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"penicillin biz" Discussed on This Podcast Will Kill You
"As well as stabilize which made experiments much easier to perform and finally on May Twenty Fifth Nineteen Forty Penicillin was injected into four of eight mice. That had been infected with. Strep podge unease and the four that received treatment survived and seemed absolutely one hundred percent healthy and the four. That did not died a yeah and this was great news. I mean not for the mice that died but for the world but there is still this huge problem of production because although he had made amazing progress in the stabilization of penicillin he simply could not make enough of it to keep up with demand. And it's not like the lab had the funds to supply the materials or equipment to ramp up production So he resorted to stealing. He took bedpans from the hospital. Supply Cabinet and baking trays from the kitchen to supply this huge amount of space that he needed to grow the mold and he basically macgyver. D- His way through the purification process through a collection of random junk that he found in the lab. I love that. He is amazing. Beginners literally needed containers to grow molden. He's like yeah. I'll use this. I'll use that coup great. You're not using this. You haven't baked in a while. Yeah it's really impressive. And in the in the book that I read there are some like figures that show his setup and it's like the just amazing it's amazing. That's there's like so much more to all of these stories so and this is already a very long story but it's just fun and it's fun to like know about the individuals themselves and the personalities and how much personality as a role. Yeah it's very cool. Yeah so in. August of Nineteen Forty. Flory felt that he had enough to go public with this penicillin news and he published this research in an article in the Lancet titled Penicillin as Chemo. Therapeutic agent but at this point penicillin hadn't yet been tested in humans. Just mice I up with someone with terminal cancer but no bacterial infection. After receiving a shot of penicillin she developed a high fever in seizures and so that led them to realize that the process of concentrating penicillin also had this unintended side. Effect of concentrating impurities So they fixed it but instead of just testing to see whether it was safe injection. They also needed to test whether it was effective needed someone with an infection and they found one in an Oxford policeman named Albert Alexander who had scratched his face with a Rosebush while gardening over the course of the few months that small cut that tiny cut led to a massive infections. All OVER HIS BODY. He was quote oozing pus everywhere growth. I think his is like everywhere just everywhere one day after just one injection of two hundred milligrams of less than five percent pure penicillin will. He had made a miraculous improvement. The pus had stopped flowing and the fever had gone but the problem was still in keeping up the supply so the researchers had known that penicillin is excreted by the kidneys. They started to collect the policeman's urine and rush back to the lab to re purify them back to the hospital to reinject but they just couldn't keep up with demand they couldn't do it until the policemen died five days after once they ran out of penicillin just said but another person. A young kid that they treated survived later on. And so this was proof enough that it worked as long as you had enough of penicillin But there was never enough. Never Never Florey and Heatley needed more funds if they were ever going to make penicillin feasible treatment for infections and so they turn to a country that had the funds and the agricultural research infrastructure that they needed the United States after meeting with some friends slash fellow researchers about the work that they wanted to do. They came to the conclusion that they needed to head to the foremost site of agricultural research in the country the northern regional research lab in Peoria Illinois Peoria. That's like this is pure. Is the site for penicillin like from when it went from a novel. Potential thing to actual penicillin actual penicillin. Yeah Wow Peoria Uria. I wonder if they have that. Just like blazoned everywhere. All their bridges like penicillin salon was found deer. It wasn't down there but outskirts of Peoria. Never she streets So how exactly did penicillin go from medical curiosity to world changing substance? Yeah there are three big developments that would make this transformation. Possible number one. Finding strains of penicillin that produced the most penicillin number two developing the best protocol to rapidly. Grow the mold and number three improving the fermentation process that actually led to penicillin to find these turbo strains of penicillin a bacteriologist at the lab named Mary. Hunt went to Peoria markets like every day every weekend to find moldy fruits and vegetables like the veg market. She's just walking around farmers market lake. Don't worry I'm here for work. And she hit pay dirt. She had absolute in one thousand. Nine hundred eighty three with mouldy cantaloupe keen elope the mold on that cantaloupe was so powerful that it became the source for basically all of the world's penicillin and as for a better growth medium the Midwest. Us is known for what type of food Aaron corn corn the corn corn corn and corn corn corn and corn and it turned out that grilling penicillin in something called corn steep liquor. Plus sugar produced one thousand times more penicillin than the previous method. Wow that's a lot way to go corn way to go corn corn for the win but once again it came time to ground truth penicillin on Valentine's Day. Nineteen forty to a woman named Anne Miller was in the hospital in New Haven Connecticut. After experiencing a miscarriage she had developed Blood Poisoning Aka hemolytic. Streptococcal septicemia her. She had like fevers of one hundred seven. She was not coherent. It was really bad and her doctor ended up through a series of pleading calls. He ended up securing a small glass. Vile containing five point. Five grams of penicillin had come from that research lab. Five point five grams at the time. Nineteen forty two was half of the entire amount of penicillin in the US. Whoa he guest at a dosage. 