This Podcast Will Kill You

Special Episode: Lina Zeldovich & The Living Medicine

52 min
Aug 26, 20258 months ago
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Summary

This episode features journalist and author Lina Zeldovich discussing her book 'The Living Medicine,' which explores bacteriophage therapy as a forgotten cure for antibiotic-resistant infections. The conversation traces phage therapy's history from its simultaneous discovery in 1917 by Felix d'Herelle in France and Giorgi Eliava in Georgia, through its suppression in the West post-WWII, its continued use in the Soviet Union, and its recent resurgence in Western medicine following landmark cases like Tom Patterson's treatment in 2016.

Insights
  • Phage therapy predates antibiotics by decades but was abandoned in the West due to misuse and marketing failures in the 1930s, not scientific inadequacy, while the Soviet Union maintained continuous research and application
  • Phages offer a fundamentally different approach to antibiotic resistance: they co-evolve with bacteria unlike static antibiotic molecules, providing a dynamic solution to rapidly evolving resistance mechanisms
  • Geopolitical and cultural factors—not scientific merit—determined whether nations pursued antibiotics or phages, with Soviet state medicine's flexibility favoring phages while Western private practice favored standardized, shelf-stable drugs
  • FDA regulatory frameworks are evolving to accommodate phage therapy's unique characteristics (living organisms that multiply and change) by reclassifying phages under biologics regulation rather than traditional drug standards
  • Antibiotic resistance mortality is accelerating dramatically: from one death every 15 minutes (2019) to projected three deaths per minute by 2050, creating urgent necessity for alternative treatments like phage therapy
Trends
Resurgence of phage therapy research in Western medicine driven by antibiotic resistance crisis and landmark patient success storiesRegulatory agencies adapting approval frameworks to accommodate living therapeutic organisms with inherent variabilityGrowing recognition that scientific innovation is shaped by geopolitical context, economic incentives, and institutional structures rather than pure scientific meritShift toward proactive, library-based approaches to infectious disease treatment (maintaining phage banks) versus reactive antibiotic developmentFood safety applications of phages (sprays for lettuce, meat) serving as regulatory proof-of-concept for medical applicationsInternational collaboration emerging between Western researchers and Soviet-era phage therapy centers (particularly Tbilisi) to bridge knowledge gapsPersonalized medicine approach gaining traction: phage cocktails tailored to specific bacterial strains rather than broad-spectrum treatmentsAntimicrobial resistance mortality projections driving policy urgency and funding allocation toward alternative therapeutic modalities
Topics
Bacteriophage therapy mechanisms and administration routesAntibiotic resistance epidemiology and mortality projectionsHistory of phage therapy discovery and development (1917-present)Soviet Union medical research during WWII and Cold War eraFDA regulatory frameworks for living therapeutics and biologicsPhage isolation, cultivation, and purification processesComparative advantages of phages versus antibioticsFood safety applications of bacteriophagesInvestigational new drug approval processesProphylactic use of phages in disease preventionGeopolitical factors influencing scientific research directionPhage library maintenance and continuous bacterial surveillanceInfectious disease treatment paradigms (reactive vs. proactive)Antibiotic-resistant bacterial strains (Acinetobacter baumannii, cholera, dysentery)Clinical trial development for phage therapeutics
Companies
Pasteur Institute
Historic research institution in Paris where Felix d'Herelle worked and where Giorgi Eliava studied phage therapy in ...
FDA (Food and Drug Administration)
U.S. regulatory body developing approval pathways for phage therapy and reclassifying phages under biologics evaluati...
University of Maryland School of Medicine
Institution where Georgian scientist Sandro worked with infectious disease physician Glenn Morris in early 1990s phag...
Eliava Institute
Bacteriophage research center in Tbilisi, Georgia founded by Giorgi Eliava; maintained phage library through Soviet e...
People
Lina Zeldovich
Author of 'The Living Medicine' discussing phage therapy history and current developments in bacteriophage research
Erin Welsh
Host of the podcast conducting interview about phage therapy and book club discussion
Felix d'Herelle
Co-discoverer of bacteriophages in 1917; pioneered phage therapy for dysentery and bubonic plague in Egypt
Giorgi Eliava
Georgian scientist who independently discovered bacteriophages; founded Eliava Institute in Tbilisi; arrested and kil...
