scary situation. We'll Katie thank you for what you're doing. Your podcasts on this topic have been fantastic so on anything I can do to help you. Get this message out. It's an honor. That was Dr Peter Attiyah. You can follow more of his corona virus coverage on his twitter at Peter Attiyah empty and on his podcast, which is called the drive. And that does it for this episode of Next Question Reminder to all of our listeners are reported episodes on topics like maternal mortality, and the environmental impact of meat are still to come, but in the next season coming out this summer, the rest of this season as we mentioned throughout March and into April will be dedicating to the corona virus. You can also follow us on instagram and other social media outlets for day to day. Corona virus coverage my morning newsletter. Wake up, call. We'll also be dedicated to this. This topic and you can subscribe to that by going to Katie. COURIC DOT, com and a quick. If you want to share a story of kindness, you've experienced or witnessed in this extraordinary time. 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#99 - Peter Hotez, M.D., Ph.D.: Continuing the conversation on COVID-19

The Peter Attia Drive

1:06:20 hr | 10 months ago

#99 - Peter Hotez, M.D., Ph.D.: Continuing the conversation on COVID-19

"Lou everyone welcome to the Dr Podcast. I'm your host. Peter Attiyah this podcast. My website and my weekly newsletter. All focus on the goal of translating the science of longevity into something accessible for everyone goal is to provide the best content in health and wellness full stop and we've assembled a great team of analysts to make this happen if you enjoy this podcast. We created a membership program. That brings you far more in depth content. If you WANNA take your knowledge of the space to the next level at the end of this episode. I'll explain what those benefits are. Four if you WANNA learn more now head over to Peter Attiyah. Md DOT COM forward slash. Subscribe now without further delay. Here's Today's episode. Welcome back to another covert nineteen special episode of the drive. Podcast once again joined by Dr Peter Says Around Vaccine. Scientists pediatrician and an expert on the current corona virus outbreak. We released an episode with Peter on March. Fourteenth received a lot of feedback. People were very grateful for that and wanted to have him back on with other questions. It is difficult to immediately address. Questions that are posed in the aftermath of a podcast. That's five days old because five days in this outbreak an eternity so a lot of the stuff we talked about today is not actually stuff. I thought I would talk about with Peter at the time that we finished our last episode and and again that means it might not be Germane a week from now but nevertheless this was recorded march nineteenth in the late afternoon evening and as such. It's probably only as relevant as that timing given the temporal nature of things at this moment in time I think podcast become pretty obsolete pretty quickly. So hopefully you're all able to listen to this today. Twenty eighth or shortly thereafter moving forward. I will continue to release shorter and more irregular podcasts. Probably trying to get out to or three week also will continue to post videos on instagram. And eventually they'll make their way onto youtube usually the next day again. Everything at this point in time is open to subscribers non-subscribers equally and we're also in the process of putting together a specific page on our site. That's at Peter Attiyah. Md DOT COM. That will house. All of the information were posting on this SARS covy to virus. That's the responsible agent for disease known as Cova. Nineteen so again podcast now with Peter. Please enjoy it. Keep in mind. Hopefully within a COUPLA days will aggregate all this stuff all podcasts all videos plus all of the internal memos that we are sending to our patients which is going to start putting all of that stuff out there for everyone. And that'll be on our site so hopefully enjoy my discussion here today with Dr Peter. Hotels Peter. Thank you so much for making time again to speak. I know it was less than a week ago that we sat down to do this but a week in terms of this corona virus seems like a year with respect to the knowledge and insight were gaining with respect to everything else in healthcare. I really appreciate the opportunity to be on. This was our first podcast together. And maybe it was the topic but the response has been extraordinary. I've been getting emails and texts from people so many individuals at all of them really enthusiastic and supportive and saying that we did such a good job explaining some complicated science and and asking questions that people actually wanted to know the answer to but maybe never articulated before and tied so many things together and connected a lot of dots and then in a few cases. We've even gone people reaching out asking if they can help to support our vaccine development efforts and we've had a lot of really good follow up so thank you again for that opportunity. I was really also impressed with expected here only from either physicians or healthcare professionals. But I'VE HEARD. Apparently this podcast is reaching people in all walks of life and people who just really are kind of sick of things so dumbed down in the mainstream media so I think we hit it at a really good level thank you that means a lot coming from you and I agree. I've always rejected the notion. That people need dumbed down soundbites. I think that's probably just a an assumption that when really vetted is probably not true for the majority of people I think if people in medicine science can explain things clearly and patiently then. I don't think you need to have a great background in this to understand complicated topics and this is a case in point. I think that's also been asked to come back. Cnn and Fox and MSNBC is. Because I'm willing to take a little bit of time and explain complicated concepts and provided I can get more than thirty seconds or a minute or two. It seems to resonate well with people. That's what People WanNa hear. They don't WanNa hear dumbed down crap they wanna hear real things and want to understand the nuance and know that certain things are complicated and that we don't have all the answers. Yeah so Peter. I want to talk about a few things that have sort of changed in the last week obviously from confirmed cases standpoint at the time of this recording which is Thursday afternoon march nineteenth. Were a little over. Thirteen thousand cases confirmed in the United States. But I think it's safe to assume that that's a small fraction of the true number of infected patients. Do you have a sense of what range you would apply to the true number of infected people a couple of things first of all. You're seeing every day. It's a big jump. Every day is the largest number of new Cova cases that we've ever seen when I last looked it was just this morning. It was just under ten thousand night. You're telling me it's thirteen. And before then I think it was eighty five hundred seven thousand so undoubtedly allowed that as we're finally getting some testing underway and it's starting to catch up with the actual population who's infected and and where this goes. I think is going to be very interesting. I don't think we have a real sense of the percentage of the population affected. I think what's happening is not necessarily that. This even new transmission. These are probably areas that have been undergoing transmission for a few weeks ago. Just picking it up now so I think that's an important component and you know there are models that say for every person you identify. There's fifty more twenty more but I don't know how strong the assumptions are for those models. So I think we have a lot but I think what's more telling is just hearing from physicians at major hospitals from all over the country from Philadelphia Baltimore New York and elsewhere saying they are just taking care of patients and they're already feeling overwhelmed. Even this early in the epidemic and that says to me that this thing is now revving up despite what the actual numbers of tested cases say and it also tells me that one of my worst fears and nightmares that I talked about on the last podcast and I've been rattling the cage about is coming true that this thing is rapidly. Approaching overwhelming health systems and doctors nurses other health professionals are starting to get exposed in getting sick and with that is a lot of worry also a lot of heroism on the part of health professionals. But I'm very worried right now that we're not doing all. We can even close to protect one of our most cherished resources in this country which are healthcare professionals. And I think we're really seeing this rev up now in a few weeks ago. I testified in Congress and I was alarmed at the fact that we weren't paying attention to our nursing facilities and assisted care living facilities and the fact that we've had twenty five destined that nursing home in Washington. State in Kirkland. That's when I use deliberately provocative language in Congress and said this is the angel of death and I knew it was going to get on make a lot of headlines in the did but it got people's attention this week felt. I had to do it again. I went on CNN. Newsday with thousand CAMMARATA and I had to do it again because I'm so frustrated that were exposing. Some of our nation's greatest treasures are healthcare professionals to this virus without making them feel safe or protected in any way and I said look if a significant number of healthcare professionals start either self quarantining or actually getting sick or if you have the situation where colleagues are going to start taking care of colleagues who are very sick or in intensive care units the term. I use it. It'll be lights out by lights out. I mean this whole thing is over things will unravel in this nation very fast and I knew I was again being very provocative but sometimes you have to do it to get people's attention and now I think it's starting to register. The question is can we mount an efficient response to figure this out? Peter you alluded to this idea of. Do we have a sense of how many people are infected as a function of how many people are confirmed so the actual confirmed case multiplier. We've been building one of these models ourselves. We've looked at other people that have built them. I've seen people estimate that look can't be less than forty five to fifty our internal estimate which I think is very conservative is probably closer to twenty five and what it's basically doing is trying to figure out what is the assumed number of days from an infection until a fatality and then what is the assumed infectious fatality rate. And obviously it becomes very sensitive to both of those but if we posit for a moment that it's on the most conservative side of those estimates in the neighborhood of ten to twenty. Do you consider that a positive or negative sign in other words if right now there are quote unquote only one hundred twenty five thousand people infected in the United States. Are we in good shape? We may or may not be because remember those one hundred twenty. Five thousand are not evenly spread across the country. Let's say it's two hundred thousand just for argument's sake. What that really means is there may be thirty or forty thousand cases in New York area and things are getting scary very quickly and there may be another similar number in Washington or California or the couple of places where there's no transmission and basically just a handful of cases maybe in Texas or places like that so the question then is if you're modeling how you're going to do this what you really want to look at it as a map of the US and you're going to see a bunch of let's say use red is your color to mark the number of cases you're going to see a red blob. Smallish Red Blob New York and Seattle. Maybe one or two other places and those blobs that are going to start to grow. And then you're going to see other small red dots appear in the country and they're going to start to grow and then it's going to be the question of whether those blobs begin to coalesce Across the country. So that's how it's GonNa work. It's not the absolute number of cases in the US. You know it's interesting because the United States is so large you wanna look at those nodes of their significant levels of infection and see how they grow and intensify and color and what. I'm hearing from Governor Cuomo. He's really sounded the and a very effective way. And that's what we're going to be in for for the next few weeks or months is a New York like situation starting to pop up other parts of the country. Yeah that makes a Lotta Sense. Let's go from that then onto some testing because testing is now going to figure into this. Of course I can't get a straight answer from anybody so I'm curious as to whether you have an insight as to why the CDC and FDA elected to go with Roche for the testing kit when they were very late to this as opposed to using one of the companies in China that had already done literally millions of tests men had pretty robust data on sensitivity specificity etc. I don't know have. They made any of their decisions around testing. It's clear they should have gone to commercial kits from the very beginning. I'm getting asked a lot of questions about what's gone wrong in the testing. What's gone wrong in the hospital? Response Assertive deflected questions a bit because right now if we have to really focus on the matter at hand. I think what's going to happen is when we get through all this whether it's in a year from now or eighteen months from now or or sooner there's going to have to be some type of independent committee to really look into the missteps and it's not for the purposes of being punitive. It's for the purposes of trying to figure out how to fix this when a new pandemic emerges next time so we don't make so many of the same mistakes and at I think we'll see a number of flaws that went on with some of the agencies. I think we'll see some of the flaws that went on on communication between the federal and local governments and state governments. And that may require us to enact new legislation to fix it. But it's just been so exasperatingly see how this has been ruled out. We didn't have a lot of time of notice but we did have time when it's not like we didn't have any idea was coming. We had at least a month arguably two months to know what was going to hit the United States and we also saw pretty quickly that this was not gonna stay confined to central China or even China. It moved pretty quickly to Asian countries and even when starting off in Italy. We were still pretty slow on the uptake. So the fact that we did not have a faster trigger is going to be really interesting and it's impossible to know right now where the fault lies. I have some suspicions which could share in private with you. But I don't think it's going to help us right now to to start pointing fingers but now it's a matter of figuring out how we rapidly fix this because now unfortunately now that we're starting now to fix the first phase the testing that we still have a ways to go were already moved into the second phase where hell systems are already being stressed. And I'm worried it's going to be close to collapse in a couple of weeks and less. We can figure this out New York as already reeling. Your singing the anxiety on people's faces in the New York hospital system and I'm very concerned. Now what do you think is going to be the rate limiting step in healthcare delivery in an area like New York or other areas? That are going to be sort of epicenters for this. Do you think it will be the healthcare providers? Do you think it will be ventilators? Do you think it will be? Pp for the healthcare providers. Where do you actually think the breakdown occurs? Well I see the first breakdown starting to happen with doctors and nurses already exhausted already demoralized. Some extent and people feeling that no one is really looking after them and they're kind of on their own so we've already had that initial breakdown of trust. Can you say more about that? Peter I WANNA make sure I understand what is that resulting from. Is that due to a belief that the the system isn't providing them with the necessary equipment to protect themselves or the necessary resources to take care of patients whereas that disdain or lack of trust coming from well. I think it's coming from seeing colleagues. Get Sick and inconsistency in what the plan is a lot of hospitals have been prepared for this adequately not seeing also this disconnect from what they're seeing coming out of the state government or federal governments when they're very worried about for themselves and their families. They're seeing colleagues start to get sick. They're hearing stories of some colleagues being seriously ill and either. It's the White House still two or three weeks behind. Still having the testing discussion or state governors. Not really saying we hear you. We know you're concerned. Here's what our plan is is chilling. Actually I think the as I say the only one now because it's New York higher profile and all the media outlets are in New York. The only governor. I'm hearing from on a regular basis. Cuomo and he clearly gets it and has sounded the alarm. But I'm concerned. And I'm also hearing about from parents of of residents our residents themselves and then on top of that now the latest story that's come out of both mmwr. Morbidity Mortality Weekly reports from the CDC as well as Italy is that this is no longer a disease of the old and infirm. It's significant numbers of young adults. People who are residents fellows young attending aged actually now with severe illness and going into ice us in this country and that buzz is already catching on among young physicians. And that's highly destabilizing. And I think that's probably our biggest link right now. Eventually it will be the lack of respirators and lack of p. p. e. but I think right now. It's the fact that you're seeing young physicians and nurses people in the best years of their life. Now getting sick and the feeling that they're feeling abandoned and I'm getting that sense from either direct emails from nurses and physicians thanking Me for speaking out and echoing their concerns in many cases it's parents of resident physicians and young and nurses as well that we're starting to see that being a regular occurrence right now. So what is the solution to that Peter? Because we can't obviously on a moment's notice ramp up. The number of doctors nurses respiratory therapists hospital staff. I mean everybody in the hospital right. It's the people that we don't even necessarily immediately think about the people who clean the ventilator the people who clean the hospitals I mean all of these people are not going to be trained overnight. So how do we solve this problem when going back to your earlier point if you look at average numbers across the United States? It's very easy to be misled. This is really going to be probably about local waves of this. So is the solution that we are mobilizing physicians from geographies that are under utilized into higher utilization areas. How do we actually about solving this problem? Well the problem is the areas that are likely covet. Nineteen are also probably underserved already by physicians. I know we're all sort of thinking out loud and I thought about that too but realistically what do you do take a physician serving the entire county an entire county in western Nebraska and take them to New York to help out? That's probably not realistic either. Maybe not as raisin example but again. I don't know what it's like in the Houston area right now or in Dallas or other major metropolitan areas that are not new. York could one repurpose medical staff from those areas to deal with the first wave in the places that are very likely to be overwhelmed quickly. Yeah on the other hand it could be but then if you actually talk to physicians in areas where there's not cove in nineteen. It's not like they're dot already stressed out an already overburdened. With their daily activities in the electronic health records and everything else so the whole system to begin with is been pretty fragile with very high rates of what some people call physician burn out which term. I don't like it all but it's not really burnout. It's making these horrible unreasonable demands. On physicians and healthcare providers to benefit the insurance companies. Save already got stressed out young physicians. Who are heavily under siege. Now you're gonNA bring them into a job in nineteen area. I'm not sure so the bottom line is I don't have. I don't have any obvious solution to figuring this out. One possibility that I thought about and have introduced to anybody yet is could we dramatically expand the US public health service especially with all these individuals who are at home now and in some cases not receiving a paycheck? Would there be any advantage offer to have this. Use a commission core of the Public Health Service or even the military to bring in a whole. Cadre I'm not highly trained individuals but individuals that you could train like medics to help out just to provide an increase in the number of people who can help manage ventilators and and that sort of thing so that's one potential possibility and then the question is for not quite there yet. It's going to be very hard to persuade. Congress to take that kind of action. So Peter What is the latest thinking you have on things that people who are presumably not infected so either a symptomatic or confirm to be not infected? Which is a very small number in the latter category because of the Earth testing the things can do to sort of reduce the probability of getting infected. So the obvious one that we've discussed of course social distancing but let's say someone has already sort of adopted that posture and now they're sort of asking the second order question which is basically working from home. My kids are no longer in school. What am I supposed to do with my Amazon package when it arrives? What's the probability that viruses being transmitted across that? How much insight do we have into the real transmissibility of this? I don't think we have a lot of data you saw this week. This paper in the New England Journal of Medicine that measured length of time on the virus on inert surfaces and actually did an interview propublica asking me about the. Us Mail is that contaminated with viruses. And what should we do? And maybe we know that the virus can live for a certain number of hours cardboard. That's been looked at but then the question is how relevant is that really? What's the real risk? I think for me. The priority is protecting people who are coming into contact with sick individuals and I come back to the healthcare providers in the first responders and you saw the CDC is now managed it so they came out with new guidelines this week. Which kind of loosened the criteria for exposure and what exposure means and basically saying you could stay in the workforce and keep doing what you're doing depending on the intensity of the exposure and I think it's sort of a desperation move but it may be something that we need to do. In order to keep people in the workforce I come back to will be introduced. Last time we spoke. Which is the antibody therapy but not using it as a treatment but using his prophylaxis. I think that could potentially help a lot. So the idea is when you harvest. Antibodies from individuals. Who got sick and recovered have antibodies? Ua for Easter blood you recover. The plasma component may be isolate the antibodies. If you give a big dose that you could potentially treat someone who sick but a small dose of it like a five M L. Does you could use that as a form of prophylaxis and the antibody would last a couple of weeks so that a single injection can potentially greatly reduced the likelihood you're going to become infected as a healthcare provider or a first responder for a period of two weeks and then you subsequently get another dose as we discuss ancient method but now refined using better technology so the White House actually came out today in their press conference in actually talked about this. I wrote it on national. Tv ON CNN and Fox a week ago and now it's out there saying that the federal government's going to do what's interesting is in the meantime over the last couple of weeks. A number of academic health centers have started to put together a network of blood banks to actually start this. And what I've heard is that none of them have actually been contacted by the federal government yet so I think we got to resolve that. Why there's that disconnect that this informal network that's already started is not better linked with the White House announcement today in the comments of the new. Fda Commissioner Steve. Haun what did you make of the recent study looking at blood type? Abo and susceptibility. Yeah I thought it was interesting. I I'm not sure what it means that I'm not sure how necessarily relevant to developing the plasma therapy so I think it's an interesting finding but I'm not sure how it applies just yet. Yeah I mean I think just folks listening so they understand. It was looking at data from China and basically observing that people with a type blood had an increased risk of infection. People with Oh type had a reduced risk. I think the hazard ratio on the downside was more impressive on the upside. In other words it was more about having. Oh blood and therefore anti antibodies that seemed to be somewhat protective so again. Does that really matter as you said? Maybe maybe not. It certainly isn't immunity. That's the point in the way that potentially convalescent serum could be since we spoke. There's been a few interesting observations now and people are scrambling to understand it better. I think one of courses in parallel studies out of Italy and the younger age group getting infected in seriously ill and the question is why. Didn't we see that in China? I think that is interesting. This very high number of seriously. Ill hospitalized people between the ages of twenty and forty. I think it's now in the. Us accounting for a third of the hospitalized. Is it that high? I saw a repeat today. That was about twenty five percent and I was going to ask you the question. You're posing. Which is what on Earth can account for this difference in the United States. It's the most disturbing thing I think I've today. Yeah so I think. The number that I saw was around a third first of all half of those hospitalized are under the age of fifty four which is very different. From what you saw in China and those and about a third between twenty and forty four is the number twenty nine thirty percent is the number that is on there is even a blip of people under nineteen. So that's a big question and I think the numbers are going to turn out to be somewhat similar in Italy. Now it's been pointed out that those individuals are not dying but I said this morning that well even if they're not dying if there could imagine if they're being in issues in intimated that is still a horrible ordeal for a young person to go through and if we have that happening over and over again. That's a huge tax on the system. I don't know I mean the question of whether smoking is responsible or even vaping has been raised. We'll have to do the epidemiology of that. And what the mechanism is we know. Smoking can up regulate the two receptor for the virus. I don't know that anybody's lifted vaping but trying to understand what it is about young people. That's different in Europe in the US Arabia's just host genetic some genetic factor but well. There's something different and I'll read to you something. It's a photo that was taken and sent to one of my colleagues from someone. He knows in London today so the piece of paper is just the ages of the people they admitted to the ICU. Today this is a hospital in London. I'll read them off to you. Forty six twenty to sixty eight sixty one fifty one seventy one thirty to twenty nine twenty eight thirty seven thirty four thirty two. He then also showed me a picture of the thirty. Four year olds chest x ray and it is effectively a complete whiteout so again. We'll these patients survive. Hopefully most of them will but as you said. They're not out of the woods. Because the long term the tail of this on morbidity is significant. I found a steady yesterday. That looked at ten year. Follow up on the SARS covy. One patients the survivors and the amount of cardiac disease and pulmonary disease in those patients was not trivial. Suggesting there was some lingering effect of that virus. Yeah and the other interesting finding when you look at the papers on Med archive from the Chinese experience. There's a lot of what they're calling acute heart injury and it's not really clear what's going on there whether that's a viral myocarditis or whether it potentially whether they're just having myocardial infarction because of the AIDS shock but you're single out of heart injury. And I suspect that's probably accounting for a high percentage of the deaths as well so the first thing people want to say as this virus mutating and I'm always suspicious when people are quick to claim its mutation. I'm guessing not but we'll have to unravel that but we need really good epidemiology now on those younger patients to try to understand what the differences are. Your Peter I've been asked this question. A bunch and my usual answer is probably in the short term but not sure in the long term in the question is once a person is infected and recovers. Do they have lasting immunity? Obviously the convalescent serum experiments would suggest at least in the short term. There's immunity do we think we have an insight into that in other words is just to speculate. Is this something in your mind based on other corona viruses that looks like a seasonal virus like influenza or more of a type of Iris. Where once you have immunity largely life lasting. I think there's a paper on Medicare cover bio archive out this week. On non human primates showing that once you're infected their immune to re infection whether that's applicability humans is hard to know but I'm going to work on. The premise that that exposure infection will probably confer immunity but the flow of course is a different story because of all the energetic drift and variation but then the other questions that have come up. This week are around these projections from the federal government in their report that they just released saying that they think this pandemic will last eighteen months. And I'm trying to understand what those assumptions are. I think they might be out of models from Imperial College which look at the fact that this virus may go down in the summer but come back in the fall and then potentially be seasonal after that until eventually enough people are infected and therefore rendered immune from the virus. And I'm guessing that's how the eighteen month estimate is coming from the other thing I'm hearing. I hope it's not. The case is that I've been told that the eighteen months is because they're anticipating after that we're going to have the vaccine ready to go and and I've really been downplaying expectations of having a vaccine in eighteen months or at least a rapidly deployable vaccine in eighteen months. I think we have to be more realistic about that. In terms of going through all of the adequate safety were just now only have the first vaccine clinical trials with technology. That's never been shown to turn into a licensed vaccine so I think we're going to be looking at five or six. We want to be fully underway for a while so even though I think we're hearing numbers like a year eighteen months for my estimate. I think it's probably more likely much longer than that. So I hope that the models of ending this pandemic are not depending on having the availability of a vaccine. I think we have to precede is though. We're not GONNA have one in the near future now. Having said that I'm more optimistic about having a lot of new technologies. Come out like the convalescent antibody. But we're hearing some interesting things about new drugs especially some of the repurpose drugs because the new chemical entities will also take awhile but not nearly as long as accede speaking of re purposed drugs. Yesterday the New England Journal of Medicine published a paper looking at collateral it was at the top level viewed as a negative study but I think many people ourselves included have looked at that and said I think the only thing we learned from that is giving collector to people who are on death. Store is probably not helpful. How did you interpret that paper? Could be you know. People often think that antiviral drugs are like antibacterial drugs and they seldom have that same dramatic effect. I mean clearly the HIV story is amazing and the and the limousine movie dean story for Hepatitis. C. is amazing but more typically. It's you don't see that dramatic impact of antiviral drugs. So you very well might be right. I wouldn't throw it out just yet. There's been a lot of discussion about hydroxy chloroquine. And there's some interesting. In Vitro data on showing hydroxy chloroquine inhibits replication of the virus. Also it has some anti inflammatory effects. Then did the a role from Marseille. Who's I've known him for years? He's amazing infectious disease. Microbiologist mainly focused on recaps he'll like pathogens published a small study showing maybe there's some effect of hydroxy chloride when I think people are over. Maybe hyping it a little much saying we have a cure. We clearly have to do much larger studies but if Hydroxy Clark could ever work out or have an impact. I mean it would be perfect to be. It's cheap you can make a bucket of it. It's orally bioavailable the nice thing is you could use it not only for the US Europe. But it'd be relatively straightforward to use and low income countries. Especially if this viruses now in Africa we don't even know about it or parts of Asia so that if I had a wishlist and it would be X. Nayan wishing for my vaccine it would be I think around something like chloroquine. We've also been reading about some of the ace two inhibitors and the energy-intensive receptor blockers and we're getting sort of a mixed picture about that. Depending on what paper you're reading so and especially around the AARP's the arbs is. They sometimes call them claiming that some of the common anti hypertensive that we use where they're saying well on the one hand. It has the ability to interfere with the ligon detachment of the virus to the ace to and therefore that blocking effect should have an antiviral property. Other saying no no no. It's actually going to up regulate the receptor and make things worse and I got a interesting email and I wanted to talk about Professor Nova Southeastern University. Robert Speth is in. The School of Pharmacy is been looking at this and he actually thinks that it could work for a totally different reason that it actually doesn't air this lot of the Arabs. Don't bite actually to ace to but other components of the NGO tencent pathway and they have anti inflammatory effect. So so I think we're on a steep learning curve about these classes of drugs in terms of of their effect but we certainly should be evaluating them especially now that we're starting to get mouse adapted virus and maybe transgenic mice with the receptor. I think it's going to be a high priority to look at some of these drugs. Have you looked at all at chemistry? It's a pretty esoteric. Deroga- Syrian protease inhibitor. I think it's only used in Japan. To treat pancreatitis but some of the preliminary work looks really interesting it's Trans Membrane protein in it appears to interfere with the ability of gain and treat. Actually I think it sits right next to the ace two receptor and impairs binding. Because there's a protease that's involved in Sarah's covy too and it's a it's a subtle aisin like proteinase which means it's a Syrian proteinase and known as a fury nephew R I N. I'm wondering if that molecule works by interfering with the fear and so that'll be interesting story and that's potentially a good drug target so there was a paper that came out dot too long ago about the fear in from this and it's relatively unique among the Beta corona viruses. That this virus has it and I can't remember if SARS Juan has as well or not the Hamas between SARS the covy one and Covy to is similar but not enough that I mean there's enough commonality to them in the spike protein. Isn't there that if you had a effective target for one you you might have luck against others which I guess is really less Germane to the question today and more about the ongoing probability that these viruses aren't really going away are they. Yeah and we're starting to think about what is the kind of vaccine that we wanted to develop. We have this SARS one vaccine that looks great against SARS one and we think it could be re purposed against SARS too and then the question is what should be the goal should we be focusing only on SARS to or should we really start thinking about a universal SARS vaccine and I think before SARS to came along we saw how all these other Beta Corona viruses where emerging bats and we wrote a grant to the NIH Shen. I don't know if that one even got scored a was but I think that's going to be an important approach. I mean we have to learn our lesson now. This is our third corona virus pandemic in the twenty first century. So we have to reconcile the fact that these are gonNA come out on a regular basis. Although technically really SARS emerged probably weren't really constituted as pandemics. Where they I mean they were probably closer to epidemics and this being a true pandemic potentially us. I don't remember how they are classify SARS one of course emerged out of southern China and severely affected Canada. So maybe it wasn't classified. As a pandemic and and the mayor's corona virus emerge out of the Arabian peninsula and then affected. Korea were decimated hospitals in Korea. Which brings us to the other point as this is the modus operandi of corona viruses. They tear through hospitals causing a lot of death and destruction the hospital personnel. This is what they do. This was true of SARS WANNA trove mayors. And now it's looking like it's true of this one as well that knows a coal meal. Transmission is a huge factor in this group of viruses. And you know if I were going to design a vaccine which we're doing in terms of the target product profile I would say a highest priority our healthcare provider. So I think again to revisit this and we started the discussion on this but the revisited unless we can deal with the healthcare provider issue in making hospitals safe places. We're going to be in very deep trouble. So I think that has to be a national priority and maybe the White House needs to create a specific task force around this is what are we doing to protect our frontline health? Care providers is at the antibody therapy. Should we be looking at Angie? Attention receptor blockers. Should we be looking at other chloroquine for prophylactic purposes? If we can't fix this problem really quickly. I said on CNN. It's lights out. But you know what I mean. I think there's just no way we'll be able to manage this epidemic. Speaking of designing we touched on very briefly. I think the first time we spoke or maybe it was just on a time when we spoke and it was not part of the podcast but I've had discussions with some of the most intelligent people I know and they've asked not in a sort of conspiracy theory way but they've asked. Isn't it possible that this was a virus that was designed for biowarfare? That was either inadvertently. Got Out of the lab or something. I have my own logic for Y. I find that theory very very implausible. What's your response to the implausibility or plausibility of that thesis? Well when the epidemic was unfolding in China and I started hearing these conspiracy theories it was easy. To debunk it. Who's going to design a bio weapon? That's GonNa Kill Grandma and GRANDPA. I mean that's not a effective biowarfare strategy but now that we're seeing now. I don't have that Pat Answer. Not that it's an appropriate answer anyway. But now that we're seeing. A number of young people affected. The plausibility goes up. But not by much and I just like to say you don't have to. Why go in that direction when we already know mother? Nature is one of the best. Buy Weapons producer. There is and and we know that these viruses have been. It's not like we didn't know where these viruses were before. We've seen a whole family of these viruses that we actually call them s-l viruses sars-like viruses in bats and even before SARS to we were investigating are vaccine to see if across protected against the various sars-like viruses that were emerging Outta bats. And and it did. Sometimes it didn't others and so we knew that there is this whole family of Bat Corona viruses that are emerging on a regular basis. So if you don't have to postulate a bio weapon. Why do it when it's so obvious that we've got all of these viruses that enzootic viruses that are circulating? Yeah I mean my response was probably a little more theoretical but it was the bio engineers of the past. Two decades can barely get a crop to grow any better using GMO or insert gene vectors through genetic engineering into adenoviruses. I mean it's not like genetic engineering and GMO. Crops have been a robust success. And if that's the best and the brightest for twenty years I don't know where they found the people that could make such a good virus. I mean let's you know I sort of being diabolical as think from an if you were designing a bio weapon most bioweapons people would design SARS one right a highly lethal virus but we actually saw that even though as a devastating disease in people who got it if you are infected. You're sick pretty quickly and you were going into the hospital and you weren't walking around the community infecting others. So that's why I think. Sars one snuffed out pretty quickly. This one is really problematic. Because it's not as lethal ours one but it's number one number two is more transmissible and number three. There is a large group of a symptomatic individuals. And that's that's what creates a toxic mix for this virus because it quickly spread throughout the community and infects. It kills a small number of people but still five to twenty times more than influenza. So it is that very toxic combination of not being the most lethal not being the most transmissible but high enough in both categories and all those ancient dramatic individuals so in some ways. It's hard to imagine one that's more diabolical but I can't imagine anybody being that clever to think about designing it in that way Peter. You mentioned something on twitter today. That just assume that when your mail is delivered to your house basically assume it's been delivered by someone who's carrying the infection whether they realize it or not. What does that mean practically? What can we tell people who are again getting Amazon packages getting their mail. Trying to limit their exposure. What actually can be done to dramatically reduce the risk of transmission through these foams based on the study you just quoted from the New England Journal Medicine. That came out. I think last Friday or this week and other things we've learned just through the field of viral Aji. Well we don't have a lot of the data. My Gut tells me that the risk is still pretty low. I mean the things that I worry about. I just don't worry about getting the mail so I right now. I'm not doing anything I think. If you're concerned you can certainly take a clorox first of all who gets mail anymore. I guess we get Amazon packages. So if you get your Amazon package wipe it down with the clorox. Wipe or one of the approved alcohol wipes you can certainly do that. I don't see any any harm in doing that my senses. What's your real risk? Your real risk is close personal contact with somebody with this virus. I think that's probably the most likely motive transmission. What about food? A lot of people. These days are in the process of ordering food now whether that be live in a city like New York. You're doing take out. What do we know about the temperature that is required to be confident? You've killed the virus and then what about when you're talking about groceries things that are very difficult to wash like lettuce or strawberries is just a time to say. Don't eat these things or do we think that pay you leave it out of the fridge for a couple of days. It's probably fine although not that you'd want to eat your lettuce if it's been sitting out of the fridge for a couple of days right now. I personally have not really been doing much with PROTAS. That's different from what we usually do. Maybe wash it more with water as the CDC put out any guidance about that. I haven't even. I have not seen it. Yeah the only thing I've seen is from the. Who Looking at SARS covy one? They published some data on temperature and again that basically suggested that fifty six degrees Celsius for fifteen minutes was about required to kill that virus. And so you could extrapolate from that. Hey if you get your takeout and you at least heated up or if you're cooking food that you can't speak to how it's been handled. It hasn't been you know otherwise sitting in your freezer for a month. You WanNa make sure. This is north of one. Forty one fifty degrees Fahrenheit for me. I just think it's the produce that strike me as a little bit more concerning just because the virus is gonNA survive a little bit longer in the cold based on the. Who report I saw and again? Maybe this is marginal. Maybe this doesn't matter compared to what you said a moment ago maybe just not being in close proximity to other people where people who are not inside. Your bubble is first second third order reduction strategy and also because the point. I mean we're already living under such austerity measures as it is with the social isolation gets to the point where we're going to have such a huge percentage of the population having our mental health affected by this. I think there starts to be diminishing returns by doing this so unless we get some clear guidance from the CDC or FDA saying this is what we found and were particularly concerned about that. At this point. I'm not doing this which gets to the whole mental health aspect Just the thought of people being in their houses day in and day out and it's been great for my TV ratings. But quite honestly I would not want to be watching Peter Hotels Day. In and day out is such dreary news that I have to believe. We're going to start seeing some significant psychological impacts and. I'm worried about suicide rates. I'm worried about and I hope we're looking out for that. Because especially if this drags on so I think it's really important for the government to be a little more clear when they said it could be an eighteen month pandemic to specify. This doesn't mean that you live like you're living right now for eighteen months. Just don't think that's doable for a large population. So there's going to have to be some kind of assessment. They're almost as worried about the mental health. Status of millions of Americans are people all over the world is I am the actual virus and I'm starting to hear from colleagues and family members that it's already creating a lot of hardship and also people are certain categories for instance. You know I have a special needs adult daughter. And now she's her routine is totally halted now in this is putting a huge amount of stress on her and then our family as well so I would imagine people with special needs. Family members in the House are really struggling right now. And I don't think or to consider what the actual infection even think about this and should we as a nation start thinking about some kind of low cost mental health activity and I don't know what that would be whether we create a network of providers a mental health counselors who make themselves available mental health counselors without Borders. Something where people can maybe either for free or maybe just some really low cost where they could skype with somebody and have that discussion. I think that potentially could be a national priority as well or have the academic health centers take this on. I can't agree with you more Peter. I've been commenting to my wife for the past few days that the days seem to be going by very quickly in isolation but the overall time seems to be going very slowly and the irritability within me is unbelievable. I mean I'm not the most sanguine guy to begin with but I think the lack of control which is probably what every person on some level feels right now I guess. Different people internalize in different ways. But certainly it just comes out is incredible irritability which may pose a greater long-term risk to my health than any corona virus could well. It's interesting my reputation as being someone who never gets angry never gets visibly upset are seldom does and within the last month in a lab meeting or I wasn't happy with the way things were going. I got pretty upset and sort of an important meeting with colleagues. I also got very upset. Reacted emotional way that afterwards. I'd kind of sorta scared by so wow. I can't believe I did that and sent an apology and I said what's going on here. In my case it's I'm not sleeping and that's and that's because the anxiety I'm not sleeping because we're trying to get this vaccine started through into clinical trials and all the teleconferences in documents that we have to put together and then all the media stuff because I'm doing a lot of early morning and oftentimes late night now when that happens you're only getting three or four hours sleep. You're doing that several days in a row and but I think being given the opportunity by Fox News and and MSNBC to talk to the country and explain things about this virus in a way that we're not necessarily hearing from our leaders. I think that's an important opportunity so I'm doing it. But that is self is stressful. Also threading the needle because all three of the Cable News. Networks are fairly politically charged. And you're being asked provocative questions all the time about this. That and trying to thread that needle to say things in a way that goes beyond the politics really addresses the virus. I think it is taking its toll assertive lucky because at least I have to really big activities that I'm doing that. Keep me occupied with my wife. And she's at home and with Rachel or a special needs adult daughter and I think in all she's got on all day is the cable news which is so dreary and I just imagine that happening millions of times over this is not going to be good for our country and ends a one of the things. I've started to doubt sets a small thing but I've been trying to in my mess gene talking about the science and a few times. I've been doing this. I think I'm going to be more of it is is to be upbeat about certain things not to drift into the the happy talk. That's not backed by data but just talk about the fact that the United States has got this great history in times of adversity of taking big audacious goals and and building out new technologies for this viruses. One of them. And that's where America shines those big audacious goals and taking on complicated projects and coming out ahead at the end. I think those kinds of things. I think we need to hear more about any get I. It's not some people so you're GonNa do you're GonNa do the happy toxic and no. That's very different. I think it's it's a realistic goal. And to say that we don't have to be passive about this simply just hunkering down in our apartments or houses there. We still can do great things. And there's probably a better messages after than staff and I think it's going to be important to hear more of that but again the psychological devastation on the United States. I think is going to be almost as big as the damage from the infection on that Peter I wanted to is almost like you read my mind. I did want to end with something sort of positive. What are you most optimistic amount of moves? Spent a Lotta time talking about things that concern us with respect to the burden on the healthcare system the properties of the virus that make it especially troublesome if you're trying to fight it but if you think about where we are today versus where we are a week ago. Even what are you optimistic about? What moving in the right direction? What trend do you see that you want to see continue? There's a few things going from not very impressive. Sounding more impressive things I think just from not selfish. I but I think we're seeing scientists being put in higher esteem. We were trending the wrong way for a long time because of this anti vaccine movement but when you hear the esteem that people like Anthony. Fauci have in the country because he is a scientist. I think that's kind of reassuring. Them Times of stress. People are looking to scientists for guidance. Not only to solve problems but also for leadership roles. I think that could be a positive outcome of this. And people writing letters to our team of vaccine scientists trying to develop the vaccine. We just had this thing. I was very moved. Their vaccine scientists are still working through this because they have to because they have to make this corona virus vaccine we just had a massive donation of girl scout cookies for the scientists really showing that the community is out there behind us. So that for me was really positive. Also science communication was already starting to trend in the right direction. But I think it's really taken off data sharing that's going on putting things up on Bio Archive. Unmet ARCHIVE IS PRE print. Servers is now become a routine form of science communication. It was already starting to take off but now it's done regularly in the fact that even the established journals like Jama Journal of Medicine. Lancet are putting their stuff out there quickly in the public domain. If we keep doing this it's GonNa change the way we do science publishing. I often say our model of how he published. Science was invented in the eighteen fifties by the German scientific institutions and it worked for a while but believe it or not communicating science. According to the rules of eighteen fifty Germany is probably no longer adequate. And and I think we started to see this SARS one and mayors and then he bola and I think it's GonNa reach its full fruition through this epidemic so the fact that scientists are being held in higher esteem recognizes -portant people. The way scientific communication is done I think and the same is true of our physicians and Nurses. I think the fact the heroism we're seeing of physicians and nurses and you saw the stories from Italy of the whole nation standing out on the balcony sharing for physicians and the nurses and healthcare professionals. I think there's maybe going to be a new awakening of the humanity behind the medical profession that I think we're starting to hear an works. Both ways not only just people standing up cheering but more and more doctors and nurses telling their story of sacrifice and knowing that when they go into work saying goodbye to their kids or their significant others knowing that they may have to be any kind of quarantine after that not knowing. If they're going home are GONNA get sick. I think people seeing the sacrifice that physicians and healthcare professionals nurses make stuff that we do. Everyday that gets unnoticed is now being noticed. So I think that's also going to be a potentially very positive outcome of all this. I mean the worry of course is out of sight out of mind. We might have said some of that. After SARS one and mayors I said the whole vaccine infrastructure will change. We'll be able to change the whole vaccine ecosystem on the basis those epidemics and really not all that much happened. If things happened but not much I was sick. Maybe this will be the one that will happen in terms of more immediate successes that you might see. What can we look for for things that are going to work? The one thing that I saw was last Sunday morning when Andrew Cuomo Governor. Cuomo wrote that what I thought was a very courageous op. Ed Piece in The New York Times saying what was on my mind for a while but I didn't want to say and he just said it. We're GONNA need to bring in the Army Corps of Engineers and I think that was an important piece to this recognizing that we may need to bring in our military and maybe sooner rather than later so we're already hearing about National Guard units being called up. I think we're going to need our military to build temporary hospitals and facilities. Maybe some of the human capital. We're going to need for. This is going to become an important piece to this as well or Peter on that note. We've gone a little over the time I know. We both set aside for this. And we've got a lot to get done even though we're sorta late in the day but I want to thank you again for for the time and obviously for the hat you're wearing which is sort of being one of the important faces of this in the public. I do think it's important that people have sort of credible information and you're speaking to people not just to the public. But also to policymakers for what it's worth. I'm a little bit more optimistic this week than I was last week in terms of the seriousness. With which this is being taken especially inside government based on a number of personal discussions and some secondhand discussions so I guess that's the thing I'm personally most optimistic about I mean. There are some people on the federal side. Who definitely been doing this? And then people like Deborah burks have been good and Tony of course is always great Brett. Terrar- is not a household name but he's assistant secretary of Health and was with us for a while here in Texas and he's been the one. The scientist finally ramp up the testing. And he's been doing that. I think we're doing a great job to me. I think the profile Governor Cuomo's had is the one that really woke us up and who got on has been getting on there every day. Saying what the Hell's going on where my respirators? Where my bed's these are the projections? These are what we're going to need. This is what's going to happen to our hospitals and being overrun. So I give a lot of courage. Points to the governor of New York on that front will thank you very much. I WanNa let you get back to work and I know we'll be in touch again soon. We'll pick it up then. I think what impresses me about our discussion. Today is how different it was compared to a week ago and shows you how quickly this thing is moving and so always happy to do this again. Some point we'll see how this thing continues to change. Because I said it last week I'll say it again this week. The stuff were saying today may look totally ridiculous in a few days or a week because this thing is moving so fast. These virus pandemics emerging threats. Set you up to make you look bad and they do that with our federal leaders or state leaders and even doctors and scientists are gone. Tv So do continue to need to refresh. Yeah I hope they make us look bad by saying we over. Responded than we under responded. I'll say amen to that all right. Good Night Peter. Thanks again all the best. Thank you for listening to this week's episode of the drive if you're interested in diving deeper into any topics we discuss. We've created a membership program that allows us to bring you more. Indepth exclusive content without relying on paid ads. It's our goal to ensure members. Get back much. More than the price this attrition at that end membership benefits include a bunch of things. One totally kick ass comprehensive podcast show notes the detail every topic paper person thing. We discussed each episode. The word on the street is nobody's shown. I was rival. These monthly ama episodes or asked me anything episodes hearings episodes completely to our private podcast. That allows you hear everything without having to listen to feels like this. The qualities jurist super short. 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#114 - Eileen White, Ph.D.: Autophagy, fasting, and promising new cancer therapies

