Invention Classic: Penicillin

I Heart Radio. Hey, Welcome to Invention. My name is Robert Lamb and I'm Joe McCormick. And Robert, I know you want to talk about D and D before we get to the real subject, right, Well, I don't know. I was thinking about doing it last. We can go ahead and talk about it up front. Um. Yeah, Well, in Dungeons and Dragons, uh, you of all these various demon lords and uh, they rule over various sort of portions of the of of the fiend population in the game.

And there are two demon lords in particular that I was thinking about in regards to today's episode. Uh, and that that would be zug Boy and jubile X. So Zugmy is the the demon Lord of fung Guy the Queen of fun Guy the Master of decay, and then opposing her Um Everett odds with her is jubile X, the Faceless Lord, which is a god of oozas and slimes and blobs, you know, all the the oozing, nasty creatures of dungeons and dragons, and yeah, theyre they oppose

each other. They're in constant war with each other, and in some campaigns like their forces and even there there, you know, embodied forms do battle with one another, and it actually ties in a bit with the 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 jubile X, being the demon Lord of oozes and slimes kind of makes it the demon lord of of microbiology as well, and you know, microves and

uh and microbial illnesses. So okay, well, so today we're going to be talking about penicillin. I guess maybe one of the great real weapons of zog Tamoi. But this this came up, I think because we've been talking about fungus on our 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 well being

and helping the treatment of the psychological issues. And one of our big take homes was that these fun Guy could help save lives and improve the quality of human life. But it would not be the first or only fun Guy to do so, because we can certainly look to various interactions between human hell, the different fungi species and their use, and your aditional medicine. We can point to various products including you know, products of fermentation, for instance,

including alcohol. But there's an even better example of better living through fungi and that's penicillin. Right, So today we're going to briefly explore the invention of penicillin, which is

often cited as the first true antibiotic technology. Of course, antibiotics or medications that treat infections by killing, injuring, or slowing the growth of bacteria in the body, and 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, an antibiotics generally fight bacterial infections, whereas you could have others like antifungals that fight fungal infections or

anti virals that fight viral infections. Now, antimicrobials and antibiotics are a gigantic subject area that we're of course not going to be able to get into every nook and cranny of the subject. But we hope we could have an interesting introductory Introduct three discussion. Maybe come back to antibiotics sometime again in the future, because it's a 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 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. Often, of course, the line between invision and discovery is a little bit gray, but we can, Yeah, we can pinpoint it and ultimately like rolled out by 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 it with the sort of clarity that we don't always have with certainly older or more ancient inventions. Exactly because we always like to ask the question on this show, what came before the invention? What what changed when this invention came on the scene. Uh, And what came before a widespread modern antibiotics was stupendous amounts of death and

misery from infectious disease in blood poisoning. I was wondering, like, is it even possible to 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. Um, you know, especially if you go back and sort of consider all of human history up to that point and the various factors that that influenced infectious disease and injury, you know, the eventually the rise of germ theory, but also the things like the rise of cities and so forth. But but luckily, yeah, since it was such a recent invention,

we have some pretty incredible stats on the matter. Um, you know, suddenly thinks to this NW miracle drug diseases that it simply ravaged 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 were often talking about sepsis, which is a term that was used by a hypocrite days back in the fourth century b c. Meaning blood rod or blood poisoning UH, and he was referring more 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 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. Adgy in the Treasure called Antibiotics from two thousand sixteen, the average life expectancy at birth was forty seven years, forty six and forty eight years from men and women, respectively, and this was due to the dangers of smallpox UH, cholera UH, diphtheria, pneumonia, typhoid fever, plague, tuberculosis, typhus, syphilis, and a host of

other ailments that could afflict you. And then during the antibiotic era that follow again, you know, arising in the middle of the twentieth century, the leading cause of death in the United States changed from communicable diseases to non communicable diseases like cardio cardiovascular disease, cancer, and stroke, and the average life expect 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 percent of the population. So you know, we're talking about, you know, profound changes, just two demographics based on this new uh, this new invention. Yeah, the change is huge. I mean, we live in a world now where if you have access to high quality modern medicine, and a lot of people don't, I mean that's mind.

