Invention Playlist 4: Penicillin

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Today's episode is brought to you by IBM smart is open open is smart IBM's combining their industry expertise with open source leadership of Red Hat. Let's unlock the world's potential. Let's put smart to work. Learn more at IBM DOT com slash red hat. Guys it's bobby bones I host the bobby bones show and I'm pretty much always sleep because I wake up with three o'clock in the morning a couple of hours later I get all my friends together, and we get into a room and we do a radio show. Wish you're alive. We tell our stories. We try to find as much in the world. Possibly can, and we looked through the news of the day that you'll care about also your favorite country artists are always stopping by to hang out and share their lives and music, too, so wake up with a bunch of my friends on ninety eight point seven W. MC in Washington, DC, or wherever the rotates you on the iheartradio APP. Welcome to invention a production of iheartradio. Hey Welcome to invention. My name is Robert. Lamb and I'm Joe. McCormick and Robert I know you WanNa talk about dnd before we get to the real subject. Well I don't know I was thinking about doing it last. We can go ahead and talk about it up front. Yeah. We'll in dungeons and dragons. These various Demon Lords, and they they rule over various sort of portions of the of the fiend population in the game, and they're to demon lords in particular that I was thinking about in regards to today's episode, and that that would be. An jubilee. So Saag Moi is the. Demon Lord of Fungi. The Queen Fun Guy, the master of decay and then opposing her. Ever at odds with her is jubilee, the faceless Lord God uses slimes and blobs all the losing nasty creatures of Dungeons and dragons, and yeah there they oppose each other their constant war with each other and some. Campaigns like their forces, and even there there in embodied forms do battle with one another, and it actually ties in a bit with this subject. We're talking about today of penicillin. Okay, so penicillin, the fungus that fights! I don't know. Would you call diseases slimes? Well I feel like jubilee being the demon. Lord of Oozes, and slimes kind of makes it the demon, Lord of of microbiology, as well and you know my groves and microbial illnesses so okay well so today we're going to be talking about penicillin. Maybe one of the great real weapons of Tavoy. Yes, but this this came up I. Think because we'd been talking about fungus on or other podcasts on stuff to blow your mind where we just finished recording a five part series on psychedelics, yeah, yeah, looking at Fungal psychedelics and ongoing research into how these substances could enhance our mental. Mental wellbeing in helping the treatment of psychological issues and one of our big take home that these guys could help save lives and improve the quality of human life, but it would not be the first or only fungi to do so because we can certainly look to various interactions between human health, the different fungi species and their use in traditional medicine we can point to various products including products of fermentation for instance including alcohol but there's an even better example of better living through fungi in that's penicillin. Right so today we're going briefly explored the invention of penicillin, which is often cited as. The first true antibiotic technology of course antibiotics are medications that treat infections by killing injuring or slowing the growth of bacteria and the body. Antibiotics are a class of what you would generally call antimicrobial drugs medicines that kill microbes that present a threat to the body of course and antibiotics generally fight bacterial infections, whereas you could have others like Antifungal that Fungal infections or antivirals that fight viral infections now, antimicrobials antibiotics are gigantic subject area that we're. We're of course not going to be able to get into every nook and cranny of the subjects, but we hope we can have a an interesting introductory introductory discussion. Maybe come back to antibiotic sometime again in the future because it's it's a broad invention that has lots of little invention tributaries throughout history. Yeah, but it is such a fascinating case to look at it and I think should make for a great episode of invention here because. For starters it's it's a twentieth century invention. Slash discovery off, and of course, the line between ambition discovery is a little bit gray. But we we can pinpoint it to nineteen twenty eight, and ultimately like rolled out by nineteen forty or so but so we can, we can look to it. We can look at the world before we can look at the world after with with the sort of clarity that we always have with the certainly older or more ancient inventions, exactly because we always like to ask the question on the show what came before the invention what what changed when this invention came on the scene and what became before widespread modern antibiotics was stupendous amounts of death and misery from infectious disease in blood poisoning I I was wondering like. Is it even possible? To get stats on what the world of infectious disease looked like before we had antibiotics around the mid twentieth century. Yeah I mean to a certain extent, a lot of the suffering is just incalculable you know especially, if you go back and sort of consider all of human history up to that point in the various factors that that influenced infectious disease and injury, you know the the eventually the rise of germ theory, but. This things like that the rise of cities and so forth, but but luckily yes, since it was such a reason invention, we have some pretty incredible stats on the matter. Suddenly. Thanks to this new miracle drug diseases that it simply ravage. The global population like syphilis could be cured. The shadow of lethal infection no longer hung at least as heavily over every scrape, injury and war wound. And with wounds, where often talking about Sepsis, which is a term that was used by hippocrates