Episode 267 - Kevin Holden
Hello everyone and welcome to talk dirty. Today is Monday Monday July twenty two thousand nineteen and I'm your host Care Santa Maria and today we're going to be chatting with Dr Kevin Holden and we will get back to Kevin and just a minute but I I wanNA thank those of you who have made talk nerdy possible this week. Remember Talk Nerdy isn't and will always be one hundred percent free to download and that's because we rely on the support of listeners just like you so if you go to patriotic dot com slash talk nerdy you can pledge your support just like filthy bear the Zombie Drummer David J e Smith Gabrielle Brielle Felipe Gonzalez Brian holded and Jeffrey soon. We'll do each and every week are let's dive into the show so like I said this week. We're going to be talking with Dr Kevin hold in now Kevin is this is such a great title. He's the head of science at Cynthia Corporation and simcoe is a genome engineering innovation company. We're GONNA talk a lot about crisper. He's GonNa explain all about what that means. So I guess without any further ado here. He is Dr Kevin Holden Kevin. Thank you so much for joining me today. It's great to be here thinks of course so we are going to be talking about all sorts of cool stuff that I'm not sure that I've talked about too much on the show do before anybody who's listening to talk. NERDY WHO's like a regular listener knows that I also work on another podcast called the skeptics guide to the universe and I think one of our favorite topics on s g you almost anytime there's like a big relevant news story that comes out out is Christopher cast nine gene editing kind of more modern approaches to gene editing and so I think it's going to be really cool to do more of a deep dive today on the podcast so Kevin you are are the head of science. Is that your title head of Science at Simcoe. That's really cool title. That's amazing so being the head of science at that means that you are a scientist and you were scientists before you started working there <hes> knowing that you do that you work in <hes> crisper cast now. Ten Marquette is a cast tenor Cossacks was people calling Cossacks seems like Cossacks Okay record in Crisper CASS acts which will get to and we'll really start to dive deep into. Is your background in genetics. Is it in microbiology. Is it in a another type of science that has some crossover. It's so multidisciplinary he disciplinary now. What did you actually study at school? Yes so I guess just refine on the title part of low vets company that I worked for Nelson to go. We've lots of engineers and and chemists and other people so <hes> we have signs people in engineering people so I get the leader of the science so that's GONNA call. That's really cool. It's kind of like a it's kind of like how J._p._l.. Is Down the street for me here. There's a lot of scientists but even more engineers doing all this cool stuff at NASA and they do kind of keep those I mean they work together all the time but keep those teams pretty separate <hes> in terms of the I guess management approach to it but like at J._p._l.. At NASA there's probably I mean don't quote me on this ten engineers for everyone scientist. I is it like that. It's simply go to is way more engineers working. There than scientists say it's becoming more than even split is probably probably more engineers. I guess the way it's going to think about my titles alot. More Star trekkie like spock sparkles. It's like the science officer and you've got Scotty engineering going back to your back to your question. Though so my training my undergraduate training was in molecular biology and then my graduate training masters a P._H._d.. Has Been in microbiology and <hes> but actually worked. I didn't I think like most people who entered the crisper. Castle field obviously back then genome engineering was was a whole different animal if you will and it's something that I kind of fell into <hes> mostly because after I left my p._H._d.. Program at University of California Davis I went into working in a a startup company that was actually trying to generate biofuels on at the time up those George Church founded startup no clue in San Francisco <hes> and <hes> that essentially when it was there <hes> you know me and a couple of other people we sort of founded this synthetic biology group that was kind of the sexy Buzzword back in twenty ten. I guess Elliott that was like very craig. Venter at the time right exactly so kind of synthetic genomics to kinda working being working taking the field of synthetic biology where we're trying to apply so engineering principles dow we build design and SORTA test biological systems <hes> you know part of that is developing and adapting methods methodologies analogies and so it could be like a method this whole published on. Maybe one adapted into your lab or maybe you wanNA combine methods or try to develop your own but I had read the early Crisper Kathleen Papers <hes> became adults. <hes> for Jennifer Cordell does lab at U._C.. Berkeley and this is back in like twenty twelve twenty thirteen and I was starting to try to adapt those methods into my work for this company. If the start accompany excess Kinda High God's involved involved in the crisper Kathleen World Genome Engineering and tried to do some genome engineering when I was in graduate school that was actually part of my research project was to do genome engineering on on a bacterial strain but it was so so much harder back then so looking back. You know it's one of those things. I wish I had this technology when it was doing my p._H._d.. <unk> much faster. Oh for sure I mean that's kind of like the big takeaway sort of when we talk about Oh crisper and we talk about sort of modern <hes> genomics is the BEF- there was a before and there was an after you know and so that's sort of something that I would love to actually get into a little bit more because I'm thinking we're throwing around a lot of terms on the show show and sort of making the assumption. I think it's a fair assumption based on my audience that people have heard the word crisper before and the people kind of generally you know aren't too scared when the here that were genetic engineering or genomics but maybe they are and maybe they don't know what any of this is and it's probably there's so much to break down so before we even get into crisper and before we get into some of these new approaches and techniques. Maybe we can talk about exactly what genetic engineering is what genomics are kind of what this whole field entails tales first and foremost even before we get into synthetic biology because that's a whole other animal I mean so when you think what it means to do genetic engineering in cell essentially what you're doing is your and all of us have DNA every cell has denied it <hes> the code of life right so as human beings. We have a copy of D._N._A.. From mother another copy for my father <hes> that are <unk> separated into chromosomes in you know entirely this is called your your genome rights. You have two pairs of twenty three chromosomes an so <hes> I I think what's really important when we start talking about genetic engineering genomics General Oh is that <hes> you have to remember the each one of us were very dynamic organism and every living thing is very dynamic in the world and so our genomes are no difference so just as we can see our hair growing and then you know <unk> hopefully hopefully not falling out but her grows replaced <hes> we get sunburned. We have freckles on our skin concern darker. <hes> are features change over time and so <hes> that we can see absorb physically and the same is true about the genomes and <hes> what's really critical remember is that your genome or my genome or anyone genome is not <hes> the sort of pristine thing that is encased in in in glass in a museum him or something like that so <hes> genomes are moved changing all the time there the Dina's breaking its repairing itself <hes> it's under attack from sources like cosmic rays radiation radiation and <hes> the the environment <hes> things that can enter your cells be numerous amount of different types of chemicals or toxins in the environment that just occur naturally and so you know Dini's under attack. They're they're also shifting around all the time. A large percentage of our genomes actually made up of these like what we call retroviral retroviral retroviral elements at some point in time. We're actually viruses INC themselves was into our D._N._A.. And so you know these things can actually jump around in the they move around so you're Dina's constantly shifting. It's moving. It's rearranging <hes> it's to that end though it is still pretty organized and it can maintain repair itself very effectively ugly and so I think when we start talking about <hes> humans US manipulating genomes we have to remember that they're always self manipulating and so if we come in and we'd tinker with a thing here or there <hes> yeah it's possible that like we may cut how to throw a balanced