The Peter Attia Drive

1:58:54 hr | 7 months ago

#114 - Eileen White, Ph.D.: Autophagy, fasting, and promising new cancer therapies

"Blew everyone welcome to drive podcast. I'm your host Peter Attiyah this podcast, my website and my weekly newsletter, all focus on the goal of translating the science of longevity into something accessible for everyone goal is to provide the best content in health and wellness. Full Stop and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we created a membership program that brings you far more in depth content. If you WANNA take your knowledge of the space to the next level at the end of this episode, I'll explain what those benefits are four. If you WANNA, learn more now head over to Peter. Attiyah dot com forward slash subscribe. Now without further delay here's Today's episode. I guess this week is Professor Eileen White Eileen is the deputy director and chief scientific officer along with associated for basic research and the CO leader of the Cancer Metabolism and growth. Research Program at Rutgers University Cancer. Institute in New Jersey. She received her bachelor's degree from Rpi in her PhD from Suny in Stony Brook and at her post doc with Bruce Doman. Cold Spring Harbor Laboratory Eileen early work focused on apoptosis, but it was doing some of the work there that she stumbled upon a tough G., and that is the focus of our discussion today now the if you're even remotely familiar with this podcast, you'll certainly know that the concept of Tafkaji has. has come up on so many previous episodes. It is a fundamental pillar of health and maintenance of health. We talk a lot about it. In the context of fasting in particular, I have wanted to sit down with I lean for a really long time and I don't think this conversation disappoints. Although we certainly could have gone longer in this discussion, we talk about Eileen career, and how it more from studying pub toast is into a tougher. Gee, we go into describing the regulation of tougher g both metabolic LII, and otherwise, and then we spend a lot of time talking about the role, a toughie plays in both the prevention of disease and also the. The treatment of disease and this is where it gets really interesting, especially around cancer and I, think that that's potentially one of the most confusing aspects of the entire discussion on a tough Aegean. That's actually one of the reasons I really wanted to talk to Eileen was to better understand something that at the surface seems confusing to me, which is that at half g seems to very clearly protect a person or an organism from getting cancer yet once someone has cancer. It appears that a tougher g may disproportionately benefit the cancer cell versus the non cancer cells, so we teased this idea part along with talking about the amazing worked at her lab has. Has Done to demonstrate the importance of Tafa G in preventing Alzheimer's disease and neurodegeneration along with the benefits of metabolic health, and of course we do talk about the age old question that many of you have heard me go on, and on about which is how do we delineate and understand the dosing and frequency of fasting as a tool in other words when I talk about doing fast of three days every month versus seven days, a quarter versus five days a quarter. How could we possibly get a handle on what the ideal strategy is, and so we talk a lot about that as well and I'm actually quite hopeful that from this discussion comes. Some research that can shed light on that so without further delay. I hope you enjoy my discussion on a tough G with Eileen. I lean. Thank you so much for extending your trip in San Diego for a day to come in MC time to talk about this stuff today l.. It's my pleasure. I'm looking forward to it I don't know if you remember this by the way but David Sabatini introduced us a few years ago, you remember and we had yeah. I still have my notes. Notes from that phone call five years ago, I took about twenty, maybe twenty exaggeration, maybe ten pages of notes in my sort of journal, and for probably have gone back to those a dozen times in the last five or six years so I appreciate it when people just pick up the phone and talk to total strangers for no reason so that's really. Excited about the science and so nerds like me like to talk about science. Well, let's actually start from there. Tell me where you're interested in science came from. Was it something that was always in you from a young age where you just naturally curious? Yeah, I've been asked that question. Many times before I come from a family where there was an interest in science, my mother was a elementary school teacher, and my father was a lawyer, but he always wanted to be in science, and all of our discussions were. Related a lot new scientific discoveries so from an early age I was introduced to science, which was probably unusual, and then went to college and majored in science and biology. And continued from there. And I decided when I was an undergraduate I wanted to get a PhD in biology, and I was very fortunate to go into graduate. School in the Department led by Dr Arne Levin. Who discovered P fifty three and that was an inspirational experience because he is got scientific insight. That's absolutely incredible. And, then I went on to cold, Spring Harbor Lab, whereas opposed with Bruce Stillman, and again another incredible scientists, and it was an incredible scientific environment. There were a whole cadre of investigators there that were making major contributions in the field of cancer at the time, and it was just a very thrilling experience, the being an environment where once a week there was some fabulous discovery, and everyone was excited about it. The even I think two Nobel, prizes awarded while I was there, and I joined the faculty a Cold Spring Harbor after that. That, and then I moved onto rockers, and I had the fortunate experience of building a cancer center, so I went to rutgers to be on the faculty, there was no cancer center, but shortly after I arrived, they hired a center director Bill Height from Yale, and I joined him to help build. What's now the rutgers, Cancer Center or the Rutgers Cancer Institute which went from nothing to. Now there are multiple buildings. There are eleven hospitals in our health system. We have two hundred and forty something members of the Rutgers Cancer, institute and we have where a consortium Kansas senator with Princeton, university and so it was very thrilling for me to not only have maintained my scientific interest by running a research lab, but also help expand and grow something from nothing where now we're treating large numbers of patients in. In in standard of care and clinical trials, and making large discoveries and moving cancer treatment, advancing cancer treatment as fast as we can. How many years have you been a rickers? I joined there in one thousand, nine, hundred ninety, so I've been there for a long time, but I moved about twelve years ago. I moved from one research building to be physically in the Kansas Center where I could be more directly helpful. So in your journey did a tough g Pique your curiosity. was purely serendipity. So this goes back to when I was opposed to act with Bruce. Stillman and I was given an oncogene to study that time. They had just sequenced the adenovirus genome. They knew what genes caused cancer in the virus I was given one of those jeans, and said figure out what it does, and that was a dream project for a post doc, and what I found was that this gene was a barrel homologue of basile to be co two is a gene. It's a human oncogene and functions by blocking apoptosis or programmed cell death. And so that was transformative to me and took other people awhile to realize the importance of that that one novel function of cancer is to evade cell death. That field grew. We and others contributed cloning the other genes that regulated. Apoptosis, we figured out how it all the mechanism by which it worked. And the pharmaceutical industry started developing inhibitors of basile to to promote apoptosis in cancer, and that was the ultimate goal was to make tumor cells die and have a drug that will do that. And once that happened the field of apoptosis I. Think sort of we accomplished what we wanted to accomplish. We understood everything and that led to the development of the first of many drugs that were in clinical trials, and in fact, my lab is still involved with taking those drugs and putting them in patients and optimizing their using solid tumors, so while the field of apoptosis matured to the point where things were being translated, we made a serendipitous discovery. We had engineered tumor cells to. Be Unable to undergo apoptosis. They were refractory to being able to commit suicide. Can we pause for a second there, Alina? Let's explain to folks exactly how a hostess works. Because shortly. We're going to obviously contrast this with a tough AJI. They have common threads, but they're different, so let's go down the path of what does it take to get a cell to undergo programmed suicide? So there's a family of proteins called the BC L. to family. They come in different flavors are the be co two like proteins which inhibit apoptosis, so they keep tumor cells, alive and BC able to is the prototypical member of that family, and is up regulated and amplified in translocated many cancers. To do exactly that and. Our Tag. To, and it's related proteins, the the beach three proteins, and they are often activated to inhibit be sealed to to trigger apoptosis, and then there's the core appetite machinery that triggers apoptosis in this backs and back they reside in the might Okon controversial membrane, and when they're triggered to undergo apoptosis, they el-agha Mera's and poke holes in the minor conroe Outer Membrane that releases proteins that activate proteases degrade the cell, and be co, two and basile excel. All the anti apathetic proteins are involved. Involved in antagonizing this process, and what are some of the things that would have to be going wrong in a cell for it to go down that suicidal pathways, so for example might Akon drill injury that is a reversible genetic mutation that is unfixable like what are the suite of things that basically take a sell down the path of I can't fix this and being around here in replicating is going to be dangerous to the host. I gotTa Take Myself Out of the game. Right so might okon real damage certainly trigger apoptosis, but probably the best way to explain it as eat by using the example of p fifty three, so people d three is a tumor suppressor and a transcription factor, and some of the transcription targets of fifty three are proteins like Puma Anoxia. Which are these antagonize irs obesity. Oh, to an activators aback some back P, fifty three as a tumor suppressor. One of the functions is to promote apoptosis to prevent an emerging Kansas south from progressing. One mechanism by which P fifty three does that is bay turning on the transcription of Puma and knocks. And then that will antagonize co to an initiate apoptosis. So then the question becomes what activates P fifty three to do that. Neck could be a long list of things from DNA damage from oxidative stress, and so forth so you can think of something bad happens to an emerging Kansas Sal and then P fifty three gets activated and one of the Tumor Suppression Functions. A P. fifty three has to turn on these promoters of apoptosis that antagonized. To now loss of function and P fifty three probably accounts for half of all cancers correct right and I assume that you have to lose both copies of it or is losing one copy sufficient well, what happens in most of the time is not deletion of P, fifty three but rather. A point mutation reduces function. It's more of a dominant negative, so in fact, there is even evidence. There's a gain of function, so they're a hotspot mutations in PD three that are very common in cancer and P, fifty three functions as a Hetero Damer, and what these mutant P for D. threes do is that they end up entering into a dime or with wild type sub-units, and that interferes with the function of the complex, so yes, in that respect, it can be a loss of function of the P fifty three Hetero timer her, but this evidence that it not only causes a loss of function, but it actually may do other things as well. Well that are cancer promoting. It's just a great example of the nuance of evolution right. I mean in Med school the classic teaching you know when a hundred years ago for me was P, fifty three loss of function, oncogene, gain of function, black and white. Of course, it's never black and white right. So what does the wreckage of a pop doses? So when a cell undergoes a pop toasties to everything outside the cell inclusive of the immune system what becomes visible in other words does an opt-out Excel once it dies, elicit any immune response or the process of APEP toes yield sort of an inert body of cellular matter that just goes away. I'm not so sure. I'm the best person answer that question I think the whole idea initially was. During the process of apoptosis you would get protein degradation and packaging of pieces of the dead cells into these appetite bodies, and then that would reduce inflammation, and then there's evidence that macrophages can then go and take up these appetite bodies, and that may facilitate antigen presentation, and so forth, so it's possible for example that if you have a cell that has become cancerous, either through gain of function loss of function, but whatever there's some mutation that now renders this cell to go down a pathway of cancer. It fortunately, it undergoes the Pop Tadic Transition. The macrophages take it. Is it likely that you get an immune response to that? That is protective in the long run against similar mutations because I mean even though the macrophages part of the innate immune system does that ever translated the adaptive immune system such that you gain some long term immunity from that specific type of mutation? Yes, I think something like that occurs, and I'm just thinking the wrong person to answer that question I could give. Give you the better names of people that can do a better job, but the I think the best way to compare it is to contrast it with the chronic sold-out, so in apoptosis you have prolific degradation and of cell, and packaging it into these bodies, and you say well. Does that limit information while the way to explain how it does is to compare it to a different form cell death necrosis so closest. So lice and that is very pro inflammatory. Nuclear Acids released you have essentially everything is released including mighty content, which is probably the most immune agenda given it's bacterial origin of the DNA absolutely and so a pop does is what I'm hearing as apoptosis, a much cleaner than necrosis. Absolutely so now let's talk about a topic G.. Let's contrast Tafkaji with a pop hostess. That's right well before we get to that I should go back to your original question. Like how did we start working on autophagy? Bridges us to what you just mentioned. So when we disable apoptosis and a cancer cell, it can't commit suicide. And we're doing that all the time we could show that then. The tumor cells become more to Mirjanic, but what we didn't expect was the ordinary propensity for survival. We could leave the sells out and put them in buffer. They wouldn't die under extraordinary circumstances that we couldn't explain so. Why would a cell that just couldn't commit suicide survive in buffer with no nutrients at all. Just for context, this is the mid eighties late eighties. This is the mid eighties craff. No, it's probably later than that. It was probably early nineteen nineties, and so it was a conundrum. I mean just because a sal can't commit. Suicide doesn't explain how it can be. A Kansas can just sit in buffer and be fine, and we puzzled over this like how can this be? And then we discovered that what these cells had done was turned on Autophagy, and we're using that for survival before you go down that path, help understand. What did you observe about those cells that were sitting there in the absence of nutrient surviving? Did you notice any metabolic changes that were unusual like? Was your clue that they were able to usurp the environment they were in. It was an act of desperation. We tried a bunch of things and nothing was informative, and then I told the people in the lab. Why don't we just look at these cancer cells onto the electron microscope and that way we can, we can see everything because we couldn't understand how they could be surviving buffer. And when we got the electron micrograms back, we saw something we had never seen before, and all these double membrane vesicles all over the south. And so that when we finally all those are auto fag zones which we had never ever seen but wait, did you? I mean first of all. This is just to me. One of the beautiful moments in science that I think I think it's so important for people who don't do science for a living to understand that while science is ninety nine percent failure every once in a while. You have a moment like that Rica moment. Yeah, it probably makes up for ten years of failure. Yes, when you realize in that moment, you are seeing something that has never been seen before, and therefore this is the cusp of new. New Knowledge. That's right that's happened to me. A bunch of times in my career, which is fortunate and this was one of those moments, and then we started reading on. What are these auto fags? What do they do? And then? When we realized from Louis looked in a yeast literature, they were meant to capture intracellular proteins wrong in house, and bring them to the back mammalian license home for degradation and recycling, and that this was a mechanism by which yeast survive starvation, and what was the tumor line or what was the cell line? You're doing this? And at the time we were using kidney. Cancer Cell Lines. Mice or human? These were mouse, but it was basically the first time this had been seen in Mammalian selling. No I think people had seen auto fag `ISMs four I mean you gotta remember in the old days when electron microscopes were first available that that's one. The things that people did was describe all kinds of different processes. So what a fag is owns were known to. To exist, but there was very very little information. Almost no information on autopay gene cancer at the time, so we went into this area where there was almost no information, and so the first question we asked is okay well. The Yeast data tells us that when you see auto fag `ISMs bat beans cells are starved and they're recycling and they're using this to survive and. We hypothesized that that's what was going on these cancer cells, and if that was the case, if a top G. was a survival pathway in cancer. That was a game changer. We had to understand it and we had to demonstrate that that's what was actually happening. And then if that was the case, if cancer cells had usurped the attack G. Pathway for their survival, Ben, we needed to inhibit autophagy for therapy. The first thing we did was. We looked to see what would happen if we inhibited Automa- Ajay in these cancer cells. and. The answer was very simple. In many many circumstances in many different cell lines that we looked at when you went to hear bitter Autophagy, the survival of the cancer cells was reduced. Let me interject for a second. Ask a question. I don't know if you've ever did this experiment. But if you took the kidney line and the kidney cancer line so basically the same histology from the same tissue from the same animal, but one has the oncogene properties in one does not and you put them. Them, in the identical nutrient, deprived stress. Can you quantify the amount of Tafkaji or the efficiency with which to cells in other words is cancer simply preserving the Ataf Aji capacity that it had as a non cancer cell, but not enhancing it or not having any attenuation of it. Is it simply just? Hey, this just happens to be something that gets preserved as you go from non cancer to cancer. Is there some qualitative or quantitative change in the character of a tough as a cell mutates? As interesting so. Let me see if I can unpack that so if you have the general observation. Is that normal cells in the Fed state don't have a top of John at functions at a very low level, and if you starve cells or mammals for nutrients, then there's a massive up regulation of topic. What was striking about the cancer? Setting was at even in the Fed. State autocracy was elevated. So there is a fundamental difference Yup yes, and then if you stress them, it goes up even further, but the problem is when it's already. Already hi, how much higher go and just to be clear lean? This is in vitro, so you can't even make when you said that. The first thought that came to my mind was will maybe the reason. They're undergoing a different stress, which is for example, vascular stress I talk six stress because you got enough. Jeff or they haven't created enough. In other words. The apoptosis is going up despite being fed. Because there's something else that's impairing them. What you just said is true. In Vitro than that wouldn't explain that would in other words if they're not limited for oxygen. If they're in a petri dish in this is happening, my hypothesis wouldn't make sense that would only make sense if what you said was trying in Vivo right so in the Fed state. The Kansas already have elevated auto fajik flocks, and when you fast them, it does go up, but it only so high it can go. I see so this probably. It's really funny. I'm sure familiar with the paper that Matt Vander Haydn and Luke Kaelin Craig Thompson. Run Science in two thousand nine, which was at least to my knowledge, the first time that someone offered an alternative explanation for the Warburg Hypothesis, which is hey, it might not be that the Mitochondria of the cancer cells are effective and can't undergo oxidative phosphorylation. It might be that they're optimizing for growth as opposed to metabolism. They don't care as much about ATP. About building blocks, and therefore they're deliberately taking an inefficient route of glycolysis to lactate, because they want the cellular building blocks, and that might be the explanation here is that the tumor cell is undergoing more constant proliferation, and therefore they want more building block exactly right, and in fact when we look at cancer cells and we studied their metabolism. What we've noticed and this is something that we found, and it's been a common observation. Is that nuclear? Seemed to be rate limiting, and so so the metabolism of a cancer cell is designed to facilitate to noble synthesis of nucleotides, so it's really interesting, isn't it? We really something about like think of all the things that could potentially be rate limiting to a sell, it think of how many phospholipids for example they need to build all of those cell membranes, and yet it's the nucleic acid to continue to propagate its DNA that becomes rate. Limiting that to me is very interesting. I wouldn't necessarily have ever guessed that. We may learn more as going forward, but that is what seems to be a recurring theme, but it's not just DNA. AREN A and you have to remember that Aren A and ribe assumes make up a huge amount or greater demand exactly and think David Sabatini has mentioned this many times at a large amount of the mass of a cell is Riva's Oh laurey and he had a beautiful paper. Where he was making the argument that rival Faye G, the top Itchy of rival psalms will was an important metabolic survival mechanism, and you could think of ribot zones as being depot a storage depot for not only nucleic acids, but also protein when the cell is stressed or starved. It doesn't need to make protein, so it doesn't really need larger numbers of homes, and so the topic G. Pathway can cannibalize those ribot zones because they're unnecessary. And then recycle all that protein and nucleic acids to support survival memorial, you mentioned of course, some of the already been observed in yeast, and the moment we start talking about things that are true in yeast, and then true in animals, mammals for example are higher. We're talking about a billion years of evolution here, so this ranks has one of the few things that seems remarkably conserved over evolution as a general rule that makes it very important. Do we have a sense of when this? I showed up again I might be out of my league and I know it certainly a big function in yeast. Prior to yeast I don't know yeah, but it's amazing. I mean it's sort of. It's in the category of 'em tour. Yes, something that is so important that it just doesn't really seem to change over about a billion years rule of thumb it matters. That's right and I. Think when you compare how yeast does attack, Jay and how mammals? G. And what they're using it for. It just looks like Mammalian. Version of attack is a little bit more complicated it's probably they have probably more different circumstances where a tougher g might be necessary, but the basic processes surprisingly the same. What are some of the other stresses that induce g? Let's maybe just for the moment. Even start with just in a normal cell, so let me sort of synthesize what we've talked about. Clearly nutrient deprivation is one of the biggest triggers for Autophagy, and I mean maybe just for the sake of time all kind of throw this out there, and you can correct me if I'm wrong, but I've always sort of thought this through three pathways at the sort of mechanistic level, so you have sort of the tour pathway, which is mostly sensing amino acids you have. Have, the amp K pathway, which is mostly sensing energy ATP in general, and then you have sort of the Acetyl Coa a protein sedation pathway, which is also just basically sensing substrate of fatty acid and glucose that sort of a fair way to say that those are three ways that nutrient low nutrients can still trigger the same pathway. Yeah, and I think you could add onto. That stresses that result in organ damage, such as deep colorization of Mine Andrea or dysfunction online Andrea. Activation of protein is folding and generation of protein aggregates so I think there's the. Things that are directly related metabolic signaling that you've mentioned, but then there are other stresses that also can tie into the top G. Pathak. Are there other stresses like the nutrient? Their stresses that come from outside the Celtics inside the cell, so the protein is folding the micon drill di polar ization, those are things that are occurring as damaged within the cell. That stress do you know anything for example about temperature do heat shock. Proteins stimulated HOFFA JR in extremes of temperature does exercise I mean which obviously is in the short term quite stressful. How does that at inducing Tafa gene normal cell so temperature-wise? I would fully expect that temperature extremes would induce. Protein is folding and induce. Top G. as a remedy for that but I. Don't recall any studies on that. In terms of exercise that's very well studied. That exercise induces autophagy very potent Louis and you actually need top Ajay, too. Because exercise damages, the muscle, and on top of G is one of the processes that helps mitigate the damage that occurs during exercise. What about HYPOC? You Oh potentally? Boxer potently induces autophagy. Wow, and in fact, one of the first things we did was when we looked at tumors, tumors well known to have hypoxia in the center when we engineered tumor cells to be genetically deficient for our top Ajay, and you look at them. They're completely hollow meaning. They have no org anals nothing not the cells are hollow. The tumor is hollow. The further the cells get from a blood supply, meaning the more susceptible they are to. Their dead right so if you take a tumour, the middle of the. Sick, that's where your top is most active and genetically blade topping the tumor. You end up with a hollow tumor because the tumor cells in the middle don't survive. Yeah, so it does come back to this idea that we talked about earlier about HYPOC SIA being potentially one of the things that atop ogies protecting cancer from absolutely. How easy is it? Create an animal model that is unable to undergo a tough AJI difficult. Is that from a knockout perspective? Well, it's been done, and we've done it, and it can be done different ways so the. The original mouse strains were made were deficient in either of two of essential atop Jean's wound called, did the five and another one called eighty seven and these mice were developed in Japan and these Mi's are born, but they failed to survive the neonatal starvation periods when mammals or born meaning once they are cut off from an umbilical nutrient source. It's almost like they have a glycogen storage disease. You know those conditions where you can't produce any glycogen that it's uniformly fatal. If not treated the moment, you're cut off from an umbilical source of nutrients. So that. Neonatal surveys period between the cutoff of the center and suckling is a common feature mammals and. There's poten induction of autophagy during that period, I can't speak for humans, but certainly I would think so and my sets exactly what happens and so these Taffy Ajay deficient newborn mice don't survive while, but really I mean again I think that simply underscores the evolutionary preservation of something. If you knock it out his uniformly fatal, do not Pasco. Do not collect two hundred dollars your gun, and then what we did was asked different questions like what happens in an adult now so in the a newborn mouse. It's very different situation because any newborn mammal. They don't have any fat. Reserves and so when the Japanese group did need extrordinary thing of trying to force feed these taffy deficient newborn animals, then they didn't extend their survival very much. There was this Yoshinori Group. This was the bureau Mizushima and the Kumasi Group I believe I think it was coming from those two labs to what happened in that experiment. They discovered that the mice jaide shortly after birth. And then they realized that they suspected they had metabolic problem and they weren't suckling, because they were probably too ill to buy the time they were would have been able to. So they force fed them, and that allowed them to live for twenty four hours, but. They still died anyway, and then are you able to induce an attaching knockout in an adult? Yes, so that's what we did because we realize that the newborn animal is just too fragile too fragile. They've known neutron reserves, and actually in setting of cancer. Were thinking of you WanNa treat? An adult with a tumor. What's happening and autophagy? A newborn animal is even relevant. And, so we engineered mice where we can take an adult mouse, and give the mice a chemical, so that inner central topic Jane will be deleted throughout the entire animal so one day they're an adult mouse with our taffer, Jay and then a few days later there an adult mass with Noah Ataf Aji. And these mice were very extraordinary. They live for two to three months. And then they died predominantly of neurodegeneration or tougher jeez very important in the brain over the long term, but if we fasted the mice, they were all dead within sixteen hours. Let's unpack that again. That's pretty remarkable, so you take a normal mouse that's got through the vulnerability period of infancy, and you genetically knock out its capacity for a tough Aji the first thing you observe as if you fasted for sixteen hours, which admittedly is a pretty long fast for a mouse that might be the equivalent of fasting a human for a week. But that degree of nutrient deprivation is uniformly fatal. If you continue to feed them well, they only survive another couple of months because they ultimately succumb to nerd generation, suggesting that the role of tough Aji in preventing Neeraj degeneration is essential, and it's really not surprising when you think about the role everything you talked about with protein folding, and when you start to think about the toxicities that are driving neurodegeneration using Alzheimer's disease, specifically as an example. There's a lot of crap that's basically getting accumulated neurons. This would be an elegant way to suggest that. is keeping that at bay exactly right? So one other way of looking at it is what tissue is our more mortality dependent than others exactly brain would be really important, and there are a few others and what we've noticed. When we looked at the mouse, the lack dot org when genetically? Deleted the topic gene in the adult mouse. was that there were tissues like the brain that were very sensitive, and there were other tissues like the lungs that didn't have any phenotype, so wait in other words when those animals ultimately dive, nerd generation, and you undergo the pathology analysis. Obviously, the brain is where you see the cause of death. You're saying the lung. It looked completely normal relatively normal. What about liver liver was very sensitive, so it doesn't lead to the death of a mouse. So, if you did a liver, specific knockout, an essential pathogen, mice have diaz and their liver gets huge, and whatever, but doesn't kill him. I mean they can live for quite a long time. So you induce fatty liver disease so again, suggesting that a tough achieve probably plays a role in preventing fat accumulation in the liver, exactly right and also protein aggregate formation, one of the other fina types of St Atto CICIS. Accumulation of these mallory bodies which are large protein aggregates composed of protein called P sixty two. When you lose a g in the liver, you're causing accumulation of fat accumulation of protein aggregates, but liver manages to tolerated. The brain however is a different story in view. Have Post my tonic neurons. Where have the capacity? To do that them in when they accumulate the crap as you said then, it's game over. was there evidence that the brain? Some last ditch effort to survive was undergoing more a pop doses of neurons. Yes, that's a common feature of these animals increased apoptosis in the brain, but before that you see all kinds of terrible things going wrong. This has been part of a major effort. To generate top AJI stimulators as a remedy were as a means to delay neuro degenerative diseases. I WANNA. Come back to this later on in the discussion, but I'll just plant the seed now. Obviously, fasting is one of the most potent stimulators of Tafkaji I spend a lot of time thinking about how does fasting? Fit into our toolkit of longevity. A big part of longevity, in fact, probably the single most important piece of longevity when it comes to the lifespan aspect of it, so you think of lifespan versus health span long delivers how well you live on the how long you live front. I think it's very safe to say based on all of the Animal Data and frankly all the centenarian data that the key to living longer is delaying the onset of chronic disease, so even when you look at centenarians who are genetically gifted with tools to live longer. If you, unpack with the gift is it's delaying the onset of the disease? Not Living longer once you have the disease, so the centenarians once they get cancer, and once they get heart disease, they die at about the same rate over the duration as the rest of US schmucks. The differences they get those diseases twenty to twenty five years later. And again that suggests to me that if you want to live longer, you have to delay the onset of these things not live longer once you have them. And, so it's hard to think that fasting doesn't play an essential role in that. When you realize the role that fasting plays in the mitigation of Alzheimer's disease and Metabolic, disease course what we're GONNA come back to in a second is cancer which seems to be this conundrum. This is the needle. We're going to want to threat a little later down the line. Plant the seed now, but I do want to come back to the idea of ways that we can also induce Tafkaji Aji sort of pharmacologically or chemically the first thing that jump your mind is anything that mimics fasting. The first thing that comes to mind would be met for men. Rapamycin things like that that what we talked about earlier just for the listener to sort of ties us together. We talked about these huge pathways. The tell the body nutrients are scarce so when mt for activity is down. That's a sign that we're deficient in amino acids. We can also do that with rapamycin. When he K is up. That's the cell. Being told were deficient in ATP. Another way you can do that is to give metformin. We haven't talked about certain sins yet. Maybe I'll pause for moment. Do we have any sense of what Sir two activity does and I'm not familiar with that litter okay I was gonNA. Say 'cause then you could get into the whole N D. H Ratios, and how that might factor into it so again. I really curious about this through a clinical lens as well which is what is these suite of products, but almost just saying that out loud, so between the two of us. We remember to come back to this, but I now want to get back to your story, which is we've got these mice? You've got this much more elegant experiment now, which is you're actually going after the phenotype of interest. Interest, which is an adult in which you inhibited Hoffa Gee. What was happening in that animal? If it had cancer, so, did you ever do the experiment where you had an adult with cancer? Then you knock out a tougher. Gee, that's actually one of the reasons. We made that mouse, so we had to questions we wanted to answer. One was if you inhibited Automa-, gene and adult mouse. What would happen because if they died in an hour than targeting? Targeting autophagy for cancer therapy would be pointless if you can't do it specifically, that's right, so the answer was it in in an hour they died in two or three months, which actually good news, because that meant that there was a potential window of opportunity for inhibiting autophagy for cancer therapy and I'm really. When died in two to three months was still from the neurodegenerative ended. They still have cancer the time of death. We had to I make a mouse. Mouse that lacked where we could switch off a Tapa G and find out what happened to them mouse. Okay, so we did that and we saw that they died of neurodegeneration, two or three months, which was good, they died immediately. Then we would have stopped. There would be no point in trying to make answer on that animal, but we did learn that they were intolerant of fasting, which was perfectly consistent with everything when you about what autophagy functionally did. So then we moved to the second step was to do the experiment. You just suggested to a cancer in that mouse, and then after the mass had cancer to then shut the autopsy pathway off, and then to ask the key question. which died I the mouth of the tumor? And the answer was the tumor died I. Wow okay, so then here's the gangster question once the tumor died. Could you re-activate a tough G to prevent the nerve degeneration, or is it? A one switched direction that required a different type of mouse model. So what we were doing was making a mouse with cancer, and then once the mouse had lung cancer. In this case, we deleted an essential topics gene in. In, the entire mouse tumor, and all, but the gene was gone, so it wasn't like we could turn tough g back on in that model, but since then one of my trainees and collaboration with the lab in the UK, they have developed a model where they can toggle tougher g often then back on again, and what they've seen is a remarkable capacity of. Of the normal tissues to restore themselves, so the experiment would be to have a mouse to induce an s hr a to a specific topic gene to down regulate the expression and inhibitor top Aji that way, and then later on take that s hr a away or shut it off and restore normal atop in the mouse, and you see a lot of capacity for. For, the tissues to restore themselves back to normal, so that experiment basically becomes the proof point that says targeting Ataf Aji in cancer makes sense. That's probably the most elegant description you could provide that that's right. I think it would be better if we had specific targeted therapies against some of the enzymes in the autopsy pathway, because these are all genetic experiments and. It's not exactly the same right. You might not get the complete prioritization with drug or inhibiting produce is not exactly the same as deleting the gene, but this is all what's called proof of principle that the concept of inhibiting autophagy in cancer is valid. So. What do we know today about what you've just described? As it pertains to two things, I want to slice the data across two variables. The first is tissue type or histology of cancer, and the second is underlying genetic mutation, so I know that a lot of what you're describing is clearly true in chaos mutation. What about other drivers? We and a number of other cancer labs that use genetically engineered mouse models for cancer have been banging away at that for a number of years and what we've learned is that. Driven Lung, cancer and pancreatic cancer are extraordinarily topic dependent and you do it, you know, make the mouse models, and the tumors are very susceptible to the functional loss of ought apogee. Can you briefly tell folks what a chaos driven cancer does like? What is it about the mutation that drives the genesis sow chaos is a gt p binding protein that is responsible for activating what's called a map kinase pathway, and this pathway is very key and driving cell proliferation, and so cancers have a mutation. or mutations in rats that leave it in the GDP bound or on state so there's perpetual growth signaling through the map kinds pathway, which of course is the hallmark of cancer, which is unresponsive to cell signaling. And when you are fixed in the on position, you can't turn off and basically that is cancer that's right, and what's particularly interesting about rash of and cancers is that? We have been very unsuccessful in drugging rast, and there's recent hope that the Sistine, the particular subset of the mutations and Rask's that involve assisting residue that there are now drugs that target that there's hope after decades of failure is the primary issue in the failure to drug rasp that you can't do it without creating toxicity, four other cells that are non cancer or that it has too many work arounds to whatever you. You put in place I think too many work arounds is a common problem with they've done is that they said okay. Targeting Rask's is difficult than let's go downstream morass and try map kinase right so there are inhibitors of Wrath Mek, and Erk which are downstream of France. Then those are actively in use in the clinic, but they seem to be not durably effective in rast driven cancers because of the work around. Yeah so are there mutations or mutant drivers of cancer that we know are not dependent on a tough AJI and unresponsive to the autophagy blockade. Yeah, it seems like there's a spectrum, so rash of and cancers are particularly sensitive. Be Raft driven cancers like be six hundred. Is a common be Raff oncogene mutation, and those cancers are particularly sensitive. Those the ones that were examined were lung, cancers and melanoma. The be rap be six hundred mutation men on Melanomas, very common Hamas. recombination deficient breast cancers in those would be well. I mean those would be models of hereditary breast cancer. Those are very sensitive to loss of apogee. ABC deficient colon cancer is another example what about non ABC driven Colon Cancer? Which of course is the majority of it? Would we know about that? I don't think I can remember seeing paper I remember the ABC deficient model. APP sets fact. The most commonly used model anything we know about prostate, cancer or other hormone, sensitive breast cancers, so prostate cancer is sensitive. We did that work and hormone sensitive breast cancer. I'm not recalling right now, but there are a long list of cancers that are sensitive. Sensitivity is not all equal for example beer, after Kansas are very sensitive more so than rask driven lung cancers. You'd just compare lung. Be Raff. Lung cancer to Razz Lung Cancer mutant lung cancers more sensitive. The most sensitive cancer that we've encountered is in fact, rast driven lung cancer with L K. B mutations, and this makes a lot of sense to so one of my trainees who has her own research lab hypothesize that we sat down and I thought what cancer would be. Would you predict to be most off dependent and it should be A. A cancer with law savell. KB ONE L K B. One is a tumor suppressor gene that's involved in activating amp, Chinese and amp kinase activates tougher G. as a survival mechanism to low energy, and so there were a whole class of lung cancers that have lost L. Cabbie one, and as a result, they can't activate this protective mechanism. This is Dr Jesse Guo she made this mouse model rash of and lung cancer without L. KB, one and lo and behold when you delete an essential top-edging, you abrogate tumor genesis, so it makes a huge amount of sense l.. K. be deficient rash of lung. Cancer is probably the number one sensitive tumor. So, how do we reconcile these two observations that almost seem to have a difficulty coexisting, so the first is everything you've just stated, which is pretty clear and unambiguously suggesting that a tofte G. is at least for a number of cancers, an important part of their survival and proliferation, and we contrast that with an abundant of literature that suggests that when you combine fasting, which is a potent inducer of a tough edgy with chemotherapy. For example you enhance its efficacy, and we can speculate about why that might be the case. These two things, although not directly comparable seem a little bit at odds. How do you think about those things? I would probably think about it in slightly different ways, so if you WANNA get at the two different roles of top G., one is cancer cells. USURPING IT and turning it on for their own survival, than the other side of it is when we know that autophagy is protective. We know what happens. If you have a mouse without autophagy, many terrible things happen. It takes a while, but the mice style neurodegeneration. Can I interrupt for one second? Sorry to do this, but I just don't forget this question. I WANNA come right back to your thought in those animals that died of neurodegenerative disease after two to three months. Did they show an increase in tumor genesis in any other tissue? No, they don't. But if you make a mouse where you bypass a neurodegeneration by knocking out an essential atop everywhere else, okay, but not the brain. Then those mice will get benign Hepatoma so benign tumors of the liver, but that makes sense to think about a half Aji in normal tissues. We know it's important because if you knock top data and a mouse, those tissue specific, but gradual deterioration, ultimately leading to neurodegeneration, and you end up with St Joseph's Luton Fatty liver disease, the brain phenotype can be explained as we discussed before neurons in the brain need this protein organ quality control function their post. Mike Todd, they have. Have to have a way of getting rid of the garbage in the liver. What happens when you damage the liver? It regenerates. It's got infinite capacity. That's right, but what happens when you unless there's too much inflammation exactly so you end up with when you inactive a tough gene liver you end up with these chronic cycles of damage repair and chronic inflammation, and that is on Ca-, Genyk and that's not you know it's particularly obvious in the liver, the pancreas as well. Very sensitive to that inflammation so I think what this is telling us. Is something very important? It's telling us that. A main function a top Ajay in tissue homies. Stasis is to preserve cellular function to be normal to prevent chronic damage and inflammation and tissues that are susceptible to cancer as a result of chronic damage and inflammation. Autophagy is highly protective, which again think about how complicated this is now a bring us back to the question. I posed a moment ago, but using this example. WHY DOES NAPA? Lead to cancer, because if you have enough accumulation of fat, you get enough inflammation. You're going to get about a cellular carcinoma saying with Pancreatic Cancer Heil, this is why alcohol is such a horrible molecule so toxic to the pancreas to the liver, and you sow those seeds of inflammation and Lo, and behold your increasing this risk of cancer, so on the one hand. We know that a tough AJI helps ameliorate cleans that up. It buffers that the same time. We just realized a moment ago Oh boy, once you do. Do get pancreatic cancer. It's K-. Roster driven cancer a G. helping that's right so now let's come back to the question I posed a moment ago that I so rudely interrupted you, answering, which was how do you reconcile these? I think it's a matter of thinking of the role of Tapa. gyn cancers being context dependent on the one. Hand Functional Law. Top Ajay can delay the onset of chronic damage and inflammation that are known causes of cancer in particular tissues, such as the pancreas and the liver amongst a few others. So, I think that. Stimulating topic. Through fasting or through pharmacologic means at one point can be thought of as preserving health. But once you have a cancer I, think it's a different ball game, and at that point it's a completely different context, and in that setting what we've learned as inhibiting autophagy. Is preferentially damaging to the tumor compared to the normal tissues, and then going back to the other literature, which looks at the efficacy of fasting, combined with chemotherapy, which is superior to chemotherapy. Do. You think that the reason for that. Is that the chemotherapy itself? Maybe once you, you're rendering the cells more sensitive to chemotherapy, and also potentially generating a more durable immune response, because one interpretation of what you're saying is a person with cancer should never be caloric restricted. I don't know that's going too far. I would say that I don't know that you can equate caloric restriction with the loss of our top J. or regulation of autopsy because I think they're not equal things, because I think that caloric restriction is limiting tumor nutrients, and so I think what that's doing in the context of cancer therapy needs to be better understood. I'm just not sure that we know. What's happening there? If I'm hearing you correctly. You're saying look. It might be that. We can't necessarily say that fasting isn't helpful cancer, because while it may be counterproductive from the standpoint of Tafkaji that may be offset by other