back in the fourth century, BC meaning blood, rod or blood poisoning. And he was referring more in generally I think to decay, but the term came to be applied to blood poisoning, which arises when the body's response to infection causes. Injury to its own tissue and organs. But just prior to the twentieth century, infectious diseases accounted for high morbidity and mortality rates around the world, even in the industrialized world, according to w a Adedeji in the treasurer called antibiotics from two thousand sixteen, the average life expectancy at birth was forty seven years forty, six forty eight years for men and women respectively, and this was due to the dangers of smallpox cholera. Diptheria pneumonia typhoid fever plague Turkey Laos's typhus, syphilis and host of other ailments that could afflict you. endearingly antibiotic Era that follow again a rising in the middle of the twentieth century, the the leading cause of death in the United States change from communicable diseases to noncommunicable diseases like Carter, cardiovascular disease, cancer and stroke, and the average life expectancy at birth rose to seventy eight point eight years, so the elderly were no longer a mere four percent of the population, but grow to become a whopping thirteen percent of the population. So we're talking about you know profound changes. Demographics based on this new this new invention. Yeah, the changes huge. We live in a world now where if you have access to high quality, modern medicine and a lot of people don't. Mind, but if you have access to high quality, modern science based medicine, and you can get antibiotics and and can get to a hospital or see a doctor. You very likely have a good chance to beat most of the Common Infectious Diseases that people get unless you have some kind of you know like another condition that exacerbates it or something before antibiotics. This was just not the people just died from diseases that you catch like diseases that are common for people to catch all the time, yeah or certain. Certain diseases like syphilis that were virtually uncurable you know, and and some of the the cures that were attempted were were pretty horrendous. You know in and had an generally did not work. You know talking about using mercury and so forth and do you mentioned before contamination of wounds? I mean this is just a huge thing. Just like a you know you might you might cut yourself while gardening, and you die from it. Yeah, heaven, forbid you undergo, say Medieval Gallstone, surgery or something like that yeah? By the way, I think tuberculosis has a you. Know is a good example to look at for some of these stats as well according to the CDC. TB was a leading cause of death in the US in nineteen, forty, prior to the rollout of antibiotic therapy in Nineteen, hundred, one, hundred, ninety, four of every hundred thousand us. Residents died from deep TB. Most residents of urban areas in nineteen hundred, the three leading causes of death in the US were pneumonia, tuberculosis and diarrhea, and interrupt us, which together with Diptheria caused one third of all deaths, and of these deaths, forty percent were among children aged less than five years old. Now to your point in not everybody has. Access to antibiotics that say and people enjoy in say Europe and the United States. Yet TB remains a the leading cause of death from an infectious disease in many parts of the world, particularly the developing world and some antibiotic treatments or antibiotic assisted treatments are more complicated and more difficult than others I mean I know the treatment for TB is not as say easy is around of just orally administered antibiotics that you might get for a standard bacterial infection right, but it suddenly was just a heralded rightfully so is is a miracle invention. When it came about you, I saw an image of a of a sign on a garbage. Can or mailbox from the Mid Twentieth Century Advertising that now you can get gonorrhea cured in in like four hours. Thanks to the you know these new developments in antibiotics you know. It can be difficult to put ourselves in that mindset, having grown up in the wake of antibiotics, or at least most of most people listening to this show I was just thinking about how many like us. Presidents died of infections of various kinds. That seems like that would be a very unusual thing to happen now, but like in the eighteen hundreds James Garfield got shot, but it wasn't the initial gunshot that killed him. He lived for like think weeks afterwards he got an infection in the wound. I think because they were digging around with dirty hands to try to get the bullet out of him, and he and they didn't have antibiotics of course when he got an infection, so he died. I think another. A US was William. Henry Harrison who I think. They think Dow died from probably like drinking, fecal contaminated water, and the White House yes, so many different injuries and infections were. Far More likely to be lethal with you know without modern antibiotics to step in and and aid in the fight. Now there were some things that were kind of like versions of antibiotics or antimicrobials from before the discovery of Penicillin in nineteen twenty eight, yeah, the best example from the period, just immediate immediately prior to penicillin would be the Safa'a, miser or the soulful drugs, and these were the first antibacterial used systematically, and they were synthesized in nineteen. Nineteen thirty two in the German laboratories of Bear AG. Now you might be thinking about the time line like wait a minute. Didn't we just say that penicillin was discovered in twenty eight, but it took a long time after the discovery of penicillins antibacterial properties for it to be made as a useful medical dry like it was one thousand, nine, hundred forty. Generally, that's the date you see for. When penicillin actually became a yeah, an actionable thing in Madison. So, yeah, before that we had the SOFA drugs and it they had a rocky start, but they did prove very effective in preventing wound infections during the second world, war