but in general we're not doing anything that's massively foreign or unique to to the sort of almost like living entity if you will this this genome so you know I I was thinking like okay. It's a painting and so maybe you come in and you make like an extra brush stroke on this painting and so you know it's probably GonNa be very difficult to notice that like you know you're looking masterpiece. The money painted and you come in you make an extra brush stroke. It's still the masterpieces just no. It's got your signature on income and so when we are talking about doing this kind of this kind of engineering like whether we're talking about how students in a genetics lab <hes> you know at a major university or whether we're talking about industry what kinds of <hes> like we'll get to the approach I think in a minute but what kinds of of <hes> reasons would people have to go in and start <hes> trying to understand and potentially change this dynamic genome of an organism and often. We're not talking about like engineering people although that that is a conversation to be had blake. Many people are using crisper cast nine or Cossacks now with like Lick Standard Laboratory organisms like your soft fruit flies or see elegance worms and things like that so what kinds of people interested in engineering yes so there's there's a whole reason why you you would want to manipulate genomes and so this really kind of hearkens back to really like a revolution. That's occurred in biology starting adding literally way back in like one thousand nine hundred seventy s maybe slightly before that which was our ability to <unk> actually manipulate D._N._A.. In Vitro in the laboratory and so the sort of like recall we call it recombinant DNA revolution so the ability to synthesize chemically strands of of D._N._A. Because Each D._N._a.. Base is essentially just a chemical and these can be made industrially using synthesis type chemistry you and so on the ability to synthesize like sequences of D._N._A.. And then <hes> kind of move them around in the laboratory was extremely powerful EN- changing to our entire world. So why would you want to do this type of thing. Will you can do a first all of the genetic engineering was done in bacteria or yeast and so we've relied on bacteria in yeast for you know thousands of years to generate food for us for example like yogurt in things like this so really the the application of this technology for industrial microbiology production was <hes> you know kind of really one of the first things that people looked into so perhaps you have a strain dean of bacteria that you used to <hes> in in your yogurt and maybe that is susceptible to <hes> a disease itself so bacteria are attacked by viruses for example on there could be way that you could engineer here that bacteria essentially become resistant to to that virus so when you're making yogurt you don't waste hundreds of thousands of dollars because your culture dies and you have to start over it also makes your food. It also makes your food saver or so. Oh really people initially started manipulating D._N._A.. In using this for comment in technology to to study organisms as well we can use it to <hes> for example you can delete a gene in a bacterial organism or sal and you can understand <hes> you you know how that gene is utilized in the cell why it's important so in order I assess gene function to like seek was the human genome all these amazing things we've been able to do leading up to you getting your twenty-three profile is his we needed to manipulate DNA and so really that's kind of where the genomics revolution like started in. It's kind of born fruit all the way through to a lot of different applications you mentioned Drosophila so this is a model what we ella model organism. It's simple it's relatively simple onto that is smaller and has much fewer jeans and you can start to map how pathways networks of proteins in and how they work and so being able to kind of perturb different nodes in those systems can help you understand many different things like neuronal development how does a fruit fly brain develop and their analogies in how that develops us to how human brain develops <hes> both from an evolutionary developmental biology perspective and also all the way through to disease. How does how does this brain become diseased and how can we make a comparison and do sort of like a comparative study to what happens in human for example yeah yeah? I mean that's obviously the way that sort of biomedical science has happened for as long as we've had biomedical science. which is you start at a like you said relatively I like the use that term relatively simple organism ah level so that you can develop models and then you can start to tinker with those models but eventually you have to move into translational research and that is where kind of the I don't know I don't want to jump into this too soon without kind of having the the foundation for understanding <hes> crisper but that's sort of where I think people are <hes> getting slapped in the face with these news articles right now that certain a certain scientists I shouldn't say certain scientists floral but that a certain scientists sort of decided to skip a whole lot of steps and try and apply these things <hes> not going through the standard ethical channels to <hes> to human biology <hes> so I wanna get back to that later but before I do we've been talking about why you might want to manipulate the genome? I WANNA get into into how what might manipulate the genome as you said. When you were in graduate school there was no crisper? So how did you have to go through and try and do some of the stuff and and what is the difference now that we have this new this new technology okay so to be to to be perfectly fair. Christopher has been around for early one time. It's like it's been around for millions of years. Probably Bacteria didn't know about it. It really important point to make I think like we haven't harnessed it. It's like fire exactly so it's something we discovered. It's analogous to I did my p._H._d.. Microbiology so I studied Infectious Diseases Nice studied <hes> what what's considered to be an emerging infectious disease and what we mean by that is that it's it's only recently been sort of identified so we've identified like the causative agent of the disease we've identified how is transmitted transmitted into humans and through different vectors and things like that so <hes> diseases have always been there. Yeah I studied lime disease in my p._H._d.. And so this was I identified in the nineteen seventies in old lyme Connecticut. That's why it's called lime disease and really it all it had always been there. We just never had made this association between the fact that you know ticks by people and they could carry bacteria that sort of passes on pestilence bacteria to humans moments in fact some. Maybe some of your listeners had seen those really good Nova program a couple years ago. I have us make a plug. Novas definitely probably the best science program on television. Yeah there was a a Nova about an early human that they'd found <hes> in. I believe it was in the Alps. <hes> you know that was thousands of years old. I almost ten thousand years old I think and when they you did analysis on him they they found you know he was found in sort of like frozen like almost like <hes> glacier they found that he'd had a lot of this tattooing around his joints and when they did some further molecular testing is d._N._A.. Testing actually found that he'd been infected with lime disease as lime disease was around back then in Europe. The tattooing probably wasn't done like for fun like people do today but it was probably done to try to relieve pressure pain in that's what they believe so fascinating crisper. Is this the same way it's always been there present in <hes> in in bacteria. It's a <hes> a form of immune system adaptive immunity. The bacteria have to defend defend themselves against viruses. It's absolutely incredible. When you think about like how amazing it is and sometimes when you you study bacteria on a low bias because I studied bacteria people think all the very simple type organisms well? They're actually quite different because each each one of our cells are highly specialized can only do maybe one thing like your liver cell. Your Pat aside can only do it can only be liver right. L. is a single celled organism in has essentially do everything on his own in order to survive in the Environment Armand so <hes> is doing a lot of things and for for to actually have for bacteria to have developed their own immune adaptive immune system where they essentially what maybe you guys have broken down crisper on your show before but what you give essentially. Ashley taken a fragment of the enemy invader in this case virus into the bacteria. You've taken some. It's genetic material. You've stored it <hes> like data recording in your own genetic material so you can recognize when it comes to attack end you can radical it