But if you have access to high quality, modern science based medicine and you can get antibiotics and uh, and you 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 give unless you have some kind of you know, like another condition that exacerbates it or something. Before antibiotics, this was just not that people just died from diseases that you catch, like

diseases that are common for people to catch all the time. Yeah, or you had certain diseases like syphilis that were virtually uncurable, you know. And and some of the the cures that were attempted were pretty horrendous, you know, and and and had and and generally did not work, you know, talking about like using mercury and so forth. And you mentioned before contamination of wounds. I mean, this is just a huge thing. Just like you know, you might, uh, you

might cut yourself while gardening and you die from it. Yeah, And Heaven forbid you undergo say medieval gall stone 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 c d C, t B was a leading cause of death in the US in ninety prior to the rollout of antibiotic therapy in nineteen hundred, a hundred and ninety four of every hundred thousand US residents died

from the TB. Uh most were residents of urban areas. In nineteen hundred, the three leading causes of death in the US word pneumonia, tuberculosis, and diarrhea and h enteritis, which together with diphtheria caused one third of all deaths, and of these deaths, four percent were among children aged less than five years old. Now to your point, and not everybody has the access to antibiotics that say people enjoy and say Europe in the United States. Um. Yeah.

TB remains a 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 as the round of just orally administered antibiotics that you might get for a standard bacterial infection. Right but it's suddenly it was just heralded rightfully so as as a miracle

and engine when it came about. I saw an image of of a sign, I think a garbage can ra a mailbox from the mid twentieth century advertising that now you can get GONA recured in in uh like four hours thanks to the you know, these new developments in antibiotics. You know, it's just a it could be difficult to put ourselves in that mindset, having grown up in the wake of antihilotics, or at least most of us, most

people listening to this show. I was just thinking about how many like US presidents died of infections of various kinds UH that 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 gun shot that killed him. He lived for like I 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 U S pro it was at William Henry Harrison, who I think they think now died from probably like drinking fecal contaminated water in the White House. Yeah, so many different um UH injuries and infections were just far more likely to be lethal with you know, without modern antibiotics to

step in and UH and EID in the fight. Now, there were some things that were kind of like versions of antibiotics or anti microbials from before the discovery of

penicillin in ninety eight. Yeah, the best example from the period just immediate, immediately prior to penicillin would be the sulfonamides or the sulfa drugs, And these were the first antibacterials to be used systematically and they were synthesized in nineteen thirty two in the German laboratories of bear A G. Now you might be thinking about the timeline, 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 penicillin's uh antibacterial properties for it to be made as a useful medical drive, Like it was aking forty generally, that's the day you see for when penicillin actually became an actionable thing in medicine. Uh So, Yeah, before that, we had the sulfa drugs and it had 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 sulfa pills and also sulfa powders that would be sprinkled over a wound. So if you've ever watched you know, some sort of period piece, so especially a war piece from the twentieth century, and you see somebody sprinkling powder over an injury, that is what that's supposed

to be. Sulfa drugs. They're not as effective as true antibiotics like penicillin um and there are a number of possible side effects that one that can take place, and it also can't be used to treat syphilis, and it also can't treat sulfa 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

photo 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 thing's like antibiotics or sort of precursors of antibiotics. Well, because in Game of Thrones, right, they have penicillin, don't they, Or they have some sort of fantasy version of penicillin. I've never heard of that, don't they They have something that the the the the old Nasters would mention having to do with with bread

and mold or something. Didn't they I don't remember that. I just remember people get cuts and then they get infected and die, giving them milk of the poppy. I mean they have milk of the poppy. Okay, our Game of Thrones are are George R. Martin readers will have to write in on that. But I vaguely remember there being like allusion to something like uh, some sort of mold based UH medicine that they were using. Uh. I

could be wrong in it. Well, I can't see that being something that's thrown in there as a little aside, but that like isn't widely recognized or used maybe UH. 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 want to look at the work of the Emory University bioarchaeologist George J. R. Meligos,

who is now deceased. I think he died inteen. But he's interesting, 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 from between three fifty and five fifty C. And so 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 belonged to

had been taking tetracycline. Now, tetracycline is not the same as penicillin, but it is an antibiotic. It can be used to all kinds of infections, from minor problems like acne I think in concert with some other drugs, uh to major diseases like plague or tularemia or even syphilis. And tetracycline works primarily by binding to the ribosomes of

bacterial cells. Ribosomes are sort of the cellular factories. They build proteins that are needed in order for organisms to live and grow, and by binding to the ribosome, 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. Uh So what was it doing in the bones of Nubian

people who live like seventeen hundred years ago. Well, our Melagos and colleagues followed archaeological clues to identify the source of the tetracycline, which was beer. Ah, of course beer is another one of Ultimately it falls under zugmoise domain. Oh yeah, though this is different because tetracycline is not made from a fungus. It is actually an anti bacterial that is a byproduct of some bacteria. Okay, so it's a bacterial byproduct, but essentially so technically it's jubilex okay,

or point to jubile This is jubilex versus jubilex. Right, Well, I mean that's going to happen with your damon law inter Jubilan warfare. Uh So beer is made from fermented grain, of course, and the fermented grain in this ancient Nubian beer apparently contained the bacteria stripped to mices, which creates

tetracycline 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 they 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 two of which arm Lagos was one of the authors.