things that are beneficial such as the reduction of overall nutrient inflammation that accompany this exactly right. Yeah to me of all of the areas of Tafa. G that have me scratching my head the most. This question of Given that fasting is one of our most potent ways to stimulate it. In fact I would argue it's more potent than metformin. Which is a NPA K. activator, more potent probably than exercise me might be the most potent thing we can do to turn this amazing tool on. How do we think about using it? In disease, prevention and disease treatment, and they aren't the same thing. I completely agree, and in fact I would ask a question of you, so there's a multiple efforts in biotech industry. To identify pharmacologic agents that are potent stimulators of Taffy and I think their idea is as a normal healthy people will take a pill atop achie- will be turned on, and there'll be some fountain of Youth. Type, Sperm Dean is one of the things that people are talking about right, so why not? Cultivate, the use of fasting instead I will tell you exactly why I lean and I love how you have fed into. It's almost like you can read my mind and know where I'm going to go with this discussion. I. Think a big part of it is. We don't have the tools to measure the signatures of tough AJI in other words, if a patient comes to me, and says Peter I want to do whatever I can to enhance a tough because I have now bought into the idea that it is going to basically protect me from every chronic disease I would say I agree with you, and they say great fasting seems like a great way to do it. I'd say you're absolutely right. And they said well. How long do I need to Fast Peter? Guess what I get to say I don't know. And I'll tell you in in reality. What I say I say well I'm really sure that after about seven days of nothing but water Tafkaji is fully cranked and I'm also really sure that if you just go twelve hours without a meal, you probably haven't done anything where I struggle is where between the now I wanNA share with you. Some personal experience I want you to weigh in on it, and then I think maybe we can pivot often to actually kind of going back to what you and I spoke about over the phone five or six years ago. which is what would a molecular signature for tougher? She look like and again I think this is. I put this in the top three most important translational questions in my field in other words, I think about the practice of medicine as it pertains to longevity. It's our inability to understand how to quantify the benefit of nutrient deprivation in other words, our inability to dose it. That is our greatest, certainly among our top three detriments to using this incredibly potent tool so. Fast, a lot, I just finished a fast yesterday, actually so I used to do a thing where I fasted seven days every quarter so four times a year. I would just do a water only fast. How hard is it to do that? It is not that hard. I'm going to be completely honest with you I wish I could sit here and say oh. I'm real Scud. Nobody can do not. Anybody can do it I. Really think anybody can do. It is not to say. Say that there aren't moments throughout those fast where it's sort of difficult, but you'd also be surprised at how resilient the body is so yeah, not that hard. You have to make some adjustments. Obviously, you have to be very thoughtful about how much water you're drinking. And how many electrolytes you supplement, there are a lot of changes that are happening in terms of electrolyte, management and things like that, but again we certainly have the knowledge to know how to manage people through that. But, it began to ask the question. Right which is okay is seven days a quarter the right dose. I'm convinced that it's a big Bolles of tough AJI frequent enough. What about three days every month? That's about the same number of total days fasted, but it's more frequent, but it's probably less potent and the reason I sort of decided to try. Three days a month was I noticed that a couple of things happened at the end of my fasts so I always check my blood before and after one of these seven day fasts. Fasts and there's a very predictable set of changes that occurs some of them that are really obvious. Glucose plummets. Insulin becomes UNMEASURABLE. Uric acid goes through the roof along with Beta hydroxybutyrate, of course, two possible explanations for the uric acid going through the roof. One is the breakdown of nucleic acid. Then obviously when I talked, go through I mean doubling of uric acid. Acid so much so that I started taking Allah pure and all during a fast to make sure I didn't get gout. Of course it could also be and I've read something that says that you're acid and be HP compete for the same transporter in the kidneys with there might also be a bit of a competitive blockade, but nevertheless we have at least one possible. Possible explanation, their endocrine function changes dramatically T- three goes down significantly and reversed. He three goes up significantly such that the ratio of them changes by four to six fold, which means you basically shut off metabolism not surprising explains why you become incredibly cold, intolerant during a fast and also genotropin atropine. Go Down, so you really predictable things, but what I noticed was. See virtually all of them, though not quite same magnitude after three days, but not after two days. So that just got me intuitively thinking in a hand waving way that three days was sort of the minimum dose, you needed to really move the needle on a bunch of these other metabolic things meaning the spike in uric acid, the bottoming out of glucose. So there's another thing that sort of happens it's. As you turn more and more free, fatty acid into ketone and turn more glycerine all into glucose, you reach an equilibrium where your glucose is pretty much going to stay at about three to four millimeter, and that takes about two to three days. And again when we think about it through the Lens, we've already discussed. Amp K. must be up through the roof. Mt Must be through the floor and Protein de escalation must be off. I think my gestalt is that that takes about three days and obviously it gets greater. The more you go, but what would be amazing is if I could draw to blood. Send it to you after a three day fast a four day fast five day fast seven day fast ten day fast. And get some sort of quantification. What is it that we would see in now? Of course it's complicated because you'd probably want to accompany each of those tubes of blood with a muscle biopsy so that you could look at c. three to and things like that so I'll stop my diatribe for a moment, and now turn it over to you, which is where would you even begin to look for that signature of a tough Aji and let's start broadly with any tissue. You can have blood. You can have muscle. You can have liver. You can have adipose tissue. How would you now create a dose effect? Well. We know that what happens I'm mouse loses. Take a minute to discuss that so Mizushima lead made. A mouse that had a transgenic elsie. Three GOP protein expressed met could use that mouse. Tell folks what else he three is just so we're GONNA. Talk about this quite a bit, so elsie three is the protein that is attached to the auto fags, oh membrane and links to the cargo that ends up in the auto. Fag Zones, supreme mechanical thing like this goes back to your observation in the electron microscope, exactly right so ill C. three, one other key proteins attached to the auto fags zone membrane. And you use it to see auto faggot zones because normally when autopsies off Elsie, three is diffuse, but when Auto Fag Soames form the O. C., three protein is attached to them, and you start to see spots where all the auto fag zooms present, and so the Musa Shema lab used that to assess automata Jay a living mouse. They fasted the mouse, and they found that they could see the formation of log of auto fag. Azzam's throughout the mouse, and could they do this pm out of blood or do they need to use tissue? They did it with tissue. What they learned was that. Yes, autocracies time. Time during fasting in mouse, which wasn't surprising, but it seem to not be uniform across every tissue. So that was interesting, but we don't have a way to do that in people all we can do because this is involved making genetically engineered mouse, so the only thing we can do, and people would be to look at a tissue section and stain it for L.. C. Three and it looked to see if there were spots. In other words, you could not look at Elsie three conversion in white blood cells. You could, but there's another problem in that you could take PBS's and do a Western blot for Elsie. And Elsie three gets processed from Elsie. Three want to and the to form someone that's attached to the order fags on membrane. So you could do a Western blot P. B.. M. C. used to measure the conversion of one to two, but then to. Ends up in the license on gets degraded so the typical. Government of autophagy flux involves measuring the rate at which Elsie three one gets converted to Elsie three two, and then the rate at which Elsie three two ends up being degraded in the lights zone. An order to see that flux. You need to block the degradation of ill C. three two in the lice, with bafflement, hydroxy chloroquine, and so you would only be able by looking at C. Three one and two in P. BMC's in a person that was fasting. You would be able to infer auto fajik flux. Because, you wouldn't actually be able to measure it. It's a clue. It wouldn't be proof, but it would be. One could presume I would expect. You would see more conversion of one to two, and then to going into the lights, and so I don't think that will get you the answer that you need. Now, what if we had one hundred volunteers who are willing to fast and subject to blood draws and muscle biopsies, so you could use the muscle biopsies to actually quantify the flocks and establish. Let's say you can do it. A different time points at one hundred people fast for different periods of time three four five six seven days. ETC, you've got tissue and you've got blood. What else could you look for so again could be HP proxy. Could Glucose be a proxy? I remember you once mentioning another organic molecule you had identified you knew it by how many carbons it had. Had and you thought it was ringed, but you weren't sure what it was yet. Have you figured that out? Yes, that was something that accumulated when Lee inhibited are tough Ajay and that was Glueck Laurent. ICK ACID, so that would be I think you're going down the right road so I think what we can do and we haven't really done this yet would be to look at metabolites, because metabolism has so drastically changed, so if we can't look at directly measure or a fabric flux in humans very easily, because we don't yet have the proper tools, we could use metabolites. As surrogate markers for the consequences of. James Vance exactly why I call it a signature as opposed to a biomarker because I. Think it's basically. How do you use machine learning to take many metabolites? There's a bunch of things we know are happening. We just have to integrate them. We know that loosing going down. We know methionine will be almost unmeasurable talking no, what's going to happen to Glucose Uric? Uric acid, and then there's probably a whole bunch of other small molecules and things in the proteome that we don't yet know. That are probably discernible from PB MC directly or indirectly through other things in the plasma, and it just seems like a problem that is so ripe for machine. Learning environment where you don't need that. Many people because you know what the. The gold standard. Is You just starve him? And then you have the check, which is the muscle biopsy which can give you some sort of quantifiable gradation i. do you get the sense that that's something in IRB would approve its invasive required biopsies and fasting and things like that, but or would they demand you? Hey, I. You have to do this in mice. Mice. That's what I would expect to, and so one of the things that we have been talking about. Is We done some of this? Probably not enough is to do a metabolic characterization of a wild type mouse fasted versus an autopsy deficient mouse fasted. I, think that would potentially identify the metabolic changes that were top G. dependent I think that would provide. Some clues as to what to look at and humans because the problem with. Looking metabolism is you get an enormous amount of data and it's very very helpful to know what to look for. We may have a list of things that are obvious to look for but right, but the fine tuning is gonNA. Come in the non obvious. It's not going to be a regression model based on five things. We know it's going to be much more complicated and I prefer not the under the lamppost science yet taken unbiased view and go, and honestly I get asked about this more than any other translational problem. So the good news is I think there are a lot of people in the philanthropic community that would be interested in this. Even if this is not a question, NIH is interested in. I doubt. An H. is interested in this problem. Although that strikes me as odd given, how potent a tool fasting is and yet we don't know how to dose it and I think it's worth pausing on that for a moment, because that is such a stark statement. If I'm correct, I believe I. AM which is imagined. We had the most amazing drug imaginable imagine we had a protease inhibitor for HIV, and we knew deep down. This could cure HIV the premise. Dose it. How long would we tolerate that ignorance imagine we had a drug that we knew could kill cancer, but do we know how much to give or how often to give it? We wouldn't tolerate that for a minute. And yet in fasting we have arguably the most potent tool, and certainly not the most potent, probably one of the three most potent tools in which we can affect human health, and we don't have a clue how to set or what frequency with which to use it. And I find that ridiculous. So I'm actually really confident that if there were. A really great proposal put together that would go from the animal model to the human model it would be. It would be fully funded through philanthropic efforts. And so if nothing else comes of this discussion I, I would love to plant that seed with you and think about what would be the right consortium of people to do that. Work My. There are lots of skill sets that WANNA have involved in there, but I really believe that could be funded quite easily, and I think that the implication of that is as potent as anything else. Because again here I am doing my three fast every month versus my seven day every quarter versus five day every quarter like we just don't know, and it really is troubling to me. It just drives me insane. Well. I think for the general community. I think it's an important question even for practical reasons because you may. Be Able to control your life to the extent that you can do all this at your own convenience, but a lot of people don't have that flexibility, and so if they can be toehold that fasting for X. amount of time is all you need to do than the beneficial effects of fasting could be. There would be more people that could take advantage of it absolutely, and if you look at the work of someone like Vaulter Longo, who his assertion is, you can get most of the benefit without actually having to be fully fasted, but to do something that is like a fast mimic where you reduce your calories significantly for a period of five days. Again, maybe he's right, but we have no idea. We have no idea what the efficacy of that approaches versus a total water only fast for five days, and it would be great to know because if we could demonstrate that you're getting eighty percent of the benefit doing a fast mimicking diet versus a complete fast. That opens the door to many more people who would be willing to do fast mimicry verses outright fast and again. I think about this constantly, which is I'm almost willing to do anything I. Just want to know what to do so i. think that now is the right time to ask that question. Let me just digress a little bit to talk about metabolism. So. We know a lot about metabolism sensually the field of not only just cancer metabolism metabolism general mapped out all the metabolic, well most of the metabolic pathways, but what we lack the ability to do until fairly recently was to have a thorough understanding of metabolism in a living mammal. As Josh Rabinowitz and I have invested a lot of effort in developing technology to use ISOTOPE ISOTOPE tracers. This would be see thirteen labeled glucose and amino acids, and so forth, and to deliver them to living mice, running around, and doing normal mice, things in a cage, and then looked to see how they're used, and how different tissues use them and how there's nutrients sharing between tissues, because when you're fasting this many complicated things going on, it's not just like there's no food and you're inducing autophagy, and that's the only thing that's happening in a vacuum, right. So you have dedicated nutrient stores, you have glycogen and your liver that's mobilized, and that's Dumping Glucose into the bloodstream. You have made adipose tissue that starts secreting triglycerides, and then you end up with Paul and fatty acids in the bloodstream, which then you know, are taken up by deliverance of what so you have all these you know if you're really without nutrients for a long time, then your muscle protein start being degraded, which is probably undesirable. That's dumping acids into the circulation so that you can maintain your survival. We have to understand all of that because it really occurs in different phases again, if we just limited to humans for moment, where we have a pretty good understanding of this, what's happening in the first twenty four hours versus the next twenty four hours versus the next twenty four hours is very different and George, k hills famous fasting study that forty day fast healthy subjects really divides it into these phases. What's interesting is by about seven days into a prolonged fast. You pretty much reach a steady state. You've got a pretty consistent flux of travelers herreid into fatty acid out of the fat cell. You reach a steady state level. Level of hydraulic beauty rates, Ito Acetate and glucose such that basically the sum total of them in Manila. Molar concentrations is about preserved to where you would be non fasting like and so it begs the question. If we posit that once you reach that steady state of seven to ten days. You're clearly in a fully turned on Tofte g state. What's the switch? Look like when you're twenty four hours or forty eight hours or seventy two hours into that, are you eighty percent of the way to the benefit or just twenty percent? That's jugular question. Yes! I think it would be fascinating to understand that and I think that. If you look back over history. Almost all cultures have fasting as part of their history, and I'm thinking that that is not by accident I think they must've learn by trial and error that this was a healthy thing to do, and so I think that a target I would expect as playing a major role in promoting health in response to fasting, but I really think well, maybe I'm sticking my neck out, but I think using fasting as opposed to trying to find some pill you could take is the something that's easy to do, and of course it speaks to the irony of it, which is if you? You took probably one percent of the budget that is being dispensed to find pills stimulate a tough. We would actually be able to answer this question clearly absolutely, and actually just have a dose response and look that doesn't mean these things can't co exist. I'm all for it and I wanted to ask you of course about some of the other pills like Rapamycin Metformin, and the role that they might have and how we might be able to measure that, but again this just strikes me as the most obvious question in the space of how to prevent disease, and it's like you have this beautiful beautiful tool. And you don't know what the doses and you don't know what the frequency is. If someone knows that they're susceptible to nudge. Disease. Has Anyone looked at those people to see if they engaged in some sort of fasting regimen whether that was helpful or not. Indirectly possible at that's been done directly and I just I'm not familiar with that I. Think what we've seen indirectly is dietary restriction as opposed to just pure caloric restriction where you improve the quality of macronutrients specifically around improving glycemic control, you can take people that are in an early stage of cognitive impairment, and delay it and or reverse it through that type of nutritional intervention. Of course that doesn't necessarily say tough. playing a role because that's doing a lot of other things, it's improving glucose and insulin signaling in the brain. It's doing a lot of other things and we were really starting to see the impact of metabolism in the brain. So that's not entirely clear. Indirectly I would say there are I think some pretty interesting compelling pilot that suggests that rapamycin. Is Neuro protective and again rapamycin a very potent inhibitor of 'em tour would presumably on some level induce autophagy I think it's. A very interesting question, as to what is it about rapamycin that induces along Javadi phenotype rapamycin to me as the most interesting molecule out there because it is I, think the only molecule that has demonstrated a longevity benefit across all four models of eukaryotic cells. So that's a really big deal. That can't be ignored. But, how much of that benefit is through Gee I'd like to turn that question to you. How much of it is through inhibition of Senescent cells reduction of inflammation again so it's very indirect, and it speaks to again again. I, don't mean to sound like a conspiracy theory guy I'm not, but it is a little frustrating that we have these amazing tools, but because they're not particularly profitable, you don't really. Really, have somebody that's interested in answering them. And that's why again come to a I think these are answerable questions, be I don't think they are billion dollar questions. I think they are really questioned. That are amenable to the philanthropic community and I think from an Roi perspective. It's hard to think of examples where you can put dollars to work in research that would have a greater impact on human life. Right and I think that our biomedical community is mostly focused on putting out fires. Rather than disease prevention although I've seen a change I'm an I've see at the NCI. The National Cancer Institute a bigger interest in cancer prevention, so I think people are coming around to realizing that making people healthier longer is probably more important than once. I discovered to have stage four pancreatic cancer. What can we throw at it to make them live another two months? Yeah, again it is sort of. To me how lopsided! Our resource allocation is with respect to that problem because you're absolutely right, we have spent probably a quarter of a trillion dollars in the last forty years on the second question, which is once you have metastatic cancer. How do you live longer, and we've done an analysis on this? So for the quarter of a trillion dollars has been spent on that problem on average for solid organ tumors. We have extended median survival by less than about a year since nineteen seventy so almost fifty years. That's pretty sad when you think about the fact that there's not much evidence. We've reduced the arrival of cancer. In fact, all we've done is basically. Come up with a second leading cause of cancer in terms of modifiable behavior, which is after smoking, it becomes down to diabetes resistance and all of the metabolic this regulation, so yeah I'll get off my soapbox now, but again. I this is in many ways, just a sort of a plea for help, which is I think there's interesting amazing opportunity to understand this. So those another component to this that worries me greatly so. What we've seen, you know so a lot of this you're talking about. Controlling metabolism to preserve health through implementation of fasting and understanding fasting, but look what's happened to the American Diet. I. Mean there are people now that don't even. Recognize vegetables in the supermarket. There are people that only eat prepared food, and so what we've seen is on the one hand you're talking about preserving health and all that, but on the other hand, the overall health of Americans deteriorating obesity is greatly increased. and has no sign of abating the Diet of Americans loaded with high fructose, corn, Syrup and diets that are disproportionate with prepared food, so the only way to globally improve the health of Americans or anyone else for that matter is to deal with both of these problems at the same time. and to me, that's probably the greatest line of reasoning that says fasting is probably protective against all chronic disease, because if you look at the three main chronic diseases that account for to our last analysis, eighty two percent of deaths above the age of fifty in the United States excluding COPD's if you take out the obvious smoking related death of COPD, eighty two percent of death is. To Cardiovascular Disease Cancer. Disease and complications of diabetes. That's pretty stark. There's no question that when you improve metabolic health, which you can do through fasting, you reduce the risk of all of those significantly. Of course, the question becomes. How much of a role does a tough edgy play in that? Specifically you look the example you gave of neurodegeneration that makes a very compelling case for it probably also in cancer. What would we know about cardiovascular disease by the way? Nothing comes to mind I. don't recall seeing anything in that area. I mean my take on the literature is that the benefits of fasting in cardiovascular disease are primarily mediated through the metabolic health benefits of IT Lower Glucose, lower insulin, lower home, assisting and time lower inflammation primarily as opposed to something that directly pertains to Aibo be or the inflammatory response to that, but again maybe it's just there and I haven't seen it. What else do you think is going on? What travels with a tough Can we talk about Senescence for a moment? Do we understand the sense of what's happening? When an animal or a human is undergoing a Tafa g with respect to either SASS, or just the overall senescent cells? Yeah there seems to be complicated roles for TAVEGGIA and Senescence. Was Evidence from the Rita lab that SAS. The secretion of inflammatory factors that occurs during senescence is facilitated by autophagy. But then in the cancer setting you, there's also examples where loss of atop A. G. Limits Senescence so I think in Senescence area. It's still a little bit confusing and maybe a little bit context dependent as to what's happening. And then going back to the question about molecules. What do we know about Metformin and a toughie? Do we know that in a fed state? If we give an animal or a human metformin, we can still induce a tough AJI. All things equal through the PK activation. Yes I think that that's true, but I think that we don't understand over the long term what happens and what the consequence of having a top Gio, not having autophagy is so for example we've never given met form to our mice that don't have a tough Ajay. That might be an interesting thing to do. What is the consequence of atop of G. Induction by foreman? It actually might be better to do that in a system where. AUTOPHAGY could be wasn't completely gone, but could be tangled up. You have the ability to turn time for g into an analog versus a digital meaning where you can actually use gradations versus just honor off. Yes, I, think the mouse model where a tough Ajay expression of essential Taffeta gene is controlled by an essay. CHARLEENA might be the way to do that experiment. And then what about rapamycin? What do we know about the use of rapamycin which has been studied so liberally across again everything from yeast flies worms, mammals uniformly extends life potent inhibitor of 'em tour, which would signal a tougher g. all things equal where we see that relationship. So there's been a lot of discussion about using. arapahoe logs as TAP AJI stimulators, but it's like what you said before. It does many other things, and it's also immune suppressive, although that also depends on the dose right I been the airlines data suggested that it was actually immune enhancing when given intermittently also have to remember that if you have a small molecule like Rapamycin, and you want to use it to preserve someone's health, you have to make sure that it's safe and I? Think that's when everyone backs away. Because if you've got cancer and they WANNA, try experimental drug and you've got no other hoping. You're going to be dead in a short period of time. Does a bit of latitude in what can be done clinically to test whether or not, there's a small molecule or some sort of drug that will be safe and possibly have efficacy. But when you're talking about prevention, it's a big problem. The drug companies are not interested in it. Because the amount of time it would take in the risk of right just a much narrower margin. That's exactly the reason we're in the situation. We're in so just to reiterate. We have a situation where. I am not convinced that longevity as a game is going to be one on the back of extending the time you have a disease I have never seen a shred of evidence to suggest that that is the answer everything in humans and animals points to the opposite end of the spectrum. Longevity is about delaying the time it takes until disease comes. The implication of that is. Prevention is the single most important tool in the longevity toolkit. How do we reconcile that with you just said. All of our pharmacologic efforts, the trillion dollars we spend on drug development is all on the wrong side of the equation. It's on the. How do you live longer once? You have a disease. And I understand why. That's the case for all the reasons you just said. And if that doesn't make the most compelling case for taking the best and safest drug of them all, which is fasting and understanding how to dose it, and what frequency to does it I don't know what makes a better case along with exercise by the way I put exercise in that same category, which is, it bothers me that we don't really know how to dose exercise either I mean it's less of a problem. I think because for most people the issue is do more, but it would be really nice to know. Know, what the dose response is on different types of exercise, especially for people who want to do the minimum effective amount, so both from exercise perspective and a nutrient deprivation perspective. There's no more low hanging fruit in terms of minimizing human suffering and understanding how these things work. You should start a biotech company to do this David Sabatini and I have talked about this at length, and he has constantly told me to do this and the way we've thought about it. It's not going to happen because I won't do it. So, someone else will have to do with the way David describes it very eloquently is. Right now metabolic response to nutrients blackbox. And what David? Thanks and I I think he's right is there's a multibillion dollar opportunity in decoding the blackbox? In other words when we understand exactly what the responses to. Type of nutrient in every different dose and frequency, and we can decode that in the way that we can do with so many other biochemical processes. You can do everything because then you could actually develop drugs. Probably they could actually do something so there's a drug development platform that comes out of that, and then for my standpoint, what I'm really interested in is is simply just on the front lines as a sort of knuckle dragging doctor. How do you even just put this into clinical practice? But again it's high risk. It's a lot of effort to do part of that. I think on the drug. Drug Development side. There's a lot there i. don't think it's very high risk on the question. I posed to you earlier. I think the let's do the mouse study and identify the fifty metabolites proteome signature things that are generally going with a tough Aji, and then let's shotgun that in an unbiased way against human subjects, like I feel like that's a project in the tens of millions of dollars, not even the hundreds of millions of dollars and again if you add one year of life to each human as a result of that, that's kind of staggering freight and I think if you couple understanding. Mechanisms of metabolic delay of. Damaging, diseases with surveillance for risk factors, I think those two things really need to be coupled together because you can. Even. If you define what the optimal diet and exercise fasting regimen is for delaying the onset of disease. There are still unlucky people and I think that we can't forget about them. In the context of health and longevity and wellbeing, because you could have the healthiest diet and everything right Vogelstein has written about this right. I mean there's clearly a components. There's a still casting yeah component to this. Absolutely and again I don't think there's any reason to believe that we couldn't be addressing both of these. Yes, I think that there's no reason to do everything one always has to bear in mind that there is this other risk factor that no matter what happens with. Understanding metabolism and fasting in good health practices that other things still going to be there. If you have a bracco on mutation, that's a compounding and separate issue. So in two thousand sixteen, the Nobel Prize was awarded for the basically the genetic Lou sedation of Hoffa Jr what are the salient features of that award? What was it about a his work that led to that award. So what he did was quite profound and very creative. He developed an asset a well, he asked. What of the I use requires nitrogen for survival. And he asked what are the genes that are required for nitrogen survival, and he identified the target essential atop jeans, and I always wondered whether if he was in the United States woodwork like that be funded because. Because it just seems like it was an important question, but it didn't have such a clear application down the line. That's right. It was a bit too high risk to fund right, and also the clear disease connection wasn't there and so forth and so on, and nonetheless he did that and I. Guess the point is, is that sometimes? Scientific discoveries are so basic. That you can ever anticipate what would ultimately lead to, and in this case it led to something very extrordinary, but he probably had no idea at the time, and once they discovered these essential genes in yeast, than it was apparent that there were homologue in memos and so forth and saw. How conserved are those genes between yeast and mammals? If you do a blast search, you can see them. I mean not all of them, but the amino acid Amal. Jay was compelling. Well so when you sort of think about the future of. I think so much of what we've talked about. Kind of feeds into what your optimism is. But how do you want to spend the next ten years of your career? What other questions you want to probe? I think I would like to translate what we've learned about. The Role of our top Ajay in cancer, and that involves developing small molecule inhibitors to inhibit autophagy for cancer therapy and film and I started a company to do that. And what we're focusing on now is defining at the molecular level, but the functional requirements for top G. R. in individual cancers. And this involves understanding the Metabolic Rollover Taffer Gee why one cancer needs top more than another, and then the newest connection is the connection information. When you went, activate atop Aji you stimulate inflammation, and this is what we've talked about earlier in the context of cancer. That could be a really good thing because the game changer in cancer therapy now is immune checkpoint blockade. Fact what I was just talking about at the as your meeting yesterday was a particular patient that came to our Kansas Center and went through surgery. Radiation Chemotherapy and it all failed, and her body was riddled with tumors, and she went on a clinical trial for immune checkpoint blockade. Enter Walla. Tumors melted away, and that was five years ago and she's perfectly fine, so what we have to do is make that work for everybody, and if inhibiting autophagy activates the immune response that can facilitate. Not People who wouldn't respond to him you and check my aid to respond. Then that would be critically important to. Me Let me. Think about that for a second. So when we think about the patients that are responsive and we really have to big targets right C. T. L. A. FOREIGN PD one. Melanoma obviously is a huge success story here because it is so mutagenic interesting, I have a friend who has lynch syndrome, so that's a familial syndrome where people are predisposed to cancer. Heap developed colon cancer when he was quite young, went on to develop pancreatic cancer adenocarcinoma pancreas, which is uniformly fatal, almost VAT exception. He presented with an advanced state, so he was not even a surgical candidate to the tumor had completely engulfed. Artery vein which meant he couldn't even undergo the surgical procedure though it wouldn't have done much anyway. I had just read a paper. Six months earlier. In the New England Journal Medicine about Africa with the paper was exactly about, but it made me think. That because he had Lynch Syndrome and he has so many mutations, he might be a candidate for checkpoint inhibitor. So we went back to his oncologist and said Hey, can we get him on Chitralada? They said which is anti PD ONE? They said No. There's no standard for that, but we found a clinical trial actually got him in. He Got Chitralada I was five years ago. He's disease-free, so you go from unrestrictable pancreatic Adenocarcinoma to know pancreatic cancer pretty remarkable. Now the question is when I think about how broadly extendable that's going to be. It really comes down to how many shots on goal do you get? How many mutations do you get such that you can? These checkpoint inhibitors and so tell me how a tough Aji fits into that because I think I missing the link of why enhanced, immune nonspecific immune response would factor into that I know there's a link, but I need you to explain it to me, so that's exactly where we're going with research and. The yesterday. So we know that tumors with very high mutation burden respond better to immune checkpoint blockade. But it's not that simple because there are patients with tumors, do have a high mutation burden that don't respond and we don't know why could be. They up regulated some other checkpoint. Inhibit more could be some other reason they don't express class. One or the the immune system can't see the tumor for some various reasons, and then we also know there are tumors that have a low mutation burden do. Yeah and so a big part. In fact, we just got an NIH grant to study this is. To make mouse models of cancer with low medium and high mutation burden. With which to. Being tough AJI and exactly we haven't done the autophagy part yet. We're just doing the generating the models using proofreading mutations, polymerase, Epsilon and Delta to generate mice with cancer with various levels of mutation burn in their tumors, and this is so cool because we'll be able to ask basic questions. Like how many mutations do you need when you have a low mutation burden? What can you do to make the immune system? See that tumor? Do you need only mutations in the nuclear genome? What about mutations in the Motto Contra Gino? So, one of the mouse models we made was to generate a mutated phenotype in the might counted. You know there are a human cancers that have. A high level of Michael. condo genome mutations whether that has any effect on anything is completely unknown. There's no reason why they couldn't be presented as tumor antigens, and you'd think if anything they would be more immunity genyk. I mean they should be all things equal just because of their bacterial origin that should elicit a much greater immune response exactly right? This is what this grant is designed to do to generate. Fina types in mouse models. Models of cancer, so we can have a spectrum from low to really high mutations in the nuclear genome as well as the minor condo. Gino, then to figure out the mechanism of response to immune checkpoint blockade to make cold tumors hot, and that's essentially what the loss of is doing by promoting information. It's taking a tumor that is not killed by t cells that does not respond to immune checkpoint blockade and rendering that tumor responsive. And where do you put this? In the hierarchy of optimism for the future of cancer therapy, I mean to me the interesting stuff in cancer therapy is getting more and more targeted and stacking more and more therapies on top of each other, so this is an elegant example of stacking. Something that is clearly going to become a pillar of oncology, which is immune based therapy with something that frankly is partially metabolic, and frankly partially more complicated than just metabolic therapy, so you've got almost add this to the layer of pieces of Swiss cheese. you start to stack on top if you have enough of them, you're not gonna be able to drop a pencil through. The cancer doesn't survive. That's right, so the limitations that we have with immune checkpoint. Blockade is some of which I already mentioned. We can identify who's going to respond and WHO's not going to respond we have to. Extend the Responder Pool, but we have to be able to model that, because it's very clear that as single agents is going to be a immune checkpoint. Blockade Therapy is not going to help most of the patients. So how do we go about optimizing this treatment and having models where you can combine immune checkpoint blockade with other therapies to evaluate what is the optimal response is critical, and that's what we're doing, and whether fasting influences this. Is completely unknown. What's the role of tough in the immune cell itself so either adaptive or innate them? Maybe both, so we know that one of the things we did was to. Turn autophagy often mouse and ask how that affected basic immune responses and the answer was. Everything in the short term appeared to be completely functional and if anything. The T. cells were more anti tumor. But, if you go into the long term, if you knock out in a central gene only Tisdale's for example and look nine months later, I think those T. cells are not going to be very functional. But it it really depends on how you design the experiment for cancer therapy. We want to know what happens acutely. When you're inhibiting autophagy. You're going to be looking at things in the short term not in the long term so the still a lot we need to do in that area, but in the short term for cancer therapy the immune system. Seems to function well, if not better in the presence of atop Jana Bishen. This just doesn't stop getting confusing. Because again, you would think that. Given the benefits of Tafkaji and preventing cancer one of them. You would think that that would only enhance innate immunity because of the role, innate immunity plays in cancer. Which again I think just speaks to. We are still really scratching the surface of all of the different tentacles that come out of these tools. Something like fasting seems very simple, and it's simple of course to do, but it has such a set of Playa atro- pick extensions and benefits that it's very unlikely that it's about all or none. There's nothing black and white here. It's really all these shades of gray that it's not intuitive when you look at them. What the net effect is because it's a little bit of this a little bit of that more of this than that. It's the balance of this versus that. Yes, I would agree and I think context is important, too. When you think of all the big chronic diseases just based on what you've talked with us today about. I think we have to be really excited about Alzheimer's disease based on the model. You've shared I. Mean that strikes me as An amazing opportunity because one. We don't have a single tool a wants somebody has Alzheimer's disease. I'm sure you saw the most recent I. Don't know if you follow that literature, but we just saw two enormous failures in the Anti amyloid. Beta drug trials, so we're back to square one, which is not a single drug that works for this condition. If any disease demands prevention, it has to be this one. It's hard to make the case. That fasting isn't going to play a beneficial role there, isn't it? I believe you. Love the test. That'd be tested, but I think that when you look at the dramatic failures in preventing. Delaying Alzheimer's disease. You have to ask the question. What is the root cause of that and? If you look at the approaches, all the approaches are designed to. Meet, a symptom and the research has not. Yet gotten to the root cause. And I think that that is the reason for these spectacular failures is they're trying to treat a symptom of the disease rather than the cause of the disease. And when you look at the genes that are involved enduro degeneration in general for they fall into a broad array of different categories, and so my thinking is that they're all doing different things, but there's some common denominator that has yet to be identified. And I think that. Until. The root cause of disease is identified. Just finding means to ameliorate the symptoms is not going to be productive. Eileen I could sit here and talk about this for hours and hours I wanna be respectful of your time because I know you've stayed an extra day to have this discussion me, which I really appreciate. Is there anything else you WanNa talk about today, either as it pertains to your work something you're excited about in the future or anything else that pertains to a tough. I mean I. think that understanding in greater detail. How, autophagy impacts metabolism we've done some of that, but I think there's way more to do. We have the technical ability to examine metabolic flux in a mouse in Vivo in normal and starvation conditions men in response to different diseases, and we're only at the beginning of doing that and I think that that's something that we will continue to do and hope that we can identify. New Targets for anticancer therapy or signatures of metabolic problems, and we will continue to do that but again. I want to return to the immunotherapy. I think in the field of cancer building on that huge gain. We can't take our eyes off that ball. Those are both very interesting, and of course the former. It sounds like you really agree with David Sabatini which is, there's an enormous opportunity to decode metabolism in a way that we should have done twenty years ago. I think we lacked technology. I mean I think that so maybe I could take a minute to explain what we do and that by using. C Thirteen and fifteen labelled tracers. You can put them into a mouse. Infuse a mouse with these tracers. And by looking at where they go by mass spectrometry over different times, different time points, you can see metabolism, and that was something that was never possible before. What is it because we've been able to label these things forever? What was it the mass? SPEC didn't have the resolution before. What is it that why is it? We couldn't do this twenty years ago. I think they could do it with radioactive material, and they could do it somewhat with the technology. They had way back when. When, but I think that the technology now is far more sophisticated by using heavy isotopes. You don't need radio activity now. There are more mouse models of disease. You could even do this inhuman so rowdy Berardino, said the South Western is infusing these isotope tracers into humans with cancer and actually measuring the metabolism of human tumors. Wow, that's interesting I did. Experiment wants myself with doubly labeled water, which of course is very simple version of doing that sort of thing to examine energy expenditure. Field Day doing that. Oh! Yeah, but I think that in fact next week I'm supposed to go to. A keystone tumor metabolism meeting where all the experts in this area. We'll get together and talk about the detail, but this is a growing field. It's very exciting and understanding metabolism in mammals at a level we've never seen before. In various disease, states is tremendous. And then lastly, is it safe to say that should there be a strong enough public demand in a philanthropic demand to go? After that question, we talked about earlier about sort of decoding the dose effective fasting. Is that the sort of thing you'd be interested in working on? Yes, I was fascinated by what happened when mice didn't have tougher G. and they died when. When they were fasted, and I am very much interested in fasting as a way to preserve health I'm also interested in is what I mentioned earlier, the dietary part because I think all of this has to go together. It's not just how many calories read or how often you eat them. It's what they are, so yes, that's something. That's very important to me. While I lean. Thank you very much. This is super, super interesting, and I know that folks are going to the cell. Propose a few more questions than than even we had time to go into, but it's you work his fantastic. I appreciate your generosity. Oh, this has been a lot of fun. I'm glad I took the time to do this, thanks. Thank you for listening to this week's episode of the drive. If you're interested in diving deeper into any topics we discuss, we've created a membership program that allows us to bring you more indepth exclusive content without relying on paid ads. It's our goal to ensure members get back much more than the price. This attrition at that end membership benefits include a bunch of things. One totally kick ass comprehensive podcast show notes the detail every topic paper person thing we discuss on each episode. The word on the street is nobody's shown US rival these. Monthly Ama episodes or asked me anything episodes hearings episodes completely. Access to our private podcast that allows you to hear everything without having to listen to. 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cancer Autophagy neurodegenerative disease Kansas Rutgers University Cancer pancreatic cancer lung cancer kidney cancer Tafkaji Alzheimer's disease Cancer Center Bruce Stillman fatty liver David Sabatini New Jersey San Diego Noah Ataf Aji Professor Eileen White Eileen Suny Spring Harbor Laboratory Eilee
#73 Steven Strogatz: Exploring Curiosities