they were used on both sides in the in the form of soulful pills and also sotho powders that would be sprinkled over wound so if you've ever watched A. some sort of a period piece, especially a war piece of the twentieth century, and you see somebody, sprinkling powder mover injury. That is what that's supposed to be soft drugs are they're not as effective as true antibiotics like penicillin. And there are a number of possible side effects that. Can take place, and it also can't be used to treat syphilis an and it also can't treat SOFA resistant infections now, of course, this is also a twentieth century invention so I was wondering. Did anybody come up with any version of antibiotics or Proto antibiotics? Before the Twentieth Century? We know that penicillin hadn't been discovered and isolated and made stable as a useful medicine, but were there any things like antibiotics are sort of precursors. Precursors of antibiotic, because in game of thrones right, they have penicillin. Don't they? Or they have some sort of fantasy penicillin I've never heard of that, don't they? Have something the the the the the masters would mention having to do with with Brad in mold or something, didn't they? I? Don't remember that I just remember people get cuts, and then they get infected indic-. Give him milk of the poppy I mean they have milk the poppy maybe. Our game of thrones our our our George. Martin readers left to right in on that, but I vaguely remember there being like allusion to something like some sort of mole based. Medicine that they were using. Let could be wrong. Well. I can't see that being something that's thrown in there as a little aside, but like isn't widely recognized for us. And it's interesting how that kind of parallels. Some interesting pieces of evidence for Proto Antibiotic Technology in the real world, even going back to ancient times so I won't look at the work of the emory university bio archaeologists George. Jr Mela goes. Who is now deceased I think he died in twenty fourteen but he's interest eight interesting scholar, and he discovered something very curious back in nineteen eighty, so the subject he was looking at was a set of human bones from ancient Nubia dating. Dating from between three fifty and five fifty C E, and so the the bones came from Nubia, which is a region of Africa along the Nile, river, but south of Egypt in what would be modern day Sudan, and what these bones showed was evidence that the people they belong to had been taking tetracycline now. Tetracyclene is not the same as penicillin, but it is an antibiotic. It can be used to treat all kinds of infections for minor problems like acne concert with some other drugs. Drugs two major diseases like play or to leukemia, or even syphilis and tetracycline works primarily binding to the Ribe, assumes of bacterial cells, ribes, zones or sort of the cellular factories they build proteins that are needed in order for organisms to live and grow, and by binding to the Ri-. Zome tetracycline makes it difficult for the bacterium to create new proteins. It was patented in the nineteen fifties and became widely used in the second half of the Twentieth Century So, what was it? It doing in the bones of Nubian. People who live like seventeen hundred years ago, well Arm Lago sin colleagues followed archaeological clues to identify the source of the tetracycline, which was beer of course, beer is another one of Ultimately, it falls under zagged Moi's domain. Oh. Yeah, though this is different. Because tetracycline is not made from a fungus, it is actually an antibacterial. That is a byproduct of some bacteria. Oh, okay, so it's bacterial byproduct, but essentially okay, so technically it's duplex. Point to jubilee this jubilee versus Gibb Lakes Right. I mean that's going to happen with your demon. Lord I introduced lean warfare so beer is made from fermented grain of course and the fermented grain in this ancient. Beer apparently contained the bacteria streptomycetes, which creates Tetra cycling as a byproduct, but a question of course so like were these traces of tetracycline in Nubian mummy bones, a sign of like a bad batch of beer, got contaminated by accident, or were these people deliberately culturing their beer with antibiotic producing bacteria, and so to look at a study from the American Journal of Physical Anthropology from twenty. Ten of which are Malaga's was one of the authors the authors examined tetracycline in skeletal remains from throughout this period, and the evidence indicates that the ancient Nubians were consuming these antibiotics on a regular basis in the authors suggest that these ancient people. People were intentionally producing this medicine and this links up with some evidence from other ancient peoples, nearby such as the Egyptians that sometimes apparently used beer as a treatment for conditions like gum, disease, and other types of infections in the author, even found evidence of a four year old child, whose skull contained lots of tetracycline from this beer, suggesting that the child had been fed high doses of this like antibiotic beer, perhaps in an attempt to cure an illness, maybe the illness that killed him, and so the levels of tetracycline residue found in the bones. These mummies is only explicable. If they were repeatedly consuming this antibiotic in their diet. And there are actually other archaeological remains that show evidence of antibiotic use in the ancient world for example samples taken from the Famara of skeletons from the Dock Leo ACIS in Egypt from people who live sometime in the late Roman period, also showed evidence of the same thing of tetracycline and the Diet and this consumption of tetracyclene is consistent with other evidence, showing a relatively rate of infectious disease in Sudanese Nubia during that time period. And a lack of bone infections apparent in these remains from the this acis in Egypt so. It really does look like people in ancient Africa discovered a somewhat effective form of antibiotics centuries before the discovery of penicillin and the isolation and mass production of