Zinaida Yermoliva
Leading Soviet biologist who organized prophylactic phage distribution to 50,000 people during Stalingrad cholera out...
Sandro
Georgian post-doctoral fellow who introduced Western scientists to phage therapy; spent 25-30 years working with FDA ...
Glenn Morris
Physician who lost patient to antibiotic-resistant infection; collaborated with Sandro on phage therapy research
Tom Patterson
First FDA-approved phage therapy patient in 2016; treated for antibiotic-resistant Acinetobacter baumannii infection ...
Stephanie Strathdy
Tom Patterson's wife; scientist who researched phage therapy and coordinated his treatment; author of 'The Perfect Pr...
Stalin
Provided funding for Eliava Institute in Georgia; later arrested and executed Giorgi Eliava during paranoid purges
Quotes
"Phages are viruses, and this is where it really gets interesting, because we tend to think of viruses as some really bad things that make us sick. Phages are different. Phages don't have the right biological equipment to afflict humans. They can only attack bacteria."
Lina Zeldovich
"An enemy of my enemy is my friend. So we can use these amazing creatures as alternatives to antibiotics when antibiotics don't work."
Lina Zeldovich
"Antibiotics are static molecules that we synthesize by chemical reaction or some other means. And they're static, they don't evolve. And bacteria are amazing at various mechanisms of resistance that they just evolved, you know, from one day to the next."
Lina Zeldovich
"By 2050, antibiotic resistance will kill three people every minute. The United Nations has never dreamed of prediction 10 million deaths annually by 2050. It's like it's pretty freaky."
Lina Zeldovich
"Science doesn't happen in a vacuum. Why it fell out of favor in some countries and lingered in others gives us insight into how external events and cultural differences can shape scientific developments."
Erin Welsh
Full Transcript
This is Exactly Right. People who didn't do what John of God wanted them to do, they usually disappeared. John of God was once Brazil's most famous spiritual healer. But in this limited series podcast, we uncover the darker truth behind his global empire of faith and fear. From Exactly Right and Adonde Media, this is Too Faced, John of God. Listen on the iHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Music Hi, I'm Erin Welsh, and this is This Podcast Will Kill You. Welcome to the latest episode in the TPWKY Book Club series. In these episodes, I bring on authors of popular science and medicine books and chat with them about their work, what inspires them, and how their book can change the way we understand the world around us. I've gotten to have some incredible conversations so far this season, and we've got even more great authors and books lined up for the rest of the year, so stay tuned. If you'd like to check out what books we'll be featuring on future episodes, as well as get the full list of books we've covered in the past, head over to our website, this podcastwillkillyou.com. Under the Extras tab, click on Bookshop to go to our bookshop.org affiliate page, which has the list for books featured in these episodes, as well as other podcast-related lists. I'll be adding more books throughout the rest of this season, so check in regularly if you'd like to read along. As always, we love hearing from you all about the books you've enjoyed, any books you'd like to hear featured, suggestions for episode topics, anything you'd like to share. The best way to get in touch is by filling out the Contact Us form on our website. Two last things, and that is to please rate, review, and subscribe. It really does help us out. And also, you can now find full video versions of most of our new episodes on YouTube. Make sure you're subscribed to Exactly Right Media's YouTube channel so you never miss a new episode drop. Alright, now let's get into the book of the week. Antimicrobial resistance is not a new problem. The first penicillin-resistant bacteria appeared just a heartbeat after the widespread introduction of the antibiotic in the early 1940s. But it is a growing and deadly one. The WHO estimates that in 2019, antimicrobial resistance directly led to 1.27 million deaths and contributed to 4.95 million deaths around the globe. Nearly 5 million deaths do in part to antimicrobial resistance. That's more deaths than HIV, tuberculosis, and malaria combined. What's more is that these numbers are expected to grow in the coming years. Our standard approach to combating these superbugs has primarily consisted of developing new antibiotics, a strategy that buys us much needed time, but is ultimately no match for the rapid evolution of resistance. To have any hope of curbing infections and deaths due to antimicrobial resistance, we need to think outside of the antibiotic box. Fortunately, some researchers have been doing exactly that for over a century. In this week's episode, I am joined by journalist and author Lena Zeldowicz to discuss her book, The Living Medicine, How a Forgotten Cure May Rescue Us When Antibiotics Fail. That forgotten cure refers to phage therapy, the use of bacteria-specific