The authors examine tetracyclin in skeletal remains from throughout this period and the evidence indicates that the ancient Nubians were consuming these antibiotics on a regular basis, and the authors suggests that these ancient 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. And the author has 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 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 of 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 fhemera of skeletons from the Doclay oasis 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 tetracycline is consistent with other evidence showing a relatively low rate of infectious disease in Sudanese Nubia during that time period and a lack of bone infections apparent in these remains from the this oasis 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'd take orally or through injection would be today, but it would have some effect, and it appeared that it probably was

somewhat effective been 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 of holy liquid that that that had some sort of curative property to it. Exactly, I mean, fascinating discovery from the ancient world. Another interesting fact, tetracycling is relatively unique in that it leaves clear signatures in the bones that can be discovered long after the person

has died. So other antibiotics don't leave these clear markers like this that make it easy for archaeologists to detect. So you have to wonder, like, are there were there other cases of ancient peoples in various places in times using some kind of antibiotics or bacterial or fungal cultures uh 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 like tetracycling does. Yeah, it

could have just been lost to history. I was reading an interesting paper from Frontiers in Microbiology in two thousand

ten by ROOFS. Dam Aminov called a brief history of the antibiotic era, lessons learned and challenges for the future, and am and Off points out this unique quality of 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 mentions that there are other anecdotes from history about like cultural traditions that show

proto antibiotic technologies. And these other examples would include red soils found in Jordans that are used for treating skin infections. It's been discovered that these soils contain some antibiotic producing organisms, though I guess they're probably also some major risks in applying soil to wounds, uh. 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 antibiotic effort is ultimately based in going out into the natural world and finding these weapons that already exist and then reusing them and adapting them for human medicine. And you know, this is essentially what is going on

in traditional medicines as well. And it also means that there are weapons out there that either have not been discovered at all at all, especially in particularly vibrant ecosystems, some of which, of course are threatened. All the more reason to uh for for us to not decimate say the rain forests or the deep ocean. But then there are also things that may have been discovered to some

degree in the past but have been forgotten. Well yeah, and that that does seem possible because despite all all this 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. Alright, well, on that note, we're

going to take our first break. But when we come back, we're going to return to the mold research of the nineteenth century and ultimately to our key inventor here, Alexander Fleming. Alright, 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 fung gui. That's right, there was. There was work going on in this area

prior to Fleming. Fleming was was you know, picking up on some of it. And uh, and really just overall just our understanding of a fun guy in general was was advancing. As we mentioned in our Psychedelics episodes. Uh, you know, there was a time where we did not recognize fun guy as being separate from the realm of plants before we realized that it was a kingdom unto itself and almost ultimately a kingdom that has a little more in common with the animal kingdom than it does

with the plant kingdom. And uh, there are a lot of talented folks working in this area, but one of them might come as a surprise to a lot of people. Um, and that's because her name was Beatrix Potter. Uh, the bunny Rabbit, the bunny rabbits, Yes, off the bunny rabbit fame. Uh. That was 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 who listen to the

show to discuss episodes. Someone brought up Beatrix's Potter in regards to something to do with squirrels, because there's a lot of squirrel uh a squirrel content in the discussion module.

And yeah, they brought up Beatrix's Potter. And Beatrix Potter actually ties into 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 important of all, my cology.

So she produced a lot of just beautiful scientific watercolor illustrations of various fun guy uh in her you know, neck of the British woods, um and you know, as part of her studies, and she studied a lot of local molds as well and did illustrations of them. Uh. You know, she's she'said. Ultimately a very interesting character that was, you know, Unfortunately she lived in a time in which, you know, the sexism of the day prevented her from i think reaching the heights of in the natural sciences

that she would have been afforded later on. But uh, and then a lot of her work is also just being I think rediscovered and appreciated for the first time, you know, in recent decades. But but yeah, the next time someone busts out some Theatric's Potter, remember this is not just an individual who wrote some fanciful tales and illustrated them like she was also just she was out there studying the natural world and uh and created in advancing our under standing of a mycology. She was sort