focused anti-microbial medicines now to be clear. I think like a beer that had tetracycline content from from being cultured with bacteria, like this probably would not be as potent and focused and effective as like the isolated compounds in the drugs you take orally or through injection would be today right, but it would have some effect and. And it appeared that it probably was somewhat effective in fighting infectious disease right, and of course they wouldn't know exactly what they had here, but they knew they had some sort of beer that seemed to some sort of holy liquid that that that had some sort of curative property to it exactly fascinating discovery from the ancient world, another interesting fact tetracyclene is relatively unique in that it leaves clear signatures in the bones that can be discovered long after the person has died so. Don't leave these clear markers like this that make it easy for archaeologists to detect, so you have to wonder like, are they? Were there other cases of ancient peoples in various places in times using some kind of antibiotics or bacterial or fungal cultures to treat diseases like these ancient Nubian people were but that we don't have evidence of because it doesn't show up in the bones. tetracycline does yeah, you could have just been lost to history. I was reading an interesting paper from frontiers in microbiology in two thousand, ten by a Rostom on Minova called a brief history of the antibiotic Era Lessons Learned and challenges for the future, and Aminov points out this unique quality of tetracycline. tetracycline and notes just what I was basically just saying like how easy it would be for evidence of other uses of antibiotics in the ancient world to be lost to us, though he he also mentioned that there are other anecdotes from history about like cultural traditions that show Proto antibiotic technologies in these other examples would include red soils found in Jordan that are used for treating skin infections. It's been discovered that these soils contain some antibiotic producing organisms. I'd guess they're probably also some major risks in applying soil to wounds, and then also plants used in traditional Chinese medicine that actually do have some antimicrobial properties. Yeah, because one thing we have to remember is like the Modern Anti. Effort is ultimately based in going out into the natural world in finding these weapons that already exist. Yeah, and then reusing them in adapting them of for Human Madison and you know this is essentially what is going on in traditional medicines as well, and it also means that are weapons out there that either have not been discovered all especially in particularly vibrant ecosystem, some of which of course of are threatened all the more reason to. US to not decimate say the rain forests or the deep ocean right? But then there are also things that may have been discovered to some degree in the past, but have been forgotten will yeah that that does seem possible, because despite all evidence of ancient sort of Proto antibiotic technologies, the worldwide rates of death from infectious disease in the periods, for which we have data right before the invention of modern antibiotics shows that humans generally did not have effective antimicrobials in that period, so maybe some of this knowledge was lost over time all right well on that note, we're GonNa take our first break, but when we come back, we're going to return to the mold research, the nineteenth century, and ultimately to our key inventor here Alexander Fleming. This episode is brought to you by IBM Today. The world looks pretty different, but already new problems are being met with new thinking. Researchers are using supercomputers to discover treatments faster retailers are turning to the cloud restock shelves more quickly. Teachers are working with ai to rethink the classroom. It's not everything, but it's a start. Let's put smart to work. See how IBM is helping IBM dot com slash cove nineteen this. This. Episode is brought to you by IBM Today the world looks pretty different, but already new problems are being met with new thinking. Researchers are using supercomputers to discover treatments faster. Retailers are turning to the cloud to restock shelves more quickly. Teachers are working with ai to rethink the classroom. It's not everything, but it's a start. Let's put smart to work. See how IBM is helping IBM, dot. com slash cove nineteen. We're back now. We'll get to Alexander Fleming in a minute with the discovery of penicillin, but Alexander. Fleming was not the first person to notice that there might be some anti microbial properties of certain fungi. That's right. There was there was work going on in this area of prior to Fleming Fleming was was You know picking up on some of it, and and really just overall. Just our understanding of a fungi in general was was advancing as we mentioned era, psychedelics episodes There was a time where we did not recognize fun guy as being separate from the realm of plants right before we realized that it was a kingdom, unto itself in the Kingdom that has a little more in common with the Animal Kingdom than it does with the plant kingdom. And little a lot of talented folks working in this area, but one of them. Might come as a prize to a lot of people and that's because her name was beatrix potter. The bunny rabbit, a bunny rabbits. Yes, okay off the Bunny Rabbit fame. It was kind of a curious coincidence, because I was reading about all this, and then just randomly on the stuff to blow your mind discussion module, which is the facebook group for people listening to the show to discuss episode, someone brought up the trix potter in regards to something to do with squirrels because there's a lot of squirrel. Squirrel content in the discussion module, and yeah, they brought a Beatrix Potter and Beatrix. Potter actually ties in to this episode a little bit, because in addition to being the author and illustrator of the you know the tale of Peter Rabbit and associated British animal tales. She was also a naturalist with a great deal