The Knowledge Project with Shane Parrish

1:35:54 hr | 1 year ago

#73 Steven Strogatz: Exploring Curiosities

"A great discovery that no one appreciates is not really a great discovery because science is a social enterprise. It's not just enough to do the work. You have to communicate it and help help other people understand why it matters Hello and welcome. I'm Shane Parrish and you're listening to the knowledge project. A podcast dedicated to mastering the best. What other people have already pretty figured out? I'm GONNA help you better understand yourself and the world around you by exploring the ideas methods and mental models from some of the most outstanding people on the world together will extract the timeless lessons from their biggest successes as well as the hard times. The knowledge product is part of Burnham Street a website dedicated indicated to helping you think better and better Farnam street puts together a free weekly newsletter. That I think you'll love. It's called BRANFORD and it comes out every Sunday our team scour scour the Internet for the most mind expanding books articles and resources so you can spend less time searching and more time learning. Discover what you're missing it. s US dot blog today. I'm talking with Steve and stroke gaps professor of Applied Mathematics at Cornell University. I wanted to talk with Steve. After reading his most recent awesome book infinite powers which explores how calculus unlocked the secrets of the universe together. We'll explore how helps us better understand the world and make better decisions and as you'll see. Steve Makes Learning Fun and practical. What's get started? It's time to listen and learn the knowledge project is sponsored by metal Ab for a decade Mandola has helped some of the world's top companies and entrepreneurs build products that millions of people. A US every day. You probably didn't realize at the time but odds are you've used an APP that they've helped design or build apps like slack coin base. Facebook Messenger oculus lonely planet and many more metal wants to bring their unique design philosophy to your project. Let them take your brainstorm and turn it into the next billion dollar APP from idea sketched Gash on the back of a Napkin to final ship product. Check them out at medal ABDUC. Oh that's metal APP DOT CO and when you get in touch. Tell Them Shane Saint you. How did you get interested in math? Was it a story that pulled you in like did this. Were you in neatly interested in it. Was it something a teacher like. How how did this happen? I well I was interested in all of school and I still am. I liked all the different subjects but so math. Didn't stand out for me I'd say really pretty much. For most of my childhood. It was just one among many but then I do remember one or two moments where it started to take special significance one was. They had two friends when I was about well. Let's see we used to call a junior highschool so was seventh and eighth grade. I must have been about twelve years. Old It to other boys and They were both good at math. And and Vocabulary and geography. And everything else I used to like to compete with them. We would play chess chess against each other and other things and at that age just being better than your friend meant a lot to me. I don't know or having them feel better than me. Inflicted a kind of pain so I do remember one time getting a little higher score than than this other kid on a math exam and it just felt good so I'm not saying this is a noble reason. Listen to be interested in math but it was just an early memory that it was very objective. Say I'm better than you and it actually meant something which to a thirteen year. Old Boy boy that was important but but on more elevated level I'd say the real turning point was in my Would have been my sophomore off more year of Highschool so by then I was about fourteen or fifteen and a teacher said something that took me aback. I had never heard any teacher say something like this. He was this. This was Mister Johnson who had a beard and had gone to Mit and to me. He looked like what I imagined. A A brilliant you know math professor might have looked like he was very serious. Not A smiler But fair and and he said that there was a certain geometry problem that he had never Christina any student solve just offhandedly mentioned it to the whole class and I thought that was interesting because I had always been able to do any geometry problem. Any teacher asked me so so he said yeah he didn't no one ever solved the certain question and then he also said that he didn't know how to solve the problem and that was very surprising because I had never bird teachers say that you know he didn't know how to do the problem so I started thinking about. I could tell you the problem in case here. Yeah please do It was a question about a triangle that sounded like many other geometry problems It says if the angle by sectors of a triangle are congruent proved. The triangle is Isosceles. So what that means is angle by sectors that would be aligned that cut through the angle picture. A triangle like say you know standing there flat on the table with its point point sticking up if you if you divide the angle and half at the base there. Two of them down there if they're divided in half by line and then that line meets the opposite side of the Triangle Angle. That's the angle by sector so if you have two of those criss crossing and they're equally long that's what congruent means so to angle by sectors of equal length proved that the triangle is II sauces. meaning that those two angles at the base are actually the same angle sank. Had the same number of degrees and so it sounded like many other questions. There are similar questions if if to angle to perpendicular by sectors are congruent or something called Medians. All these questions are pretty easy to prove. Prove that you would get an Isosceles triangle but but something about angle by sectors made the question very hard and when I tried it I couldn't do it and that that data ready caught my interest and I I I worked on it a lot. I couldn't do to spend a day or two on. I still couldn't do it. And then days became weeks and weeks became month breath and I think I spent about maybe six months on this question trying things getting stuck trying other things getting stuck you know and sometimes it would come close to working out but I could never get the argument to go all the way through and my friends would get annoyed with me like come on. Let's go to the movie now. I feel like thinking about the angle by sectors. Here's or in French class. You know when the some We used to have this klay conjugation train where the teacher would give some verbs to conjugate educate. And you'd feel the it'd be going around the room and you could feel it's GonNa be my turn soon and but I was still thinking about the angle by sector so I had was obsessed with it and I didn't realize it at the time. Ah doing research that where I was thinking about something for the just the pure pleasure of trying to understand it and ultimately got something that I thought was was a proof I eight. That was a boarding school. My teacher lived nearby and I asked if I could come over to his house on Sunday morning. He could still remember him there and his beard and his pajamas wasn't his little kids running around in his house at breakfast and he checked us this proof line by line very slowly and you know with his serious stern face had while yes that's correct argument very good and then he wrote a little note to the headmaster of the school which meant a lot to me that you know my teacher said something like Stephen has real talent you know so I don't know it just it was definitely a pivotal moment. It's interesting like what a difference teacher can make. Yeah of course I mean for partly that he really set the bar very high but also he was humble. You know he he. He was strong enough to admit there was something he didn't know. And and I apparently other he probably mentioned that another years and other students hadn't either risen to the challenge or weren't interested. Why would you do homework if you didn't have to? But something about it caught me and Yeah he was a very inspirational teacher and and it's interesting too that he's not. The Hollywood inspirational teacher wasn't like you. You know such a loving sweet guy or certainly not interested in building your self esteem. He was just all business but There's a line in that movie about another other. Great teacher stand and deliver about Hymie Escalante. Who taught in East Los Angeles Who says in once critical scene in the movie the students will rise to the level that the teacher expects and so if the teacher expects something really hard kids? Don't even know it's impossible. They'll try I try to do do that myself with some of my students. What do you see? Does that prove out. Sometimes it does especially younger ones you can really you know by the time. They're seasoned if they've been in college a few years they start to know the game but but freshman don't really know what college is going to be like. And so you can do mercilessly unreasonable things to to the bright freshmen in math. And they will do it will astonish you with what they can do. Yeah we see that all the time. You didn't have an easy path in Matheu food. Was it first year university where you sort of get the worst grade. You've ever gotten any switched to physics or was that when was that that is true. That was my first year. Well well that was that class so I was just describing. How ours freshman the first year students can do astonishing things I was? I was Supposedly one of of those students when I went to college. So they grouped a bunch of us together in like Whiz. Kid Linear Algebra and For this for all the kids who had done extremely well in calculus in high school cool so we and it's sort of like you had a little a mark on your head. This is a future professional mathematician or early potential to be and the other thing though. Is that the professors know that kids are good in math in high school. A lot of them are going to get so to speak weeded out. They don't really have the right stuff to be mathematicians of the future our elise that was the thinking at the time. It's a pretty nasty pedagogical philosophy. I must say but but they would throw all of us in with one of the worst teachers in in the school. I don't know why they assigned him to us. I mean this was a really pathetically terrible person for teaching. I mean the first day of class. He came men and sort of slithered along. The Wall didn't make eye contact with the students. Free very shy person who didn't say welcome to Princeton. Welcome to the you know this is is going to be exciting. Nothing you just just started with the definition of the key ideas at the beginning of Linear Algebra. The definition of Field Blah Blah Blah. Here are the axioms that that satisfies anyway extremely dry and I couldn't understand what the heck was going on and and the textbook had no pictures and as a visual thinker. I found that very problematic. I couldn't really understand what was happening and weeks would go by. I could feel myself falling behind and not you know. My homework was getting worse and worse grades and I didn't know certain basic things like well try reading a different book. You idiot or go to go. Ask for help from the teaching assistant. I didn't know I had never done that stuff before. So it didn't occur to me. I thought I should be able to understand and I was having trouble. And so I did end up getting B. minus which was a pretty low grade and I wish I had your transcripts. Well okay but it was. It was a low grade and it was discouraging because I didn't deserve a B. minus. I really knew that I knew nothing. I probably should have failed. But they didn't want to do that. For some reason so was yeah very demoralizing experience and it made me think think. Wow I maybe I don't have the right stuff for this. Maybe math is different in college. I stuck with it for one more semester and took a second course in that. Same whiz kid sequence honors this time honors multi variable calculus. Night could feel. The same thing was happening again in that second semester I was on track for another lousy performance while meanwhile I saw other kids doing fine I mean they were raising their hand. They seem to know everything. So I you know even in a relative sense not just an absolute salute sense. I could see that I was weak compared to the people around me and it was a formative experience because I think it's given me a lot of sympathy as a teacher When I see students will struggling I? I don't always assume that they're hopeless or they can't be rescued or they have no future future. In my case I mean it's it has stuck in my craw now forty years later. You know when I teach linear Algebra. I realize it's not really that hard you can do better than my old teacher did. Show some pictures. Give some intuition talk about how it's connected to the real world. Tell history you know. Bring it alive Jesus. It's it's a really exciting subject you don't have to suck all the blood out of it so I also the idea of being made to feel like a weed. You hear this idea of weeding out the people who have the right stuff from those that don't I really don't accept that idea. People have a lot of potential more than that kind of superficial analysis would lead lead you to think so I was practically I was I could have easily been weeded out except that I just love the subject so much I stuck with it. Even though I was always one of the weakest math majors in my cohort I just loved it more than than most fascinating story at Lick it strikes me that math is something that we develop this mindset Eh for whatever reason that we're just not mathematical or math isn't my strong and you know this sort of like happens around great for five or six it's sort of like follows is. Is that a teaching thing like. Why do most of us find Massa Boring and drive? You're right about that aren't you. I mean I mean that is if you just look around and ask your friends. The average person did not have a good experience in math class. Although tends to be a little more complicated than that most people will say I did. I'd like math until and then they'll tell you until we got to fractions. Those were really confusing with the nominee denominators. or or I liked it until we got to Algebra and then was all of those XS and ys instead of numbers and I didn't really know what was going on I even liked Algebra but and I lost it geometry or I hit the wall and Calculus so different people people have these different places but it seems that sorta happens to everybody at some point or almost everybody and so why There's a few explanations you know. One is that the subject the way it's traditionally taught as is made to seem like a tower each thing builds on the the topic before before it and if you fall off at any stage It's a long way down off the tower. You know that that is. It's a very linear architecture. Whereas the reality he is the math is a web? Not a tower. The you can jump in at different points in the network of ideas and then find your way around from there and so it's not really true. I mean it's complicated. In some ways it is sort of like a tower the idea of Algebra and variables and functions. And I know you know. Computer Science So you will know what I'm talking about here. Those are fundamental ideas. If you can't think abstractly about a variable rather than concrete number you're going to have trouble with breath. Allot of math. Because that's a fundamental idea. So if if you don't get that pre calculus is going to be trouble. Algebra is going to be trouble so some things are indispensable but there are other things which okay you know. Maybe you missed the idea of an awesome. Tote you can get on. You can still keep going without that. So there's that I mean it's it's partly the structure of the subject object partly Partly it's often taught in a very top down way. You know that. The teacher presents material almost like pouring liquid into to a student's head almost like a curriculum dump to right. It's like we have to cover all of these things and we're gonNA start here and we're going to progress and I don't care if you're interested or not it's just just this is the standard curriculum Though you hit a bunch of important things there so one is the feeling that there's a lot to cover. I want her to teach her say. Don't try to cover the material. Try to uncover it Right I mean there's a lot to be discovered a lot to be uncovered the to remove the fog to remove. Remove the crust of of you know difficulty or misunderstanding. Reveal something rather than cover it but okay. That's just a silly use of the word cover and uncover cover but The notion that there's a standard curriculum sometimes stifles exploration. There is a certain amount of exploring that even a very young on student can do where if you know. The experience of being a mathematician is so different than that of being a student where we're frequently in the dark and were poking around and and trying to make sense of some new territory mathematical or mental territory and You're an explorer. You're lost you're in the jungle. How do you get Out or how do you make progress. And that's very valuable skill in all aspects of life when there's uncertainty and Sometimes fear but excitement. exhilaration listen you know the thrill of problem solving an inching. Your way forward applies to everything and so we could be spending more time on that. Rather than here's here's an established body of techniques that you have to learn and I'm GonNa dump it or pour it into your head that's a very artificial picture of the mathematical enterprise and Why do we do it? I don't know I mean maybe there's all kinds of standardized testing. The teacher has to get through certain material to satisfy local authorities. Sir Because tradition says this is what an educated person needs to know. And there's some truth to that so I don't know I mean I don't have an easy solution to this. But Times I've taught taught courses with this more exploratory mode where there was no place we had to get to. We just had to do the process in an honest way. I mean the way a real mathematician breath mission would do it students love. That math is not boring. That Mathis. That's creative Oh yeah I would love the. Yeah what we do that. I mean I teach a course called math explorations orations with students who are required to take a math course before they graduate and they dread it they. Don't you know these are the people who are the real Dead Enders like the. They're putting this off until their last year of college But they get out they have to go through it to graduate then once I I teach it this way with them doing explorations together activities working in groups and thinking and sharing ideas and give me some examples of like the stuff that you cover. Oh Oh yeah sure. So here's one you know. We're used to a standard kind of geometry but there are other geometry's here's an example. Suppose were in New New York City or some other city that has a grid of streets so if I say how far is my location from some other location and you could say it in terms of miles or kilometers as the crow flies but that's not very relevant. If you're driving on the grid you might be more likely to say you have to go. Three blocks exp north and eight blocks west or something like that. She would give units of blocks as measured on the grid. Now that's an interesting kind of geometry maitree if you if you define the distance between two points in a plane as being The number of units north-south plus the number of units East West are you can define distance like that. It's not the EUCLIDEAN distance. It's not the standard one because you're not allowed to take diagonal paths in in this. Geometry can only go on the grid now. If you ask someone a question like what is a circle. Look like in this geometry mm-hmm that's an interesting question. You know what late in other words. What's the set of all points three blocks away from a given point so try to picture that in your head you could go three blocks north or you go two blocks north and one over either east or West you could go one up and to over and if you can picture what those points look like do you? Are you picturing it. I'm trying to yeah. Yeah do you. Do you want to draw. Do you have a piece of paper in front of you or anything or maybe you have it in your head having my head. Okay Yeah you WANNA say or should I not make burst myself enough in this conversation. All right then I'll say So I mean if we if both okay well we'll look should look like a diamond. I mean should look like tilted square. Yeah okay so so when I show when my students discovered that one person started screaming. She's saying that's wrong. That's that can't be right. That's crazy so I said what's the problem. She said a circle is round. This thing has points. It's I mean this has corners this. This is a look around so I said who will who says it should be round just because a Euclidean circles round in traditional geometry. This is a new world. We're making new rules. This doesn't have doesn't have to. Who says the last? Oh look around. It doesn't look around so and then you can do more. You could say what is Pie. You know calculate calculate pie in this geometry now that takes you back to fundamentals again while what is Pie. I mean some people have memorized three point. One four one five nine like that but that just memorizing. That's not thinking thinking would be what does pie actually mean. It's it means the ratio of the circumference of a circle to the diameter of a circle. And so would this diamond shape. You have to now think the financial point like assume nobody knows anything including myself so circumference is the area around around the circle and the diameter is the way to the circle. That's right exactly good right so the circumference would be just that it's the distance. You would travel if you moved around the circle circle the total distance following the circle around on its rim and exactly the diameter is the widest distance across the circle. So so you know again. You have to try to calculate that or see what it would be for my little example with the circle of radius three in this funny geometry and at the radius is the point from the middle of the circle to its half the diameter. I'm guessing that's right. Sure that's right. The radius would be half the diameter right so from the center of this. It's been a long time time since I did this. Good okay. I'm glad it's coming back to you So I don't know I mean we don't maybe it's not so good to do it In this audio format. But if I'll tell you the answer comes out before you calculate the circumference and you calculate the diameter. You'll end up getting that. They're always in the race. I think I'm doing it right. It's always going to be four times the The diameter will be the circumference. Which is interesting? That pie is is actually a whole number. It's four in this geometry instead of three point. Point one four so I mean okay. What's the use of this? It's not like it's so important to have the geometry for getting around cities with grids. It's just to make the point that that this is a playground. You're you're this is the realm of the human imagination you can think of alternative geometry's and explore them and and you can point being. It's very empowering the students feel hey I can do this I mean they can they. Don't tell them the answers. The whole course is based on me. Never lecturing I just give them puzzles and then they try to figure them out yet they do and they do figuring out if they're stuck I say okay. Let's figure out what to do. I mean now you're you're stuck. What are you going to do? And then people learn how to get unstuck which is really valuable to have problem solving strategies for coping with Frustration we also talk about emotional stuff like okay. We're stuck. How does that feel all? I'm frustrated I'm mad. I'm curious whatever and people talk and now there's a a lot of people these days. Criticizing the notion of safe-space. You hear this that that this is a snowflake thing I okay we. We're not shouldn't talk politics politics but I'm sure your listeners. Know what I mean that that you hear about in education especially higher ed that there are things that we're not supposed to talk about because it triggers people bowl and this is a safe space where we're not going to trigger anybody and that's usually presented as Very negative thing that stifles free speech etc.. But I want to Bring up the possibility because I've lived it with these students that when you make a space that is safe for mathematical confusion Meaning nobody's GonNa feel stupid huping here. We're all we're all confused. Confusion is the normal state of affairs. When you're trying something really hard in when you're exploring the unknown so it is a safe space in the sense that you can trust us that we're all on the same team trying to figure this out together and Don't worry about looking stupid confused over here too. That sounds like a great environment. It is it is and it's and when you collaborate on on research at the cutting edge of math where nobody knows the answer you can't look it up. You can't ask a professor because no one knows and it's the same thing with science or any other thing at the cutting edge of knowledge when you're collaborating it really helps to be vulnerable and to have a safe enough relationship with your collaborators that you can say I don't get this could. Did you go over that again or I don't see what to do or or to suggest a stupid thing that someone else rather than jumping down your throat or they tease you. Maybe they do jump down your throat a little. But it's ultimately ultimately safe to take intellectual risk. That's the point as you were saying that I remembered a momentary panic. One of my kids brought home some homework last week and who is is looking at it going. Oh my gosh. I don't know how to do this and I sort of like. What does that mean does it mean? He's GonNa think less of me does it. I mean both. My kids are pretty good at math right but I was like hall and you just getting all these memories start coming back and I was like this is really hard problem. You're in grade five like this is pretty difficult. I don't I remember this difficult. Well so what can you tell what you did. Oh tell us I posted it on twitter. I even tagged you. I think at the end of it because I was like you're going to be my best friend is a good. I missed it. I did. I respond. Oh No it was sort of the question I posed so oh my kids are both pretty decent math way beyond me already and it was like you're standing on this forty meter building which is twenty meters away from a tree and at at a forty five degree angle. Uc like the height of the tree. I think was like fifteen meters or something like how. How tall is the tree I Ah I was like Oh my God I was like Holy Khairullah Great Five. I thought I was doing multiplication and division what the heck is going on here Ah The whole point of that was basically you have two daughters yes. How should parents engage their kids? Emma like rather than give them the answer. Or how do we get kids excited. And how do we find that in ourselves again as we're helping our kids yet because I think I think the parents are critical to this in that apparent who says while I never used math in my life so it doesn't matter that's not going to help you know. We have to try not to pass on our own anxieties to our kids. What I try to do and what I would recommend other people do is to not be afraid to admit that you don't know something that's that's a big strong reaction to say I don't know let's figure it out you know either we can figure it out by thinking thinking about it or we can look it up on the web? I mean that's maybe the second best choice but sometimes that's the best you can do But but the key being being it's okay to not know everything. Now some I suppose. In some models of parenting the parent is the authority. Figure and to relinquish authority is a is a big concession and so these are maybe more traditional homes the parent will never do that. You're not supposed to be the equal or even the lesser of your kid but In intellectual matters I happen to like honesty. And if you don't know something why are you trying to pretend you're going to get found out anyway red you know and if you don't it's going to be ugly there's there's a scene I'm trying to remember. Yeah it's in my left foot. Do you remember this Daniel day-lewis movie. He's he's the what was the name of. The Guy was a poet. Patty know was his name. I'm not remembering but you know the movie I mean right. He's completely paralyzed except that that he can move his left foot. The young boy and he later goes on. It's a true story. Goes on to be a magnificent artist. who draws fantastic drawings and does paintings with the toes of his left foot But early in the movie we see him with his father And he's thought at that time to be mentally challenged the young patty because he has trouble talking Question comes up. The the his older sister is is working on her homework and her father. Is there sort of reading a newspaper or whatever in the daughter says what's twenty five percent of a quarter and the father says that's a stupid question you can't take a twenty five percent is a quarter. You can't take a quarter of a quarter and then young. Patty of in a very dramatic scene starts making noises over in the corner of the room. Nobody's been paying attention to him the whole time and someone says he's trying China. Say something what are you saying. Go Patty what are you trying to say he. They put a piece of chalk between his big toe on his left foot. And his you know pointer toe and he starts art scratching out something on this chalkboard and you can tell as you're watching. He's trying to do one sixteenth because one quarter times. One quarter is one sixteenth. Pink has figured out twenty. Five percent of a quarter is a sixteenth. But it's pretty hard to draw the the one in the slash and the sixteen with his foot in a It's a it's a sad scene because you can find it on Youtube. The father says he's an idiot. You know just ignore him because they can't figure out what he's drawing but he he's giving no the right answer anyway the point being that this father Who didn't know how to do the problem could have stifled all discussion in the family except Patty atty broke through so I looked this up? I looked up. The Question Migrate Five. Came home with and it's a telescope is set up on the roof of an office building so the lens is fifty meters above the street. Okay a scientist notices that when he looks out the telescope at a forty five degree angle to the Horizon Isan. He sees the top of a nearby tree that is along the same street on his walk to work. The scientists measures that the foot of the tree is ten meters along along the street from the entrance of the building What is the height of the tree? Assuming the tree has grown straight up. Wow all right. I'm drawing a little picture picture here. Fifty Tall. It's not obvious the momentary panic and I was like I don't know but we can figure this out. I'm sure her. We ended up doing a lot of youtube and figured out. I think how to solve it but wow but you could easily be like I don't know and then you leave this great five to sort of like figure this out on his own which probably thought that an optimal strategy. But did you ever come up with the answer. I think they have an answer. How did you do? I'll tell you if men's right well I don't know I may be misunderstanding question. But I've drawn a picture with something that it's Align standing up fifty units tall fifty meters tall yet now when you said forty five degrees viewed from the top of the building to to the horizon. It wasn't clear to me if that means forty five degrees down downward no forty-five up Sarah. Yeah forty five upward from the horizon. Yeah that's one heck of a tall tree. Yeah okay so so. Let's see all right so forty five going up. That wasn't what I had drawn but So if I do that The forty five degree angle makes an interesting if I if I go over to where the tree is and then continue up vertically from the top of the tree okay. Let's see sorry. The tree is very tall late. I guess I'm I'm hitting the trunk of the tree. It looks to me like I have to go fifty plus ten. I mean it'd be well. Is that wrong fifty. It's she's I'm going to embarrass myself here. The professional mathematician but it looks like it. Looks like it's a fifty foot tall building and then because you said forty five degrees that's going to make a half of a square right. That's a forty five forty five ninety triangle so to speak. That's a half of a square. A right a right isosceles triangle one so it was ten units over East or west to the tree. Then ten units North North would be to the top of the tree so looks to me like ten plus fifty. I would have thought sixty. Yeah I guess we. We probably didn't do it right. I what we did was doing it wrong right. Enjoy A job. You're doing it wrong. We drew triangle basically from the top of the building And that is all we had to do. Calculate the the height of the Angle Engle opposite the forty five degrees from its business. Engine I think I think so. How do you figure that it was like I would use a calculation so so when you could use the tangent but it's but with a forty five a right triangle the has a forty five degree angle as one of its angles? The other angle is also forty forty. Five degrees rank is forty five plus forty five plus ninety makes one eighty yet. So that's what I mean by saying it's a half a square it's a square sliced along diagonal. That's a forty five forty five nine okay. Yeah so it's like it's your stacking a square on top of the whole picture. And so the fact fact is that when it's a square. The ten units on the bottom translates into ten units on the vertical. saw her the Muslims. Wear what you would have gotten from your tangent your tangent engine of forty five would give you one so that so you would have concluded. It's ten units up on top of the fifty that were there to begin with so yeah I think sixty but okay well. This is what I usually do to do. Math over. podcast what are what are the other things that parents can do to. WHO's help their kids with math? And and help I mean Encourage curiosity and for US probably fairly natural with your daughter but for for many of us people have the same reaction. I probably do come home like oh no. Today's Homework de Videos and I'm going to have to look up when he goes to today. So that that I can answer questions in the morning One thing I suppose the parent could directly. Try to help immer herself. I yeah apparel of the parents started to like math and felt more secure. That would be a big help so when I wrote Back in twenty. Tell twenty ten I I think that's when it was two two thousand ten I was asked by the OP. Ed Page editor of New York Times to write a series about math for for that kind of reader for just the educated sort of the person who's curious about wide range of things who would be reading the times and so that was the the proposition do fifteen weeks of math in the New York Times starting from preschool. You know like the idea of numbers up to as far as you can go to graduate school or beyond and make it understandable. Make it fun and so it was a fantastic challenge. I really enjoyed that later. Grew into the book the joy of ex but the it was always written with the parents in mind mind it was meant for adults and so there's a lot of references to things that only adults would know about literature or philosophy or sports or history or whatever And yet I find that these columns tend to get used a lot in schools Because they do cover the standard curriculum all the way through Grad school but the especially a lot of elementary school and middle school and high school. Anyway so I think you know parents could try reading those columns. They're they're free. If you have the time subscription or you can get the first ten of free or you could also There's so many things on Youtube. Now you mentioned you and there are a lot of good resources There's I they're just excellent. It's like a golden era of math communication. There's someone named three blue one. Brown has his handle on YouTube. who makes really great videos videos about everything just more pedestrian level? There's Khan Academy where you can learn all kinds of things. He's very good. It's like his vision is bringing being education to the world at no cost and to a large extent. I think he sort of succeeds. It's really very good. But they're others person a methodology or it's interesting because now the best teachers have unlimited reach. They do right. The Internet has enabled like before it used to be that you would get You know if you're lucky you would get the best math teacher in your community And now you can. You can access by and large the best math teachers in the world. Yep that's how it's done unless the kids are already doing it so I I had occasion recently to meet a seven-year-old boy whose mother said he was very excited. She's actually a professor at at my school at Cornell and the mother said that her son who is seven even You know that he was very excited to find out that. A mathematician whose books he reads for Fun Actually teaches at the same school as his mom. Could he could he come meet me so I was talking to this little boy and there's actually a clip of that might encounter with him because I didn't know anything about him. I just thought I was going to shake his hand. And you know who who knows what assign a book for him or something. But he's no. He's got all kinds of math. He wants to show me and so I thought this could be fun so I told his mother take a little video of us. Turn your phone on and just let's see. Maybe he'll want to watch video afterward. Anyway she records and we're talking for about forty minutes where it begins with the boy whose name is Emir. Mir Samir shows me I I don't know what is he trying to do. He's just telling me to do some games on the calculator then. I realize he's making a thing called a magic square So just to remind people if they've ever heard of a magic square played with one. This is a three by three square of numbers The traditional Magic Square. You put in the numbers one two three up to nine such that every row adds up to fifteen an every column adds up to fifteen and every diagonal adds up to fifteen. There's a way of putting those numbers one through nine in the you know arranged them in this course that every row every calm and every diagonal adds up to fifteen. That's an ancient idea. That's a magic square. What this boy Zamir had figured out how to do something similar except that every row column and diagonal multiplied applied to the same number rather than added if you multiplied the three numbers? You'd always get the same number. So he's he's explaining to me how he figured this out and I saw. This is pretty good. This kid has seven. This is amazing. But then he says to me. After about like ten minutes it also worked with natural logarithms. So and this is all captured on tape. You know you can see it on youtube millions of mirror talking and you'll see my eyes pop out of my head because they wait a second. What is this kid knows natural logarithms at seven and pretty soon he says yeah no works with imaginary numbers to and you know I got onto this because you were asking what can parents do is Amir had already? I guess the thing was that Samir and other little kids are very aware of what's out there in the world of the Internet And so he knew me from the Internet. He knew other mathematicians from the Internet and he doesn't really particularly read books. He watches videos. That's where a lot of learning is happening for kids today so I would say parents should try to learn. I mean sure they could help the kids. It's with the homework but but there's a lot of good learning to be had on the Internet that seems to connect very well with this generation So I would I would try to use. Is that skillfully. It's not that hard if it's so to speak gifted child or someone with a lot of talent that's poses a different set of questions then the kid who's very frustrated and And hates math or is demoralized or even filling shattered about it because it can be super soul crushing it can also. We're just boring. I mean there's all kinds of different negative reactions. Some people feel ego deflation. They really feel like they're stupid You know other people can do math but they just don't see any point to it. They think it's boring and and then there yet others who find it very exciting and you know so there's challenges for parents of all three types of kids. It's the board child the depressed or you know distraught child who has tremendous math anxiety and then the kid who's wants to do more math but is limited by the the environment so I don't know I would have different ideas. I guess for each one make sounds tailoring suing. Here's a little bit sharing your recent folk what what is Calculus. Calculus is one of the greatest ideas of all time I would say it ranks right up there with relativity theory from Einstein with quantum theory of the atom. You know with evolution from Darwin and and I mean it's just had an enormous impact on the history of the world it's It's the mathematics of change. If you had to say it in one word that's what calculus is about how to quantify by things that change especially things that change in ever changing ways. So it's it's the first part of math that can cope with the dynamics of the world. And you know what do I mean so. The simplest kind of changes something moving Literally moving moving changing its location from place to the place so you could throw a ball or you could you know hurl javelins. You could be thinking about the planets moving around the sun you could be thinking about Um The concentration of virus in the bloodstream of a person with HIV after they take a combination drug therapy their viral concentration nation will plummet thankfully and so when doctors develop strategies for The life saving treatment nowadays the triple combination therapy that it has turned HIV into a chronic illness. From what used to be a near certain death sentence calculus played a big part in quantifying the dynamics of how the immune system system interacts with the virus and what role the different drugs. You know that have been offered would play and all that. So that's it I mean. Calculus is the math for describing in a world in flux and since everything is in flux you could see that it's bound to be pretty useful to have the ability to do that. Can you tell us the story of how our math I guess in this case in calculus influenced Our treatment options for HIV. Well Okay Yeah So take your mind back to. I'd I'd say you know like the mid nineteen eighties wherein the West here in the US or Canada the the HIV epidemic was really starting to hit. It was just very mysterious disease. wasn't so clear what was causing it And Ah but the symptoms were very predictable. That a person who got infected would at first show flu like symptoms. They'd feel kind of sick for two weeks but then they get better. You know they might have a fever They'd have could see their T.. Cells that want some important components of their immune system had a measurable change Could detect some virus in the blood. But get over it you know and so after two weeks it seems like the personal sort of better and then years could go by without any particular symptoms except for this strange low level of T. He sells these crucial components in the immune system It seemed to be that the T. cells were being depleted somehow by the by the presence of the virus but otherwise people weren't that that's sick but then after maybe ten years suddenly tremendous crash would seem to happen they would become terribly sick. And that's one issue would become AIDS AIDS at which point all kinds of nasty opportunistic infections would set in weird kinds of pneumonia that you wouldn't normally see weird cancers that were very uncommon and then you know at that point the person would only have a very short time to live maybe a year or two so that the mystery. I mean what was thought to hold a clue clue to what might be going on. Was this bizarre. A symptomatic period of ten years. What's going on in the body for those ten years when the person has HIV heavy? But they don't seem very sick Is it the case for instance that that HIV is hibernating during those ten years that it's just somehow lying dormant in the the body waiting to come out and become full blown AIDS if you believe. That's the picture and and certainly some viruses do that. You know people who have been infected with Different types of herpes viruses. Let's say we'll know that they can have long periods with no symptoms in between outbreaks. So we do know an and and chicken pox is a similar thing where people don't get shingles until they're much older after they had chicken pox as a little kid so you can have tremendously long dormant periods of viruses viruses. Not doing anything in the body so if you think that's what's happening with HIV then. That would mean if you had any drugs to treat it. You shouldn't use them at the beginning when a person is infected. You should wait until the symptoms start showing after ten years because you don't want the person to develop resistance to the few available drugs this being being back in one thousand nine hundred eighty five or so so that was the way issues to be treated that they really wouldn't do much until full blown AIDS and then it turned out the available drugs. Drugs didn't help but all of this changed around nineteen ninety four. When a new wonder drugs called protease inhibitor became available and The trouble even though with that is that just one drug people would always develop resistance to any drug you gave them an. HIV would come back so so where math comes into the story. Is that in. The mid. Nineties Dr David Ho an AIDS researcher and a mathematician Alan Peril Jason Work together with the team of other researchers to figure out what these protease inhibitors were actually doing with HIV. How're they working and they showed that After taking one one of these drugs that the levels of virus in the blood would drop exponentially fast. It would really plummet And what was important about that is is that by making measurements on the rate of this exponential drop Carrollton Ho were able to show that the body was producing about a billion virus particles articles every day. HIV was making an enormous amount of new virus. The immune system was clearing it out and flushing it onto the body just as fast as it was