of looking into the hidden life of nature in multiple ways. Yeah, and you know, and I see some sources out that they're like asking the question, Okay, was Beatrics Potter or she or a true naturalist, a true natural scientists over she just a uh, you know, an amateur that was just very interested in these things. And I don't know, it's kind of a complicated question to ask when you consider like the limitations uh 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 authored or co authored one paper if I remember correctly, so I'm gonna give her give her full credit. Was it about fun guy? It was? It was it was a mushroom in particular, um, I forget it was one of those related to the rusula mushrooms, but I forget which species. But but yeah, basically she was you know, she was kind of up up against the patriarchy for the most part. Though. Yeah, Well, is it time a

turn to penicillin itself? Yes, let's turn to this the key discovery here and our inventor, our discover, Alexander Fleming. Okay, So, who was Alexander Fleming? Okay? So? 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 he observed and studied a great deal of death from sepsis in World

War One. He observed that while um antiseptics worked well at the surface, a deeper wounds sheltered bacteria from the effects of things like sulfa drugs. Right, so, if you have a 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 gonna get lodged in there, especially with your war wound. Swhere there is a you know, a stab or you know, or or a deep cut or a bullet entering the body.

What makes me think about the when we were reading about the idea of Stegosaurus perhaps weapon I I mean not consciously, but the stegosaurus perhaps uh having an adaptation to weaponize infection against its enemies by dragging its thagamizer spikes through the dong exactly, Yeah, having dirty thagamizer spikes and then when it wacks the t rex in the crotch with them, that that gets infected later and eliminates

a predator from the area. Yeah, And that the predators of the day would not have had access to antibiotics certainly, not or even that beer from that we mentioned earlier. So uh, Flaming was you know, devoted himself to research and he uh prior to penicillin, he discovered lysozyme and naturally occurring enzyme and mucus and other parts of the body. Then inhibits bacteria. So you know, he was already you know, in this this area, you know, looking for for new

new breakthrough, his new discoveries. But then his biggest breakthrough of 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 to 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 like ninety seven or so, he had engaged himself in studying um staff LCOC either or you know staff, and he had stacks of Petrie dishes dish specimens in his lab, which I've seen described as being kind of an untidy lab, so you know, imagining all these like like Petrie dishes, full staff all over the place, notes

and so forth. And so the key moment comes in September of ninety right, right, So he has he has the staff Petrie dishes out and then he leaves them for the weekend, go on holiday with his family, and he 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 narrativised, So you do have to wonder if some details of it are embellished, 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. Uh. The way that I've seen the story often told is 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 know, normally what you would see is that if you've 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 dead zone. Now, of course we know Staphylococcus is is a bacterium group linked to all kinds of human disease and misery. I think staff infection is right. If this mold could kill staff, that seems medically relevant. So what happened here? Well, Um, he realized that he was dealing with some sort of a fun guy, you know. So he Luckily there was a mycologist with a lab just below Fleming on the floor below his lab, a man by the name of C. J.

La Touche. And in fact, it's also been suspected that the mold and question that killed Um Fleming's staff might have drifted up from a Latch's 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 or down the floor. That's that's what That's not. That's not a theory that's presented in every source, but

it does pop up fairly frequently. So specifically, this mold was what would later be identified as a strain of Penicillium notatum, and it was obvious that it secreted something that prevented staff back to area from growing, and so Fleming followed up in studying this secretion, this this mold juice as I've seen it called. Uh, He found that it didn't only prevent the growth of Staphylococcus, it worked against common bacteria like Streptococcus or Menninja caucus and UH

and the back also against the bacterium that causes diphtheria. Interestingly, while Fleming did see applications for penicillin and curing disease, and he mentioned them briefly in the paper he published in ninety nine about this discovery about a the the anti bacterial properties of Penicillium UH, he primarily thought of this secretion of penicillium as a tool for bacteriologists to sort strains of bacteria basically into penicillin sensitive versus non

penicillin sensitive species, and that that that could be useful in the lab. Yeah, so, he sometimes criticized is really not understanding completely what he had here, 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. Um. So Fleming and his assistance Stuart Kratak and Frederick Ridley tried for years to turn this accidental discovery into a stable, isolated compound

that would be useful. And this is this was a problem because like, so you've got this secretion from the mold, it molds making some juice. It's kind of 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 Amanov's paper Amanov 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 penicillium strain to anyone requesting it. But he he could never crack the nut ultimately, and he didn't finally make this discovery of the process for for stabilizing and isolating the compound, and by Amanov rights that Fleming