of interest in astronomy, and most importantly of all my college. So she produced a lot of beautiful scientific watercolor. Illustrations of various fun guy in her neck of the British would. As part of her studies, and if you studied a lot of local molds as well and did illustrations of them. She's ultimately very interesting character. That was Unfortunately she lives in time in which the sexism of the day prevented her from reaching the heights of in the natural sciences that she would have been afforded later on, but in a lot of her work is also just being I think rediscovered and appreciated for the first time. you know in recent decades, but the yeah, the next. Next time someone busts out some the trix Potter A. Remember. This is not just a an individual who wrote some fanciful tales, and illustrated them like she was just she was out there, studying the natural world, and in Crete in in advancing our understanding of my college, she was sort of a looking into the hidden life of nature in multiple ways, yeah. I, see some sources that are asking the question. Okay was Beatrix Potter who she a true naturalist, a true natural scientists over she just to. An amateur, that was just very interested in these things, and it's kind of a couple of question. Ask when you consider the limitations. In the Victorian era for women but I think undoubtedly she she I would side with the fact that she was a natural scientist I, mean she? Or co-authored one paper. If I remember correctly so I'm I'm gonNA give her giver. Full credit was about fungi. It was a mushroom. In particular I, forget was one of those related to the Russillo Mushrooms, but I forget which species. But. Basically, she was you know she was kind of up against the the Patriarchy for the most part though. We'll. Is it time to turn to penicillin itself yes? Let's turn to this. The key discovery here and our inventor are discover Alexander Fleming. Okay So, who was Alexander Fleming? Fleming was born in eighteen, eighty. One died in nineteen, fifty five, and he was a Scottish biologist physician, microbiologist and pharmacologist. He was the son of a farmer, and he observed and studied a great deal of death from Sepsis in World War One. He observed that while antiseptics worked well at the surface, a deeper wounds, a sheltered bacteria from the effects of things like sulfur drugs right so if you have the kind of superficial wound, you could clean it off pretty good, and that might help protect you from from bacterial infection, but if you have a deep wound and say like dirty stuff, bits of soil and other you know just crud gets lodged deep in there. You might not be able to clean the wound out very well right and that's exactly the kind of stuff that's going to get lodged in there especially with your war wounds where there is a. Stab or or a deep cut or a bullet entering the body. We'll makes me think about The when we were reading about the idea of Stegosaurus, perhaps weapon I. I mean not consciously, but stegosaurus perhaps Having an adaptation to weaponize infection against its enemies by dragging its Dagga miser spikes through the Dung right exactly yeah, having dirty Bagga miser spikes, and then when it wax the T. rex in the crotch with the that gets infected later, and eliminates a Predator from the area and the the the the predators of the day would not have had access to antibiotics, certainly not or even that beer from the. We mentioned earlier so. Flip Fleming was devoted himself to research he Prior to penicillin. He discovered a lifetime naturally occurring enzyme and mucus in other parts of the body than inhibits bacteria, so he was already. You know in this area looking for for new new breakthroughs new discoveries. But then his biggest breakthrough, all is this discovery of penicillin, and it's truly one of the more amazing invention slash discovery moments from history, because while he was exactly the right person to make the discovery, and then deserves all the credit he was given. The key moment comes down really too pure luck, and we simply don't know if anyone else would have made the discovery if he had not been there to observe it, okay, so what happened with this discovery so around nineteen twenty seven, or so he had engaged himself in studying STAPHYLOCOCCI or Or staff, and he had stacks of Petri. DISHES DISH SPECIMENS IN HIS LAB, which I've seen described as being kind of an untidy lab, so imagine all these likes Petri dishes, full staff all over the place notes, and so forth, and so the key moment comes in September of one, thousand, nine, hundred, twenty eight right right, so he has these staff petri dishes out, and then he leaves them for the weekend. Go on holiday with his family any when he comes back, he expects you just see how they've progressed. See how they've grown. But he finds that they haven't grown. In fact, they have died. Something has ravaged his specimens. Yeah, now it's this is one of those stories where it gets very narrative is so you do have to wonder if some details of it or embellish to and how the story may have changed over time, but this is the way the story has been passed down and and I think it seems to be largely basically true the way that I've seen. The story often told us that. He comes in. There's a blob of mold growing in one of the plates and all around the mold. There's this halo of nothingness where you normally what you would see is that if you got a plate for culturing bacteria, there would be these little dots and blobs on the on the plate. But instead there's this halo where there's no bacteria bacterial deadzone zone now, of course we know staphylococcus is is a bacterium group linked to all kinds of human disease and misery. staph infections right if this mold could kill staff that seems medically relevant. So what happened here well? He He. He realized that he was dealing with some sort of a fungi. So he luckily, there was an ecologist with a lab just below. Fleming on the floor below his lab. Man by the name of CJ La Touche and in fact it's also been suspected that the mold and question that