being made made so it was a completely different picture. That was not the case that the virus was dormant those ten years in fact it was in this all out fury. Just a battle Battle of attrition basically with your body yes exactly. It was a furious battle of attrition. An all out war there was there was being held to a standstill. The Immune system was holding HIV AT BAY until it gets exhausted and that's it also showed that gives us furious replication rate of HIV. It was no wonder that it was able to become resistant to essentially any drug mutations. Were happening so fast when HIV would get copied because it gets copied inaccurately really. I mean it's a an rn a virus with a bad copying mechanism. That's that's actually to its advantage because it can generate many variants. That can escape any drug. You try to hit did it with but Boa Harrelson's math showed. Is that if you did to drugs. Your odds were a little better because then the virus would have to do to simultaneous mutations. The odds of that were lower within one but three drugs would be sweet spot where the odds were so low that HIV could mutate three simultaneous ways That you could you could basically keep it at bay for a long time. And that's now the modern regimen the three-drug therapy so so math was key understanding that. It didn't certainly didn't solve the problem. Monotone you needed the immunologist and the doctors to and of course the pharmaceutical companies but but with all of them working together calculus was a key supporting player in In helping change the way we look at HIV and certainly how we treat it and are affected nece at the and it also played a role in GPS. Can you explain that one or does it's the fundamental role in. GPS thing. Well that's right sure anytime we use our. GPS Gadgets to find our way to a strange destination or sometimes even a find our way home. We're lost after going far away The GPS wonder of Calculus. It's got so many different aspects aspects of calculus built into it in the way that it acquires signals from the satellites overhead The way that the satellites and the whole system estimate distances by doing complicated mathematical calculation. You know it has to look at distances to three or four. Different satellites overhead If there's also really what the GPS system does is it doesn't directly measure distances. It measures time and converts those into distances so the time is the time it takes for a signal to go from the satellite to your. GPS receiver given that. It's traveling at the speed of light because it's an electromagnetic wave the signal so It's GonNa move at the speed of light and so by you have to time very precisely how long it takes for the signal to get to your receiver from the time. It was emitted headed by the the satellite overhead. Now what's really tricky about all that is that the The satellites need to keep extremely accurate. Time they they have on board atomic clocks in them. The most accurate time pieces we know of that are based on principles of quantum theory which itself is built on Calculus as it's math it's infrastructure. Sure but more than that when the when the satellites are moving so fast overhead. They're actually going fast enough. That Einstein's theory of relativity applies to them in a a significant way and they The clocks on board those moving satellites run at a different rate from the clock on the ground In other words time changes take time doesn't move at the same rate. It sounds unbelievable. I mean Einstein thought of this idea about more than a little more than one hundred years ago. Time actually changes. If you're moving it can speed up or slow down. Can you explain that for me. Well God it's not. It's not an easy thing to explain. Okay okay I mean you really have to go into a bit of relativity theory but it is a consequence of relativity that time can change into as it can actually slow down when and you're moving fast it can also speed up when you're in a weaker gravitational field okay. So when these satellites because they're farther from the center of the Earth author in a weaker gravitational field slightly than we are on the ground so these are miniscule effects. Were never aware of them in our ordinary life but these. GPS satellites are so accurate the in their atomic clock timekeeping that they can actually and they do all the time. Effectively confirmed Einstein's relativity predictions. It to to this in the percents if we didn't build in the Einsteinian corrections to timekeeping the whole. GPS system would fall apart in about twenty minutes. It would. It wouldn't be able to keep accurate time. I'm so okay. It's a big long walk. I've just taken here to give it to you but I mean there's a lot more to this but but suffice it to say the. GPS has has a lot out of Calculus and advanced physics built into it. And we don't give it a thought you know. We're just trying to get home at night or if I understood this car Klay Ceo I plug my phone into my car. Our turn on Apple carplay get directions. It's triangulating between three or four different satellites. And the time that the satellites sync up their atomic clocks hawks and then it's triangulating between how long it gets from each of those satellites to my phone and then based on that it can triangulate where I am. Yup you got a perfectly it. Because those those clocks on those satellites are very accurately maintained and the military keeps extremely care careful full measurements of where the satellites are so they have to know exactly where those satellites are and also you know what time it is on board the satellites and so as you say you know they're all at somewhat different distances from your car from your receiver and So yes you get to measure as you say triangulate you get to measure several distances. Three three or four distances to all those different satellites and knowing those four distances knowing where those satellites are that places you uniquely on the Earth Earth Not only that it also places your velocity I mean so. GPS can tell you how fast you're moving as well as where you are in three dimensions. How does it tell you how fast you're moving just based on where you were and where you are next okay? That's right so we can measure your position a nanosecond later or whatever. A small unit of time later in all those four distances have changed slightly. So it's that's of course one of the key ideas of calculus figuring out a rate of change will we call a derivative That's an example that the the rate of change of your position at when a short time interval elapses that's quintessential calculus calculation ordering the the other terms that we would use around rates of change. Well in economics. People are always using the word marginal so if they say the marginal utility you know oh how much extra pleasure or utility do you get from something for the next dollar that you spend or. What's your marginal return on investment? You Invest One more dollar. How much banged banged get for that? Buck so those are rates of change at the rate of change of return with respect to investment that would be an example and and that's a common commonsense thing you know you don't want to at some point the marginal return start going down so it's not worth it to put in that extra dollar of investment So we used use that idea a lot there but certainly in physics we talk about speed. That's a rate of change of position with respect to time we have acceleration. That's the rate of change of velocity city but even something as simple as a paycheck. You know when I say I'm making six dollars an hour Bill well let's not say that that talk about minimum wage. Let's say we're making okay. Fifteen dollars an hour is what they're talking about like. Everyone should be able to make that if you know if you had a decent wage that's still a rate of change right. It's dollars per hour. Anything where you say per is a rate Exchange rates you know. How many marks marks per per dollar are how many pounds per dollar those are rates? You mentioned economics and curious as to why physics math is so accurate. Accurate and economics. Math is so wildly inaccurate. Is that because the Mo the mathematical models don't apply as as well or I mean to. What extent is biology? Give us a better model for economics. Physics lots of great ideas in that question. Well Okay Ah the short answer would be the physics a lot simpler than economics. You know when you when you measure the moon doesn't mind it doesn't react you know it's just just an inanimate thing The laws governing inanimate bodies are just a lot simpler and more easily quantified than the laws governing populations reeve or individual people so the task of the social sciences is extremely hard They get to feedback on the system. That's measuring them. It's also their ethical issues. You can't do experiments as easily or sometimes you can't do them at all on people or on populations of people It's much harder to do controlled experiments. You try to pin down some variables in ages pop up somewhere else so if you think about the history of science which sciences worth solved I or where did we make progress. The first science to really make good progress was astronomy which I think is kind of surprising at first given that the moon and the stars and the planets are very far from us. They're very remote and you might think like why shouldn't biology be the subject where we make the most progress. Progress is very important medicine and helping. Sick people and prolonging life and all that you would have thought we devote so much attention to that but it's not we did you know we had witchdoctor medicine for most of history and even to this day. There's still a lot of black art and medicine And it's because it's it's intrinsically complex where astronomy if you think about it has a lot going for it. The motions of the planets are very repetitive. And regular they the moon is very predictable It's also very slow. It doesn't change that much from night tonight. And it's very observable you can just look up there and see what's going on and make measurements pretty decent ones. So it's it's at a time scale where it's not too fast or too slow for naked eye observation whereas the processes is in the body are are so fast sometimes in the molecules or the cells involved are so small that biology is just intrinsically really hard an economics economics and sociology and psychology are even harder still do you think biology is necessarily valuable than or is it a matter of like we don't once we understand more will be able to measure and predict with the degree of accuracy that sort of like rivals physics or is it something that is just. It's inherently too complex unknown. Yeah no none of computing power is going to be able to solve it. Because it's a dynamic system or I think it's closer to the second though I wouldn't be as fatalistic about it as that. We we have made a lot of progress in understanding all kinds of things about say Arrhythmias in the hearten which are ultimately electrical problems of You know abberant waves propagating in the heart electrically. That shouldn't be that are making muscles in the heart contract at the wrong times so that so that blood doesn't flow effectively. You know so. There's some parts of of biology where it's really almost like mechanics the the heart as a pump But there are other parts arts of biology. say you know emotions in the brain and Mental illness things like this are still very very the problem. Attic were so you know that's in a way it's a good thing. We have a lot of work to do. That will keep us busy for generations to come but I think it's just in the nature era of biology that it's much harder as you say it's it's very complex there. Lots of parts. Also keep in mind that there's enormous diversity in biology that My jeans are different than yours. Even though we're both human beings there's a right are molecules are the same. But we're configured differently differently whereas in the love and physics it's not like that any two electrons anywhere in the universe are absolutely indistinguishable. There is no diversity of Subatomic particles articles. I mean there are different. Particles electrons are different from protons but every electron is completely the same in every respect as every other electron same charge say`mass mass. They never break. They never age. They never chip. You know I mean so in that way. Physics is really simple whereas hemoglobin molecules also in our could all be a little bit different. There's also a lot of noise in biology lot of randomness. That's just because of molecular jiggling. More cad it's just this inherently chaotic. Yeah so it's it's really hard and it's going to keep us occupied for awhile but still it is ultimately chemistry and physics. I mean there's no I don't believe even any vital spirit or soul or anything like that. I'm sure some people do but I don't I don't mean to me it's all material it's GonNa ultimately be understood in purely materialistic meaning. I'm not talking about money. Obviously I mean. I don't think there's anything there but atoms and Subatomic particles configured and increasingly subtle title ways in. Correct me if I'm wrong. You're you're more interested Intellectually in the orderly side of nature than the chaotic grant. I I would say that's true. Yeah my my interest has always been in how does order emerge from chaos. So I do find chaos interesting as a starting point but whereas whereas some people revel in the chaos I I like self organization systems that spontaneously show astonishing feats of Collective behavior where they somehow get their act together on their own with no no commander no outside force telling them how to behave. 'cause I think that's you know we see that all around around us. We see. I assume life evolved spontaneously you know in the consistent with this position. I'm giving that it's all materialism I think that's one of the great mysteries mysteries. How do you get life from non life without a creator? You know how it must somehow be in my world view that the laws of nature in the right conditions will lead to life emerging from chemistry but understanding. The origin of life is one of our great scientific mysteries. People are working on. It's not hopeless but it's we don't have the answer just yet. Where does morality come into self organizing morality? Well Good thorny question. There you know a traditional view would be I suppose that cultures and religious traditions and our parents give us they help us learn right from wrong and moralities something that's passed along through culture but From a different point of view it might be an outgrowth of biology I what do you mean okay. Yeah well so I'm thinking of A series of experiments. That were done. If you could call them. Experiments that were computer tournaments run by a political scientist named Robert. axelrod out of University of Michigan. So axelrod is is one of the great political recall scientists of our time and he asked Experts in many different domains economic psychology Game Theory Math Physics Computer Science Alliance to come together and play actually to submit computer programs to play this famous game called the prisoner's dilemma I suspect you're many of your listeners. Will know the prisoner's dilemma. But I'll just remind people I mean. The prisoner's dilemma. is a model for thinking about lots of situations that occur in real life where you and someone else have basically two decisions. Are you gonNA play nicely with each other. And are- going to sort of cooperate the scenario that is always talked about as you and your friend are both Being held by the police accused of having committed did a crime okay so that the name comes from his nineteen fifties era scenario of of the two guys are being questioned separately by the police uh-huh and they're you know each in their own room and the police say look. We've got lots of evidence on both of you guys. We know you committed that burglary together If you will just just confess we'll go easy on you and we'll go hard on your partner will put him away for a long time and You know you'll get off easy but you you just got to. Let's go you have to confess. And of course they're saying the same thing to the other guy and the question is. Are you going to rat out your friend. Which is considered not cooperating reading so the word is used in a strange way game theory? You're cooperating with the police. But you're not cooperating with your friend by being a rat and it's it's relative to your friend that we're talking about so so that's the question does like it's an each player's interest. I'll think of these players playing a game. Now it's an each prisoners interest to rat out his his friend but if both of them rat out each other then the police have a very easy case. And it's bad for both guys they'll end up going away for a pretty long time in the in the normal normal setup the person who doesn't cooperate if one rats out the other and one keeps quiet. The Guy who kept quiet goes away for a very long time. So that's the worst. Outcome is to be a soccer where you keep quiet and your friend you know cheats on you so anyway the point being that that this prisoner's dilemma. Is this interesting uncomplicated. Scenario where it's in everyone's narrow self interest to be mean and not cooperate to defect to defect. Is the jargon exactly to defect. Is the jargon used in the field if you defect on your co player your partner but then assumes a one iteration game right. Yeah that's right so in the in the thinking where we're only gonNA play once and I'll never see you again then. It's always in presented as the rational thing to be a tough guy and defect on your partner and both players think that way and and why. It's considered a dilemma. Is that if we would both just cooperate with each other it would be good for both of us rain but the the problem is if we both have this mindset. It's always tempting. You know to then say well maybe maybe just this one time I'll take advantage because there's so much reward to be had by doing that so anyway so back to axelrod he set up. I mean it's been a real paradox. Like how to play prisoner's dilemma. If you imagine playing the game repeatedly if I'm GonNa see you again and again maybe then there's more chance for for cooperation to evolve between us because although in the short term I might benefit from screwing you you could always screw me back and you know maybe if we just a tour to develop trust with this could be good for both of us over the long haul. So why. We're talking about this as you asked me earlier about morality and I I found axelrod's experiments very illuminating in this respect. What he found when he ran these tournaments of all these programs playing against each other He found that the programs that tended to do well in the tournament had four properties in common and he summarized these four properties by saying that I they were nice ice which he defined as meaning they never were the first one to defect if they were playing another program. They would always begin by cooperating on the first move and then if the other program cooperated back they would continue to cooperate because they were nice programs they would never defect I so they could set up these long strings of cooperation in with other players. And both do really well. So being Nice was principle number one that actually works well in an environment where there's a lot of players of equal strength equal power playing against you in this vicious prisoner's dilemma game. And what's so interesting is. Nobody's being nice for moral reasons there. These sir egoists okay. These are classic Adam Smith self interested. I'm doing what's good for me. Players they're not trying to be nice. They're not altruistic us for any moral reason. They're just trying to do what's good for them but it turns out being nice good for them if they're in an environment where there's a lot of other players equally strong you know who can inflict as much harm on them as they can on the other player Ray. So that's that's principle one be nice principle to that was found out you know and I'm not talking again here about any kind of moral philosophy. This is just what worked in the tournament. Be Nice but before giving if the other player cheats on you sometimes well don't just retaliate forever. You got let-bygones-be-bygones after a while so it's good to be nice and forgiving. But it's also not good to be a patsy not you should be retaliatory you have to inflict punishment if someone has abused you for no reason that is they gave an UN provoked defection on you. Then you have to hit back so be nice be forgiving be retaliatory Tori and finally be clear the programs which were too confusing too subtle and to brainiac like there were some programs that tried to make a a statistical model of what the opponent was doing right but then they become unpredictable. I would imagine sometimes. That's right there so inscrutable. They're so unpredictable that you don't know what they're gonNA do and it's almost like you're playing them anew each time you play so you might as well defect on them because you don't know you can't figure them out you can't build up a relationship so be nice listenclear forgiving in retaliatory and that's what emerges as a way to thrive in this environment and what's so interesting about that is that this is a culture that has evolved around the world many times. This is I for an eye and a tooth for a tooth This is this is Old Testament Morality and computers discovered it on their own. This is not was is not programmed into them this is just what worked so it becomes our system because of biology and how we evolution basically. It's natural selection in the science people who employ that strategy are more likely to spread their genes. Well that's so. Yeah okay I mean the argument would be if you play. Hey this kind of style axelrod actually did do an evolutionary version of the tournament where where programs that did well got to reproduce more more copies of themselves so just like you described and so then he looked over many generations. What how did the population evolve? And he found that it sort of evolved toward players players. Who played this style? Call tit for tat which is they always? They always cooperated on the first move the really simple programs in fact it was the shortest computer program submitted. Only only four lines of code. I moved cooperate and on every subsequent. Move do whatever the opponent did on the previous move you. Just give it back to them. If they cooperate you cooperate right. And that's what we know of as as tit for tat. Yeah that's the tit for tat now but the story is more complicated like everything in life because although Acura did find that tit for tat worked well in his tournaments It's not some kind of universal best way to behave it turns out it's a little the two ungenerous it's a little bit stern and what's really. Here's the weakness of tit-for-tat. Sometimes people make mistakes and not because they're mean on. I mean just mistakes happen bumped sometimes you Are Trying to be nice and a person interprets it as an insult. Now if that person is following tit for tat and so are you then when this accidental defection happens. They'll say well. Now I okay you now I gotta give back to you. So then they'll defect. But now you being tit for tat player after defect on. Now you're in this vendetta that it's very hard to get out of. I have a friend who who his approach coach to. This is. Forgive unless it's malicious. Yeah yeah good well. Yeah I mean there's a there's a computerized version of it. Which is tit for tat right? You know or some number of tasks and so there are generous tit for tat s- Yeah anyway. It's a it's an ongoing story and Game Theory. This is a branch of Game Theory that people call evolutionary game theory but just to not get lost in the weeds the point was it starts to give the contours of a story in which morality can evolve from self interested individuals playing against each other. Now is that really what happens in evolution ocean. That's that remains to be seen. There are some examples of it in evolution. You know like when Animals that hunt se picture. I don't know lions the female lions out on a hunt. It can be dangerous to try to go after a big scary wildebeest and they can kick you or hurt you. You know when you're trying to kill them so so maybe it's better to let the other lions get a little head of me and I'll just kind of bring up the rear. You could be a free rider and it's tempting there. That is all the lions are kind of playing a type of prisoner's dilemma. With each other. where it's tempting to cheat on your on the rest of the what would it be called a heard? No that's not what it's called. What is with the Lions a pride a pride upright but anyway So there are instances in biology. Where something like a prisoner's owners? Dilemma is happening but Yeah anyway so. I don't know how much it really tells us about morality but it's an interesting story. It may tell us something. Let's talk like a little bit of very Decision making in terms of matic's is a hyper competitive world. Imagine you're you're an adviser to students. You're you're part of their publishing papers. There's sort of like credit natural. Bution how do you think about this with your Grad students. Do you advise them. How do you help them make decisions? How what models did they use to make decisions It's something that we think about a lot Because really the first issue for a student is what to work on on the getting a PhD is all about discovering something new staking a claim in in the intellectual ferment in the mathematical landscape. You know you have to come up with something new and interesting that is yours. You have to innovate. And where do you find a good idea. Because there's everyone's trying to do the same thing and these are also smart mark ambitious people too so one of the things that comes up a lot. Is that the first few ideas that you'll try They might seem promising but then at some point the going gets rough. It's hard to make progress. Maybe you don't have the technical tools to solve the problem even though you're fascinated by it or for whatever reason is not turning out as interesting as you originally hoped And then there becomes a I know sometimes sometimes on your show you like to talk about like sunk cost and other fallacies and you know we've spent a here's a student has spent a lot of effort on something. Yeah they've put in the cost right. Should they keep banging their head on that same problem or is it now time to give up like you know. When is it time to quit yet? talked to me about that. Well it's a very hard decision because you've spent a lot of effort you've grown attached to a certain question If you quit on it you may feel like well. That was all a waste but on the other hand if you keep banging your head and not making progress then you're there's an opportunity cost you could have been thinking about something else and maybe you would have made progress on that new thing. So it's it's an since you don't know how it's GonNa turn out because this is an issue of genuine discovery and uncertainty. It's not clear what to do. This contrast also also come into it too like contrast. Yeah are you trying to think of others other students working on this but they may not be as clever as I am sorry. You're trying to like also ascertain. What is the thing that I like doing that? Other people are not doing or I'm thinking about this out sense of you know if you take somebody who is really intelligent and you apply yourself maybe not the hardest problem but the second hardest problem. You might have a better chance to to ascertain. Does that make sense Totally make sense right so promise. Election is such an art form. You know that you sometimes it's better to go as you say after the second hardest problem some maybe the the gold ring you know is premature we have to build up to it so There are people who try for the hardest thing and they never succeed because they're gone for pie in the sky all the time There's also you sort of hinted at it The idea of comparative advantage. What is it that I bring or my student brings? That might give us an edge that that other people don't have or you know they're all these different things to think about The kinds of edge that we tend to have we. I mean really litter. I guess me and my students is that we're very widely interested in many do things So mathematicians are narrow and deep deep is our highest compliment actually in math. That person is deep. That work is deep. That theorem is deep. That's put that's the standard of excellence. But Not really for me. I I mean whether it's just not capable of it I don't know but I kind. I don't like shallow and broad. Maybe shallow is you know to to self deprecating but broad. There's so much to be gained by thinking out of the I. I WANNA say that cliche out of the box. But you know I'll have the square okay out of the square being interested in wacky things. Things like humanities or philosophy or or sociology That has often really worked well for us. How does that help you? Because I see Zeke icy problems that other people don't realize problems so an example would be. Okay so yeah. Let me give you a little story so probably on on paper or and maybe in reality my most successful student is a guy named Duncan Watts. Who was Australian from he was a physicist he was in their naval defence force. They wanted go to Grad school to study chaos theory which was something I worked on a lot and so he became my Grad student. And the first few problems we worked on together together It was just like this scenario I was describing earlier. He was getting stuck. We weren't really making good progress. One was something about the way. That lymph emph- lows in the vessels of the lymph system. It makes certain oscillations. We were interested in things that oscillate and go up and down and have cycles. You know so as an expert in cycles cycles I thought maybe we work on lymphatic all solutions. That could be important but we couldn't make progress. We kind of got stuck. We didn't know enough about the lymph system so then we had to do what I think of as strategic quitting that we have to decide. It's time to cut our losses. This is not going anywhere. Let's do something else so we did. We stopped and we. You know we quit. What the the thing your college or High School Coach tells you? Don't be a quitter. Yes I do be a quitter. Sometimes you have to quit when it's not not panning out But then don't just give up. You have to come up with something else so we we kept thinking of things to do and finally in Well I want to see in desperation. We started to work on a problem about crickets now. Crickets chirp crickets chirp. They make a rhythmic chirping. Sound sound at night and in Ithaca New York here where I live or cornell is we have a species of cricket called the snowy tree cricket that They chorus in unison. They all all trump together in these vast choruses so that they make this enormous sound at night in the in the fall or in the summer and that's a fantastic aspic kind of synchronization where these are not very clever creatures but they somehow can harmonize an all chirp in unison and biologists have wondered. How can they do that? And it's partly interesting using because the crickets are interesting but partly because a lot of things in biology synchronize like the cells in our heart that tell our heart went to beat our pacemaker cells get in sync brain sales get in sync when we're having epileptic seizures so we would like to understand how to stop that anyway. So crickets are one instance of synchronization and we thought they might be a tractable one to do experiments experiments on because they live right here. In America we could capture them and do experiments on them and maybe figure out how they are able to synchronize in their chirping. Anyway Wall Dunkin was working working on that he made this interesting creative leap. His father had said something to him once. This was back in the nineteen nineties. did you have you ever heard that that you're only six handshakes from the president of the United States or from anyone else on earth and this idea of course everybody has heard of the six degrees of separation idea but Duncan put put this together with what he was trying to think about. What the crickets that? They're out there in these orchards. He wondered which cricket can here which other cricket like are they all connected connected just maybe to the nearest wants to them or are they listening to the whole field or are they somehow connected in this network. That's reminiscent of you know like what if thrall just a few handshakes away from each other in terms of who. Here's who so he put these two things together this this thought from sociology about social networks. And this well before four facebook or anything else you know. What is the basic mathematics of things that are that are you could think of as networks? Where every node in the network work is just a few hops or just a few handshakes away from every other node? What would a network have to be like to have that property? It's really true that the planet earth the Social Network of the planet has this property And what would that tell us about. How crickets can synchronize now? Other systems that worked in this way could behave so. Oh I'm bringing this up because look at how weird this whole thing is. We're talking about crickets or suddenly talking about six degrees of separation which comes from a movie and play by that title which originally came from social psychology experiment. Nobody in the math department is thinking about that kind of crazy stuff this is. I'm I'm interested in pop culture. I'm interested in science and so I think about weird things and sometimes there are really important and relatively easy problems it was just waiting for a mathematician to look on. It is because you're applying sort of mental models from other disciplines to the one you're looking I guess so. Yeah it's different mental models knowing knowing what questions arise in what fields what things have long been problematic like you know. The sociologist will tell you. The social network problem of six degrees of separation was solved in the nineteen sixties. They thought that problem was done I maybe from their point of view. It was but from a mathematicians point of view it was certainly not done. I mean it seemed to me. We don't have the foggiest idea. mathematically which networks would have this small world property I say small world because of the you know the old idea you meet someone someone on a plane and you start talking to them and you realize you know someone who knows someone you know who knows their cousin or something so this phenomenon of it being a small world it's right under our noses yet. It's not understood. mathematically we don't really know why is it so small so there's a math problem there and and recognizing and what is right under everybody's noses you know but seeing something wonderful in its seeing something mysterious in it that's That's a kind of skill and that's the skill that I you know. I'm very interested in trying to develop in my students and that I've been able to leverage in my own career over and over again when it comes to strategic couldn't just for a second is there that sounds more like an are than a science. There's a lot of things that come into it. You know I mean you. You have to decide how frustrated you feel how much time you have left like for a Grad student. There's often real world questions do I. Maybe I have a family I need to graduate. I need to get a a job so I get really paid properly In that case we better quit that much sooner and make sure your next problem. Is that much more tractable. You know it's almost like with stocks and bonds and things. They're they're safe investments. That don't return that much. There's riskier investments. That might return a lot but could also go belly up very easily so you have to think about similar issues right like what's your time horizon one. Do I need to get out of here. How much payoff in my looking? For how much my willing to gamble Campbell. So all those different things go into thinking about what. What question should I work on? Next is anything else. Come to mind when you're asking that question of your students since or yourself. Yes big thing is personality. I mean in Duncan Watts case since I was just talking about him with the cricket problem that became the small world problem and maybe I should just just say I mean it's gross. It's Kinda Kinda come off like bragging but just to finish that thought. It's this paper is now among the hundred most highly cited papers of all time in any any scientific discipline I mean. It's the biggest home run I'll ever hit in my life for sure and long after I'm dead it's the one thing that Duncan and I will be remembered for or this was a monumental game changing bit of work that started from you know from just a crazy question. Yeah I love those solutions where you're pulling something from other disciplines and you're seeing something that nobody else sees. Even though it exists within the world. Yeah as far as like what does it take to you you know. How do you decide about the quitting? I knew something about Dunkin's personality. which was that before? I had even really gotten to know him. I had observed a picture of him on his his office door of Him hanging by his fingertips literally on a cliff. One hundred meters above the sea in Australia. Place called point perpendicular herpin dictator He's a rock climber and he's a little bit of a crazy person. Also physically very very impressive he looks like a Green Beret. Like someone that could kill you if he wanted to and He's the kind of guy who hangs off of of precipices by his fingertips and does for fun so it seemed to me like with that student. We could work on something extremely risky and extremely exciting and he would not be afraid and he would find a way to make it work. He wasn't the technically best mathematician. He still not There were other kids that were more Math Olympiad caliber. Who could solve any textbook problem? You gave them Dunkin. Wasn't like that but he could muscle his way to a solution. It wouldn't be elegant but he could get it done and He was fearless and so we worked in this area that I mean I had to tell him at the beginning. I know nothing about social networks. That's GONNA use a part of math call graph theory which I'm not an expert in if we were talking about crickets operations I know about that but I don't know about networks and actually nobody really knows so. We're going to be way out of our comfort zone here. We might night embarrass ourselves and so we were very secretive about what we were doing. We didn't tell people we worked on it for maybe a year or two and You know we had nothing to show for it for that whole time but the hope was that it could be really big when it finally came out if we got lucky and it turned out we did to. What extent does that raw skill matter in comparison? To what other attributes do you see in students that make them successful. Well roskill certainly has its place. you know if you don't have any skill and I'm talking like skill in the sense of technique like if you were a composer and you couldn't really play on the piano to hear what you're trying to compose you're going to have trouble and in math you have to have certain technical skills and I'm sure sure in every discipline and computer science if you can't program with some facility there's only so much you can do but but skill is so much what we emphasize technique. I guess I should call it. Technique is so much what we emphasize in school. And it's just one part of the of the portfolio Encourage is a big part judgment You know these are hard. They're intangible I don't even really know how to define a lot of these but a snow's having good taste knowing what's going to be cool if it works Knowing what other people might find interesting like my dad my dad didn't go to college. Neither did my mother but my dad had a shoe store and he said to me. It doesn't matter what shoes I WANNA buy. You have to know what sells you have to know what the people want to buy and So sort of true in research. I mean it might sound a little mercenary. Put it that way but we're sort of in the business of selling ideas. I don't literally mean for money. I mean our currency is is status and getting nice jobs and getting recognition and also the thrill role of discovery and all that but still a great discovery that no one appreciates is not really a great discovery because science is a social enterprise. It's not just enough to do the work. You have to communicate it and help other people understand why it matters reminds this this story were a guy goes into tackle shop and looks at the lures and says the fish eat these green to go after these green lures than the guy working. There says I'm not selling to the fish. Well that's funny. That's good I mean. I wonder about that story. I mean that's that's sort of not really right. Is it because if if that the guy is the fish don't bite. You're not going back to that store while I think it's sort of goes back to that organized morality in this sort of one off. Are we playing what I'm thinking. We're replaying a one time game and it was interesting. I was traveling with my kids this summer. And we sort of went to this Tourist trap and we ordered a bottle of water without even thinking and it was eight euros and I was like oh well. Let's work through this problem and we were sitting there at the table like I was like just regis got you know We just learned something here like. Let's let's pay attention to it and try to take a little bit and I'm like well. What would the difference be? This restaurant was full of local. People do you think that they would do that. No okay so if it's full of tourists. How can they do that? We'll probably will never be back and so you can get away with this not saying as right. There's no sort of moral judgment on my part art here or wrong But you can get away with it whereas if you were serving an audience that is not a tourist place or customer. You can't sort of get away with that type of behavior because you go to business because people will just wouldn't come back but when you're at the place in town for this particular type of piece of cake that the the town is known for you know everybody goes there and you order cake and then of course you get thirsty and you you know the cake is cheap and the water is ridiculously expensive. No it's a good example a real world example of what we're talking about that there's one shot businesses and there's long-term relationship kinds of businesses. Yeah and they and they will tend to evolve different strategies. It's understandable what's really fascinating to me is like so often we. We know we're in a long term relationship with somebody and and will convince ourselves that will make it up to them if we take advantage of them rights. If you think of four permutations of relationship. There's win win win lose lose lose lose win but if we map that to biology one of those survives across time right which is The relationship has to be win win but I find a lot of people who are going to take take a little bit of advantage of you right now not too much but I'll make it up to you later and then we never sort of re we always know what it feels like to be on the lose sight of that relationship ebb and It never sort of happens that it sort of equalizer gets made up or suit even if you think you're playing a multi iteration shing game. We often make these trade offs. I think our head where it's like all make this up to you in the future and then we we are inaccurate at that sort of scorekeeping if you wall and I think that so often how a lot of our relationships that work become after we leave work. I mean noticed a trend with a lot of a lot of people. I know colleagues colleagues who retire and then they go from having sort of all of these friends to not really having many friends right so their friends in for their position or sort of at work anyway. Their friends France came from their position. impart because they had all these trade offs that they sort of realized later that day achieved success may be in a way that was mutually exclusive from relationships that meaning uh-huh uh-huh Very interesting there were there were actually you know in a primitive way a computer programs that tried a similar thing in this axelrod tournament after he announced the community. What the results of the first one were that? It was at the time. Good to be nice and and Forgiving and then you would think many players I mean it was much bigger tournament the second time many more entrance and you would think a lot of them would submit submit tit-for-tat now that they learned how well it did. They didn't though everybody thought they were cleverer than that. And they would submit things that were They thought thought basically could do pretty well against tabby occasionally taking advantage of it just rarely just like testing it. You know or test the other program and then if there was too much retaliation allegation they'd back off and go back to being nice and it turned out that that little variant that Kinda mutation if you will was a really deleterious mutation nation because it led to exactly what you're talking about it would lead to a breakdown of trust that had been delicately established before then and it was very hard to get back. Yeah Gaz especially in human systems right because you can appear to trust somebody but not actually trust them so young you can sort of trick them in a way that maybe Dissimulations in the computer can't can't do that's right which is sort of Makes everything a little bit more complicated but also really more interesting from a sense of you should go positive go i. I always end my friends principle of sort of forgiving us. It's malicious seems like a really good lifestyle. Yeah it is. It sounds like a nice friend to have you know. Generally a sweet soul yet definitely was this has been a fascinating conversation station. I've really enjoyed talking to you. Thanks a lot. Shane was the pleasure to be with. You you can find show notes on this episode as well as every other episode that F. S. Dot blog slash. Podcast if you find this episode valuable shared on Social Media and leave a review review to support the podcast F s dot blogs slash membership and join our learning community. 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HIV professor YouTube. US Facebook Steve Triangle Angle Patty atty Cornell University AIDS Shane Parrish BRANFORD Christina metal Ab Stephen Mister Johnson Mandola professor of Applied Mathemati
1245: "Mask Up!"