finally abandoned his quest. But fortunately it was right about that time that a capable team at Oxford University, including the researchers Howard Floory and Earnst Chain or China, they picked up on this research and they they kicked off the research project that would eventually break through on this. Uh, and they're all these interesting stories. So of course this is wild. World War two is going on, so research

conditions are not ideal. And uh, they're all these stories about how they turned their lab at Oxford into this giant incubation center or sort of factory for mold. Like they employed all these lab assistants who are these women who had been referred to in some sources as the penicillin girls, and they would work to like they would work to grow the penicillin and buckets and tubs and basically every container that they could um and uh, eventually

they did. They were able to isolate and stabilize this compound, so to quote from an article from the American Chemical Society, quote in nineteen forty Floory, and that would be Howard Floory carried out vital experiments showing that penicillin could protect mice against infection from deadly stripped to cock eye. 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 had developed a life threatening infection with huge abscesses affecting his eyes, face, and lungs. Penicillin was injected and within days he made a remarkable recovery. But unfortunately, despite this recovery, which lasted for a few days, they ran out of the drug 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 it could be re administered to him. Uh. And I should mention also that the process that the Oxford team relied on to extract and purify the penicillin and the mold juice was led by another important biochemist, a

guy named Norman Heatley. But this case of Albert Alexander shows an obvious early problem they had, which was the problem of scale. They simply lacked the ability to make penicillin at the scale that would be needed to treat

even one person, let alone the whole world. Uh. 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 Penicillium, which would maybe they thought, produce higher concentrations of the penicillin filter rate. And I was reading an interesting article by the University of Michigan physician and medical historian Howard Markle that tells a really interesting story. I've never heard about this. Uh

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 cantalope that she'd 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 is picking over the

fresh produce produced to like find the mouldy one. But the mold on this cantalope turned out to be a strain of penicillium called Penicillium chrysogeum, which Marco says naturally produced at least about two hundred times as much penicillin

as the original strain that they've been studying. And then later Marco writes that the same strain was subjected to mutagenic processes in the labs like bombarding it with X rays and stuff to produce a mutated strain that would make up to a thousand times as much penicillin as the old school fleming mold. So by ninety one, penicillin

is on its way to becoming a viable medicine. All right, On that note, we're going to take a quick break, and when we come back, we're gonna look at the impact of penicillin, and we're gonna look at it, and I think a fun way by considering a really interesting what if. Alright, we're back. So we often don't don't

do a lot of what ifs on invention. I thought we we kind of do, it's a certain extent, but I mean a lot of times it's a harder case to be made for like what if this had not been invention, invented right or discovered because in most cases you can you can you can look at the data, you can look at other individuals work, Like if the Right brothers had not invented the airplane, had not you know, created that that first prototype that really showed what was possible,

Like clearly there were there were other individuals in the world working on this. Someone would have cracked it. If if Runkin had not discovered X rays and eight nine, whatever year it was, somebody else would have discovered them pretty soon. But when it comes to penicillin, uh, it potentially gets a little more complicated than that. I ran across a cool article on the topic titled what if

Fleming had not discovered penicillin? And this was published in the Saudi Journal Um of Biological Sciences by al Harvey at All. The authors admit that that certainly if Fleming hadn't 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 it have arrived in the anti bacterial age. However, they also explored the possibility that we might have simply not made the

discovery at all. And it's an interesting argument. So I want to 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 that took place as a result. Anyone taking an interest to penicillin during the nineteen thirties did so

in the knowledge of Fleming's work. In particular, there seems no reason to believe that Flory and Chain would have discovered penicillin, since their work depended on Fleming's famous paper and their access to one of his penicillin producing cultures. Okay, so that's referring to the thing I mentioned about how how Fleming and his assistants were just like sharing the penicillium straining out with everybody, like, hey, can you figure out what's going on with this? Can you isolate the

secretion or the compound in the secretion? Yeah? So, so think about that. There was there was, so far as these researchers could determine, you know, no other effort out there that would have struck paydir. In the absence of Fleming's research, the Oxford group wouldn't have been looking for it. Selman Waksman, the father of modern an hibotics is he sometimes called, who made several key discoveries later, was also inspired by Fleming. So it's it's one of these cases