'cause he there's no Renault guidelines and he injected the drug into an. She survived the night and the next day and the next day and the next fifty seven years after that. Wow yet her chart her medical chart from this. Time is actually in the Smithsonian's National Museum of American history. So you can go and see it. I love that museum. Yeah Oh it's amazing. Yeah and this marked a real turning point in penicillins history by nineteen forty two and nineteen forty-three many pharmaceutical companies in the US including Merck and Pfizer got into the penicillin Biz and worked on their own production processes meaning that mass manufacturing was just around the corner and so were massive profits just like heaps and tons and loads of money money money money money money money and where is the successful treatment of an Miller with penicillin had led to the biomedical industry. Taking note of the drug a horrific fire would wake up the public to it on November. Twenty eighth nineteen forty two and artificial palm tree at a Boston nightclub called the coconut grove caught fire and within minutes the entire club was consumed wo four hundred and ninety two of the over. One thousand partners died. Isn't that it's one of the one of the deadliest fires in in American history. That's terrifying. It's horrible and hundreds more were horrifically burned at mass general hospital. The doctors decided that rather than debris down of the burns. They would try to administer and sulfur drugs. It's hard to say whether the penicillin did perform the miracles on these burn victims as the newspapers later claimed but regardless it had now become firmly established in the public's eye as a wonder drug demand for penicillin reached new heights. But the mounds of this dry brown powder weren't just there for anyone to use because there is a war going on right and so basically until the war was over. Penicillin was strictly reserved for troops allied troops with most of the drug being used for wounds received in battle and also gonorrhea most civilians and there were a few exceptions. Wouldn't enjoy the benefits of penicillin until after the war was over and Australia would actually be the first company to open up. Its use to the public. Even with all of these amazing advancements in penicillin production. There is still one big piece of the puzzle that that had yet to be solved that of its structure so chain had made some progress towards this but only in that he could produce crystallized degradation products which he offered up to biochemist's Dorothy Crawford Hodgkin. Who had already made amazing amazing discoveries about the structure of many large complex organic molecules such as cholesterol testosterone? Epson insulin and many others using x Ray crystallography so with the crystals that chain had given her Hodgkin used x Ray crystallography to get a clear idea of the different components of penicillin. But a clear idea is not the same thing as a clear idea and without that clear idea penicillin would never be synthesized. In a lab where it could be produced in larger quantities. Were more stable. More pure and more efficient. The breakthrough came when Hodgkin proposed a Beta Lacombe ring necked. It's amazing and by all accounts just like Heatley not only amazingly brilliant researcher. She was also really kind and well loved by everyone who knew her. Oh I have a baby book that she is the letter D for skin. He's so that makes me happy. So anyway penicillin wouldn't be synthesized until nineteen fifty seven but knowing its structure was integral not too not just making it in a lab but also in trying to look for other compounds that have similar structures and could be used to treat bacterial infections so the recent that I spent so much time talking about penicillin in this history of antibiotics as a whole is because it provided this new framework for thinking about what these different antibiotics might look like and where you could look for them right so namely in the existence of other living things but as you talked about Aaron Penicillin acts on only a subset of bacterial. Species gram positives. It's not effective against gram negatives like you're sitting at pestis or limited trachomatis or vibrio cholera or acid fast bacteria mycobacterium tuberculosis and up until the early nineteen the second leading cause of death in the US was bacterial. Pneumonia which could be caused by. A variety of gram positive and gram negative. Bacteria and tuberculosis wasn't much farther down the list. Sixth-place so the war bacteria was far from over and spoiler still not over today and besides penicillin years yielded more than just penicillin in terms of antibiotics to other drugs named Tiro Thrice and Grandma Sidon were developed from compounds produced by a soil bacterium. But there's a reason that those two might not sound familiar even though they're still occasionally used today. So one of these works by stopping proteins from being made as you had described and the other make cell membranes impermeable both of these things will definitely kill bacterial cells. But in these cases they also killed animal cells. So they're useless pretty limited but why important thing they did was give people a reason to look in soil for other possible antibiotics and whereas flemming's discovery of penicillin had been possibly fortuitous accident. The hunt for antibacterial compounds soil was grueling systematic trial and error search full of long days of hard work. Which is I mean. Let's face it. That's how most scientific developments actually happened right one of the people doing these long days of work and often even sleeping in the lab was a PhD candidate named Albert Schatz. His particular obsession was with acton. My CDs which is a group of soil bacteria and trying to find a compound to kill mycobacterium tuberculosis. And if you listen to our two regulus from way back in Season One. This story may sound a bit familiar to you. As we know to recuse is very deadly and at the time there was no cure so Schatz was basically exiled to do his work in the basement by himself. How dangerous he was. Culturing asus okay. Yeah but this isolation I guess paid off on October. Nineteenth nineteen forty three. He discovered that bacterium named streptomycetes gracieuse produced a substance that killed mycobacterium tuberculosis. And that substance is what we know as trump to mason stripped in my fan but just like with the early days of penicillin. There was a production issue. How do you make enough of the stuff to actually perform meaningful experiments? And that's where Schatz advisor Salman Wachsman leaned on the labs connection with Merck to enlist their help in ramping up production so eventually they were able to make enough streptomycin to test tested on. Guinea pigs infected with tuberculosis. And guess what it worked it worked. It also worked on humans which was again viewed as Miracle..