so <hes> really powerful mechanism and you know it's not very different to our own. Immune systems have evolved in in mammals to protect us from viruses and bacteria so yes so comeback. Originally you're saying <hes> immune to go to side note there but no it's great and I think we'll probably dig even a little bit deeper in a minute after you finish answering this core question back to kind of how crisper works because I haven't done a deep dive on the show. I think it's probably a good idea to do that. Yes so I think you know going back to what you're asking on. Yes Oh crisper wasn't around <hes> as technology at least when I was in graduate school so we were relying on <hes> I'm on more basic approaches to do genome engineering and the main problem with that was I was trying to engineer a bacterial strains so specifically <hes> I was working on lime disease and I was very interested to know we we had this model for lime disease. You lime disease can affect mice that can affect <hes> ticks and later humans and dogs and so we wanted to understand why exactly where some of the genes doing in this bacteria that were allowing it to kind of develop this like pathogenic genyk niche so it could survive in host <hes> that bacteria is very successful surviving hosts for very long time and it can actually evaded the immune system. It's quite almost like until you study disease. You realize how almost perfect at some of the designs and the engines are GonNa say designs but <hes> some of the adaptations are and so it's really was really interesting. was you know we were trying. We'd identifies putative genes that we thought were interested in particular aspect of the the disease and so you WanNa go in and you wanNA perturb those genes maybe if you remove those genes <unk> is the bacteria still capable of infecting a host the same way maintaining the disease date itself inside the host and so in order to do that that we had to use which rely on <hes> I would say barbaric techniques but much more blunt instruments and so we couldn't go in and actually make <hes> you know very specific changes or very easily so you know it's orders of magnitude difference between using crisper and the technologies we have before to do genome engineering words like maybe in the past if you wanted to make specific change you'd have to screen hundreds of thousands ends of cells just to find the one had the change wanted now. It's sometimes virtually every cell has the change you want so like that kind of jump has been just game changing in in the way that the and Gino manipulation could occur and this is because crisper has has arrived. It's really going to push a lot of R._N._D.. Much faster. It's a very powerful molecular biology tool probably I would. I'd say I'd like to think about the technologies that have really changed molecular biology in health fast we can do research which helps us to discoveries faster therapies faster and there've been several sort of like jumps. We think about like U._C._R.. Is a really one P._R.. Technology <hes> you know sequencing <hes> the the use of <hes> the ability to <hes> synthesize molecules like I mentioned d._N._A.. <hes> these types the things <hes> yeah it really it's right up there with like one of the the formative like steps. I think people will look back on this leg in some time in the future and say hey that was actually a landmark discovery. <hes> that really changed how people could do oh for sure genetic manipulation and analysis and do disease research on all these other applications you get from crisper and I think it's one of those things where like we don't really even necessarily obviously I think hindsight will be even stronger but the actual practitioners who are doing this work right now are well aware of how much how much more accessible crisper has made this kind of work both in terms of like a speed and like exhaustion level but also just in terms of a monetary level like labs that don't have quite the same funding or startups kind of industry startups are able to do things that previously you could only do massive N._I._H.. Grants or with <hes> you know a lot of institutional support which is which is really really cool but I think before we even get into sort of what synthetic biology is or <hes> <hes> how things have changed between <hes> crisper cast nine which when we say crisper were usually or at least historically referring to crisper cast nine but now casts X.. I'd I'd love to even just take a a more fundamental approach approach to talk about. What crisper is so? I had to Google this because of course they don't know it off the top of my head but crisper stands for clusters of regularly Inner Space Short Pailin dramatic repeats so what we're actually talking about. There is base pairs like nucleotides. We're talking about little sections of D._N._A.. Essentially yeah we're talking about shorts clustered regularly interface so what it means. They're just like just as it says these are. You're correct though these assured sequences of D._N._A.. And they would be double stranded D._N._A.. So they'd be base paid yet so they're short <unk> sections of sequences of D._N._A.. <hes> you know that were regularly into space so they were spaced at regular intervals in genomes and said it was called Crisper by <hes> by the scientists that discovered this originally in bacteria and so it was when they were starting to sequence bacterial Kiro genomes because we started developed technology to do whole genome sequencing people started looking in in different bacteria may be the bacteria they were studying for interesting motifs than in genome and this is something that came up that that a lot of bacterial genomes had these like sequences that were highly repeatable. It's very strange to see those like why would why would have bacteria sort of maintain this what we call Junk D._N._A.. The time just a bunch of random repeats in a row so it's almost like looking for a pattern in the noise like something that's like Oh. Why is this doing it over and over and over and over again? It's very recognizable to like a software program right yeah so it's sort of like these very strange why they hear <hes> one function in purposes they have <hes> you know it's there. There is really sort of like no reason to keep something around if you don't eat it and so there was a big reason for this turned out and that was well that was the fact that <hes> so it actually turned out that the the repeats that were common <hes> they form one part of the <hes> of the crisper defense mechanism mechanism so if you will so what we call crisper even though we call crisper cast nine or Cossacks whichever one you WanNa talk about kasten whatever if W- actually it's actually named for the for the the region of the D._N._A.. That's that interesting so there and so the repeat region is known as a tracer Arnie and so this is a standard piece of of <hes> DNA is later transcribed into Arnie in the cell and this piece basically accident anchors who anchor onto a protein which is cast nine or or casts X. would have when you're working with <hes> and originally it was discovered <hes> in some of these organisms though the work <hes> <hes> <hes> the Jennifer Domino's group did <hes> where they showed that <hes> you know this repeat region this tracer region was binding to this cast line protein <hes> at the time they were studying a Yo streptococcus pile Giannis which is the the bacteria that causes strep throat and so <hes> it turns out these repeat regions they anchor onto a protein what's more interesting as the regions are in between the the regularly inter spaced <hes> sexual so in between the repeat regions are regions of Unique D._N._A.. In the very short has the typically you know there were somewhere between twenty and thirty bases D._N._A.. And these represent these were actually <hes> the memory if you also these were the pieces of foreign d._N._A.. That been incorporated in between is the space or regions so in between sorry these tracer region so Christmas really named for the repeat section. It's probably like not the most interesting because it's not the part. That actually does the business. What does the business is? <hes> the piece that is immediately preceding that <hes> repeat region which is known as a Crisper Arnie on so this is this is d._N._A.. That is derived from <hes> an invading <hes> <hes> <hes> virus in in the case of the bacteria and <hes> The D._N._A.. Gets shared up for the virus one inside the cell. Sometimes the viruses die their D._N._A.. Shared up these pieces will get put inside of these repeat regions back in the bacterial cell and keeps it. There is a way as a as a piece of memory and so when the when the saugus infected again with with a virus that contains that piece of D._N._A.. Invariably that virus will lose some D._N._A.. Will some of the Modem the break-up an open the D._N._A.. Watts <hes> these viruses are trying to do our they're trying to incorporate their genomes into the bacterial genome so they can copy them