where like he seems to be the epicenter. Uh well, not not only him, but just then the the the the seemingly chance encounter in his lab that day that that where suddenly this halo appears in the Patriot Dish, and that gives birth to a to a whole class of other discoveries. Right, because not all uh antibiotics are derived from penicillin, the penicillin class of antibiotics becomes 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. Yeah, and there are various 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 have what would have happened in the wider world, because again, penicillin comes online during the Second World War, and so you can easily ask, well, what would have happened if Allied troops had not benefited from access to antibiotics that D Day? I've never thought about that. In fact, before looking at this episode, I probably would not have known the answer to whether or not they had access

to antibiotics. Well, penicillin production was actually swiftly scaled up just to make sure that Allied soldiers had access to it at D Day. Um, so there's a legitimate question to be asked, might the Allies not have won the Second World War without penicillin? Um? I think there are a lot of factors to consider there. I don't think that it's quite a got you question, but it's it's

worth thinking about. The authors argue that without Fleming's discovery, we would have had to depend on the sulfa drugs, uh, you know, an imperfect alternative to true antibiotics, and these uh you know, 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 sulfa drugs might have become the standard and even pushed the discovery

of true um antibiotics well beyond the nineteen sixties. And this is also true if the Access Powers had risen in victorious in World War Two, because the Access Powers depended on sulfa drugs as their their key treatment. Um. You know. They do point point out that, you know, quote, despite the fact that the Germans and their allies were at a considerable disadvantage, uh, the sulfa drugs did a

relatively good job at reducing battle casualties. So not to just completely um you know, cast aside the effectiveness of sulfa 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, it also gets interesting.

Already touched on presidents who died that would have lived potentially if there had been penicillin around, And so they point out that that sulfa drugs save Churchill's life in ninety three when he was suffering from pneumonia, as well as FDR's life. But there's also evidence by the way that actual penicillin may have saved Hitler's life following the

Staffenberg assassination attempt of July nine. This was the plot that tried to kill Hitler with a briefcase bomb, like where some of the officers conspired against him and they put a briefcase bomb in the room with him, and it did explode, but he was protected by like a heavy table that prevented it from killing him. He was obviously injured, and I think he had like nerve damage after that. So the idea here is that perhaps his

injuries were treated by by penicillan. Yeah, that's 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, I'm sure maybe there's a spy story there. I don't know, but the idea being well, if he had if he had didn't have access to penicillin, then perhaps he would have died, and that would have arguably ended the war, you know, in a different manner, forcing us to reimagine

an entirely different post war world. So again we're playing with with what effs here? And and also we my understanding is we don't know for sure that Hitler had access to penicillin following that assassination an attempt, but there is the overall scenario of the Allies having penicillin and having this ramped up penicillin production leading into D Day. Yeah, that is really interesting. I had never contemplated that before.

Um now, something that I we do often have to think about and we should probably acknowledge at the end here before we move on. Maybe this will be something to come back and UH do in the future with a recent invention episode. Is the idea of a possible end of the antibiotics age. I mean This is a kind of scary thing to imagine, Like what if the antibiotics age is essentially a period in history that has

a beginning and an end. Because as we you've you've probably heard about this, many disease causing bacteria and other disease causing microbes are over time evolving antibiotic resistance are evolving to to be powerful enough to survive our 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 Zagdamoya jubile X war scenario, you know, it is an ongoing battle and the forces evolve uh to uh to better deal with the threats on each side. And so you know, we're we're we're we're seeing this occur.

We're seeing the overuse of antibiotics producing uh, you know, 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. Oh yeah, we should come back and revisit vaccinations or 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 nineteen forties through the nineteen seventies are are considered like the golden age of antibiotic research, and we haven't seen, at least if we 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 modifications on existing classes of antibiotics, sort of 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 when we had

we keep adapting that fire to our own purposes. But we haven't. We haven't found any new weapon from that world. And uh, and then their ongoing war continues to change. I'd be interested. Do you out there, you the listener do you work in medical research? 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 look like to you?

On the end side, absolutely, we would we would love to hear from you. Again, we've only really scratched the surface here though thanks to antibiotics, hopefully that scratch will not uh get interesting life threatening infection. But yeah, 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 and 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 totally. In the meantime, if you want to check out other episodes of Invention, you can check out our homepage. It's invention pod dot com and that will have all the episodes right there. If you want to support the show, and we would

appreciate it if 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 then if you have the ability to do so, rate and review is wherever you got this podcast, huge thing as always to our excellent audio producer Maya Cole.

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 of I Heart Radio. For more podcasts from my heart Radio is the i heart Radio app, Apple Podcasts, or wherever you listen to your favorite shows.