killed. Fleming's staff might have drifted up from a Lotta Shays lab, adding an extra element of weird chance to this whole situation. Okay, so perhaps his samples were contaminated by stuff from the lab next door down a floor, right? That's one that's not. That's not a theory that's presented in every source does pop up fairly frequently so specifically. This mold was what would later be identified as a strain of penicillin, no Tottenham and it was obvious that it's secreted something that prevented staph bacteria from growing and so fleming followed up in studying the secretion. This mold juice says I've seen it called. He he found that it didn't only prevent the growth of staphylococcus. It worked against common bacteria like streptococcus or Meningococcus, and and the back also against the bacterium that causes diptheria interestingly while Fleming did see applications for penicillin and curing disease. He mentioned them briefly in the paper he published in Nineteen, twenty nine about this discovery about a the the antibacterial properties of Penicillin he primarily thought of this secretion of penicillin as a tool for bacteriologist to sort strains of bacteria, independent, sensitive versus non penicillin, sensitive species, and the that that could be useful in the lab. Yeah, so he sometimes criticised is is really not understanding completely what he had here not. Not Having the vision to see where it could go well. I don't think he completely understood, but he did indicate that this could possibly have uses in medicine right so fleming and his assistance, Stewart, crowder and Frederick. Ridley tried for years to turn this accidental discovery into a stable isolated compound that would be useful and this. This was a problem because like you've got this secretion from the mold molds making some juice. It's getting stuff wet with this this stuff that that that fights bacterial growth, but they couldn't isolate the compound that was causing the effect and stabilize it and make it make it generally useful so to quote from. Paper that I mentioned earlier quote for twelve years after his initial observation Alexander Fleming was trying to get chemists interested in resolving persisting problems with the purification and stability of the active substance and supplied the penicillin strain to anyone requesting it, but he really he could never cracked the nut ultimately, and he didn't finally make this discovery of the process for for stabilizing and isolating the compound, and by Nineteen Forty Aminov writes that Fleming finally abandoned quest, but fortunately it was right about that time that they capable team at purdue university, including the researchers Howard. Howard, Florey and Ernst, chain or Chine. They picked up on this research and they. They kicked off the research project that would eventually breakthrough on this and there are all these interesting story so of course this while World War. Two is going on right so research conditions are not ideal and They're all these stories about how they turn to their lab at Oxford into this giant incubation center, or sort of factory for mold like employed all these lab assistants who were these women who had been referred to in some sources as the penicillin girls. And they would work to T-. They would work to grow the penicillin in buckets and tubs, and basically every container that they could And eventually they did. They were able to isolate and stabilize this compound so to quote from an Article from the American Chemical Society. In nineteen forty fluorine that'd be Howard Florey carried out vital experiments, showing that penicillin could protect mice against infection from deadly. STREPTOCOCCI, then, on February, twelfth, Nineteen, forty, one, a forty three year old policeman Albert. Alexander became the first recipient of the Oxford Penicillin. He'd scratched the side of his mouth while pruning roses, and developed a life, threatening infection with huge abscesses, affecting his eyes face in lungs, penicillin was injected, and within days he made a remarkable recovery well, but unfortunately, despite this recovery which lasted for a few days, they ran out of the drug and. and Alexander eventually got worse again, and he died, and I was reading that they were so desperate to cure him that after Alexander urinated while on his antibiotic course, they would collect the urine and try to extract the penicillin. He excreted again so that they could be re administered to him. and I should mention also that the the process that the Oxford team relied on to extract purify the penicillin and the mold juice was led by another important biochemist guy named Norman Heatley, but this case of Albert Alexander shows an obvious early problem they. which was the problem of scale? They simply lacked the ability to make penicillin at the scale. It that would be needed to treat even one person let alone. The whole world the strain of mold that they were using didn't make enough of it, and this led to the search for other species of the same fungal genus penicillin, which would maybe they thought produced higher concentrations of the penicillin filtration, and I was reading an interesting article. Article by the University of Michigan Physician and Medical Historian Howard Markel that tells a really interesting story I'd never heard about this so the story goes like this. Apparently, one of the assistants at the Oxford lab showed up for work one day in nineteen, forty, one with a cantaloupe that she bought at the market, because it was covered in a weird looking golden mold, which is great because this would be the one case where somebody. Somebody is picking over the fresh produce produce to like find the moldy one but the mold on this cantaloupe turned out to be a strain of penicillin called concilium Chris, ogsm which Markle says naturally produced at least about two hundred times as much penicillin as the original strain that they've been studying and then later, markel writes the same strain was subjected to mutagenic processes in the lab, so like bombarding with x rays and stuff to. To produce a mutated strain that would make up two thousand times as much penicillin as the old school fleming mold so by nineteen forty one penicillin is on its way to becoming viable medicine all right on that note we're GonNa. Take a quick break when we come back. We're going to look at the impact of penicillin and we're GONNA. Look at it, you know and I think a fun way by considering really interesting. What if? 