No Agenda

3:26:44 hr | 8 months ago

1245: "Mask Up!"

"Attended you listeners. Boys Nice boys it just. Did this show Adam Curry Johnson. Devora twenty four twenty twenty. This is your award-winning nation media. Assassination episode twelve hundred forty five. This is no agenda. Muzzle Van Broadcasting Live from opportunities thirty three frontier of Austin Texas capital of the drone star staying in the morning. Everybody I'm Adam curry from northern Silicon Valley. We're all watching. Joe Biden scrambled to the finish line. I'm just he'd been buzzkill. It never ceases to amaze me how around the globe and of course I monitor British papers and Dutch papers and some German that it doesn't matter how many people are dead or presumed dead from covid. Nineteen a good racial controversy. That is what get everybody gets pumping with. That would have been better. Food is a gay controversy now because no no. That's your old theory. Not My no. He doesn't know he. He needs the black vote not the votes. He's got the gay vote. If I can just call that screw that up to I could just call it that everybody. You're now the gay vote this gave. Oh this is what I'd like to feel black. They go you gave vote black. Vote now man. They care about this. Did you talk about this with moe facts? Well thank you for asking Mo- texted me normally. Would we do the show on Saturday? He said I have to see the Sunday morning shows. He says I'm building the files so they were GonNa do it tomorrow and I can't wait because you know this is this could be a real make or break moment for Biden. I don't think I don't think you can overcome it. You know why I'll tell you why. Okay I'm all ears. This is his very fine people moment. This will be used by the right by the Republicans are chain you. As their version of very fine people people was a ally did do this. Yeah but I'm just saying it's something that keeps coming back and we'll never go away and it's written you know it's it's reasonable to that yet. Is I kind of like have mixed feelings about it? Because on the one hand we're always giving trump a passers joking around and binding. Kinda joking around this is what is his campaign. That woman campaign manager of his She's dancing around the Simone Sanders. Actually pretty good deflecting in pushing away just rejecting it and you know she has the right. She has the right look to do that. She's black yes she has the right. Look exactly it the whole thing you want. Let's play cut. Let's play through it. Was you or me was a me odd. Okay do well. No I heard it? I heard a window sound very odd. That may have been the printer. All you mean a windows one of those messages bringing some like that. Yeah we got a bunch of so we got some buying clips I have two of you know besides the breakfast club disaster. Which is what you're talking about. Did you see the whole interview? I did not. I saw a good part of it. I did not see the whole thing. Don't wait Zephyr three or five. Six seven still low ball economy. This is the official Zephyr economic indicator. We are not out of the woods yet. I repeat we are asked go to eight. We have seven car Zephyr economy at the moment. We need eight to see green shoots. See I've got I've been watching C. N. electrolytes until yes. He's part of our L. recovery plan so biting. I think we have a lot to do about the clip showing. You probably have a couple things. Yeah I just have a couple things and then we will obviously get to some corona virus stuff but this is just so much so lighthearted is more entertaining definitely virus. This shows is depressing. So right I just have some general kind of booby stuff that he was saying although this popped up and this is part of because he did a number of appearances in the past couple of days and this was part of it. I'm sure you've heard this. I'm going to be Joe Biden a worthy contender for End of show ice but he and I thought it was. He literally said that and of course no one bats an eye. I'm going to be Joe Biden. All Right Joe fine but what I wanted to play. Just a little bit of the whole thing is seven minutes and You get the idea and it's actually more fun to watch. The video is what is trending on social media. Now is the it's titled Black. Americans have a message for Joe Biden just to give you an idea of what kind of impact this has had in our fellow. Americans a problem figuring out whether you're for mayor trump and you ain't black Joe Biden things. I'm not blink. Jill Biden does not big on Black Joe Biden said if auto for an black Joe Biden does not think I am black. Doesn't think on bland so I've got a message for by doesn't think that I'm black if I don't vote for him. Joe Biden the black because the money give Joe Biden. Newton cannot say you. I'm black okay. I don't support Joe Biden support. Donald Trump thank you very much. I am black in. I'm not voting. Joe Biden set for seven minutes. And it's It's kind of a a mega cuts bigger than a super cuts. And it's just really like to me devastating a the impact that this had could. This has an impact and this is a core problem with the Democrat Party and how they've treated African Americans as I've learned from Mo Mo facts without him curry because I'm not a some. I've picked up some knowledge along the way but the idea that you're black vote Democrat. That has been the idea. It's been and there's a whole history as to why that is Kinda came about with Lyndon Johnson. He's the one who set it up. And he's the one who talked to his recordings in in the museum with him going on as keep the black vote for the next one thousand years. It was a civil rights. Act Yes and if you really want a whole history in that show or something you can listen to from episode. One is not that many anyway. It is incredibly insulting it. It confirms so many things that are said already. You know the plantation all of that. It confirmed everything and and the thing was I think. I don't think it was simone but one of his handlers was trying to almost if they knew that his time is over you you. You've got no more time for the interview. Vice President we gotta go. It's like oh come on man and he's in all of a sudden he spits. This one out at the very end interview was over. He was safe. You have no no. I don't have do you have it? I want to hear it added a bunch of these start with By the way I want people to know part of the process. Is You do your clips a day earlier when I get into the studio in the morning and I have a whole list of stuff I wanNA do. I'll look at what we're overlap. There is an AL pullback so I saw what you got you know I saw hydroxy so biden them like groovy so I got other stuff and let's row abroad. Clueless just showing podcast is how to do it by non to be fast club combative. He's he's combative on the show and I thought that he was like getting into arguments constantly and this is a good example. A lot of black voters including myself feel in the Democrat. Take Black voters for granted. I want a larger share. The black vote than anybody has including Morocco. They're the folks as they say. My Way Brung me to the dance. That's how I got elected. We had Hillary on a few years ago. Mrs Clinton said that the Crime Bill May of mistakes that and she wanted to atone for that by becoming the next president like Jane was wrong. What happened was and wasn't a crime. Bill it was the drug legislation. That's really our time I apologize. You can't do that. The black media that the white medium block made it because my wife has to go on at six o'clock. I hadn't actually focused on. What just happened there. Charlemagne who is basically Comma Harris a surrogate and very well connected in upper circles to. He says you can't do that to black media which by itself is is has racial connotations. He's kind of setting it up. It's like you can't do that to black media. Then Joe comes back with something about black and white media hadn't even heard that part that the white medium block media because my wife has to go on at six o'clock. What does that have to do with his wife? I don't know I can't do that to white medium block me because my wife has to go on at six o'clock you gotta come see us when you come to New York. Bp By will that will. That's one of the other one is this. This is Biden versus breakfast club. The short take you got more questions. I tell you if you have a problem figuring out whether you're for mayor trump and you ain't black. They don't have nothing to do with trump to do with the. I want something for my community. I would love to see my record man. I said at the voting REX. Twenty five years. I have record that is second to none then. Aa. Cpa's endorsed me. Every time I've run the world I mean. Come on take a look at the record this this. This could have been a win moment right here if Joe had uttered the word tangible Of course reparations. But he's not going to do that but if he had said. Yeah we'RE GONNA I'm GonNa do something tangible. He would've had fifty percent of the battle one because it's all coded words at this point. And that's what Charlemagne was asking for is like I want something for my people. What are you going to give me and Jogos come on man? Look we gave you. But charlemagne anything not just bragging about in another interview. Charlemagne was on another show on. Msnbc and he says the problem was which would have you done for me lately. Yes and so and now. I've got one clip here. This is one of the MSNBC political analyst during the back story on the whole event. And I thought this would be worth listening to care. What does this titled Biden Back Story? The back story on this whole conversation actually goes back quite a ways into the primary in which just about every Democratic presidential hopeful appeared on this a popular. Show the breakfast club except for Joe Biden. And what was so interesting about that? Of course that the black boat they African American vote was so critical for Joe Biden. It's really the reason he is now. And so the show had been very critical of him in pressuring him to still appear on the show and finally they managed to get together and during was really a twenty minute conversation. There was some tense back and forth really pressing Joe Biden about some of his past policy positions like the Crime Bill. Nineteen ninety-four Crime Bill. Of course like on drug legalisation marijuana legalization specifically but even with the you know tough back and forth was moment at the end there. That was what really got Biden in trouble just as they were wrapping things up and of course. The trump campaign jumped on that so quickly we did see of course as you mentioned the former vice president racing this afternoon to try to clean that up we also saw his campaign trying to take do some damage control during the day. Let's take a listen to what Simone Sanders said on? Msnbc earlier this afternoon the tone of the interview at the end were set in jest. But I want to be clear about what he was saying. Well Vice President Biden Los Angeles put his record and his track record up. Um With the African American community an in the African American community up against Donald trump any single day period. John Oh exactly so after this by. Does this apology. And we knew what kind of apology was going to be performed. It was GONNA be no apology and it should. Klein explained the performance of just a moment. That's where you don't really you. A good example is. Let me tell you this. Thank about that you just did it. Which means or here's the truth about that. Even let let me tell you about that. It's just like you're not. Why don't you just say is almost one of those tricks of watching a body language? Guy One of my favorite ones is crazy looking character who did biden a saying that Tnn read the whole thing. This bullcrap right and the by language guy was finding stuff there that it was obvious. That Biden was lying the whole time but all the things he was doing and the way was presenting things in a way it was denying everything was always just kind of US almost secondhand this particular apology by buying a lot of people played. It's hard to get the whole thing. I've five found where I think is the whole thing and it had been edited. And they edit. There's a there's a funny thing these guys. I think they're doing it on purpose. Because they edit in such a way. That is obviously been edited. Have you noticed this like you? You play something but his poorly edited and is almost on purpose sir. Well I think it's become a form very similar to the jump. Cut AND FLASH. Cross that has become rampant on television. That is just style and this is a part of the shock. Me To renew labs. So here's the apology. And you tell me. Where's the apology? The last thing I wanted to not shouldn't have been such a wise guy I shouldn't have been so cavalier and responding that I thought was a anyway was I. Don't take it for granted at all and no one. No one should ask the vote for any party based on their race religion. The background for african-americans. You think that trump is worth voting for. I don't think so. I'm prepared for my record against his. That was the bottom line and it was. It was really unfortunate. I shouldn't have been so cavalier. It sounds like he's apologizing for responding to the comment about black media. I think that's where that's consultant wrote. This is up there with this up. There was your clip of Cuomo. I don't know if it's as great as your clip with Cuomo not apologizing for all the dead people in the nursing homes. But it's not no it's not. It's not groveling this this this really required some groveling and he ended when he's in. Biden's when he says well I'm just wish I was just responding to then. He cuts himself off like he does half the time because he can't finish the sentence but he cuts himself off and so we don't know what he was responding to but when he's now you think he was just probably responding viscerally comment about black media. That's the way he's making it sound. But that's what consultants told him to say. I guess I don't know or the job will worse than that. I have two more clips in relinquish the Biden stuff unless you have anything. He'd also appeared on some other shows and it was on Cnbc TOLD JOE is watching. This is a short clip. But just listen to what he plans on doing about taxes when asked specifically its vice-president. Did I just wanted to clear one more thing for sure. You're on record. You would repeal the tax cuts immediately and then raise taxes even further right away even if the economy is still in the midst of this pandemic. Would you do that? If elected I would repeal the two trillion dollars tax cut for the folks who making over a million bucks a year because as demonstrated as demonstrated little or no grow for the corporate the corporate tax rate. I moved back to what I had proposed at twenty eight percent but we have proposed at twenty eight percent. What is he doing? What does he know what he's talking about repatriated billions hundreds of billions of dollars? So now is that was. That was the deal. Bring it back here. Build some stuff. I think. I think there's been some bright that was idea. We don't corporations going overseas right. Emigrants went to corporations in China was I guess I'm sure some Republicans wanted to but it makes no sense. Yeah that was the deal with the corporation to China. But that was the deal you know. We have companies building chip fabs in America apples building on all kinds of stuff entire spaceships. I mean If Joe please don't do that if you get elected joe like that. He's not getting elected. Cause night's sound like clooney back exactly so Joe Did a speech to the Asian American Pacific Islander Group of some sort. It was one of these. And he was just rambling. He's low energy. Must've been at the end of the day but but again here he goes. He's being ruined. I only have a few sub clips. He's being ruined and this is actually what you're going to hear is is not anything. I did or anything anybody did. This is actually on the feed to the Pacific Islanders. An Asian American Group of people that were Democrats. I guess. I don't know they're supporting. He's very low energy as tired pooped and but to make it. Worse IS TECH. Team doesn't help much in this binding versus the phone as we speak today. More than ninety thousand Americans have now lost their lives. A bag and infuriate more the nats heartbreak to think how much fear how much loss. How much agony could have been avoided? The president had wasted so much time and taking responsibility. If if we were writing a sketch for Saturday night live. You could come up with this and it would be funny at had to happen one. More time at one point he says rises the phones raises. Whose phone is that so ice. Got that going on. And it's really again low energy so the thinking is dragging his ass through this thing. He's not for ten minutes or more and so and he's an he's in that upstairs area to some guy lurking in the background. Who's in the shot? Yes I just thought it was really weird is head pops around and then POPs back. I saw that too is funny. Yeah and then. His whole body comes out later and then he's saying there and he's begging for meanwhile. I don't know why they're doing this or who's Mike in this? I have this Guess Mike. The which is no audience so they might the geese so they so they have joe talking here. This is the second clip and IT S. He's trying to make some points a bunch of honking geese start making a racket. As though they're laughing at him it's almost sort of cosmic. Thing is the damnedest thing I've ever heard trump cruelly. Senselessly determined rollback that progress. We're going to stop him in his tracks together. We're GONNA take back the White House together. Insured of their government wants to reflexive country as a whole including my cabinet. We're going to build on the progress remain to deliver for this community on healthcare on climate. I'm building accommodate. Leaves no one behind right now in the midst of a tragedy and so many levels the pain? Your family members of France is so start so consuming can be hard beyond that. Okay I have geese and gives you can sum up had Swan Swan's or okay geese are dicks and and they have that. Honk is in a mid range. That just pierces through everything as. It's no wonder that that's that's really accentuated. In this you know again. Someone's clearly stuck a microphone into an iphone and there's no mixing going on. It's its head Shaker. This is the future the future of PO potentially future president. No no no. But it's it's unbelievable rings the geese there. Why is the door open wild tape? I mean what is the point of this to get the door open? Got A guide lurking back there. There's geese honking. Don't they rouse the geese? There's plenty of room move on. Get Him Outta there. This brings me to a clip that I put it in here just for fun and case we're gonNA just fits perfectly. I would like you to now. You remember Jill Abramson I think you know obviously I read the New York Times like all day long. Manley on my ipad so Jill Abrahams a former editor of the New York Times. When I heard someone sent me a recording of a Raven and hurry all day. Long mainly on my ipad could be maybe. She's a raven vocal. Fryers are actually ravens and they fly away notice. It Raymond's had vocal FRY. But now that you think about we have ravens around here. They don't show up a lot. There's we have crows mostly and they keep place area variants with the Ravens. Do Show up. They make a lot. Of course you're in Berkeley course. You've got the ravens that's where the Hummers are from men that is that is the og Berkeley Hummer sound. So you've got ravens. I just I'm just saying when you hear. Raven careful could be vocal fryer in disguise. Be Okay Let's talk about mass moment masks or muzzle saw masks masks Ramaz. We went out again. this at Texas is now under a pretty much. We're open do your own thing although technically restaurants at fifty percent the still I think gyms they can't go to any a exercise places. They're still kind of limited for some reason but everything else just feels open. Heb The major supermarket chain at Texas his own. Heb No mask required. There's no Nazis at the door lines. No line no line even come in and go out as you go now. They say it's because they have everything properly ventilated which they do and they have a good system and they feel that they're comfortable and they're done and there are I'd say sixty percent people wearing masks outside inside everywhere and there's the other forty percent and we're not wearing masks and the most noticeable thing. No one cares no stink. I know no crazy looks either way. It's just whatever I don't care what you WANNA do. Fine go ahead. We went to the mall. The mall a when you come through one of the store entrances and we went through nordstroms and leave it. There are still malls in Texas at are operating and profitable operating. I've I don't know this one is ever going to be profitable after this half of it is it's a real problem. So nordstrom's big signs requirement all customers. We must wear mask and so we're walking around a little bit I. It's not a pleasant shopping experience with the mask and then we walk out into the mall. Boop mask comes off you can walk around whatever you want plenty. People without mass with mass stores mask no mask looking like I don't WanNa go on there. The require a mask and you just walk on. It wasn't super-busy but there were people. There was commerce. Were opened. it's I think we're just basically open here in Texas and it feels pretty good so the beaches open well. I have a clip but I I have some news one of our producers on just want to get his name right because this came in In my very own. Po box you know exactly. This is this is Mark from the United States Space Force paper lasers Pew you've seen using donation notes so we sent the keeper and I two beautiful covid nineteen. Antibodies Positive Armband. I have an issue with them. The color I have an issue was made. I have an issue with the color. Exactly it's the wrong color. It should be green. This is more like great. Exactly I know I know. I know this is why we discuss these things on the show. It's very important we to in this case because we both saw the same thing I also received from Philip. Kerr who Very interesting fellow sent me along beautiful. Note Philip is a certified financial professional. Like Horowitz. So we can take your money and invest it and give more back to you how it always works. But in his spare time he makes holsters and since I was going to open. Carry with our new with our masks here. It's like. Oh you aware mass. I'm GONNA open carry. He made a beautiful hand tooled holster from my bursts of thunder. Three eighty. And just and I can't wait to have a full on shot with my cowboy boots with my covert band with my holster. And I'm good to go and my no agenda mass now. What more can you want? This is definitely Texas where things are good and we're open and I have a clip hathor several weeks being stuck inside thousands of blocks to Ballo peninsula to make the most of their time while court scene and I need get golds G. weekend beats and a few drinks and GPS that in full swing get beaches on Bolivar peninsula. This comes in. It's just across the state or reopening the coronavirus pandemic and beachgoers Chelsea call. Your are still taking precautions to stay safe. Why some hands for twenty seconds. Keep them clean with their German mortally. You have a good time. There's no issues but when you start acting silly like the sheriff said on previous interview we've got a jail. That's got a whole lot of empty holes. The sheriff's office have made at least sixty three arrests so far and connection a jeep weekend. Ask for the enforcement of social distancing. They say it's challenging to enforce. It's not possible to do that on this beach with the amount of people that we have here this. We can't do that. The additional presence of law enforcement has been a welcoming site for beachgoers given the history of this event so we're open in that regard that's Galveston Texas there. A little crazy over there but it does give us another two possible. End of show does ACORNS and like I need to get then. She looks just like she sounds and Then there's this one twenty seconds there's are both good. Let me give mine. I only have one well. Isn't that the one okay? Is the divide in one. So you ain't black it strong. It's very strong. I think it'd be a decent. Ender little traumatizing. The last show. If you if you recall the last show we went to a rigmarole to all these different ISOS and then you picked an old evergreen. That was yeah. I don't know I'm sorry. There was a reason for it but I've forgotten anyway. This is Memorial Day weekend in the United States where we honor the fallen soldiers of all of our wars who have died to protect your freedom and mine and so we need to go out and we need to celebrate. You heard how they're doing it in Texas. The Colonel Ambassador. Dr Colonel General burks the scarf lady. I've totally fallen out of love with. She had to something to say about how to do it. And listen children this introductory bakes. But it's also why we continue to recommend to the public very clearly that you can't tell who's infected and so that's why you have to continue to social distance. There's a lot healthy people out there with cove it at look healthy and so we're asked to be afraid in continuously for you all to be outside to enjoy your Memorial Day weekend. Do Play Golf to hike. Doctor felt she said do play tennis with Mark Balls and to be out with your families that you have a psychological trick that she did you know. This is a throwback or call back to the tennis balls. That need to be marked. That was funny. I think it was very enlightening moment for everybody to remember that she yes. She said play tennis with marked balls. But but there's no reason of all the things she could say. Yeah I agree. There's no reason to say. Just say play tennis. Yeah but but I think this is like a psychological trick to get you. Lighten up or loosen up to what she's saying. Cam Do play golf to hike doctor fouled. She said do play tennis with Mark. Balls and to be out with your families that you have been in the household with and to even consider sharing social distance space as long as you have utensils that are belonged to individuals and maybe can be thrown out immediately. There's a lot of things to think through. I know you can do this. I know the American people can do it. And so please go out this weekend understand you can go out. You can be outside. You can play golf. You can't play tennis with Mark. Balls get you know what I think. It's a sexual thing with her she wanted to have. She wants to be the sexy ha but it was. It was the New York woman this is this is where problem this New York woman where this comes from player lasted from the same household has to bring her own tennis balls so that you don't touch other people's with your hands you can kick also Hansen. So that was a funny moment at first and she's trying to capitalize on it like. Oh look at me. I'm also I can't help but feel bad and it's disturbing woman can do it and so please as you go out this weekend understand you can go out. You can be outside. You can't play golf. You can't play tennis with Mark. Balls you can go to the beaches if you stay six feet apart but remember that that is your face. And that's a space that you need to protect him. Ensure that your social distance for others on thank you so this was a guidance. That was very cavalier. I was very cavalier but there was something that I thought was weird She says you can use these that utensils as long as you destroy them immediately and she didn't even consider the idea of taking the utensils and putting him in a dishwasher. I am with my family picnic bench and I got a bunch. Why do I need plastic forks? Why are plastic forks? My family eat with the utensils in the house. What do I need? Some special utensil. On Him in in the park I will get tossed. Makes no sense exactly but a lot of it doesn't make sense and then we had just before the weekend. Another twist remember that most of the country is is still in some form of lockdown and people definitely are not as into it and out the way we are here and we've also we have a little bit of a head start at of course. Florida and Georgia. But you don't hear about that. You're not going to see any of that. We have to see suppress people and don't sit on the beach and all that now. Here's Us. We're supposed to stay home flattening no I. It was flattened the curve for the hospitals for the for the system. Then we have to. We have to lower the the the case rate death rate but yet we're testing there's more cases and then he comes out with this well eight. I have no disagreement. We must protect the most vulnerable and be yes depending upon the dynamics of the infection in the particular State City Region County. That you're in. We certainly want to in a cautious way reopening. We can't stay locked down for such a considerable period of time that you might do irreparable damage and have unintended consequences including consequences for help. And it's for that reason why the guidelines are being put forth so that the states and the cities can start to reenter and reopen. So we are enthusiastic about reopening and I think we can do it in a pace. That would be reasonable and that would get us back as a society from a morale standpoint as well as the economy. I don't want people to think that any of US feel that. Staying lockdown for prolonged period of time is the way to go. We had to do that when we had the that was exactly the way to go. That was exactly what we were supposed to do until the end of summer July toilet June was. That's exactly what we were told to saying. Kill December explosion of cases. But now is the time depending upon where you are and what your situation not not notice this but notice this. There's not one single mention of of curve models infection rate case rate death rate recovery rate antibody tests nothing. Just kids probably not a good idea to do this. This is not scientific. This is not a man of medicine speaking. This is a dip shit. Who doesn't know what he's talking about it so bad. That governor Cuomo is using this to his advantage to of course deflect from his culpability in sadly having thousand six seven thousand elderly New Yorkers being infected subsequently dying so he gets to say stuff like this and he's right. We've been on pause for too long. The economy is slow. I don't have a paycheck. I have to get out of the house. We're all about an eugene aggressiveness. In New York the caution flag is they keep changing the facts on us. You know we make a decision based on facts but then the facts change and you revisit. The same decision with a different set of facts. And it's different. Well if you get this disease you have antibodies. And then you're immune okay so let's plan that all the people who test positive for antibodies. They can be the workforce that goes back safely because they can't get infected again they could get reinfected. That was the fact they gave us. So we test antibody tests came up. That's why there was such demand we do. The antibody test your positive for antibodies. You're clear to go back to work. Okay hold on. We're not sure about that anymore. What you said they the antibodies they were immune. Yeah but now. We're not so sure okay. New set of facts children and not affected. Okay let's see what we do about camp. So let's see what we do about school. Hold ON CHILDREN MAY BE AFFECTED? This inflammatory syndrome is more frightening than covert respiratory on this in some ways. Yeah I don't think he has that right but you see what's happening is he gets to push back essay and it's true because this is what's happened consistently every single fact has been changed has been moved and if anything comes out of this people will have calm. I hope lost some faith in this science and medicine shut up and let the professionals do it because they didn't know the unintended consequences actually ever set of the crash at the top and is the different you know they always science science science. Science is always throw this one little tidbit in there. You're saying science as your science nut beauty to discuss them safe nuclear energy and the science all will no. We can't do that. I mean how you'd be all science science science and then when you bring up. Something like that a heyday. I can't as dangerous any of this is all bogus bogus technocratic malarkey. There's no science here that it's all guesswork. Shot up already science. And you said I want you to know you did say Malarkey here. Here's a set order lark yet used to before. Here's a sad sad tale every year. My mom my mom's birthday may twenty first dear aunt meg who of course is married and still happily married together with uncle don there now in their nineties. They've been Holed UP IN THEIR HOUSE FOR THREE MONTHS. Because you know they actually are the people that need to be protected she always sends an email and she always talks about the yellow rose. Which was my mom's favorite. You send it to myself my sister. There's always a it's beautiful and it's so nice. She remembers she. She and my mom close and so this year she sends a note and at the end. Says we are so ready to bust out of here. But we're doing well. Thank God. We have governor Cuomo. He's our guiding light and we can't wait to dump trump and I thought it is exactly these daily chats that he's doing the working that are very effective. Because what else are people going to do? Who are locked up the sitting there going okay. And he has no bells and whistles and then even the his brother calling in it's I'm sure it's some version of entertainment. And he took it to an extreme with via the mask competition because we. We know that we're not going to stop people. From leaving their homes and going back and getting business started the genie's out of the bottle but we need to have that final bit of control and it is the mask culture. The Muslim masks. Whatever you WANNA call it and he did a whole campaign a user generated. Psa contest may fifth. We announced a wear a mask in public campaign. And we asked people to submit vide- videos that and we would pick the winner by vote of the people and the winner would become a public service announcement. We had over six hundred submissions. Isn't that amazing? The competition still open. And we're going to show you now. Five of the runner ups United we stand divided. We fall we go not just obey the law but to obey the laws of nature. Hope for unity. In Our community we pray for normality in this calamity mask of not because I feel sick because I fear getting you sick mascot because days weeks months of breath and trump's is better than no one. My wife will soon have to raise the father. The son Now that's the public making that s the public max up mask up and I've noticed something and this was very apparent the mall where there's a lot of medium to Sub High Fashion. There is a model of mask which almost looks like The lower half of a football helmet if an enclosed football helmet with has a Chin Guard. And it goes what is it has pointy the two sides meet in the middle in a seem. It's in the front and what did effectively does is it. Sits away from your nose and from your mouth and it's not really an effective mass because stuff can get into the top. It says no pinch at the top it and it's a fashion item and the market is being flooded with these. And this is what you're going to see the Gucci models and and you know obviously we saw this coming but it's really going to be something that will be with us for a long time. People are going to have masks. It will be a fashion accessory. I don't know if you saw a list of Milano she This was pretty funny. Oh a Friday or Saturday. She Posted a picture of herself and her family like everybody. You got a mask up mass. Look at all the different masks John. She's wearing a knitted mask. Yeah this is typical a knitted mask. She just wear pantyhose so now this goes along with and luckily we have some documentation to back this up with the control. That governments are trying to enforce upon people in this situation what is leaked out. in the UK is a document from sage SAG. That was their advisory board. A Neil Ferguson. Was on this these guys that advise the well. I maybe go for her immunity. Then oh no we change the model. We got all locked down. So this isn't advisory group to the government and one of the documents which will be in the show notes and h show notes. Dot Com is From March twenty second options for increasing adherence to social distancing measures and they have a matrix. It's only eight page document. But they have a matrix at the bottom. And I'll just go to that quickly. I so they have all these different things in different steps. You need to do so. I'll start at one. Provide a clear precise credible guidance about specific behaviors. This is to get people to lockdown to US media to increase sense of personal threat. Note the words use media to increase sense of personal threat US media to increase sense of responsibility to others use media to promote positive messaging around actions Taylor messaging using promotes social approval for desired behaviors? I'll read that one again. Use and promote social approval for desired behaviors doesn't mean they're right consider enacting legislation to compel required behaviors consider use of social disapproval for failure to comply stink guy develop mobilise adequately resources community and infrastructure and provide financial material resources to mitigate effects. Now let's go to some of the specifics. Because it's just going to pick out a line to the highlighted in this document. This is all the guidance guidance now needs to be reformulated to be behaviorally specific. Who needs to do what precisely. And why and here we go. The perceived level of personal threat needs to be increased among those who are complacent using hard hitting emotional. Messaging to be effective. This must also empower people by making clear the actions they can take to reduce the threat. This is the author of this thing. Burn as it's out of the handbook man. It's it's one O one. Let me see if there's a thing at the bottom. What do they say? There's a lot of different credit references sinister document. You're reading yeah. I was so disgusting that it's in the public domain. You think they could keep it a secret but these guys were so full of themselves. They don't see any reason to now. Let's put it out there. We'RE GONNA. That's manipulate the public and tell them how we're going to do it. Fifield Green Bay packers. Just ranch Tom what you're GONNA do it. Messaging needs to emphasize explained the duty to protect others. Messaging about actions need to be framed positively in terms of protecting oneself from the community increase confidence that they will be effective incentives them. Communication strategy should provide social approval for desired behaviors promotes social approval with approval within the community. Now we have a skip ahead a little bit to the fun stuff. Enablement weight had the complete compliance coercion. Coercion comes with legislation. That's the last the last part incentivisation. I mean have a look through it. And they're not bashful at all about how they're going to use media and messaging to make you comply and part of that apply to what to stay home and do as the government tells you and listen to the drone. What's the point of it? Well the point where they thought the point was was to save everybody's life member. I told you points and exercise in one world government. Well that's what it starting to look like. Yes do you remember. I told you about Maurice. The dog motorhome. T's a very famous statistician in the Netherlands who's been completely marginalized because you yes. Yes you have actually given us a little lecture about this guy. He has been marginalized. He's been kicked to the curb so I sent him a note. I said Maurice I gotTa Talk to you especially about the marginalization. He's like within two seconds. I'm on we'll do it Tuesday. I also have sensational new material. So that could be thousands of sealed indictments. I don't know but I'm very excited to talk to the dog. He's very he works with my dad. The guy's been around and he's he's he's quite famous. He's worked for big corporations and doing stuff but always says the political analysis to us. Pretty Funny Interestingly a public health officials in Ohio just talking about masks and coercion have Well he came out and they said hey could anyone who's black. Avoid gang symbolism on your face mask I guess they had to apologize for that and then I thought wow are no agenda if masks are kind of kind of gang looking in a way careful but then the unintended consequences and this is what I think. people will. I believe that worldwide people are going to say hold on a second. No one told us you know like the a bold churches are closed. There's no a now In in San Francisco California suicides or outnumbering Corona virus deaths. Sex workers are in big trouble which you can imagine hertz. Car Leasing Company Rental Company Declaring bankruptcy I don't know if just protection or bankruptcy protection protection right And the Big One is liability insurance and this is this is going through Congress right now every sneeze every cough. Everything has a lawyer attached to it now and there's hundreds of lawsuits for mistakes. Governments have made corporations have made and you cannot get business insurance and so the insurance company is trying to get a bill in in a pass through congress that gives them six to eight months of Or It gives business owners six to eight months of complete immunity from liability tort cases. And this is a real problem in America because that our system runs on drugs and lawsuits concerned and banks and banks too. We'll see use drugs which is also insurance companies which is also a healthcare and the and the worst part I for some I would say is Unintended consequence number. One one million seven hundred ninety seven thousand nine hundred. Ten firearms were sold in April on in the United States. So I think that kind of says we are interested in our own interests. And we're going to probably step up a little bit if we feel it's necessary and I think people are hearing it. This is a lot of studies. Do after this is said and done and it turns out this thing was created in a lab and the whole thing was like suppressed in the information was bad and they just. It's going to be studied to. Death is going to be one of the biggest moments in history studied to death by contemporaries mostly sociologists in the next fifty years it's going to be studied to death and all the one world government people are. GonNa be beside themselves because they had none of this went quite as planned. I'd like to talk briefly about vaccines and not too long. Because you know there's all kinds of stuff going on all kinds of trials all kinds of things happening But the number one thing that we need to stop in his tracks right now. Is this idea that Bill Gates is at the CIA presenting Vaccine Yes let's which clip is. This is a clip. I met Bill Gates once briefly. You knew you knew it. I mean you hung out with him. You Guys Bang hookers all kinds of stuff. You've got great stories that far but did hang out. I didn't hang out but I was at a world series game with him. I've known him since about nineteen eighty. Two and I've talked to him about different things on the you know. He's he's not the friendliest guy in the world. But he's not but I have. I know him. I know if I saw him he'd say he'd say what's divorce doing here. I mean it can. I mean literally the oddest people. Look at it John. Mcafee is like of course. I know divorce accurate. You know you have friends in low places I do. So I very impressive present company excepted very impressive gates in the CIA clip is the clip. And this is supposedly in two thousand and five presentation that bill did to the CIA about a a vaccine that would kill a gene and in people that there's a thing called the God gene over ethnic remain. I've talked about some time ago. Yeah and the Guide. Gene is apparently people who have this genes tend to be re- very religious and sometimes fanatical so. Let me complete so over here. We have individuals who are particularly fundamentalists. Not particularly religious. And you can see. There's a much reduced expression of of this particular gene. The demand to gene another evidence that that supports our hypothesis for the development of this approach. what you what you see. Aguirre's but most virus good news from going into a market so our hypothesis is that these are fanatical people that they have over expression of the two gene by vaccinating them against this will eliminate this behavior so we have some very very remarkable data in this next slide. Here we have to brain. Scans these are is. These are two different. Individuals with different levels of expression of the to on top off is an individual who's a religious fanatic and individual. We repeated this numerous times that has high levels of the to now This individual down here who had low levels of the be meant to gene? This individual would self described as as as not particularly religious in in each case these individuals were were read religious text. This individual light lit up the right middle frontal gyrus shown here and that's the part of the brain associated with theory of mind. It's a part of the brain that has to do with intense and and beliefs and desires contrast in marked contrast. Here's an individual who would not particularly South describe as as religious thing is this clip. Was doing the rounds. Several years ago it was not associated with Bill Gates. At the time it was just Cia is planning on doing this and now someone it was. It's an interesting observation. Vitality of bull crap. Yeah now editing of course immediately came to me was. This isn't Bill Gates. I know build enough. I knew him in the early years and then I've Kind of through their heyday of windows. Ninety five that period. And that's when I I would be talking to him. He was a little more open. I think he had a couple of trespassers. Live started getting security source. Cnn less and less. I saw him in a Less than last You sitting at First Class Airplane and I called him out on it because he's used to be the coach. Yeah but he said to me that well He. They won't let him sit in coach. He buys coach tickets security risk and so they put him first class but then I kind of lost touch with him. Probably I would say the last ten years but I've seen him on TV. And I've seen him in these presentations and what I can say for. A fact is that his voice hasn't changed the same voice he had in one thousand nine hundred eighty two and he pauses a certain way. He says on a certain way to lower drawn out and he never talks. This guy's up talking be at the anti goes the theory of mind up talks. Dad talks a bunch of stuff. This isn't even close bills voices a little bit at the very beginning where you can almost hear bill but the rest of it's nonsense so this is not Bill Gates. You can slow it down speed up anything you want to it. This is bullcrap and is going around and everyone's all look at this. Look at this. This is useless. This is bad. This is not the kind of thing we want floating around. Because it's IT'S DISINFORMATION. It ruins any solid argument. It makes everyone look like a conspiracy night. It's it's a negative thing and is came out of Cunanan or some other door shit. That should be avoided. John Accident a nice France. My friend Nice one. Well pick the ball up from there. This is Bill Gates and then we're taking things that are genetically modified organisms and we're in checking them in little kids arms. Just shoot them right into the bank. Sounds like bill doesn't it? I got a little laughing. Shoot into their vein now. Important because there is a disagreement in the constitutional law arena and we have a knock down drag out fight between on one hand. In the Blue Corner we have a we have Alan Dershowitz constitutional scholar who claims that the forced vaccination by the state onto human resources and citizens of the United States is constitutionally legal constitutionally. Legal and here is what he says about that the Supreme Court to say yes. The case came to the Supreme Court. Today they would say yes would either be ninth and nothing or eight to one it is not a debatable. Issue CONSTITUTIONALLY LOOK. They have a right to draft you and put your life in danger to help the country. The police power of the state is very considerable. But let's distinguish mean the constitutional issue on one hand which is settled and the Marla show on the other hand. I think wanted make plausible argument that nobody should be required to be subject to a dangerous vaccination. Help other people as plausible arguments. And I think we should have continued to debate that I wouldn't choir. People take vaccine unless through very very safe now. Any ejection can cause of useless is directed at the site and he can cause a problem but in general if the vaccine extremely safe in the state does have right can tell you to take remember. Vaccines Work. Now let that little bit in on purpose because I feel that Our good Professor Dershowitz First of all is arguably on the wrong side of the law but also seems to kind of like immediately go from a constitutional argument which he didn't really argue. Just it's clear. The court decided on a nine vote. It'd be straight up and down not going to happen into vaccines work. Listen again can a problem. But in general if the vaccine the extremely say the state does have right to compel you to take remember vaccines work. This has been taken to task by our very own constitutional law. Professor Professor Jones and Professor Jones has written quite the screed which you'll find in the show notes he wrote it up specifically for this program but I can paraphrase it quite quickly The case law and by the way are professor as he states in. This document is it. Constitutional scholar has taught constitutional law as a professor and has read almost every single case law on this very topic. I didn't know this about him. He's been a a producer of the show for a long time. I think he lives in. He may live in Asia. And he says the particular case law that this is about is very famous as Jacobson versus the Commonwealth of Massachusetts. And this is around nine thousand nine hundred three. I believe it's very early. On small pox vaccine he and his son were both vaccinated. And which is interesting. Because you think that this was someone trying to refuse vaccination but it wasn't there are both vaccinated and they both got sick and so when it was time to relax innate they even had it back then the he said No. We don't WanNa do that because we got sick from it and the what would spark this case. Is they said to him? Well you have to take the vaccine but do his underage son. You don't have to so there was a split there. How come. What is the difference in age that he does that? He doesn't have to have this force vaccine. And the other guy does and so it all boiled down to these the actual conclusion the actual What's the term looking for? The outcome of the case was not that the state has the the outright the right to force vaccinate the citizens. It was about the the penalty if you refused. And so I read from the actual case. This is from one thousand nine three quote if a person should deem it important that vaccination should not be performed in his case and the authorities should think otherwise it is not in their power to vaccinate him by force and the worst that could happen to him under the statute would be the payment of the penalty of five dollars. That is actually what came out of the out of the out of the case but Dershowitz is making it sound like well it. Was this whole problem with that case it was upheld by the Supreme Court. Yeah but this is this the Supreme Court of the Commonwealth of Massachusetts who made this decision so he didn't have to be vaccinated had to pay five dollars and all the Supreme Court they say yeah. We uphold and throughout one hundred years now. More Than One Hundred Years Alan Dershowitz v Constitutional law professor. That I trust Harvard as I think on the wrong side of this and I encourage everybody to go read what What are professor said is a beautiful document? And he has everything expect from a full on A full analysis leads me into sorry. Does he going to say it should be up on cosmic Weenie? I'll send it to you. We definitely need it there. That's a hot spot for good. Docs at all the kids are talking about it. Hey doing paper go to cosmic Weenie. Some good shit. They're just use a curl. Download everything so obviously. This is all scam. This there's so much nasty as early up to I don't know but I think he's in bed with him and he's not to be one hundred percent trust at this because this is not a cavalier issue. He's really dismissed. This from the get go. This is the second time of hurt him like Cranston decided shut up already can do whatever you want as long as a safe vaccine. That's not what the law says very disappointing. If you WANNA know how. These things work with forced vaccinations. Let's take one particular case in one minute and thirty seconds. Of course it's a Robert Kennedy junior and it's never good audio with is good audio but his throat as tough. But it's worth listening to. He's going to explain how force vaccinations work. And why in this case the hepatitis? B Vaccination which every child in the United States receives at birth how that came to be a mandatory vaccine for children in the United States. And I'm sure it's similar. In other countries. Appetite is back in ways that was the sign or hypolite is really only acted groups which were smell homosexuals intervene. His drug users share needles and a prostitute engage and protected tax knee back. Pain was designed for the US groups because they were getting hurt. My appetite is a when Merck created the vaccine it turns out it couldn't sell an economy. Those particularly no interest in buying a burke went back to see and said listen. We made the factory or not. Make any money on those vaccines. You need to do something to help us. So she said Oh problem we mandated for babies but normal childhood some other is not infected as arrest and will not have as at least until their mid deans change and yet we give that every day. They're born with seen only lasts for two years that he has been injected on own between the they're worn day. They're two years old. There is zero chance that they are going to engage in sexual acts or be involved with the prostitute or shoot share needles. And so all. This is the only reason for that. Accident is eight financial benefit at Berkeley and now glaxo amounting mandated to children. It's disgusting and they tried to pull the same thing with Gardasil. It was the same idea. You need this young young child baby baby boy for for Genital Warts. Baby boy go. You need this is discussing. And you know how many schools have not mandated by into it. And if you're against it you're an anti VAC sir. Well that leads me to the last series. Then I can rule these out. We have a new doctor. Who's making some noise disguise? Very well spoken. He is from California was on another local station out in Sure we're in Orange County. His name is Dr Jeff Bark and yeah this thing is going around the I. I'll tell you before you play it. I had this clip What bothers me I like. I like his message. I think he's right on the money he gave a spiel and it was done. It's like kind of a video. Pike is what bothers me. He's got two little little emblems on his jacket on his collar. One of the American flag. And that's on. The looking at him is on the right and on the left is A. Don't tread on me flag. I have one of those on my my new holster do you. Yes it's beautiful. Wait until you see this fantastic. So that media. I don't like to sort of type of virtuous signaling right. I don't like yes. Well in fact I was going to play it with that in mind and pre announcing I have three short minutes fifteen clips from him. What he's saying is correct but he is he. He actually says well. It's too bad. This is being politicized. But he's obviously politicizing and himself and that's an overall issue but I just pulled a couple of things. I thought were interesting as he identifies. I and complains about the incredible pushback that medical doctors and professionals have received from the mainstream over alternatives to lockdown or even discussing it in general and we have examples where that actually didn't happen when you look at Sweden when you look at South Korea when you look at Thailand and other countries where they didn't have the draconian lockdowns like we have here. So it's possible that there'd be more people killed as a result of this virus but it's also possible that we would have reach herd immunity quicker and we'd see this virus now quieting down like we've seen with other respiratory viruses in the past and there are