many times. That's what viruses do right like in any sort of <hes> organism awesome they sort of inject themselves into the cell and then multiply and the cell actually takes in some things like I mentioned earlier our genomes have lots of Viral Dini say ancient viral d._N._A.. In them and some of them are able to actually jump around a move around different places the nature what D._N._A. Does it can it can sort of homologous Lee recombine with regions that are similar to itself and Nestle just the nature of the chemical in a way and so you know what's happening in what was happening. Christmas system is that because <hes> the what the bacterial cell will do would actually translate it would actually copy that close that repeat region along along with that unique piece of D._N._A.. So cooperated and it would generate this piece of aren't we call it a guide Arnie guide that cast line nucleus that protein. It's basically a piece of software code if you will that can tell that that protein like where to go at it can direct us specific address on genome but that's that's the way it works. Works is cast nine the nucleus the protein we call it a nucleus because it's capable of cutting nuclear acid d._N._a.. Enzyme that can break down D._N._A.. <hes> what that what that protein actually does actually scans through entire genome. It's constantly Tara getting genome and sort of coming up to L. Location and it saying do you match with this piece of code that I have on that. I'm carrying with me. No you don't match. I'm not interested in you a moving on if it does match it says <hes> you match what I have have carried here. I'm going to come you and then we'll make a cut and this is why you often hear the term like molecular scissors like that's kind of what what you do with <hes> with Christopher's. They're like little molecular scissors exactly exactly so at this point. You know it's located match for what is carrying around with it. It's basically it's it's code if you will that. It's matched up to something. It's made a double stranded cut. It's cut both strands of of the D._N._A.. And now the cell has to figure out what to do with itself has to repair itself if it doesn't repair itself will die because these breaks can be very toxic because essentially will screw up all of all of the coding regions and things like this in energy no okay so oh so it's gone through. It's it's gone through this whole process. It's done this. We're talking about kind of natural crisper at this point like this happening in nature. How did we figure out how to harness harnessing and actually use it for our own purposes like where did that leap come through <hes> yeah? I mean that's that was really that's really Kinda. The genius pointed this whole thing right so this was identified by <hes> you know <hes> several different groups in in bacteria I would say probably the most notable of these was Francisco Mojica who was at University of Alicante in Spain and he was studying. What will we call halo file so bacteria that loved to live live in salty areas and he he'd been looking at genome sequences in in these bacteria that he was studying and found that they contain these repeat regions and he was actually he was actually one of the first people to name the same crisper the I guess I should before going further <unk> Kinda give a little bit of a plug so those a very good very well written new documentary signing documentary film <hes> the premiered at South by southwest is called human nature and if you WanNa see a trailer you can go to Human Nature Film Dot Net? That's my movie plug. I'll be on the tonight show next week anyway <hes> so did you. Did you work on this film L.. Yes so we were actually you know. It's not my show well so this was a film that was directed by Adam Bolts and he was part of inside job which was fantastic film. Dan Rather was one of the producers uses this film and <hes> along with several others <hes> including Sarah Goodwin who's part of this ideology project that U._C._S._F.. Does and I'm essentially what they wanted to do was to to make documentary film that kind of showed not only the history of crisper on but also how how was discovered and so forth how it actually works how it's being utilized also talk through a lot of the ethical questions around owned the use of this technology so it's a fascinating film <hes> <unk>. My companies go was involved with the film. A little bit actually came into some filming at the company. I think appear in the film for about fifteen seconds is my fifteen seconds of faint literally but it's it's told from its narrative completely by all scientists were involved in the development of technology so <hes> for anybody. It's they're looking to get a wide release into into into cinemas for everyone to see they've been doing some different showings. I went to the premier south by southwest but <hes> it's a fantastic film in. I guess what I'm trying to say. Is that a really does for any your listeners really does have some fantastic visualizations about how crisper works and also documents the history of this amazing discovery and it's different applications all right everyone. I want to take a quick break to thank the sponsors of this week's episode starting with calm. I love calm. I feel calm Tom. Just telling you about calm and that is because com is the number one meditation APP and APP for sleep. I use my calm APP literally every day. I do a different meditation every day. Sometimes I do the daily Com Tom more often. I like to go through and find the series based on what is going on in my life right now so I might use a focus series or I might use a calming anxiety series or maybe like a self care series. 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There are world maps and my favorite or the Outer Space Globes. There's actually forty different more than forty different designs the outer her space ones used graphics from NASA J._P._l.. So they're accurate graphics that were actually pulled from the cameras that are used on these different spacecraft and they've got planets moons and asteroid and even constellation designs these things rotate on their own with ambient ambient light. That's the coolest part of so you don't have to plug them in. You don't have to worry about plug being nearby. You don't have to charge them or put batteries and they're always going to work for you and right now. There's a brand new globe that I'm really excited to tell you about. It's the NASA Apollo Fiftieth Fiftieth Anniversary Globe <hes> So it's got the fiftieth anniversary logo on one side and official mission Pashas showing where the Apollo touchdown on the lunar surface on the other side. It's a really popular preorder so if you want to get that one and you want to like actually ensure that it's going to be delivered you should go ahead and go to Mova Globes dot com slash Apollo Dash Moon and put down your preorder our guys. Let's talk about how you can get yourself a brand new new Mova Globe and you can actually get ten percent off your purchase. You've just gotTa go to Mova Globes dot com slash nerdy and use the coupon code nerdy that's M._o._V._A.. Globes dot com slash nerdy and use the coupon code nerdy for ten. percent off all right guys. Let's get back to the show well and that's so helpful to I think sometimes the podcast medium you know allows us to do so much because we can really do these long-form deep dive more nuanced interviews and talk about things in a way that you could never do with like you're you know minute and a half N._p._R.. Interviews but that said it's an auditory medium it's not a visual medium and the truth is you're right in order to really understand this. I think we can understand it at a at the level all of analogy and metaphor and we can understand it from a practical perspective but if you really want to understand it technically and like logistically it does help to see graphics to see <hes> <hes> animations so that you can actually see what's physically happening opening inside the cell down at the D._N._A.. Level <hes> when when crisper is doing its thing so thank you for that. I think that's really helpful one more time. What's the film called is called human nature human nature very cool? I would say for your listeners. They should definitely try to check it out when they get a chance and I end for sure like this would be very helpful because this is definitely one of those topics where like I said my other podcast. We talk about it literally all the time. I'm always reading about it and every time I have to give myself like a new primer on like how it works because it's not my field and I think for a lot of people who don't work in the sciences at all. It's like each time. They have to remember her with what's going on now. Why is this happening and I think there's a lot that we can sort of take for granted and say okay sure going in editing the genome <hes> using this really cool tool that makes it a little bit easier and a little bit more precise <hes>? There's a lot of wonk