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What was possible like clearly there were there were other individuals in the world working on this someone would have cracked if Rontgen had not discovered rays in eighteen ninety whatever year it was, somebody else would have discovered them pretty soon right, but when it comes to penicillin potentially, it's a little more complicated than that. I I ran across a cool article on the topic titled What Filming had not discovered penicillin, and this was a published in the Saudi Journal of biological sciences by all Harvey at all. The authors admit that that certainly if Fleming had made the discovery, someone else might have in the years to follow. Probably you know in the early nineteen forties. They estimate so we could still well have have arrived in antibacterial age. However, they also explore the possibility that we might have simply not made the discovery at all, and it's an interesting argument, so I wonder I. WanNa read a quote from the paper here. Quote of course penicillin could have been discovered. The day after Fleming missed the opportunity, but in reality there was no parallel discovery. The took place as a result anyone taking an interest in penicillin during the nineteen thirties did so in the knowledge of Fleming's work. In particular, the seems no reason to believe that Florey and chain would have discovered penicillin since their work depended on Fleming's famous paper and their access to one of. Of his penicillin, producing cultures, so that's referring to the thing I mentioned about how how a Fleming in his assistance were just like sharing the penicillin strain out with everybody like hey, can you figure out what's going on with this? Can you isolate secretion or the compound in the secretion? Yeah, so think about there was there was so far as these researchers can determine you know other effort out there that would have. In struck paydirt in the absence of Fleming's research, the Oxford. Group wouldn't have been looking for it. Someone Walks Walkman. The father of modern and Botox sometimes called as we made several key discoveries later was also inspired by Fleming so. He has one of these cases where like he seems to be the epicenter. Not only him, but just then the the the the seemingly chance encounter in his lab that day that that we're suddenly, this halo appears in the Petri dish, and that gives birth to a to a whole class of other discoveries right because not all antibiotics are derived from penicillin penicillin, class of antibiotics become sort of like one sort of grandfather class, but then there are all these other classes that are discovered during this golden age of antibiotics that takes place over the next few decades. Just additional medical breakthroughs that would not have occurred without penicillin such as organ transplant. But then there's also the question like what would've what would have happened in the the wider world because again, penicillin comes online during the Second World War, and so that you can easily ask what would have happened if allied troops had not benefited from access to antibiotics at D Day I've never thought about that in fact I. before looking at this episode, I probably would not have known the answer to whether or not. They had accessed antibiotics well. Penicillin production was actually swiftly scaled up just to make sure that allied soldiers had access to it at d day. So, there is a legitimate question to be asked. Might the allies not have won the Second World War without penicillin? Factors consider there I. Don't think it's quite a Gotcha question, but it's it's worth thinking about. The authors argue that without flemming's discovery would have had to depend on the SOFA drugs. An imperfect alternative to a true antibiotics and these. These were described in the nineteen thirties and Fleming worked with him prior to his discovery. But without penicillin in play, the authors argue that sulphur drugs might have become the standard and even push the discovery of true. Antibiotics well beyond the nineteen sixties, and this is also true of the Axis powers had risen in victorious in World War Two because the access powers depended on sulphur drugs and their their key treatment Point out. Quote, despite the fact that the Germans and their allies where at a considerable disadvantage the drugs did a relatively good job at reducing battle casualties, so not to just completely cast, aside the effectiveness of soft drugs, but still they were not as effective as true antibiotics. It's weird to think about the political implications of specific medical technologies. Yeah, and then when you get down to the curious cases of individuals. Yeah, it also gets. Gets interesting where he touched on presidents who died that would have lived potentially if there had been penicillin around right, and so they point out that that soft drugs saved Churchill's life in nineteen, forty three, when he was suffering from pneumonia as well as FDR's life a, but there's also evidence by the way that actual penicillin may have saved Hitler's life following the stuff Enberg assassination attempt of July twentieth nineteen forty, four. This was the plot that tried to kill Hitler with a briefcase bomb. Right like where the some of the officers conspired against him, and they put briefcase bomb in the room with him, and it did explode, but he was protected by a heavy table that prevented it from killing him. He was obviously injured I think he had like nerve damage after. So be the idea here is that perhaps his injuries were treated by by penicillin. Yeah, that's it. At least an argument has been made