some prominent epidemiologists Envir- Allah that put this message forward. But what happens there band on Youtube? Facebook blocks them the mainstream narrow narrative the mainstream media never gives them any airtime except to criticize them. Here's Dr So. And so who says the following then they have their own expert that says no way their fraud and and by the way did you know that they got a speeding ticket. A few months ago or something of that sort. So there's this narrative that's going forward and I'm not sure why I don't want to believe Mellon tent from a motive standpoint but it's hard to believe say what I believe Mellon Tent. He'll bring that ordered. I'm not sure why I don't want to believe Mallon. I think the reason he saying this is because he's very political and he's got to read his thought bubble. I think this is mel intent. I think that's what he's saying. Really come on we. We know how this goes and especially with the. Don't tread on me. So we know his position from a motive standpoint but it's hard not to believe that some on the left in the mainstream media really hope that we can continue this on long enough to elect our president and. I'm sorry to say that but I think there's some there's some truth to that. I don't want to believe that politicians and decision makers have that perspective but I think some of them lean in that direction where. They're not entirely disappointed. That this mainstream scare is going on To the extent that it helped bitter did it. Hurts president trump? I think he's absolutely correct. But let's get down to the basics and not the political part the coating of Covid nineteen death. This is a big issue. Even with the New York Times they had one hundred thousand death the faces the names hundred thousand names at which already one has been identified as a gunshot victim just recently. There's an article just ran and the Pacific northwest. I think I may have posted it on twitter where It looks like two or three gunshot victims have been credited this coded. Yes and this possible. This is what I hope comes out of. This is that the public at large stops believing stops believing in the bull. The starts doing their own work. That we have enough connectivity. You couldn't believe what you want to. There's a lot of documentation lots of the by the way. Trump is not absolved of any hanky-panky with the vaccine and pharmaceutical business. Here's one I found you remember when he fired bright the farmers she'll who've been in and out Rick Rick Brightest his name at bright. Yeah Dr Rick Rick. Bright yet so he is far Michelle. He's been in and out of government and Vaccine Business for the twenty years three years in three years out doing his business so trump somehow he gets demoted pushed away and then trump brings in Dr Slowly S. A. L. O. U. I. Along with a general and they're going to be running operation warp speed. There's about one hundred vaccines now in development one hundred different companies. Well Dr Slough is a former member of the board of Directors of Moderna Inc the number one vaccine contender. So it's all shoes everywhere and digital anything about the vaccine is not that they're gonna even develop a vaccine. It's the money the just the money they don't even care if the vaccine designed to get everybody's frayed nobody blinks and I when they start throwing tons of money at Vaccine Development The problem we've seen over and over is we have no reliable data therefore the models are good. We have just numbers of people who are dying. Did they die do they is another great document in the show notes the CDC numbers just good to look at them comparing twenty eighteen. Nineteen Twenty Nine Thousand Nine hundred twenty twenty season actually saint. We had four thousand less left desk less deaths overall in In two thousand nine look at the chart. I'm confused now. Anyway that's the point who's dead. What were they coded as in Koo? Who's who's who is infected. Please tell me what's happening Dr Bark? I've heard that some doctors are attributing cove in nineteen as the cause of death with a lot of their patients are doctors motivated to get as many code of nineteen patients as possible so he can receive federal funds. So I don't WANNA say they're motivated to but there are incentives in place and the incentives are based on good motives. Meaning that if a hospital system is overwhelmed because we're treating patients with his virus than we're gonNA reimburse them at a higher rate to make up for some of the work in difficulty in trauma that they've been experiencing by taking care of these patients so there are mechanisms in place to reimburse hospitals but the only way they can track that is by tracking the number of covid nineteen patients and the number of deaths that are associated with covid nineteen patients so what we do see is happening is is patients that died but without a laboratory diagnosis they're getting coded covid. Nineteen and there's this natural human tendency to lean in the direction of something that is economically benefiting their healthcare system when I code On our electric medical record systems there are coding for covid nineteen and The the the the organizations that provide these coatings let us know what the what the what the cost and benefit is for for making these codes. So I don't WanNa say there's dishonest doctors out there that are doing this purposely. But there's this natural tendency to lean in the direction and code in a way that will ensure higher reimbursements for a healthcare system. That's overwhelmed then. You heard right there in the beginning. He says we get reimbursed. Was Different Reimbursement and I. It's administrators I don't know if only the doctors are doing this or whatever it is but it's clear that the data is not clean which another reason excited about talking to the dog on Tuesday to more clips. I'm going to lead you right into your Roxie series is going to be beautiful. The testing there's an issue with the PR tests and the standards that are set that could be producing very high false positives which again screws up. All the data means we have nothing. We know nothing and it seems to be not one of those less really. Try and do it right everybody which backfires this is David Crowe. He's an investigative journalist. He's going to briefly. Explain the problem with the testing process and effectiveness very simply. The process is that you have aren a insane is a swap so you. I need to extract the irony get rid of the DNA which interferes with the test. Get rid of various enzymes and things that can affect later processes that is not a perfect process so the amount of Arna you get it step on will vary depending on which lab do it in the second stage is that piece you are only works on DNA. Not Ernie so you have to convert the Arnie DNA using an enzyme called transcriptase and the efficiency of that according to buston varies by a factor of about ten so what that means is the amount of DNA you end up with at the end of the second process is can be quite different by probably more than a factor of ten between different. Labs the way you tell if somebody is the way you say. Somebody is positive or negative is by running cycles of each of double the amount of material and you say for example if we get to thirty seven sample thirty-seven cycles and we haven't found any material. You're negative de choice of cycle numbers in in tests that are approved by the FDA varies from thirty to forty five. The second point is if you push the test to heart you can get false positives. Stephen Bus Recommend recommended no more than thirty five cycles and the tests the thirty three tests approved by the FDA. Go from thirty to forty five and only three of them had less than thirty five cycles. So what they are doing is they're pushing the envelope because they don't want to miss somebody who's infected but the consequence of that is could be generating massive number of false positives and they could have generated an entire epidemic by a massive number of false positives and if somebody tests positive on this test there's no way to determine whether it's true or false positive. The whole thing is a mess. It's a mess and for we've been taught trust the science the Science is in Charlotte Wall rated it's evidence based fact-based poll crab. It's just not true. You don't have all the it's okay. This is this has been proven out by the whole global warming scam well and this is GonNa listen to anybody else. They close the door on discussion. Ninety seven percent of all scientists. They say it they lie about it and it's all about the money. Do you remember when it was only a week ago. China's going to test all eleven million people in Wuhan in ten days stunned. In right we got our our producer boots on the ground in John. He checked in a week ago. The reality of testing has changed. They are not testing all of who we no longer need to be tested because we were tested in March. My Co workers are also exempted since they were tested last month. I have no idea how many were tested into no longer reported on the Chinese news television the CNA. I work all over. Wuhan and no longer see the big testing stations. Wuhan is thirty two hundred eighty square miles so maybe they moved to another section of WHO? I don't see but this testing is over. They're lying. They're all full of crap testing testing ten million people in ten or eleven million people in ten days bullcrap now taking into the hydroxy take into the hydroxy. This is the final one and I thought it was quite brilliant. That you came up with the concept that this virus had back door and the back doors hydroxy chloroquine and then you insert the zinc and then you Effectively neutralizing the that somehow could have been known at least to the president since he was so early with this. Yeah very I think he was read in on something something somehow somewhere. Here's the final clip for me. Dr Bark again The politicization of it. But IT'S A. It's a good clip from a doctor. Who prescribed it and a little interesting tidbit so hydroxy chloroquine for example has found to be very safe effective cheap readily available now but if I use hydroxy chloroquine now and I read a prescription not uncommonly. I'll get a phone call from the pharmacy for me to justify why I'm prescribing this medication. I've never had this happen in my thirty. Plus Year Years Prescriptions. He'd never had someone really questions. And whoever nope never but now every time I write it I get a response back to justify why either the patient is sick and they meet a certain protocol of a particular age or this that and the other. I've never seen that before and I know I know that this this drug is being used throughout the country successfully and safely yet. It's now a political drug because a few months ago can't remember how long ago now every day just seems like you know a year but maybe a month and a half ago. President Trump said on public TV. I remember I was driving to work listening to the news. One of the press conferences and I heard him say it and immediately when I heard him say something about Hydroxy Click when I said. Oh boy here we go. How long is it going to be since till my phone blows up till I start getting emails from patients and sure enough by the time I got to the office I had already received emails? Enquiring about hydroxy chloroquine. But now immediately the press picked it up and now hydroxy. Chloroquine is a political drug. So if there's a study that shows that it doesn't work mainstream media front page news. If there's a study that shows that it has some benefit it's ignored or when it's presented right next to it is a so-called expert to immediately shoot down that study to say that this is not a good drug to be using and I think as a public service. You have some information on this This sixty year old drug seventy year old drug seventy year old drug the been long since proven to be quite safe. Of course. There's a lot of stories but let's go back to the doctors that were discussing. This whole issue We had on the last show. People like these clips. This is continuation These are a couple of one of these. Two of these are long kind of but let's start with clip to set this up. This is a Again this is the discussion of why this discussion of people get it. Why more men get it? A concept called co morbidity which seems to be an element of Y. You get it what the older men would get it. And then it continues with And then we'll continue where they get into the oxy. Chloroquine d three and vitamin C. discussion especially the vitamin Z discussion. Which has a fascinating. Punchline started started off be interested to see who expressed the disease state and what they were taking to support their their prostate. Because I think there's a correlation there but we would have to really research that so when the change of somebody was using finessed ride or something. Although there's there's with and the advent of viral treatments in lieu of say maximum with the only real treatment you'd have for for viral infection right out the symptoms and treat those something called protease inhibitors. Now and there's a protease inhibitor. That both blocks TMP RSS to and I think there's other ones for ace to but again you don't want to get into the ace inhibitors because what we already mentioned. But that's already approved in Japan for a pardon escalates coma stat mesylate. That's the we tried to order some studies on it. I tried to get. Api brought in. And there's also no famous that mesylate. It's pretty much the same family of drugs. Yeah both are approved. They're both been used great success the long and the short is when we talk about different medical interventions or supporting. Those that are at risk. These are prime candidates prideaux. Some of that. The virus comes along. I can't their immune system takes care of it. They Ciro convert make their own antibodies. Because you'd inhibited. The cell from delivering its virus. So we've already agreed on or we already put a hypothesis together here that the viruses manmade. I WANNA go to the next level for a minute and say if it was man made is the groups that it hits coincidental or was there a deliberate nature behind that. I don't know that it's coincidental. I think when you when you enter into gain of function type research and you start pumping up. It's it will naturally naturally go a become more virulent income morbid patients. That's that's a given. What's interesting with this? Is that normally. You would expect immuno compromised patients to be hit just as hard as co Morbid patients that that's usually a given but in this particular virus it's not because children babies are immuno-compromised I mean. They do have passive immunity from their mother. There's no doubt and if you're breastfed you'll have more passive immunity but not like an adult. Now what they mean to kind of break this down. A children don't have much immunity. It takes years and years to build it up. You're exposed to all these viruses. You're out floating around you out. You get sick. You get sick you get Willia- develop a lot of immunities and Co morbidity refers to having to chronic illnesses at the same time which is mostly older men right and they discuss how it should be mostly women who get this disease just naturally based on the nature of this virus of the coronavirus but men that have co morbidity and that would be for example having diabetes and high blood pressure That would be like having hypertension and a Enlarged prostate which every man after about the age of fifty. So so men. Have this this this these issues and it turns out that the virus needs to couple of things going on for it that to latch onto to get going walking. The latching on is the easy part. It's it's developing the open. Getting the virus load into the cell is hard part via the viral viral load. And Anyway so now. We're going to discuss the mechanisms that stop it and it turns out that oxy chloroquine is one of them. So let's go to clip to not like an adult so the fact that it it's a non issue and kids it literally is a non issue and kids and babies tells me that that is the priority here. The priority is is the binding sites and the commodities. It's not immuno-compromised nation in this case. So there's more of a risk than somebody with benign prostate issues than it is with somebody with like a Lupus or a particularly lupus. If they're taking hydroxy taking hydrochloric Say Though let's talk about that for a minute. Let's talk a little bit about you. Want to speak a little bit about that. Or maybe talk a little bit hydrochloric. Zank can some of the things that are you think are effective in treating this now again. Just explain to these These people are. They're they're Credentials Darah the woman is an MD and a pathologist and she specialized. There's they're all researchers and their job is to the guy that she's with is a the guy was doing. The show is a doctor. She's a doctor but their research doctors and they do mostly drug testing for for approvals. Should they're part of that scheme of things and they're just kind of in the mix and this in their wheelhouse of expertise Bob. The beginning of these of these clips to guide spends a good fifteen minutes boosting their credentials. And it's a very interesting interview overall. But they're they're they seem knowledgeable. Mindy sure. Yeah we do these big one. Actually in keeping people inside is not good way getting back to hydroxy corker. Now that I'm sorry to interrupt. That is actually such a good point and The dog is GonNa talk about that. It's the same thing with influenza. Why does it happen in in these particular months one because of the humidity in the air but to everyone's inside the altogether grandma kids everybody and they have all the doors close and the new? There's no ventilation and that's what happens and that's why it spread so quickly the best ways to actually be outside breathing. Fresh air being the sunshine if you got it. Let's think about what it treats or prophylactically treats and has for seventy years right. Plasmodium Falciparum Modem fell supermac tyrian. However it's not your typical bacterium. That's me right. It's malaria correct. And the way it works. I'm going to back to what you said about talking to the general not losing losing my on air but basically it's preventing the virus from entering into the cell. It blocks it the same way it would block plasma fellowship room from entering into the red cell and then when you add on a zip reminds in zithromax is a MAC relied antibiotic that has antiviral anti viral properties. It does have antiviral properties. When you hear people say you. Don't use an antibiotic for a virus. In general that's true as through my sins a little different and when you are suffering from covid nineteen and you have the damage to the lungs your more. Apps to all of that opportunistic bacteria to also take hold so it will ward off struck new mo- or any other kind of respiratory bacteria in addition to antiviral properties. Such gather if taken at the right time and that is key you can have a patient crashing on event that it's going to make a difference if that point. It is so interesting the time that we're in because we're not the only people who are listening to this confined. This are sharing it with each other. These are not crackpot. Dr These not nut jobs. He's not anti vaxxers. These not science deniers might believe in global warming for all. I know these are smart people who have different opinions and I and I go back to their mainstream to be honest about. This is the thing that bothers me but so is it true. Is it really true? Then that these studies bogus studies. So Oh yeah. We did it with the with With with with zinc with the with a Z. Pack that we'd the study didn't include the zinc and it was people who are already unventilated. All these different studies are only meant to discredit this. For what reason in right it's one part of fuck trump. It's they're willing to put people's health endanger or kill him now. Let's especially all people you want to get rid of them. Let them vote for trump. Well there are also good because they cost the system too much you know. Hey let's just back off on that. Let's go back to this this issue that you just brought up. Which is the De Studies? If you remember the last few studies they keep bringing out to discredit oxy. Chloroquine hydroxy cleric went the last one that we plan this show was that was was on. Cbs said they took a bunch of people that run ventilators short. She just said that when you're on the ventilator already too far gone and we think that bad is going to happen has happened to the Hydroxy Clark was going to do Jack and then they said that they gave him a bunch of hydroxy. Clark win at that. Point and and the morbidity was hire more people died and that was the conclusion of the study. It's even funnier so this is a. This is a major propagandistic effort but it's multiple people taking advantage of the crisis clearly the health the pharmaceutical the the medical industry is in on it for a number reasons. One then they need vaccines vaccines keep people sick and it's just true vaccines make people sick. There's all kinds of side effects as a huge industry ten times the size of the vaccine industry to does huge money in not going with the pretty much open source. If I could just call at the next day bring this exact issue. Okay do we go into it? Yeah you finish the other right. Yeah okay yeah played around for no. We're three three think that it's going to make a difference if that point well behind the eight ball. The side of storm already happened. You have viral. That is really tough to to fight. You have to do this beforehand. I mean my suggestion is to do it. At the onset of a fever so at the onset of symptoms fever or respiratory rate or something like that he were to start. Roxie Clark Mice Zinc Vitamin D. Those guys a thanks. You be in pretty good shape of coming. Through certainly -solutely there's no doubt it's been reproduced and reproduced reproduce. Preventing hospital admits has been a non issue. I can't believe that it's even a controversy. I don't understand why and I even have documentation of Faucher speaking to a group at the Rockefeller talking about back. In twenty eleven talking about how effective it was for SARS one two different in the binding nats where it acts hydroxy. Chloroquine is an issue because it's a political issue not Not a political issue and it's also cheap. It's so cheap three dollars for thirty tabs and you only need sixteen. There's nobody there's no money in it the yet there's no money Disa- veer has. Has they have their own. Great test results. You Recall I. It was disappointing stock tanks. Then oh wait wait. We figured something out so I got the study and these are pretty easy to look at. And you don't know if it's factually true. What's in there? I'm not a scientist but I can read the abstract and conclusion and not lying about the conclusion. Which is that people who took rim disappear. This is the Gilead drug fourteen hundred dollars. A pop versus three dollars people who We're taking Gilead in the same situation in the in the hospital. They recovered up to five days sooner. However the actual mortality rate remained the same. So if you are not going to die you didn't. You did not die faster but it didn't stop anyone from dire identical identical so but but that's so disturbing you have the the the medical people who who really have a there. They live in their own world. They had their their rockstars. Fauci is a Rockstar Julia. Roberts calls him because they know each other from the Elton John AIDS Foundation. This guy is a Hollywood star. They all hang. You can find pictures of him with every celebrity in Hollywood and so it's the money train. You're so right and then the everything needs to the whole system has to keep working so we've got pushed that stupid Hydroxy Clark away. We don't care we'll make something just as good. Just give us a few extra weeks. And then the because of how they report of how they present things and the willing mainstream media. It's taking away valuable in. It's providing false information to people could actually used this for the for their health for their lives. This is the takeaway from this. This is what we have to learn. Well I wish you all I know you now. What IS CLIP for? Because I'm not sure how it's coded here. Oh there is no actual four. Goes One two three and then Vit- C. D. V. D.'s vitamin D? Okay you want that one I. Yeah Yeah and the other thing real quick on Vitamin D. I don't want to lose. That one can get it from the Sun etc the long in the short of it though there's plenty of papers that go back in the nineties where they were looking at corona viruses and again the coating on the corona viruses says all but identical upwards of eighty percent so to defeat them is very similar regardless of which corona it is site and D. As well as I that and see at levels that exist in your saliva we're founded destroyed so B C and D. What is that? That's not vitamin D. Say No it's an enzyme in the saliva but it's directly manual vitamin D creates the up regulation of sites that directly when you hear patients say when I first got it. My sense of taste was gone. My sense of smell was gone what happened. That's directly linked the vitamin D Chiba. I adore has been doing videos and Ben on all kinds of shows talking about the need for vitamin D during this time and he's talking de Zinc and Saleo Tennessee wrecked and zinc doesn't increase bioavailability in the classical sense. Or the amount of drug that your body absorbs but what it does is help drug binds to the viral site. It's almost like a facilitator for the hydroxy corker known. Of course they mentioned Dr Sheva who has already been marginalized as a Kook. Oh yeah he's been kicked off the air course. He's a Kook because he was he's also running for Senate. I believe he's Kook. He doesn't know what he's talking about. Everyone's a coup. But that's why I can't wait to speak to the dog man to talk about being marginalized. Sc had the JC had covert. Jesse had probably had the baby probably had it because he thinks the baby was the carrier from from preschool and Jesse had the the was like a week or two. She said no smell no taste. Wow which I still. She had it. That's a long time though and did did now. Did you do your typical You you pump them. Full of D three minute. They pump them through full of d three JC. It have Jesse's a liberal and I don't think she buys into it does she have a mask. She doesn't wear the mass when she comes over here. But I'm sure she has. Everyone has mass in California masked by law. You ask the so. This is again a situation where the liberals are kind of. I don't know I I should another whole Jan. We don't need to go down that road. Let's go back to this presentation with the last by and this is a real interesting one because I had read a number of because I've been reading some very kind of real deep papers on Especially about this kind of enhanced Pee Pees which is always called P. Threes and some of these other development of these things in labs and how it works and how they get funded and how they will haunt was doing. I'm in how we do him at Fort Dietrich and elsewhere and in it and in the process I ran into a add more than one reference to this idea that if you put somebody down on a on a stretcher and your pumped full of vitamin C intravenously. It will knock this stuff out and it's a it it's just a couple of papers. Documented is not like a crazy therapy but is it does apparently works for now. I A doctor friend of mine swears that he has cured people with eight not as but HIV virus with a two week vitamin C. Intravenous regimen. It's possible I I I I believe him. But what's going that's here on. This clip was going on with this treatment. What about vitamin C? Because we've heard about code for me and support. We all know that Linus Pauling sets them and your body clocks rather rapidly. So if you're going high dose obviously I've used to go to the. Fbi is is. I mean now the FBI shutting clinics down that are that are doing the right one interesting shutting down clinics that are administering vitamin C. intravenously shutting down FBI FBI. What does the charge? I don't know we need to go into it. They just mentioned it in passing because it's a fact that they've noticed and they don't talk about it any more detail and the guy says what and she says yeah interesting and then that's it that's all I say. So that's now there's a little rabbit hole for us. What the Hell's going on VK got it here? I got here. I got it here Thank you troll. Room troll room on Point F. B. I. Rage medical SPA providing false corona virus treatments high doses of Vitamin C. So you can probably do that but you can't. You can't say we have a cure. That's that gets you kicked. That gives you D platform from society. Kind of harsh. Yes yeah the FBI busted in so one of the things. I ran into stores. I'm still concerned about this I did a little research going to get it out of the way before we go into the further to the next segment so I started doing some research on because I'm concerned about this main. The lab or not made in the lab. The lab were not made in the lab. And why is make such a big deal of a big not made in a lab? So what if it was made in the lab? You mean the virus that Caro- virus a Chinese lab which funded by the US government. Do we funded him to three point. Two million bucks foul cheese. The one push. He's the one who got the money over to the Wuhan lab to develop enhanced. Ppe's right MPP is a potential pandemic pathogen. And they're being invented there invented. There are a lot of these are illegal to do in this country even though they've relaxed the rules so I started looking into. What the Hell was the? Uh The causal wise. Why does everyone say for example? Hurry screen of Austin says this debunked because he gets paid to say that is debunked. So I said okay where get debunked debunked it so I ran into a lot of pieces that were just bogus poorly written planted articles. Many coming out of Indiana running than being pointed to buy Yahoo News for example knowing who's good founded the set I found by found the next US I found a point of debunk. Aw Okay let me guess alternate knowing that when be it has to be a good sources. Nature Medicine magazine. Nature has another magazine called Nature Medicine. Very famous peer-reviewed. Good article how this nature dot Com right. Yeah it'd be a nature dot com. Yeah so so. In March of March seventeenth to twenty twenty issue. There's this thing posted the proximal origin of SARS. Cova too so to this was cited by the New York Times as an article that was cited by PBS. The next day every major newspaper the United States ran the debunk. De Debunk. Because of this particular piece but what was this piece well I have a copy here it. It was run under correspondents. It was a letter to the editor by Christian Anderson or guy named Rambo. These guys are scattered all over the World Christians in southern California. This is this is some Rando who wrote a letter to the editor on these are not Rando. Expertise are famous virologists in K. scattered around the world They wrote a letter. To the editor strategically scattered yes strategically scattered. And there's articles all over the world about this calling it an article calling it a research paper. It was eight letter to the editor that looked a lot like a research paper but it was still to the editor letter to the editor showed up in the correspondence section and they went on and on and on with a very long right up with charts and graphs and stuff like this. This is the nut graph here that it was not a peer reviewed anything. It was a murder to the letter to the editor. I mean everybody ran. Adult was an article or as something or other and it was. This is the thing that note. Not One of these not the New York Times Washington Post Not People. Nobody ever said it was a letter to the editor but I have right here a letter to the okay. Let me use read one paragraph to this letter to the editor. It's a great catch. I thought so but thank you thus this is just a all arguing bus. The high let me get. The right lasts for this way. Do you need your highest entity. Binding of the SARS COV to spike protein to human ace to which they were talking about right. He's South Korea the ace to most most likely the result of natural selection on a human like ace to by the way. I should mention these guys cannot and nobody can find an animal that has this virus in it. No they keep doesn't exist trying to tell us to. Yeah monkey natural selection on a human or humanlike ace to that permits another optimal binding solution to arise. This is ace. This is strong evidence that SARS Cov to is not the product of purposeful manipulation. Okay let's look at that sentence. The wording this is strong evidence. I'll go back to the previous phrasing. The strong evidence is this phrase as to is most likely the result. It's like you goal from the word most likely to strong evidence within two sentences. The strong evidence is something that was stated as most likely this is horsh it and the mainstream media the next day ran this as Gospel and that was the debunking all in one. Right there unseasoned. It's disgusting that's Great. Work of what a bunch of Ho. Oh man well again this is the takeaway if we're going to learn anything this is it. This is it. I mean you're not a you're not a doctor. You're not a scientist. You just follow your nose. I mean we're barely reporters were podcasters. Yeah we're to podcasters while they go and no wonder. People are flocking to alternative sources of information. The official thing is confusing. And then all you have to do is peel back. One little layer and the bull is right there. They can't they can't keep it cleaned up and at this point. What was the president thinking when he allowed this to happen? And I'm talking mainly about the shutdown and then got the two weeks the dig. They shut down Italy. They shutdown France. They shut down Spain. They every everyone's shutting down he was our president was td very disappointing. Well there's only one country that wasn't duped in Sweden while that's not true because they last there half shutdown anyone that half the restaurants were curbside pickup. Only it's just. That is a lot of republican right wing by the. Where's the country that's really interesting is Japan? Japan has an as we heard from our Duke and Duchess a marketing astronauts have total. Like foot seven hundred. The whole country is open. Never shut down and catch this. The keeper an are definitely going to Japan because tourism has dropped a get some deals. No no we're talking like a hundred billion dollars. They're going to put getting people to come over. Risk free we should. We should have own plane. Should have a driver and escort. We should have a nice hotel. Hey we'll talk about on the show. Just give me the talking points. I'll tell everybody how great it is. But that's the Japan. They really did it now why I think. They have more respect for their elders. In general have very careful with their elders. We clearly don't care about old people the way nations do. They are very cleanly by by nature and everyone has a but washing toilet in masks are very commonplace. And that's if you're sick you wear a mask or if you could be sick to now. I don't necessarily want to live in that type of you know full on like Japan but it may not be necessary. Maybe they just didn't count bogus Numbers maybe they're hospital system isn't incentivized to lie maybe they don't have provinces that are so desperate for money because they screwed it up the say this desperate to lie thing. There needs to be a fraud investigation now and jail time for people. Doing this guy dies of gunshot route root wound and then they check it off his covert because he may have been you know tested positive that this is just scamming the public yes and the tax payer et Cetera et Cetera et Cetera so signal. Everybody get your sweaty socks not sack on and let them know that you're on board with the program and with that. I'd like to thank you for your courage and say in the morning to you with the man who put the sea in the Counterfeit Bill Gates John. See Tomorrow morning to you Mr Adam cree. Also in the morning all the ships to see boots on the ground feet in the air substantive water and all the dame's nights out there and a big hefty hardy in the morning to the trolls in the troll room. Let's see seventeen four. It's usually a little higher about eighteen nineteen but so good to see you all here. Thank you very much and I want to welcome to the Joel Rogan tribe crossover. It's pretty amazing. How have seamless? That has been everything fits beautifully. It's Overlap it's nice and I get a lot of emails from people who And I think we even have some donation. Now so yeah. We're going to thank people for the value that they have supplied to this program. We all we can do is value for value and that keeps US clean so we can talk about these things. There's no commercial interest. We don't have to worry about which Pharma Company or derivative thereof is going to cut us off. Say the wrong thing but that means as vow of poverty unless you keep us out of it and that's been working reasonably well for twelve years and counting so no agenda stream dot com as we can hang out with the rest of the trolls ask him in there for an invite to know agenda. Social DOT com. It is part of the federated Social Network known as MASTODON NO AGENDA SOCIAL DOT com. Just follow me or John. You can follow at no agenda. Social DOT COM and a big in the morning to the artist's who brought us the art work for episode twelve hundred and forty four. Now this was Tonto nail to a which you that's the Dutch pronunciation. I'm pretty sure. The artist is Dutch. Which means ant net lance wrote in? Yes aunt Nellie is a free translation and this was just well done and you know we. We both kind of liked. It was the the Fox farm channel folder in case something bad happens which clearly was accessed by. Neil cavuto the minute the minute. The president said that he was he was taking hydroxy chloroquine with zinc. Any had what we played down the last show he immediately went into how you can die and crazy and that was the folder. You'RE GONNA die and the artwork was perfect. We liked it hit now. There was other stuff. I remember we were eight was something we had to talk about. There was a farm. Couple of other Pharma will gags and then there was There was something that was discussable. I remember number of Fox Farming News. Kaley the evanger which I used by the way on twitter. It's very funny Piece ages us. The wasn't gonNA work way of Joe with his head sliced open which is funny but no a lot of the Karen stuff and then there was the trump tweety bird was another example of a comic strip blogging paying any attention to our our against rise that we should write up a little memos certain things I love the the Katie mcenaney your your girl surrounded by hearts. Please tell me. You've paid attention to her so we can talk about talk about on this. Show your new wave. I do have one clip and one and a half clips. His stuff is kind of already getting on my nerves. There is light. You know the honeymoon. They're starting to get you know they're starting to the media's not you know they're they're to gang up because there's a whole bunch of them and they have meetings you know they're sitting around going. Why are we gonNA do about this horrible woman? Well we should do is is about something you know. And so they're they're working on strategies are strategies. You didn't really have you know she's just her? She's natural I think we have noticed also something creeping in some people using our images which had been banned from the art work. Yeah no new artists. Well thank you very much. Great piece of art. We love having the artwork. It it POPs on twitter pops all the PODCAST APPS. May It helps. It helps the show. It is tremendous value and a lot of these of course also wind up on products that no agenda shop dot com which is own standalone entity. Everything is shared equally with the artist with the shop with the show where everything you purchase. Their advise love how that works in the value value system and if you'd like to contribute with the artwork knowing art generator dot com. Where you can do that. And we have a number of good notes today there long long but people have reasons for it and they are executive and associate executive producers long note. Delong note is the first note which is from Mike in his as at darter. Dart are and Nichols Hill. Oklahoma gave one one four four three three or not one two three four four three three. And which is always show club member which is well that was probably the last trying to hit twelve forty four with twelve forty five. He'll get it got some change in their we can throw in the extra coinage and make it an must have some money around or somewhere. Abby GonNa need sixty seven cents a quarter John and atom. I apologize inexcusable. Delay in getting this to you and I mean need of a major. You spend. Deduce tie was a consistent fan from around two thousand eight to two thousand twelve and donated montly under defense tactics. Yes I remember at the time I was working at the ATF. I remember that too. And we have great producers and traveled a lot that's alcohol tobacco and Firearms. I would listen to the podcast while commuting back and forth from Oklahoma City to Dallas while traveling around the country. I left the ATF. At the end of twenty eleven after twenty years in law enforcement I decided to start a new company based on experience I went through during my career. I was sued in Federal Federal Court in reference to a shooting. I was involved in. It's a police officer. Because I was a member of the fraternal order of police. At that time they paid for my legal representation which alleviated much stress. During that time I won the case I was thrown out at it was thrown out at summary Judgment but it took about a year and a half to get there. I would guess that it would have cost me around two hundred thousand dollars or more if I had to pay for it myself. It took years to build but we are now the only company. Ccw SAFE in the industry that has actually successfully defended of full murder. One self-defense. Trial that trial was in two thousand seventeen in North Carolina Adam. I'm glad to hear that you're exercising. Your Second Amendment right please. Check out the free breakdowns of high-profile self defense cases that we put on our site to help concealed carriers mitigate their risk the articles a free no subscription required and a written by our national trial counsel. Don West who is the leading self defense attorney in the country with over thirty five years experience and self defense cases over the past year or so. I've been listening again. And you guys are my only news source that can only assume that my previous of the show is what provided the Karma for our success. So please accept this donation and my renewed monthly support. You provide a much-needed calm in the in the Chow Chow. Tick chatter the chaotic chatter. That fills our society today. One last shameless plug John. I lead wildlife and nature photo tours a few times a year around the world for AARON'S TOURS DOT com out of Seattle check out my photography site at J. M. Darter Dot Com. I'd love to send you an atom of print. If you have an open walled that could house thirty by forty five wildlife nature print or painting. Got Yeah you guys rock. We need to get in on that John. I always take your advice. He can get something from the artist. Go keeping them in the mouth and keep up the invaluable analysis that no one else will report on Nj n K. needed Mike Daughter. Mike thank you so much. It's highly appreciated night. Yeah it was Nice. Not to and yeah. We'll get on that we love to have. We'd like to get on artists early in their career. It's just don't let me marry you. That's all Howard Morgan. As an inside joke six six seven Saint Charles Missouri Surf of Saint Charles for the record. I think it was the first. Jr Listener that helped produce the show three hundred thirty three thousand March twenty second. I guess I made the mistake of sending the email to Adam telling him I discovered this show from. Jre appearance emails. Sent on the twenty second of March I am sure at md not mean to miss my email But maybe he was stressing the depar- probably put cutting and pasting into the box on paper. Maybe he was the key the cower in place order thanks for opening my mind to the sins of the media. This donation gets for two thousand dollars. At this point I ask for a title. Can I have the title sir? Howard I of the Gre Order. Keep up the fight to enlighten the public to the fact that our major news sources and politics are bought and paid for but the Chinese and Big Pharma. That's that I the Jerry Sir. Howard yes thank you. And this is what I was talking about the Joe Rogan producers. Who Join US here as well. They're giving very early early. Have People that have been listening to show for two three four years five years? They say know. I've been listening to Joe for five years now. These are the ones that came over. Probably brought them over from the twitch show. This is the difference so five years later they give us fifty bucks. I'm not complaining. No I'm not complaining. Nobody's complaining. We don't complain about fifty bucks. I'm just a week complain about the length of Time. It takes to give us even five bucks. Well the the JRE people are quality. Man That's obvious and this or Howard You will be today as such of the first of the this or Howard I of the J. Every order and you shall be our official ambassador between the two media tribes very excited about that all right Barron. Husky bottoms of the hardwoods from Franklin Tennessee. Four hundred seventeen dollars and three pennies. Sure why but maybe to contain than his not. Hello podcasters came up with the nation about by reminiscing about the four dogs. My wife and I have shared since we met And the seventeen years of marriage celebrating our twenty four th today as well as the three beautiful children she home birth and my honor to be the first to catch all of them. That's a beautiful story catch. Hey baby can you little better? I'm making ground with my strikingly attractive bride. Nice one and a snippet approach of your deconstruction over the past few weeks as this insanity becomes more elongated in some of the thoughts. I've been vocalizing starting to resonate with her. My hope is not is right around the corner. He's GonNa hit her in the mouth. Last Thursday's deconstructs analysis of the virus or nation was a Hawker and hoping Sunday's promised clips by John are the setup. I need for an overhand right. I would love some Karma from my fifteen year old Corgi. The Duke who has lived his best life and I will see again in a few weeks in court sized Ziplock in cheap chewers ziplock and cheap jewelry box. He was a great dog and I was glad to share his last mornings in gorgeous. Tennis in a gorgeous Tennessee meadow where the vet joined us to help. End his pain. The comfort and sunshine and the blanket. I selfishly hoped that an ending will be a viable option for humans in the coming years. Such an ending will be vibe allows for humans in the coming years as I explained to my son who join me for Dukes passing as a big difference between being alive and living and he closes with. Ain't no virus that done not. GonNa make me not stop living words to live by baron. Husky bottoms with the hardwoods. Thank you very much sir. Robert Conti over here in Oakland comes in with three hundred thirty three dollars and thirty. Three cents gents. Thanks you for all the producers for the job Karma. I was lucky enough to recently. Land my dream job at a vertical farm growing vegetables and yes we grow. Kale the least bitter most flavorful. Kale you've ever tasted okay. Boss is an older guy in Berkeley. Who has a lot of opinions about food and calls Grocery Outlet? Gross Out. Must BE A meal. You or something. I'm going to stop here. Gross out which is the case right out. Actually that's where I get all these crazy things. You can buy grocery outlet which not named gross out with that. I never knew about that nickname. I used to shop there all the time. And the nickname was given to me by millennials. They're the ones who came up with gross-out Anyway. Check out the willow willow well dot com if you're in the bay area and interested in delivery of locally grown high sexy aero panic produce owner. What two different through that hydroponic and salad kits? I'm grateful to sort gone earth for hitting me in the mouth some four years ago. My quality of life has greatly improved by no agenda improved by keep stacking Keep stacking sats Adam Stack. We need bitcoin Karma Jingle for this bull market coming up could I hear WTC seven. We'll go away followed by. I got ants interlude. Thank you John. An atom and I'll throw in my own little bitcoin jingle for you. Good enough that's right. Thank you very much. You're sequence coming up we'll start it off with the answer Allowed you've got Karma I should mention Like to off opted. Is there a website or something because I be interested in some of these vegetables? If they're growing stuff is actually tasty willow. Well Dot Com. That's it is you check it out. No I'm just looking at the funk of the and the Anna Three thirty three thirty funk funk John Unblock may have information that will lead to the arrest of Hillary Clinton also. Can you change my table selection from early times and be four? What's be at four on the list of stuff for is visit? What is I? Don't know what it is to war zone improper. Twelve thanks gentlemen. We'll do that for you. Know where you blocked. I sent him a note or I put a note you blocked from what I don't know Kevin McLaughlin. The people were not specific enough with these things. Sir Kevin McLaughlin in locust North Carolina. Three thirty three thirty three jobs. Karma go to Health Garner Israel Royal Highness Duke of Luna His grace or Kevin McLaughlin Memorial Day message. I don't have to tell you how fragile is very precious gift. Freedom is every time we we were noticing it every time we watch here or read the news. We're reminded that liberty is a very rare commodity in this world. Our Great Nation is forever indebted to those who have served and given their lives that we might be free. That's right I agree. And especially especially this Memorial Day. Which is not veterans. Day is for people who died yes You know just think about what kind of courage you can show. I tell you the people and this performance for me. I tell you but people I know in the military are reasonably perturbed and disturbed by the Pussy factor of the American public. That they have fought so hard for. I'm generalizing but this is quite a quite a theme and rightly so as he finishes with allows dot Deo which is Praise be to God and this is not the time. But you know it's like you can't just have a bumper sticker support. The troops are where little ribbon? Thank you for your service. Yeah you gotta actually do something. Now you've got to be out there. You've got to be courageous. And and that may be running for city council to get these a holes out. And when you're in there admit you don't know nothing that a good start Yes Jobs Karma and good health Karma first jobs jobs and jobs. Let's go job you seen. This looks like Warren piece. Your Turn Adam yes. Hey let's be honest about it. It's so long I can't read. It does not been on my screen. Hayden Rowling three hundred and thirty three dollars and thirty three cents from somewhere in California you can also call them. Han Sui pronounced over you like I'm calling hunts unsui McKenna navien living in northern China. Sorry for this long report but I feel. Most news is fake vague exaggerated or extremely biased especially reports about China. Yes that's why we love having our producers with be ot g reports. Here's the real thing from a neutral and indifferent firsthand source due to higher infect tease per capita and ongoing newly reported case clusters my area is more restrictive than other parts of China are pubs and schools are still closed. Others have opened up in China over a month ago since January. The shutdown consisted of restricting traffic to and from certain cities and provinces and using a pass stamp system to allow people to exit their community residences once every two days. Yes we confirm. We heard that from the professor. This was lifted. Last March people still cannot enter community residents other than their own mass temperature checks. Qr Code. Scans as we all know are mandatory entering but not exiting any enclosed area except for small convenience stores the Qr Code scanning at prompts a confirmation. It starts a timer. Oh you're on. The clock. Slave is required before returning to your home so it has information. Gosh Golly Gee so has information a great idea well about whether you return to your home that day or not. Well no I want that to. Is that in the new apple? Thirteen point five update. Do we have that cool feature? That's hope so. I don't know how strongly enforced the QR codes scan is as I have violated at once without any consequences by not returning to my home overnight and have been able to enter into some places by registering with my name and phone number. Instead of scanning careful last March China announced that foreigners would not be allowed to go back into China as March twenty seventh even if they have a visa which we can understand definitely know to be true because of severe warnings. Receiver colleagues trying to return around this date. My most important report is that this means it is not possible for newly reported cases from people returning to China to be foreigners and that all new cases from people returned to China must be Chinese citizens. Despite this fact of course the news reports new cases are from people returning to China showing national flags beside each number and are definitely. That's right look at these in America. They're bringing it to us and are definitely informing people that the cause of new cases are primarily because of foreigners entering China. Well that's bogut. The evidence we have of this is friends. Claiming China victimhood of foreigners mentality really and that despite our province having zero existing cases during the past few weeks my colleagues and I have experienced Chinese refusing to enter into elevators. With either of US. Well yes now. You're black in China and last weekend while ordering in a sit down restaurant with other Chinese customers we asked to move to the third floor and use that other washroom while you're at it a which was totally empty along the second floor and after finished we were instructed to stay until the restaurant closed all of the customers left so that we could either not be seen or not infect the other customers. I hope people aren't enraged over this. But instead look at their own news critical with critical thought. Because it's like it is like this to a degree in almost every country. Thank you for your courage and happy to have become a fellow producer and thank you so we very much for your courage for this Thomann. Does this report that gives us a lot of information? I'm happy about it. Thank you Addison. Todd's next three hundred thirty three dollars his name. Why do I know Addison Todd? He's a Saint Charles Missouri. If that means anything maybe it's a good name could be. Anybody does my second donation after being awarded the title of producer. Fridge episode. Twelve hundred has been too long since I put my cash into helping produce. What I feel is the greatest regularly available media deconstruction. I've ever seen and that's interesting. Since he's listening to it can actually see it. I've been consuming some form of alternative news for twenty years and this is the best work I've found. I liked this guy. I says. Hit my mom in mouth. Who will text me to ask me? If I've listened to not almost every week she's found a connection with his son. I love it son if you did you listen to those boys. The last ten did you listeners. Boys Listeners Nice boys did a show and they finished it and I wanted to know what you think you need to do with. What's crackpot in the buzzkill? You've got to up it a little bit. What is I'm I'm convinced your ability to see past the bullshit in medias literally saving lives now? I'm going to get selfish. Put a years worth of our Indian to a product that I was working on bringing the market when all of a sudden out of nowhere cash flow for retail wholesale businesses like myself ground to a halt. Thanks TO BILLY GATES. Well the products on the market and I like to hit the audience with Eagles. Ab ELLIOT'S DOT COM IS MY CBD company my producers and Douche bags alike can use the code no agenda to save thirty three percent for life. Unlike lavender blossoms bombs and solves this is a dropper to ingest. Keep up the good work I the everyone's got different way of doing these things. Jambo has a spray. Keep up