there but but what happens we edit the genome so there is this portion where I think it's so important to understand the how of it but the Y.. Of It is a whole other question and the what happens next of it is a whole other question that is really really important and and I think not to transition to early but that's really where synthetic biology comes in because crisper and genetic engineering or gene editing is one thing it's technique. It's an approach synthetic biology is is a basically it's a whole new field. Isn't it so I think really depends on what you define as genetic engineering because essentially an villgers this and it's something that's well known as well we we've been. We've been manipulating genomes for a very long time is a species so whether you know now we're doing in the laboratory. It's a little bit different but we've actually been manipulating genomes for aw literally tens of thousands of years by breeding plants together breeding livestock together utilizing microbes to make food for example so yeah and this is something that we do talk talk about a lot on talk nerdy because we talk a lot about the G._M._o.. Debates and things like that and we talk about the difference between <hes> conventional breeding and transgenic technology which all gets lumped together when we talk about G._M._O.'s which is very confusing but yeah we have been manipulating sort of quote unquote natural selection and doing artificial selection for as long as we've been a species and figured out well as I guess as long as we've been doing agriculture. Maybe when we're hunter-gatherers I weren't doing it quite as much but even with selective breeding of people right we chose to mate with people because of their traits right there we started to manipulate the genome exactly yeah and so we're all kind of I think as as we go forward in time to to we're we're going to be doing this more and more. I'm sure one day people will say hey let me look at your twenty-three profile before you know I want to go on a day with you ride so it's GonNa we're going to be we're going to be kind of selecting a for traits that we wanted in some kind of way yeah. We already already do that into to some degree already do that yeah. They're definitely people who who know that they're carriers of certain genetic diseases that actually have to do these kinds of of counselling before they get married or before they decide to have children. <hes> you know people with <hes> Huntington's disease or people who have like tastes acts or things like that. They're actually pretty knowledgeable about this kind of stuff but you're right. I think it's just a going to become more commonplace a place in the future okay so but when we use terms like synthetic biology because the company that you work for since ago this is a Silicon Valley company this is you went from academia into industry which is a whole other thing that I feel like we could talk about for like an hour because it's a big part of the show as well as like quote Unquote Alternative Charisma Sciences which aren't even alternative like it's an average just a career in the sciences <hes>. You don't have to stay in academia when you finish your P._H._d.. If you finish your there's a lot of cool stuff that you can and do out there but so you're working in industry and you're working for a company Simcoe that I take it from. The name of the company is a synthetic <hes> synthetic biology company. What is a synthetic attic biology and be how does that roll up into? What you do isn't the go yeah I mean if you if you take the definition of synthetic biology and I'd say it's actually one of those things that people are still contingent continuing to define the is a synthetic biology conference a large when that happens every year called Syn Bio Beta? That's put on in San Francisco. Sometimes in London and you know I'd say at each one of these conferences this kind of like a almost like a redefining. What exactly does it mean to do it but in general it's sort of taking homelessness engineering approach to how you do biology because <hes> you're actually trying to <hes> design and construct a new biological entities if you will I don't necessarily mean living living things but <hes> new biological enzymes or genetic circuits or even sells <hes> or maybe redesign existing biological systems and you're trying to use like almost like a <hes> like a a a standardization type approach to do that and so that's kind of also ties into the company a workout Cynthia go because it's really has a lot of engineering foundations that we could talk about this is pretty interesting story at some point but the the the two brothers founded us go my compal Dubrovsky they were they used to work for Elon Musk's spacex they were pretty early employees there <hes> and so they were really interested in understanding how they could apply enduring principles into do the world of biological research because if you it makes sense to me now but before it didn't really but it really does make sense you have more engineers scientists working together because if you look at what happens in a biological lab the still a lot of done by hand and unfortunately humans make mistakes? I'm not suggesting that we have an army of robots that does all the policy in the world science and takes away all the intangibles intervals but sort of general really does need to be sort of better levels of standardization in science and part of the way we can see this indirectly is how many publications are put out where people produce data that is actually not reproducible reproducible by other groups or methods by the groups so this is kind of a big problem in biology people. Don't really WanNa talk about a too much but <hes> you know if you can build levels of standardization into how you do biology the and in the case of the company worked for Nelson. Go how you actually do a crisper based genome engineering <hes> it really can sort of move everything Ford faster and so were going to. It's going to help us get to discoveries faster therapies faster and things like this <hes> earlier. You asked me the question about like how did we how did the actual formative like change. Four people realize that you could utilize this crisper technology this biology if you L. Home Crystal was existing in <hes> in cells and utilizing an industrial way <hes> there was kind of you know kind of a couple of different moments that happen one of them was <hes> you know those scientists scientists at the Danisco <hes> who which is a Yogurt Company which is making yogurt who realize that they could use this as a way to protect their yoga cultures and it was kind of really the first like <hes> you know I would zeh industrial application of this <hes> and then and then came out <hes> the papers from Jennifer Dow does lab and also Funk Zang Slab at the road institute and they were really the first one <unk> to show. Hey wait a minute like you've got modest system here where you're actually directing a nucleus to go to a specific address on genome and make change and that's what nature does in like hey you can actually one of those. Oh Shit moments right. It's like you actually use this to <unk> as a very powerful tool in the laboratory if you could if you can take the kind of barebones part of that system and you could get it to work in in a lab you could essentially manipulate any piece of D._N._A.. You wanted to like in a specific manner and and so those were definitely I imagine at some point. WE'RE GONNA see Nobel Prize for Crisper just because they really was like one of those like lightbulb moments <hes> that several groups had <hes> really really really was like Oh shit like this is we could use this techno this biology to to do this. Yeah sorta like P._R.. Right so for sure. It's like such an interesting thing that it's a fundamental process that then has been harnessed in an effort to basically develop a technique that's foundational to almost everything in this fields now and it bypasses so much headache for so many people to be able to do this cheaply easily and probably it's much easier to train people to do it as well right like you don't need nearly as much <hes> fundamental education to be able to <hes> to like overcome potential mistakes so potentially although I will always be an advocate for people to have the right kind of training to use this type of technology and the right on this for sure but you don't need a p._H._d.. To be able to work in a crisper crisper lab do you know I'd say you don't but I'd say the same is true of anything like sequencing A._p._R.. Any of these other technologies reviews <unk> routinely <hes> people in the in the profession who just maybe have a bachelor's degree or doing this kind of work as well. That's true I guess lab. Engineers are generally not <hes> lab technicians. I apologize are generally <hes> either still in school or they have yeah that that that basic degree that than they are able to you're right. It's all about doing it over and over and over and having