that they had access to penicillin. I'm unclear on how they would have obtained it. You know through. Maybe there's a spy story. There I don't know. But the the idea being well, if he had if he had didn't have access to penicillin, then perhaps he would have died, and that arguably ended the war in a different manner forcing us to re. An entirely different postwar world. So again we're playing with with what ifs here and also we my understanding is. We don't know for sure that Hitler had access to penicillin following that assassination attempt, but there is the overall scenario of the allies having penicillin and having this ramped up penicillin production leading today. Yeah, that is really interesting. I. I'd never contemplated that before. now something that we do often have to think about, and we should probably acknowledge at the end here before we move on. Maybe this'll be something to come back in. Doing the future with A. New Invention episode is the idea of a possible end of the antibiotics I mean this is kind of scary thing to imagine like what if the antibiotics age is essentially a period in history that has a beginning in an end. Because as we you've. You've probably heard about this. Many disease, causing bacteria and other disease, causing microbes are overtime evolving antibiotic resistance are evolving to to be powerful enough to survive are antimicrobial drugs and I think specifically one thing that's exacerbating. This is overuse of antibiotics and people, not taking the entire course of antibiotics when they're given them. Yeah, because again to come back to the Zagged Moya Jubilee. War Scenario you know it is an ongoing battle, and the the forces evolve. To to better deal with the threats on each side and so. We're we're we're? We're seeing this occur. We're seeing the the overuse of antibiotics producing. Strains that are that are resistant, and it's reversing some of the therapeutic miracles of the last fifty years, and and underscores the importance of disease prevention in addition to treatment, and that means not not abandoning some of our other vital tools for human health like vaccination. We should come back and revisit vaccination. Maybe even various different vaccinations in the future. Yeah, another thing to keep in mind that. I don't think we mentioned earlier. was that the nine hundred forty nine hundred seventy s? Are are considered like the Golden, age of antibiotic, Research Yeah, and we haven't seen at least if you haven't seen any new classes of antibiotics emerged since that time period right now there have been new developments in antibiotics, but I think the way I've read. It is that they're generally modification. Houses of Antibiotics Sorta like we. We haven't. We haven't found anything radically new. Since then. Basically, we reached out into the natural war between. Between Fungi, and the microbial legions and we, we stole some of the tools. We stole some of that Promethean fire. We day we keep adapting that fire to our own purposes, but we haven't. We haven't found any new weapon from that world, and and then they're ongoing war continues. To Change. I'd be interested A. Do you out there? You the listener you work in medical research, or are you working on areas involved in antibiotic resistance, the future of anti-microbials I please get in touch with us. I would like to hear about that. What what are you doing in your work? And what does the future like to you on the inside? Absolutely we would We would love to hear from you again. We've only scratched the surface here. Though thanks to antibiotics, hopefully that scratch will not. Get the life threatening infection. There's a lot more history here, but but hopefully what we've done here. Today is of course, highlight just a very very cool story from the history of inventions and discoveries in human history, and outlined the impact of of one of the greatest inventions or discoveries again. However, you want to classify it from the twentieth century yeah totally. In the meantime. If you WANNA check out other episodes of invention, you can check out our homepage invention pod dot com, and that will have all the episode right there. If you want to support the show and we would appreciate it. If you did support the show, there are a few simple things you can do. Tell friends about it, you know. Tell Tell Your family members about invention and. And, then if you have the ability to do so rate and review US wherever you got this podcast huge thanks as always to are excellent audio producer Maya Coal. If you'd like to get in touch with us to let us know feedback on this episode or any other to suggest a topic for the future just to say hello, you can email us at contact at invention pod dot com. Invention is production iheartradio radio for more podcasts from iheartradio. The iheartradio APP apple podcasts wherever you listen to your favorite shows. Here's something. Good is a new show from the Seneca. Women podcast network and iheartradio each day. We aspire to bring the good news. The silver lining the glass half full because there is good happy the world everywhere every day. We just need to look for and share it. Here's something. Good is a short daily show. That offers positive stories, helpful suggestions and shared experiences to inform and inspire you every day. Listen to hear something good on the iheartradio, APP apple podcasts or wherever you listen to your favorite shows subscribe now. October sixteenth, Nineteen seventy-two to Congressman Vanish on small plane in Alaska. Despite a massive search. They're never found. The case goes cold. That is until I. Start Researching it. I'm standing right. Portage Pass and Alaska my name is John. Wall Zach and what I found is one of the strangest stories you've never heard. Did he indicate what was in the suitcase? He said it was a bomb. So join me as I travel from. To the Arctic Circle trying to crack this case. Listen to missing in Alaska on the iheartradio. APP Apple podcasts or wherever you find your favorite shows.

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