the good work and now my mother will never miss an episode very cool. I'm looking at eagles. Dot Com. Right now I I liked. How interesting is that we have? We've got Jambo Joe who's got sprays and THC of course he's in California and then we have lavender blossoms which has fan the bombs and the solves have been lifesaving to many many people arthritis. We we just heard it and now evils joins the crowd with the drops. I like this. We've got like a whole coming by combined we've combined. We've got a whole Alex Jones. A kit we can send off. We can bundle. This shit man managed like some of these products. We need some Boehner pills. Surely this own producers doing that somewhere g jobs garment and John's GonNa read The New York Times. You'll never find that. I am gentleman. I have been listening member. Who had the segment of the show right reading times? Yes I've been de laughing. I've been listening for several years in decided to get my knighthood for my fiftieth birthday in November of this year is listed as a birthday boy to really push it that far. Yeah a former former coworker. Who is this search birthday there? It is okay birthday so now as the federal dmv employee a federal DMV employees. What is that? Then animus monthly. Donate her so. I can call him a Douche bag. Oh here we go through former CO worker. Who's focusing. He me on the show because I was already cutting through the M.'s. Bullcrap and he knew I could enjoy. I would enjoy the show. And he was definitely most definitely right. Pleased deduce me spend deed? Do any needs a good. Karma with our jobs car with twisted goat like to wish my country. My Country Cutie. Roommate Cheryl Happy Birthday on Monday. Thank you for your courage and stay. Woke Mo- foes yes. It was probably the second year of the show and I was primarily in the UK when we did the program and you would read the Sunday New York Times or pieces of it that we did. We even have you back then. John Back in the oldest we had. We didn't have a lot of clips. There wasn't a lot we could pick up on. It was early days. We we we didn't really get into Max clips or peak clips Probably until five four years in. That's what I'm saying and Kevin Receives made this little diddy John's Ghana on the Sunday. Yobs jobs and that's her job Karma I'm sorry can you say I would never find. It said that because you will never find. It was five worse enough time time to give you. That's right exactly find. It was a stalling tactic to Lao. You the extra five words worth of time you find you did. John was correct in my assumption. We together are too tight for this market. Some believable betty bloodlust of the black rock black thumbs checks in from Ohio. Vada Nevada Navy Nevada row Veda or vodka two hundred and sixty seven. I for the last show. I sent him my first donation. I Apologize For trying to slip. A note under the allotted amount for note reading honors. Yes I did get the memo. Being cheap broke ass farmer less code cash to the rescue better than blowing it on hookers. Thank you for your wife's choice now. That's not why I'm broke. I now make this donation. Two hundred sixty seven dollars was to bring my total donation amount to date to three hundred thirty three. He says numbers matter in the last show is thank using my real name which is fine however going forward like to be known as Betty Bloodlust of the black rock black thumbs no other group affiliation just my own please split this donation with my Hercules Hot Hobby Aka Hercules Hubby as explained in my previous note I cannot be married to a douchebag please also refer to my previous note for jingles etc. I would appreciate all the Karma you can spare when you're done with me as about to move into our first of four harvests in farming season for the next two weeks will be at the mercy of Mother Nature. Cooperation means more cash in our pockets. Trying to keep this short as I would really like you to spend more time with my previous note. Do it has photos and information dynamic. Yes it has photos and information of interest in particular regarding Adams. Kobe immunity bracelet idea. I sent it to John Divorce. Act Dot Org on the night before. Show twelve forty four. Yes I recall this note. I will look up note and we'll play it later in the show and I reference road. Id in the subject. We saw these. We talked about the road ID bracelet. It's the perfect bracelet. Yeah we did all this but typically we problem is. I don't know what her email addresses. What may take me a second to find so I will while dig the note up by by the end of the show we will go over the. We'll give you your jingles. Then it'll be a belated but still have the same effect but I will roll out some some Karma for you and thank you on the topic of missing notes. Yes Sir Reddy Kilowatt. Two hundred dollars in Battlement Mesa Colorado Aka ears Sir Reddy Kilowatt of the room. He's always in the troll room adding to my annual tax refund donation because to Joe Rogan. Podcast BUBBLE IS INFLATING. Also figure essential workers need to stick by each other in these uncertain. Times COULD GET QUICK. Sharpen respect and a little. Karma might be a good idea as well you BETCHA body. Spic you've got Karma. And I'd like to just go back to bed less than the black rock black thumbs. Could you inform us? More importantly than your jingles. Could you inform us what you need mother nature to do so do need does? Does it need to be dry. What what are probably a little water. I would assume well this is what I do. We need a range. I mean we have controlling stake can provide the rain but it just. It's it's ought to control what's out of Control stateside to rain stick. It'll make Iran places to no no no we just wouldn't Australian fires we overcompensated honestly. And so you know we put out the fires but we flooded the damn place but that was my fault. I did I recall. I did the three extra shakes after both did a full on shape. It was your fault take full responsibility. I'm no governor Cuomo. I take responsibility for my my actions. Well you'll get your aunts. Vote then read their Mount Albert. The note is all debate and engage in healthy ways. Thank you have a wonderful holiday? And don't forget to enjoy your farm attainment while you and this is these guys get it. This is someday dame of little Beirut. If you'd have time for Jingles John Brennan people are innocent. The Hague protests. What I know. They protect our freedoms and rebel and although Haig Bald Guy not protect our freedom relies out okay and was there any Karma associated with this or was it just these modules those jingles. I'm doing Karma I'm just doing. A Karma people are innocent until alleged to be involved in some type of criminal activity. Intelligence work take place with a strong legal. We operate the whole our accountable for southern countries. Secret Intelligence is used to control that people in hours globally exists to protect freedoms. Pretend PRETEND INDIA HANG AL by three thirty three thirty three eastern Karma you ask. We play issue. I forgot all about that. One on word With did I think we did? It didn't do that. Yes yes sure reddy kilowatt in their battle Mind Mesa Colorado two hundred. I I read now. Here's what's interesting. Lorraine asked for a jingle which was actually made by already Kilo Watt who comes in with the donation right after her. Yes which already read I know but you have to understand. This is the random number theory. Does she know him? Yeah sure that's an Oregon ones in Colorado. I don't think so very odd. Anyway thank you to our executive and associate executive producers for episode one thousand two hundred and forty five of the no agenda show Good News We had a number of Dame's who have come in and picked up on her dog patches dame drive so we'll be bringing them to the roundtable later on sometime before the show is over which I think will end before the month is over. So that's good looking forward to that and thank you all so much for producing this episode and you can use those credits. Proudly wait a minute. What's the official credit? Because you have special ones this the show John Special. Titles is the Memorial Day. No special twenty twenty for all the executive producers came with three three three or above exactly so you can proudly display that anywhere as executive or associate producer episode of the No Agenda Memorial Day Special Memorial Day. Special Twenty twenty and again. Thank you so much for supporting us. We'll be here all week. Thursday come on by supporters by going to Iraq dot org slash for sure. You're more speed than most around the water cooler. All things. Kobe. Formula is this. We go out hit people in the mouth. Why some hands for twenty six speaking of spooks There's a podcast called winds of change. I think I've seen this or heard this podcast. Well it's very interesting episode five Although I'm not mentioned by name I was in Moscow at the Moscow Music Peace Festival where the Scorpions also perform. This was nineteen eighty-eight just before the Wall came down. I'm sorry before David. Hasselhoff brought the Berlin Wall down but the song of time that was the top song on the charts was wind of change by the Scorpions and it was used incessantly with pictures of the wall. Coming down it was played everywhere I was. I'd been there I that actually not moved away from Europe but two and a half years before that and but this I mean I have a long long story not for today for some other venue. I'm sure about the Moscow. Music Peace Festival but it the essence. The reason why it was put together because Doc mcghee who was the manager of Motley crue Bon Jovi. His plane had been Intercepted carrying think. I thought it was weed but it could have been cocaine from Bolivia or somewhere. He wasn't on it but his his learjet was filled with Dope. So they got him and then the some miracle plea deal. He did not have to go to jail all he had to do. Is Put on an anti-drug anti-alcohol concert in Moscow which became at Lenin Stadium the Moscow Music Peace Festival. I was there covering it for For MTV as you can imagine an anti-drug and alcohol concert was pretty. Everyone's pretty hammered. Twenty four seven starting on the plane ride over but I remember a couple of things very distinctly and one is that we we left Newark everybody. On board. Bon Jovi Motley crue Ozzy Osbourne with all black Sabbath skid row missing a few. I'm sure and we stopped in Germany to pick up the Scorpions and I thought that was weird and there were other weird things. They had a little different accommodation They also had hookers right away in their room. Because I walked in on a one of the two brothers was at Rudolph or whatever receiving services like the first day so the what what. This podcast is about episode. Five is is the Moscow music. Peace Festival is that this was the biggest hit. The Scorpions ever had and the only song written by Frontman Klaus Minor. And the the PODCAST. What it what is trying to figure out who did the CIA actually right and promote that song to help bring the wall down. And I can tell you for sure they were spooks and all kinds of weird crap around Moscow. Busy Peace Festival. But it's really cool to listen to and then I think it's a great example of of American policy at its finest have a listen to the winds of change podcast. Oh you ought to play a clip. No no play is not all that great. I mean my version of it will be fantastic. Yeah well you should go on on their show. I'M GONNA I'M GONNA do. I'm with theater. Show VEGAS OUT ALL RIGHT. What else we got We do have a number of things are. Let's do Charlie. I WANNA get designed Katie. Mcglynn talk about some flint stuff. Yeah there you go Flint Flint. Lauren brings in this. Brings in Kaley Kaley mckinney Monahan. Haley had a couple of little beef. She had a thing with the just play. A little short version ever going after the these all these reporters bitching and moaning about opening churches. And she's fighting. She's fighting them off left and right she has a little zinger in here. Which is Kinda funny? This is Kaley church fight purchase three unseen and do it in accordance with his vision of federal law allows the President to override. The president will strongly encourage every governor to allow their churches to reopen. And boy. It's interesting to be in a room that desperately wants to seem to see these churches and houses of worship stay close presidents objective that I go to die birth. Here's the objection the media that they they love to ignore the states in the Fourteenth Amendment and the Tenth Amendment. They like to ignore that when they wanted shutdown. You should shut it down you. Should you should use the defense production act you need to force people into doing things Man You have no right to adobe churches well today Oh I think if the current of our consultant group to advise Katie mcenaney. I would say bring some extra stuff in there like we discussed on the last show. Churches are very important for places of worship but they also house many. Aa meetings around the country. These are important places to open up. That would have been better if if they had added that or some touch like it and take it away from the religious thing because it's never ending story by journalists who have never read the First Amendment of the United States Constitution. You don't need any permission to do this. It is your God given right. Yup beep well anyway so then. David harassing her a lot. She was in a bad mood. And what is she gets? No kidding no kidding. She's in a bad mood. What kind of GIG is that? She's in a bad mood as somebody brings up something at the end. Of course he's going do dry mic drop thing and walk but she has a presentation a powerpoint. Powerpoint was it or was it Was the fake apple one. What is their spotted against a bunch of slides? That were very but they were. They were art director. Was it libra now? They were art directed with somebody in the back back office knew how to had some style. Lots of pictures of Obama Akina right so she goes Is She decided to turn the tables on him and she gives him crap about not covering any of this flynn stuff and she thinks is shameful in the media stinks and so here we go share. Here's a rant is a little long but this is a good one from politics. I HOPE. Presents consider pardoning president law for immediately wiretapping on top risk. Us citizens an auditor. Potential tangible cries out. There has considered so I have not spoken to the president about that. But who I did speak to you about President Obama and unmasking. Michael Flynn where the men and women in this room. I haven't spoken to him on that. Specific point have spoken to him about the matter generally and I laid out a series of questions that journalists would want to answer about why people were unmasked and all sorts of questions and I just wanted to follow up with you guys on that. Did anyone take it upon themselves to pose any questions about Michael Flynn unmasking? President Obama spokesperson not single. Journalists has posed that question. I was like you lay out a series of questions perhaps if I write them out in a slide formats. Maybe we're visual learners and you guys will follow up with journalistic curiosity so number one. Why Obama Administration US opposition opposition research funded by a political organization and filled with foreign dirt to survey all members of the trump campaign number two. Why was Lieutenant General? Michael Flynn Unmasked. Not by the Intel community entirely but by Obama's chief of staff by the former Vice President Joe Biden by Susan Rice by the Treasury Secretary. This is extraordinary. And you know if it were political appointees in the trump administration. I can guarantee you. I'd have questions in my inbox right now but if I despise that I do not like them if it was this way if trump that's what I'm saying she's in a bad mood. She's not performing. Well this is not one of her better performance but the content is interesting. Apparently Obama's spokesperson does not. Why was Flynn's identity leaked in a criminal act? It is a criminal act to leak the identity of Michael Flint. The press but it happens. Where are the questions to Obama's spokesperson because my team would be running around this building? Should this have happened under the trump administration why did the DOJ gates learn about the unmasking from President Obama? So much for going by the book as Susan. Rice said three times now dot protest too much Susan Rice and then finally question number five. Why did James Clapper John? Brennan Samantha. Power and Susan. Rice privately ADMIT UNDER OATH. They had no collusion while saying the opposite publicly. It's a long weekend. You guys have three days to follow up on those questions and I certainly hope the next time I ask some hands go up because Obama. Spokesperson should be asked those questions because President Trump's spokespeople certainly very interesting tactic and so she buffalo one or two like someone tried to say something she buffalo right right over the over that steamrolled. Yeah but there's something about because I'm sure that it is this even being played mockingly on CNN or MSNBC mockingly like Oh look because that's what they did with. How many press secretary's has president trump? The First Guy Spencer Sean Spencer Spicer. His first day was shit with with the he was a he was nervous. He wasn't charged. He was combative in a in a not a very good way and so they hated him into he didn't perform well. Became a blood. This but this is an interesting approach. Although she's got to cut out the part she's got to stop that I'm sick of it. It's not productive. If the way rent. Listen we know exactly how it was when Obama was president and it was the other way around. It was the same bullcrap. So don't give me that but to call journalists out and say hey how come we not reporting on that is valid and I liked that. She's doing it that way because they really have no no no answers. They know they can't talk about it there. Flat-footed have you. Did you see this? Evelyn Farkas which I think was the truth. Wants to come out. Maybe I'm missing it. Maybe I'm misunderstanding. She was on with Mika. Brzezinski Meeker Brzezinski Of the Brzezinski family fame over there on MSNBC. Evelyn Farkas was the A- deputies state. Let me see Deputy Assistant Secretary of defense for Russia Ukraine and Eurasia and when the trump administration was coming in. She's what she's going to say here. I think is what she's admitting to is that they they. The outgoing administration hid all of their evidence of them spying on the trump campaign because they were worried that the trump campaign might find out. They were spying on them. And then all of those connections of their spike connections would be compromised. So they wouldn't have any tabs on what the trump's were doing as they came into the White House. Which is bizarre bizarre. Because you're supposed to give everything but of course if they were gonNA give all of the information this is where flint enters the picture. Because they knew that he would figure it out then there would essentially be saying. Oh by the way. Welcome to the White House. We were spying on you. Here's what she said and just listen is only a minute but I think implicates herself in doing this. You actually knew about this attempt ticket and preserve information and transparency. We're doing some work yourself. Tell I was. I was urging my former colleagues and and frankly speaking the people on the hill. It was more actually aimed at telling the hill. People get as much information as you can get as much intelligence as you can before. President Obama leaves the administration because I had a fear that somehow that information would disappear with the senior people who left so it would be hidden away in the bureaucracy that the trump folks if they found out how we knew what we knew about their the staff. The trump's staff dealing with Russians that they would try to compromise those sources and methods meaning. We would no longer have access to that intelligence so I became very worried because not enough was coming out into the open and I knew that there was more we have very good intelligence on Russia so then I had talked to some of my former colleagues. I knew that they were trying to also help. Get information to help a lot going on today. Yeah Mark. The leaking. Exactly are worried. It might crazier. Is She basically just admitting what they did? Well I think you can see it that way. I don't really know what she said. What she said is we had all this in in Spy and it didn't pass on because we didn't pass it on. They never had a good reason. No no you to pass it on. Because then they would know. They've been spying and they couldn't spy anymore. That's what she's saying. Maybe I I just couldn't issues. It was convoluted probably make Santa. Because that's exactly what went on. They were spying and they didn't tell anybody about it and they kept doing it right after. Why even on his office recall from all the leaks in that first year? League time o'casey McFarland was at one of the. She was his chief of staff for Flynn and she senior ability. Time She's one of those women that Of some sort. But we don't know what kind or were who she works for whatever And anyone what is she hot. No she. She's just a she's just a she's not. She's not one of those types of spooks. The ones that looked like giambi should be in the field doing doing work. If you can't seduce man how can you? How can you seduce the country has okay I got? I know seen senior. She's she's good. She's been very talented good. Choose to be on the show. She's a intelligence officer basically but she got they tried to. They tried to railroad road her with along with Flan and I didn't know any of this story but let's listen to. Let's listen to her our interview about the flint case. Listen to what the president said about you watch I watch. Kt McFarland the other day. I watch where she was. Knock knock. Fbi The FBI okay. This was all Obama. This was all by. These people were corrupt. The whole thing was corrupt and we caught them. We caught them. You saw just now. I WATCH BIDEN. Yesterday could barely speak. He was on Good Morning America right and he said he didn't know anything about it and now it just gets released right after. He said that it gets released that he was one of the unmask irs. Meaning he knew everything about it so he lied to your friend George Stephanopoulos. Kt The president reacted to the unmasking list. As soon as we were about to sit down and we both got the list so it was like immediate live reaction but but what he said she about you knock knock FBI. Can you tell us what happened? What did he mean by that? It was back. Fbi They showed up at my head left government. They showed up at my house on Long Island. Knock knock knock the FBI. Can we come in? We WanNa talk to you about there. Were from them arbitration. We Wanna find out from you. What happened during the campaign and I said well that wasn't part of the campaign. Well we want to find out what happened during the and I said well I never met with any Russian stirring the transition. That wasn't my job and I said well we just wanted to get some get some sense of what went on and then I asked them Redo. I need a lawyer. Am I under some kind of an investigation and they said Oh no Gatien your fact witness We can't tell you not to get a lawyer but we're here we're already here. We've come all the way from Washington. Let us just ask you a couple of questions. So this goes on and on for several more meetings for twenty thirty hours of now becoming an interrogation by the FBI agents DC four. And now the US here and so the this brings to mind the old clip of Thomas. Drake the NSA whistle blower legitimate guy whistling county taught FBI ever ever ever ever so. She goes on with the rest of her story now becoming interrogation by the FBI agents and they sees my files. My phone rockers might text messages my emails. And they wouldn't give me access to them. They would sort of hand them out one at a time redacted out of sequence and then quiz me about them and if I got something wrong if I said well I'm not sure if I talked to. General Flynn an hour before his phone. Call with the Russian ambassador or I talked to him that morning while they would then say well. You should've remembered that that's so important. We think you're dissembling. We think you're lying to us. And that's when they tried to trap me on a perjury charge. And that's what president trump was referring to they. Try to trap you charge and then I you to plead guilty because you know why they can bankrupt you if you have to go to court. And that's their ultimate weapon to general. Flynn that's what they general flint and then they try to corner him about his son. Father would be like way. Leave my son out of this and so he just went along with it but with the story that you just. Maria gets excited. The voice goes a little into screech territory. I know that sounds misogynistic. I'm a big fan of the money. She needs to calm all worked out and let me say something else. Women like hearings needs to calm down a little bit. Wait another word relax. Maria bother would be like way. Leave my son out of this and so he just went along with it but with the story that you just told. Katie is disgusting. It's disgusting you're there in your home. They knock on the door and say oh. Yeah let me just casually ask you a few questions hoping to entrap you. Did you ever get a lawyer? Katie Oh did you cut it off. I did I mean I got the best in the country Bob from Celena Cromwell and then that that sort of things out but it was so bad Maria they they were stopped at the foot of my driveway. They waited for me to come back from exercise class and my husband to leave and then that was not knock so they were way they health plan from the beginning they were trying to attract and collateral. Peter Struck. No that went to General Flynn. No he was not the knockback man. But I will say that with General Flynn as you point out. They blackmailed him. What bankruptcy but he sacrificed himself research and this was all a setup they knew there was nothing to it and yet they dragged people like me as collateral damage under this. They drag the country through three years of division. We're at each other's throats. We were not paying attention to business in the National Conversation. And why because they hated trump they. That's not a bad clip and I learned surprised by it. I've learned some words. I learned a new word dissemble. I heard that too. I've heard well. That's that's a That's obviously a trade term. Oh must be definition. Conceal one's true motives feelings or beliefs. It said disguise or conceal dissemble. So it's not quite lying. You're just concealing your true motives feelings or beliefs. Yeah that also plan treatment. I think the word I'm working on plan treatment planned entrapment plan treatment just working on words. Here's Nunez making some short comment about Flynn. I don't know if it's a good clip but gives shot just throwing away clips now and you know. Let me go back to what you just so you know your first question on on Obama and Biden. I don't want people to think that Obama Biden are are innocent. In fact I think they're very much involved in this. I think they knew a lot about it but just because knowledge about it doesn't necessarily mean that they were in on it. Did they break any laws? And that's really what we're trying to get to the bottom. Still very confident that Durham is doing the job that we expect them to do. Wait what did you just bring me? A thousands of sealed indictment clip is that which she just played there. Well almost it's pretty close closed. But it's not quite. We got to boots on the ground report for just looking at some trump hate from Sir David dementia be and it was surprising and I'm glad he sent this in. You may have seen this. This is regarding the trump death clock a good the good read. I wanted to get your clip. Wasn't it of Amy Amy about the The trump clock talked about that trump death clients see. Was this time. Is this fifty six foot bill? This is an older clip but this is the clip and I want to tell you what it is fifty six foot billboard called the trump jeff clock has been unveiled in Times Square here in New York the billboard which created by the Oscar nominated filmmaker Eugene Iraqi so the trump difficult is a billboard that hangs over time square and what it shows is an estimate of the number of US covid nineteen deaths that resulted from the president and his teams failed response to the coronavirus outbreak. Thanks to up found she and leading epidemiologists we now know that had the mitigation guidelines put into effect just one week earlier on March ninth instead of March sixteenth sixty percent of US covid nineteen deaths would have been prevented. That's an incredible number and on behalf of all those who leaked needlessly lost their lives to this failed leadership and a pandemic we need a symbol symbol that cries out not only for accountability but also for more responsible and responsive stewardship going forward at the time of this broadcast. The trump death clock stands at forty six thousand. Four hundred eighty five and growing. So this was virtue signaling this director but it turns out very very flaccid signal and they showed pictures of this billboard like Oh my God. We've got a clock counting the dead people in Times Square. So Sir David Dimension be when over to take a look at it. And he sent in this report Adam John went on my third trip into Manhattan for housekeeping at the office and decided to investigate the trump death clock a the wikipedia page provided a location West forty third and Broadway. That's right by kings right by my old office but the billboard was actually hard to find why because it's relatively small and the death clock is just one of many digital ads that shuffle through on rotation a fact acid rotational. It's it's it's an add on a screen effect absent from both the wikipedia page in any of the reports. We've heard now. The death clock is up for about ten seconds at a time. Depending on how many ad slots are filled by the way we could probably get a no agenda. Add on Times Square right now for nothing because there's no people they're advertised too. So that's your virtue signal. What else was on while Sir David? Dementia be looked at it. Well Stop Horse. Slaughter Governor Cuomo message of support buzzed balls cocktails colonoscopy ad from the colon cancer coalition new age spiritual website a native ad for the led company that manufactured the screen Venezuela tourism. And then every pretend seconds that trump death clock. How about that for some we? Thanks amy for scamming us. I mean that is also the way she ended that an counting I mean is it really counting or do they have to send in an update every every minute. The numbers accurate I mean. How does that really work? How does that really work? You know it's not real time. I mean are they. Are they injecting inserting brand new updated numbers with the trump clock? I'd like to know. Otherwise it's fake your. I think your earlier comments more important than than that conclusion. What was that we should put an ad up? It's cheap gonNA show must move by donating to know agenda. Imagine all the people who could do five D. We do have a few people think now. I will mention that in in the process of doing the as we're doing the show. I was doing some background. Tasking and I can not find the note and considering the fact that I get about five hundred pieces of email per day and that note it would be seven days old thirty five hundred pieces of email. I'd have to go through one at a time to find the note I have to tell her that. dame black thumb or would. I can't remember name she has. She should've put the note. Recent note with with the second donation. We will read the note by. We're not reading it on this show. 'cause I don't have it. I need another copy all right. I think that was the best I can do. All right now we do have people thank for show. Twelve forty five. We have mentioned the show number enough starting with a Abbas Rudolph in Auburn Washington. One hundred dollars fan middle Coop Middle Coop in Del our okay. Well Dell Dell Fan van meter coop in del Cow Holland right now. You can do this you. You've got the chops ready. Spend Middle Cope outspend middle COOP COPE COPE in dealt. How IN DEPTH COW? Perfect Scowl Fairfax. Thanks I appreciate it. He says we do a frequent sanity. Rinse like your sanity sanity. Rinse Sanity rents here at the show. Chris Dirk in Chicago hundred dollars. Ian Field in Eastleigh Eastleigh Hampshire Hampshire. Sure sure a Great Britain hundred dollars Tore Lang Lang. Oye La Goi in London now. London Netherlands their London Holland. Not that I know of Geoffrey Chambers in London Ontario. Seventy FOUR RANDOM NUMBER THEORY. Londoners from different. London's Sir. Chris the DRUNKARD Minstrel our buddy in Australia yes I fifty five years a little note there be s Just because you fall off the face of the earth doesn't mean you still can't donate happy birthday to me. And then what does he say? Furthermore he says double nickels on Wednesday Adam Q. The Horn Party. Jingle love you all thank you occurred crispy drunk Minstrel yes. We celebrate his birthday and he sent in a killer killer. End of show an original song. I'll just give you the title. And we gotta do some credits for that later and that will be the cold cove it quarantine blues coming up right after we finish up here. Thank you David Terry. El Dorado Hills California fifty five fifty five Thomas Miller Shamburg Illinois To five eighty five toes in a gratuitous prediction slow. Joe Won't be the Democrat nominee November. Okay it'll be a white male with a black. No NO NO BLACK. No black females going to be on the ticket. I said it before. I'll say it again. I'm not GonNa say it again today. the Democrat Women. Mostly white will not vote for a black woman. Hillary is their choice for first female president. Not a black woman. Random Black woman and Adam now in London Ontario another Londoner fifty five fifty five. Kate pat around him as a birthday Adam. Now for the twenty seven. He'll be turning thirty two greetings from the. Now's family of Southwest Ontario. He said like to call Justin Trudeau as a douchebag. I don't think that's appropriate. Douchebag ING is for people who don't donate now. I'm sure Trudeau does not donated. But it's just kind of a gratuitous out there we don't WanNa know that's easy because then all of a sudden you're douchebag in every way thank you appreciate yes and the now family's very important to our show s Schram Dubuque Iowa fifty five twenty six hold on on. It's just 'cause it's birthday. Donation made on behalf of my smoking. Hot Hubby bobbies SCHRAMM. Who will be thirty five on the Twenty Six Adams the birthday to be grateful dedicated listeners and value analysis love. You both. Thank y'all for the no agenda Thank you for all you do for the no agenda tribes as kate shrank. Thank you is this on the issue on the list. He sure is. It's a lighter. Is Lighter Shiites? That doesn't come across my screen Brian. Richardson and Aurora Illinois. Fifty five twenty five also make the cut for Sunday yes Birthday shout out his on on Monday. The twenty fifth. He'll be twenty seven. You says bring back the sash which two sash was. It was a failed fashion accessories. It failed failed work very well. Fail onto dying. Brian Ragle double nickels on the diamond. Encino California STOSKOPF parts unknown double nickels nine fifty five ten Neil in Elm city North Carolina. Sam Van you're in Amsterdam on horde and I think we're mess think so Anonymous read this fifty three thirty three. This donation is to honor the memory of your mom. Adam I remember that you and I remember when you announce the sad news when she had passed away which is now crap like twelve years ago. No no no. That was my dad. I also remember when you talked about being in school in the Netherlands in the nineteen seventies when a teacher stated there were fifty states in the a fifty two states in the USA. You knew the facts where you know. What the facts were not even consulted with a diplomat. Presume with your parents help to back up your claim. I'm guessing that experience planted the seeds. What was for what was to become the no agenda. Show rest in peace to both your mom and Dad and thank you and JCD for all you do is very kind of you Actually I called the embassy myself recorded on tape recorder where my mom helped me. The most is whenever I built some fifteen whenever I built a crazy little. Fm Transmitter. She would drive me around the neighborhood. See Far my signal would reach as a pirate. I've always appreciated that so I had. I had a similar kind of a moment where I would were the. Bs was obvious and it was about the same time as the International Geophysical Year. And this was a moment. When you're a little kid like third grade. Second I don't know what it was. But whatever greater was I'm looking at the world map and I'm looking and I'm thinking I'm thinking you know this thing is flush out the America looks like it would fit into Africa. Must've been one continent at some point. Oh no Yo- there was for Bolton today now you're an idiot this data. That just looks that way. It's a coincidence. Do Stupid Kid and did the international geophysical year determined that they were hooked up and there were these things called tectonic plates and was moving all these continents around. So why were they so adamant about this? This like hydroxy cloth. Quincy these guys so adamant. Why don't they say something like well? You know it looks like I don't know I don't know maybe some time ago. We don't have the evidence one way or the other. No No. That wasn't was like there. They were adamant very bothersome. And I remember very very fifth grade teachers like so. There are fifty two states. My hand goes up and others fifty there fifty two well. There were fifty then they then you bought you people. Because they didn't like Americans you bought Alaska and Hawaii said. I'm so sure it was forty eight. Nash shut up and then I came in and I played the embassy the assistant ambassador. Whatever on my little cassette deck and I think the teacher was more pissed than ever expect my first Experiences to be learned a lesson learned learned the dead. He should give us fifty two dollars and eighty cents from Virginia. Baroness Monica's on the list would fifty dollars to sixty cents from Drayton Valley Alberta says it takes a ninety percent Irked about the value of their money. Yeah Krista Scott in Tucson Arizona. Fifty dollars and twenty four cents birthday coming up for her boyfriend. Gary He'll be twenty six on. May Twenty four th. This donation is an honor of him. We are truck. Drivers spend a lot of time listening together while driving. He brought so many amazing things into my life and introducing me to know. Agenda is just another wonderful addition. Ataman John thanks for all the hard work you put into making this the greatest podcast in the universe. You make us laugh and smile every week to my sweetheart working boyfriend. I hope you're twenty six years the best yet. Happy Birthday to my sweet baby Gary and thank you both for putting food on our on. Our tables literally almost close close enough for US MARTIN'S NEXT ON THE LIST. Fifty dollars and five cents. The following people are fifty dollar donors name and location if I have it Jillian. Robbins and APP does California. Hey seuss Alan your buddy and Austin Texas Mitchell Kaufman in Hillsboro Oregon Sir Silver Duda to the silver dolphins in severn Maryland. Patrick Sir Patrick Maycom in New York City and do Newton in swindon. Uk Fantastic Info on the Orient. Good Alexa Delgado. Also APP tose. Did I do her Jillian Robbins above? There's APP does California yeah. Alexa is today. Alexa and Julian should get together. Hang Out Alexa. Delgado in Julian Robbins both in APP. Does Stephanie Sutton both gave fifty while. Wow Wow wow Sutton Mesa Arizona. David Wilson's spring sure than Queensland Australia and last but not least Travis Randolph in Auburn Washington. And he did This is another guy you listen to his note in the morning to you gentlemen. I was hitting the mouth from Adam's appearance on the job experience you quickly become my most favorite podcast. This is my second donation of the day. Second Jerry tribe. I didn't always realize I needed a pay pal account to make comments. Thank you to mark on Gender Social Dot Com for helping me realize the error of my ways that would be zero. Probably as a Newbie. Please explain how their donations work. And what it takes to become a knight or baron. I cannot in good. I cannot in good concise start to make my way towards knighthood until Joe Rogan joins the round table. That said please take today's donation of donations of one hundred and fifty dollars. That's interesting and apply it to future Rogan's Knighthood I champions all douchebag from the are- to donate to the cause much love friends. I only ask for SHUT UP SLAVING JOBS. Karma did Travis coming with one hundred earlier than did we. Is that what he did trying to figure out? What the Name Travis. Earlier yes he. Yes Right. He came in with one hundred two crap. Well thank you very much. The rogan people classy. Yeah it's really surprising is expected no less clowns me when you listen. I mean Rogan. He promotes the kind of the socialist agenda as a big Bernie. Bro and he backed off really fast when somebody thought he might vote for trump he's a L. A. Guy he's living in. L. Noises the like it but everyone in La. You can't ever do that. You have to be a dedicated Democrat in L. A. Or you're just a slime ball. The rumor rumor. The rumor he's moving to Texas is not moving. Okay thank you. All funny thing was in the process of do my research agendas especially enhanced P P P P P STA a lot more podcast in Austin and we think there are other one. There's others here yes it's a nice little it's an interesting. Little Place Niche here. I was here earlier. Very interesting. Lives there that Be Nice doing interview with Bobby Inman. Is He still alive? I know exactly. So we gotta find him all right. Thank you very much producers once again. You've pulled us through it. This is your podcast. We really appreciate these Notes of support and the value. That you've signed to that and always loved the number that you come up within the reasoning behind it. Of course they want to thank everybody under fifty dollars in on our subscriptions etc. You are highly appreciated. That wish everyone would do subscription. It would be great for us. Thank you for your courage. Thank you for your support. And if you would like to participate in this little gambit of ours and if you'd like to learn about the different levels and how they work just go to Daveramsey dot org slash and got all the bases covered some extra jobs. Karma which can't hurt in these times jobs jobs and jobs that's you've got Karma the twenty fourth of May we are moving along fast here and twenty twenty. Here's a birthday list. For No agenda Producers Sean Smith does happy birthday to his country Cutie. His Country Roommates Cheryl Cer- Chris Drunk immense well. Of course we celebrate Him Adam. Now stearns thirty two on. May Twenty Seventh Kate. Schramm's as happy birthday. There were smoker. Not Helping Bobby. Shrimp Thirty Five on the twenty six. Brian Richardson will be celebrating tomorrow. And Christopher Scott KRISTA SCOTT SAYS HAPPY BIRTHDAY TO BOYFRIEND GARY. He turns twenty six years old. Today may twenty four than we say. Happy Birthday from everybody here at the best podcast in the universe. Well let's see no excuse me. We don't have any title changes we do have let me see One to two dame's and three nights now. These are Dame's who've come in on the ceramics of Dog Patch and lower Slovenia dame drive. I believe is that correct? I believe so and they they will be designated a order of unanmous the designated order of and includes all the benefits it includes all the benefits of a damehood or a knighthood and. I figured we might as well shit out. Let's get it ready for the one. I'm going to need that one for sure on stage. I need Richard L. J. Record of Londonderry out of Warranty Meredith Matt Roles and Howard Morgan because all of you know become nights and ordains of the no agenda roundtable. I am extremely proud to pronounce the case. Sir Dude of the Dice Dame Unicorn of Londonderry Sir. Adamus Tim Real Dame Meredith and Sir Howard I the first of the JR reporter for you. We have hookers and blow poison chardonnay cookies and vodka warzone and proper twelve worn beer cold women. Jin Driven Gerbils Bong Hits Burman and mutton and mead. It's a favorite. Where the dame's head over to know agenda Dot Com Slash Rings Eric. She'll will take your information there. We'll get them out to you as soon as we can. Thank you so much for supporting the no agenda. Show your no agenda. Show the best podcast in the universe. If you don't believe me check out the Miller report fact fact fact. Okay quickey for you. Quick Euroland Nigel. Frosh a Sky News the France in the UK have always had their little issues and with the with the road. The Hundred Years War angry each other and so with the Ronan situation the UK said well. If anyone from France comes here you're going straight into quarantine for fourteen days to which France said though. Yeah well come over here and you're in quarantine for fourteen days so travel pretty much impossible between the the continent and the islands But it also appears that The French have are assisting at least the migrants you recall before all this went down we had migrant camps huge migrant camps in France near the channel near the ferry anywhere because they all want to get over to the UK and it appears. Now that that's being facilitated by the French Nigel. Farraj went out in the English Channel to report middle of English. Jonah were run on the edge of British and French. Territorial Waters It's a pretty calm day already. Living three migrant boats spotted clubs to such inventions. But the truth of it is this is a massive criminal. Surprise that his organizing making ball sums of money you can see the votes absolutely pat all being charge a minimum of five thousand euros eight the criminal gangs to make this crossing. You can't believe when you see how close the water is to the edge. I mean how massively crowded this as we could put them onto but there's no point because we know the border false the best on his way from Davis we will just kind of keep hip. We are now getting back into bridgewater's won't we know? Is it a French? Naval vessel is being seen as school saying but house of ritual to get into British waters. Burnett off so these dinghies packed with maybe thirty people apparently paying five grand each. And they're being escorted and the little little fifteen or ten horsepower. Outboard engine Putt. Putt putting just to cross and the French escort the right up to the British and the British taken and Bingo. You're in something not right with that idea. No especially when you're in quarantine if you happen to be a legitimate traveller him by the way two week. Quarantine applies to Americans going to England. Oh Yeah Oh. That's that's not over yet. That's not over by a long shot. You Know Christina and Shanta were supposed to come The nineteenth of May two now and it was one of the first direct flights. Amd Austin. That's gone that may never come back direct flight which I was pretty pumped about. Well no more okay. I'M GONNA. I'M GONNA play this my last clip than I have just let you know I have a couple of things I can play but I think I'm only gonNA play Well but says you just did that. Let's get this out of the way since you. That's an international report. I wanted to do a covert beaches in Barcelona clip. And I have the the Harrison Rut that the camera Harris Clip which is kind of interesting but but at least get this this out of the way as a international report about beaches in Barcelona are open. Beaches in Barcelona have finally been allowed to reopen albeit with requirement for social distancing although with temperatures soaring keeping apart from others is a tall order for some Alexander or has the story but last the chance for people from all generations to go for a paddle and feel the sand between their toes. It's a part of everyday life that puzzle lunar residents had badly missed until now people were only allowed to exercise alone between six and ten o'clock in the he's new. He's can with strict new instructions. What looking is allowed but sunbathing swimming and playing games in groups of forbidden? Stop whether face mosques especially be worn instructions repeated on loop through loudspeakers although some people say they haven't got the message stupid. I don't I can't even laugh about it. And so dumb. Wouldn't linking an exercise your six and ten. You may walk. Should've said don't play games. You'll they walk people resist. Here's a ass John. Tell me in. This isn't ask John. I'm going to play. A clip is twenty nine seconds. The president receiving the The space forced flag in the oval. Office then tell me what is interesting. About what the President says in this clip I call it the super duper missile. And I heard the other night seventeen times faster than what they have right now. Then you take the fastest missile. We have right down. You've heard. Russia has five times China. Working on five or six times have won seventeen times and it's just gotten to go ahead seventeen times faster if you can believe that general that something right seventeen times faster than the one we have right there. Fastest in the world by a factor of almost three okay. Did you notice anything interesting? The president said there. Will he said that there? We have a missile appearance. Seventeen Times faster than anything ever built right right which is also three times fashion. The Russian Hypersonic need to put on the glasses industry. Which talk what you're dealing with here. You got the Q. Glasses on I do. I'm wearing now. He said seventeen five times. What letter of the alphabet is seventeen? Six what three what letter only three. What letter of the alphabet or the outbid six Duh? I don't know I don't know I mean I could look at the Ben Count but you can just tell me easier Q. And off they come. He said Seventeen five times clearly. Trust the plan where we go one. We go all Q in the house space searches. I well I got my last clip. Rose I love it. I follow ups. Things ever to come down the Pike dight. Virtues CIGNA laying kowtowing to the Chinese. The Chinese are behind most of the today's show Was discussing whatever we discussed. These things are happening. A lot of it has to do with the Chinese. Why were denying the viruses made in a lab is because the Chinese media has told us is not for some reason? I think I have my thoughts about this discussing later shows Listen to what Tom Cotton. is asked about the Combat Camera Harris Resolution Hate speech resolution. And I'm just It's my eyes. I guess I just can't find what you're talking about here. Cutting hot on Harris resolution. I'm sorry got center. Also I think you know that this this whole thing started in Wuhan and you know that many people call this the Wuhan or the Chinese Virus Kamala Harris had enough. She has resolution. It's going to work. Its Way through the Senate to make to ban the phrase Wuhan Virus Anti Calls It anti Asia Asian your feeling on this while I objected to that resolution. Brian first off when it's just a city it's not even a people. I guess she's going to have to call that lyme disease for being anti Connecticut or maybe legionnaires disease for being anti Veterans Deka since Zeka forest in Africa but this political correctness run amok covers a more serious point. The DEMOCRATS WANNA wave their arms and say this is racist or xenophobic. And that's because they don't have an answer for China's rise and the threat that China poses to us. Joe Biden as we said has been WEAK ON CHINA FOR THIRTY YEARS. So they have politically correct distractions to distract people from his terrible China. We can't let that happen. We're cotton business. The whole thing is virtue signal laying and then kowtowing to China. It bite the last thirty years. A lot of people made a lot of money off of letting China in and setting up. It's not you know there's reasons why professors professors being arrested arrested. This cannot be overlooked. I know it's out of control. We get up identified. We get wall to wall coverage of Laurie. Laughlin pleading guilty. Yet we have Chinese spies. Professor Professor Orioles spies gets a mention little mugshot boom done. The media's not serving you this is why we exist this is why we are the no agenda show we are your podcast and we will be here again on Thursday to diss serving you. That's correct. They've got something do dissemble and we've learned a new word coming to you for shoot. I got to tell you about the end of show things. We've got Tom Stark weather. We've got A Fletcher got a great Jesse Koi Nelson. And then I have the man. I had the credits for Christmas song here. Oh yes the covert isolation Blues Sir. Chris. We've got Dave Bruce on Bass Joe Rami on drums and of course guitar. And that's a Gibson Les Paul seventy-seven Vintage Company who from opportunities own thirty three in Austin Texas capital the drones star State Fema region number six the governmental maps in the morning everybody. I'm Adam. Carre. A northern silicon valley where everybody's just all rolled. Joe Sleepy Joe. He's GonNa win. He's going to be president. I'm Jesse Devora. We return on Thursday right here on no agenda. Remember us at Daveramsey dot org slash. Na help us out for the next show until then smoke and such key so shoulders thicky locked inside. They say it's for our own good things they're trying to the that's quarantine Solit- the healthy sounds lack tyranny to me And so we're asking continuously for you all to be outside to Joy Memorial Day weekend. I'm going out. Who's on the phone all of us? It's the future can go out can be outside now. What goes good with sunshine. Here beer. Beer how is only toll house cookie yes please? You can do this at home if you'd like to sin slices of onion and then with your reading whatever you want to know what type of flour and seasoning strict by little wine which is about the only one. I drink have my little cracker form of asking for forgiveness. I do that as often as possible because I feel cleansed. Okay Hi everybody I everybody. Thank you for that beautiful introduction. The world is turned upside down by global pandemic which is why things are so screwed up and given the current state of the world. That may be kind of scared leaving behind all the old ways. Thank you that. Divide US my goddess hard. One responsibility. Find Him some of you had overcome serious obstacles along the way and as much as I'm sure you love your parents turns out. They don't have all the answers. A lot of them aren't even asking the questions and those were struggling before they're hanging on by threatening. No you're too young to understand which means that you're going to have to grow up faster than generations. Also not many people. Great in those gaps. Figures like guys. I won't tell you what to do with this. Do what feels good. What's convenient? What's easy slavery? Civil WAR OBAMA DISEASE. Get a right. Every time took the stakes like no one does big things by themselves but what remains true. Everyone around you is hungry and sick. Realization may be kind of intimidating. But I hope it's also inspiring. He's a lot of people. WanNa assume you on that ticket and the answer is of course I would be honor to run for vice president with the nominee. A problem figuring out whether you're familiar trump you a block teams really not just for me to say that out loud. Since I'm not you know was asked me so. I hereby present buy a pack. I think that sounds pretty. Good the salad using a comb from her bag. I think that sounds pretty good. And the head of the trump to her aid and told him to clean it free polls. You're the top choice for voters. As far as they would like to see as a vice presidential having conversation about women have come forward. They disembarked to be heard. They deserve to be believed to. The charges are terrible. A Cooler for news of Newtonmore many Laker but one can only dream of a more exciting twenty twenty presidential tickets Mr Vermin Supreme. He jokes he says you know. We make a feature shortcomings. My name is vermin supreme. I'm a friendly fascist. That you should trust. He makes up for a lot more my short commission either. Here's number one. Whoever the next president is should have somebody they trust Mr Vermin supreme t said conditions. I said joking to things. I'm not wearing funny hats and mocking change. My brand we have giant turbines that we're working on and we will have lots zombies and we'll this short dangle brains in front of them and then they will turn the giant turbines creating energy to lessen the tendency on foreign oil in America. Today Ya Moepo dot org slash and a block.

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