a lot of training meaning in the area to that kind of expertise yes. I'd say one of the things you mentioned earlier in the interview was that <hes> you know this is something that has kind of made it almost a level playing field where a lot of people can use technology and that's actually really an a really important point is what are the great things about this technology. Most labs already have most of the equipment they need to do crisper experiments in their lab so anyway so it doesn't require a new piece of capital equipment or large investment to start doing crisper in your lap so yeah that's or I start up so that is actually really important point but you know you hear these. This is the part where we're going to start like crushing headlines and things like that but you hear these kind of fear mongering stories to about the fact that now that this is such a democratize democratize technology and you're right it does require training and it does require a lot of reading and understanding how to utilize it appropriately but you do often hear that once these kinds of things are democratized once they become cheaper easier faster faster than somebody in their basement will be able to utilize crisper technology and do all manner of a horrible things and I think that's really where the education is so important both from journalistic perspective <hes> but but also from an academic perspective sort of understand the <hes> the realities and also the fearmongering that it is true that people have access to technology technology that they may be didn't have access to before because they simply there's not a financial burden but you still have to be like a scientifically minded per and really understand this kind of stuff and have a important hypotheses you. I'd like you have to have a purpose to be able to do that like I don't think crisper by in and of itself is causative for any sort of like nefarious <hes> practices. I think you're right. <hes> the other thing thing. Is that like you mentioned you need to have a particular degree of training or to use this. I think people need to understand that crisper crystal technologies the tool that that we can use for many different applications nations we can use it for research we can use it for <hes> <hes> to develop therapies and you know it can also be used for further further purposes. I think this is true of many different technologies. <hes> whether we're talking about computers others right computers can be used like we're using now or they can be used to hack into. You know everyone's bank account so I think whenever there's a new technology that's that's SORTA transformative like this. I think there's always sort of like a segment of the population this or naturally questions. Do we want to adopt this knit. Nets okay. That's part of like human dialog. That's part of <hes> you know discourse and so <hes> you know I think what we have to be careful. Is that <hes> you know in order to a lot of people fear things when they don't really understand them right so this really comes down to <hes> not only the scientific community but also <hes> I would say mass media <hes> educating people the correct way about what this technology can and cannot do and you know so I think we've already seen a few like Hollywood films. You know where they I think they had this film rampage writing like base after the nineteen eighties arcade game where the giant animals moles and they're like US crisper to make these animals. That's not going to happen anytime and then starts to go back to like you know all. Let's thinks like Jurassic Park model like you know. There's a famous line in that film. Were I think if you didn't think about you know what you could do but like you would do with it or like what can happen right and I don't think I think in general like any scientists or like really thinking about like Oh. You know. Let's do something for the sake of doing it. On this purpose to research. There's always a purpose to developing like therapy for example <hes> and so. I don't think you know unless you got specific purposes to like you know. Try to do harm with technology than it's. It's really it's the responsibility of the of the people using it also developing its educate everybody about what accounts gotTa do absolutely and I think that that's where these <hes> these stories like the Chinese researcher and the quote Unquote Christopher for babies really captured people's imagination that this was a function and I think in many ways that answers all of the things that you just said this was a sort of kind of rogue researcher who was actually trying to solve a real problem problem and was actually trying to do quote unquote good with this and sort of didn't for several reasons that we could probably open up at that's not what this episode is about <hes> and fundamentally the real issue there is that he you decided to to move forward with research that was not probably I are be approved. There were no ethics boards that were weighing in on whether or not this was something that <hes> the scientific community was ready to support <hes> and <hes> basically basically he went rogue and that's really the problem is that science doesn't work that way and that's why there was an international outcry and backlash because every science experiment that's done at an institutional or industry level apple has to be approved. There are mechanisms in place to ensure that the ethical sort of guidelines and boundaries are respected and that's just something that didn't happen in this case which is why it was such big news. I think it wasn't just that I think is also the fact that I'm a a lot of scientists. We looked to what what experiments for done in we have realized like. Hey you know even though they didn't have the necessary. Approval actually was done as a very good experiments. <hes> what I mean by that is like this research tried to solve a particular problem like you know the he didn't even actually target probably the right location on the genome to have the expected outcome and when he realized that he didn't have the expected outcome he went ahead and did the implantation anyway so which is like he was aware of it. He was aware that he probably didn't manipulate the appropriate gene and also again. He didn't people yes so you know I I mean obviously you know I think this person is going to become ostracized for the scientific community and you know it's good to the consensus among the site of community like you know what the this particular exact experiment was was was unethical. I think in general though like you know some of the people committed said like hey we should have a moratorium on doing this on doing these types of things <hes> it really. I think it really depends on if like we have to think about like what the needs are you know where the technology is and I think most of the people calling for more tournaments or saying on we're talking about germline editing now it is the technology really is not ready for that. It's maybe not necessary because there are other ways that we can enact <hes> we we can be preventative when it comes to prevent diseases search like in this case <unk> research was trying to prevent H._i._v. infection or many different ways you can prevent h._i._v.. Infection Yeah wasn't even the standard of care like there's there's functional appropriate options available that don't require such kind you've dramatic approach but just to be clear on the point that you just made which is such an important one. <hes> germline editing is very different from editing somatic cells because germline cells are passed onto offspring and so that's a like it's one thing to alter somebody cells in their body that will affect their own lifespan and their own phenotype or disease state throughout their life. It's another thing to edit cells that then if they mate are going to continue to be passed down until that that breeding line <hes> is no more 'cause now all the sudden you're affecting the population genetics not just the individual genetics so that's like a totally different ethical conversation. Yes it's true so I think that's the first Christopher based therapeutics that we're seeing now the first human. Trials started in order to to try to treat <hes> sickle cell anemia which is a a genetic disorder this actually not that rare and affects millions of people on the planet and is quite debilitating dating and is actually caused by single DNA change to a single d._N._A.. Base and so there were there are groups that are working on a developing therapeutics for this as a human trial that crisper therapeutics vertex pharmaceuticals are doing in both Germany and the U._S.. For sickle cell anemia Beta fell cement which is related disease based on similar mutations in the similar gene in in the same gene and these are based on somatic cell editing so <hes> you know <hes> and if you going back to the film human nature one of the I would say in the main stars in the film is Matthew Portia who's A._M._d.. P._H._D.. Clinician Stanford University and he's developing it follows his patients and he's developing developing a treatment for sickle cell anemia similar to the <unk>. Some of these trials are happening and they'd like to start their trial soon but he makes a really valid point which is like hayward. We're doing somatic cell editing here where we're editing cells of <hes> patients who have debilitating genetic disorder and so <hes> to be able to improve their quality of life <hes> we're doing this <hes> this crisper gene engineering in some of their own cells in the lab than expanding expanding those corrected cells and then putting them back into the patient <hes> as a way to secure their disease and so you know the same will be true in the future of using this crisper technology to to battle cancer in in the case of what we call the Kartini therapies where we can actually direct immune system to destroy Cancer Celso <hes> from somatic cell editing point. I don't think there's any real controversy about using this technology to do genome engineering in somatic cells <hes> I think we go back to the germline engineering point. That's really where the controversy starts to come in. We have to admit though we do our journalism engineering all the time just we we've kind of have <hes> you know whether it's through exposure to environmental toxins or sort of <hes> selectively picking your your meeting partner or things like this <hes> those are all types of germline engineering if you will and I guess just add on there's a we we recently did a screening of the human nature film <hes> as well for all the employs <unk> and we had a few of the people who appeared in the film do like a panel not the end to one of them is a gentleman named by Hank Greeley who's <hes> <hes> a professor of Law Stanford University but kind of specializes in ethical and legal social issues and one of the things he said was really profound which was so I won't take credit for this is really profound. He said that hey we had a technology. Gee that was the had a lot of fear mongering associated with it about seventy five years ago was the nuclear bomb and we decided as as a population as a species that we were not going to use this technology in even though we proliferated created for some time we actually like de-escalated that and up until this point you know we've done some testing but we actually have utilized this technology again and so the same could be said of the crisper Kathleen Technology right like we use nuclear technology reggie to make a power plants for satellites in space or we use nuclear technology to for other reasons right for medicine but crisper Commu the same way. We don't have to use it for for to do germline editing of people we can use it for all these other applications that are really amazing and helpful. Yeah I mean they're so there's so much potential there so I guess that that that's an open place to start to transition a little a bit into some of the things that you're doing at Cynthia. Go like what that you can probably tell because I'm sure there's like N._D._A.. kind of stuff going on there too. But what kinds of approaches are you guys taking. What kinds of problems are you trying to solve so I think one of the things that company did was actually to build a platform for actually synthesizing <hes> the the the molecules that people used to do crisper and this has been good because you know it so it turns out the Arnaiz the way you program this nucleus you can make these vomiting in the lab but the vary from from who makes them in the face of the moon things like this and if you could make these kind of a standard is way using chemical process and Jennifer Dalton's group showed that you could make hybrid version of these are molecules the slightly longer different what nature does where it connects to pieces if you could make a single piece an synthesize as a chemical? It's really the most effective way to to to do crisper engineering so we the company built a platform for making those molecules really took a lot of innovations in how we do that chemistry and because the the company has it engineering background there was a lot of engineering and software her applied to how we can actually operate machines that do this at large scale and so this was a really fundamental because it really opened up allowed a researchers to access on this new material that was really the most efficient and almost standardized doing crisper up so that was really important and then you know beyond that the company sort of layered that out into different levels of abstractions because you know built a factory that could generate these molecules that could allow enable people people to do to do a lot of crisper. <hes> we started do a lot of crisp ourselves. We started thinking about how we could automates a lot of these workflows <hes> and then we thought hey we can actually use to kind of build another factory that could <hes> generate <hes> AH mutations in cells that people used to studied disease and so forth so what we call cell lines these immortalize cells that grow in a dish. How can you engineer these at scale using this kind of a standard is opposed? You're starting with a standardized region and maybe maybe you can layer some automation some almost like machine learning to understand the best way to to engineer a cells sellings at scale so you can kind of build a more standardized a group of cells if you yeah well the people will use to study to to do their disease research for example and so that will that was kind of the next abstraction of the company and then from there you start thinking about the things and you know I think the company will do other things as well like you know. How can you actually use this to build pipelines for discovery or how can use to do functional genomics screening? If you think as a company right now you sell some of the region to do crisper than you can actually do the crisper for them more efficiently than they they can do you can essentially essentially you have all the methods figured out have to waste time developing their methods <hes> you've kind of that you've kind of standardized that and they can spend more time in their experiments than than their actual <hes> met method veldman and then if if you do that maybe the next obstructions also also you can actually just give them a piece of data they can say hey a WanNa perturb this <hes> I want to generate this mutation in in the cell line and then I wanna run this essay and understand what it means. It's a really I think kind of the future of synthetic biology in biology is actually going to be that where <hes> people whether it's large Pharma or research labs electorally what they what they really need data and so where they where they get that data from isn't necessarily incredibly important <hes> a lot of scientists they wanna do things their own way with their own and that's fine but I think if we can help to build standardization through platforms like this. It's really beneficial to the research community. Oh absolutely so I mean what I'm gathering from. What you're saying is that at Simcoe as opposed to answering these like <hes> more narrowly focused and more I guess <hes> translational research questions you're really focusing on providing scaffolding so that to empower scientists all over the world to be able to do that like this is much more of a foundational approach approach to being able to solve some of these problems <hes> because there's just so many potential utilizations of this technology so a you're making it easier for people to use this technology and be in the future? It may be that the actual methodology legiti portion of the research is just farmed out to to organizations that do this all day every day and they do really really well. That's that's kind of the direction as a company that we're headed and and I think the other thing is great his two we also do a lot of education like seeking check on our website if you want to <hes> I don't WanNa give another plug but if you check out simply go dot com you can learn a lot about Christopher so we do. We tried to be very interactive with the community we do a lot of interviews with people's while all we also do our own podcast and you know so we're we're also trying to educate the scientific community and people who want to start using this technology kind of what like Best Practices Beth met best method so they can really you know <hes> get to the results. It's much faster and officially very cool so I mean I'm definitely interested to know from you. Like what are the next steps like where for you personally but also four kind of your role in the company like what is the future look like for you. This always difficult to say what do you see self in ten years always say sitting on a beach doing nothing accomplished. Everything is really good question. <hes> and I think for me at least I'm definitely excited to see this company grow and develop into like a like a platform technology that can be utilized for many different applications me I see the company myself maybe growing into space where we're interested in many different aspects of utilizing technology whether it's for doing a development of sells for people or or working king with other researchers collisions to develop this material that can actually I in a grade that can be used therapeutically in in a clinical trial to me. That's really exciting because it kind of off issue that inflation every scientist wants is that hey I'm doing something this helping you know humanity and you know not only that that also how can we you know how can we actually translate what we developed at this company into something that could actually help humans from a therapeutic take standpoint. I think <hes> seeing this company grow from whereas it's relatively new company. We've been in the public for about three years. It's been really exciting process A. C.. <hes> company grow in this technology assist exploding everywhere right crisper has nine so it's really exciting to see what's GonNa Happen next. I definitely want to stay in this field. It moves very quickly. <hes> there are new discoveries. We made all the I'm and it's difficult to keep up but it really isn't exciting time to be a scientist <hes> particularly in this field so it's it's where I wanna stay right now. Absolutely will I would love to then sort of as we as we round the interview and and get ready to to to say our goodbyes I would love to close by asking you the same two questions that I ask all of my guests on the show <hes> especially because I think that they <hes> well. I'm just interested to see if they're connected to your work in this field or if they're completely separate I think both of those things would be fascinating to me. They're kind of big picture. Future oriented questions. Are you ready for them. Sure all right so when you think about the future in whatever context is relevant to you right now so it could be you know your own your own life your own work. It could be your the company it could be something much more global and connected. I WanNa know a what is the thing that actually keeps you up at night that you're sort of maybe pessimistic about maybe even a little cynical about like what are you truly deeply concerned about when it comes to the future and on the flip side of that <hes> you know what are you you have genuine actual optimism for what are you actually looking forward to okay. I'm GonNa try to answer this unlike the lease political way possible totally fine. I mean it's up to you WanNa do that but like ah no no barriers here okay so I think what keeps me up a night. Sometimes is <hes> an this in a way does relate to the field that I work in technology in general. I think what keeps me up a night. A A little bit is what concerns me deeply is that <hes> is that sometimes I get the impression that education is about among our species and what I me by this is <hes> I always sort of like I grew up watching star trek the original one and also you know the next generation all these all these star trek things I loved album but kind of this vision of vision of the future where humanity humanity at least as learned to to work together and <hes> I think we can all see this like individually when we work at a company I work at a company and we can see that like when people come together as companies we can do amazing things right and you know I think about all the things have happened in two hundred years industrial revolution getting people to work together and you know hopefully we don't exploit people on the way but like doing all these things getting people to work together use their brains together is we can do a credible the things we can manipulate our world <hes> and now we can also manipulate genus and so I think what keeps me up a night. Is that <hes> you know there are large numbers of people still in this world that <hes> and even in our own culture <hes> whether it's western culture wherever you on that essentially they don't pay a lot of attention to things like this they tend to read headlines and they don't really want to deeply understand how things work and part of this is because they haven't developed critical thinking skills and so I think he's me up at night is that there is still a lot of ignorance in our world especially particularly when it comes to science and this leads to things like fear mongering and this leads to people passing bills to like inhibit research or cut funding or things like this and then I think sometimes you kinda see like this sort of rise of like of of ignorance from particular segments in the population and then it kinda quells down again on the seems like a rise again. I think though my optimism is that it's slowly getting better all the time and what I mean by that is <hes> sometimes progress. Chris can be slow but I do think eventually humans will learn to stop like doing harm to each other and humans will stop start to think about ways that we can all be nice to each other and that we can be much more productive as the species and because there's some significant challenges coming right as significant challenges in what's going to happen to our climate. There's significant challenges in terms of like what's going to happen with with food plastics in the ocean like all of these things and it's really GonNa take a group effort and everyone needs to be on the same page and a neighbor for not and you still got people who are questioning. Why are we doing this? You know it really really takes away from <hes> from ability to solve this problem and to be more successful as a as a species so but I do think there is sewn overarching trend towards getting better and <hes> I think for every time we see some like large acre occur there are other groups of people that come forth and Ed try to educate and I think slowly it's sort of leaks in an and opinions change and <hes> people's mindsets change you know now I think Burger King just announced they are using the impossible burger right in the wolpert sandwich and honestly like ten years ago people would just be absolutely disgusting grossed out. I don't want to eat a burger. That's not made from Macau and now we're talking about like hamburger that tastes like hamburger and comes from a renewable source and and that's that's amazing so people's attitudes have changed and <hes> you know that could do a lot to solve a lot of problems. I'm hopeful that you know attitudes change and that the people people will become more educated mostly. I won't have to be a scientist. Everyone has to understand science but I think they need to. have it appreciation for it. Yeah I think a basic level of literacy is important in an effort to be like a participating kind of citizen and you're right like for every outcropping that we see of like antitax hysteria and individuals of you know having these small not as small as we'd lake but semi contained measles outbreaks and things like that <hes> we always do have to remember that there are massive organizations like the Centers for Disease Control and like these pharmaceutical companies and like these academic and institutional organizations that are actively developing thing new vaccines for Ebola and for a lot of infectious diseases like we we sometimes get. I think a little bit <hes> depressed because we see that individuals who may be aren't in the positions of <hes> don't have the basic education and our behold into some rhetoric making bad decisions and we think that colors the entire world but it's true that while that exists and there's always he's GonNa be this kind of anti science <hes> sacked segment that that is not actually in and of itself preventing scientific process and I think we have to remember that 'cause sometimes the best science is happening. Maybe a little bit behind the scenes and we're not as privy to the really cool stuff that that happens because it's so <hes> <hes> iterative that it doesn't make for a great headline <hes> and so we have to remember as individuals that there's so much important progress progress that's being made and those are very different. People the people making that progress people like yourself as opposed to somebody who's like just an out loud outspoken ANTIBAC- cer- you know those things can exist within the same global society and we can still make progress even when they're people who are desperately trying to to prevent it. I think Gosh I just went on a little tariff policy for that on my mind a lot lately you know so Kevin Kevin Gosh. This was a fascinating conversation. I have to be honest. I feel like we could do part you and apart three and apart for it because we could just dive deeper into all of these different topic well of course you. This is what careers are made of. There's no way to cover it all within an in our podcast but I do thank you for helping at least in terms of <hes> a fair amount of breath and in a bit of depth as well helping us understand crisper at a more basic level in sort of the the potential that.