viruses, called bacteriophages, to treat antibiotic-resistant infections. Many of us, such as those of us here in North America or Western Europe, may have learned about phage therapy in school only as a blip in the history of medicine, if we learned about it at all, soon overshadowed by the development of antibiotics. Or maybe you learned about it in our antibiotic resistance episode from years back, which featured Stephanie Strathdy sharing her and her husband Tom Patterson's story. But in other parts of the world, phage therapy never faded from memory. Rather, it remained a leading treatment for bacterial infections and a central focus of medical research. Why it fell out of favor in some countries and lingered in others gives us insight into how external events and cultural differences can shape scientific developments. As we're fond of saying on this podcast, science doesn't happen in a vacuum. In The Living Medicine, Zeldowicz takes readers through the history of phage therapy, where we get to meet the visionary researchers that championed this treatment, discover how phages are found and administered, and learn of the profound promise they hold for the global problem of antimicrobial resistance today. This book will have you marveling at this forgotten cure and grateful for those who did not let it slip into permanent obscurity. I have always been such a fan of phage therapy, and it was a joy to chat with Lena and learn more about its history and current developments in the field. I am so excited to share this conversation with you all, so let's just take a quick break and get into it. Lena, thank you so much for taking the time to chat with me today. Thank you for having me here. I'm very excited to talk about all things phages. Let's start at the very beginning. What are bacteria phages and what is phage therapy? What does it mean if someone is receiving phage therapy? Phages are viruses, and this is where it really gets interesting, because we tend to think of viruses as some really bad things that make us sick. Phages are different. Phages don't have the right biological equipment to afflict humans. They can only attack bacteria, and that's why they call them bacteria phages. They prey on bacteria out there in nature, and they've been doing this for millions of years, kind of evolving and excited each other. Typically, it's like one phage per one bacteria. They're very picky at what they eat, and that makes bacteria phages our friends. So basically, an enemy of my enemy is my friend. So we can use these amazing creatures as alternatives to antibiotics when antibiotics don't work. There are different ways of administering phage therapy, but basically you either drink them for intestinal diseases, or you put them on skin or wounds. There are some trials out there that inject bacteria phages into the bladder for people who are dealing with recurring UTIs. You can also administer them intravenously nowadays, but it's more complicated because those formalations must be cleaned from all sorts of things that may trigger your immune system to go haywire. Yeah, I mean, it seems like it can be quite a complicated process from finding the right phages to purifying them to then administering them. And I was wondering if you could just walk me through how people go through this process. Where do you find phages? So phages, you can find phages everywhere. There are out there in soil, in water, in air, in sewage, on rotten fruit. They're basically everywhere on this planet where there is bacteria. There are phages that are preying on it, and like I said, they've been doing this for millions of years before humans came along. And the way scientists find these phages is they go out there and they take samples of everything. They come back to the lab and they use these samples to isolate phages and test them on what bacteria, phages that you just found, will work. And that's how they know that they've got a phage for, let's say, this strain of color or this strain of dysentery or this strain of something else. And then once you have that phage that works for whatever bacterium you're trying to attack, what's the next step? Like how do you grow these phages? And then what is the purification process like? Or maybe why is the purification process so important? The way it works is that first you grow your bacteria, which is very easy. Most bacteria is fairly easy to grow. You just put a bunch of meat scraps. You cook basically a bullion and you see this bullion with bacteria and they just love it. They're so happy there. They procrate, they grow. Once you have enough there, you inoculate the brew with phages and phages set to work and they attack this new bacteria. The way they work is that they get into bacterial cells, they multiply inside them, and they burst bacterial cell open. And once you have almost no bacteria there, you know you have a lot of phages. And that's when the purification step comes in. Again, if you're just putting phages on your skin or drinking them, you can actually skip that step. Historically it worked just fine. What gets tricky is that if you want to give it somebody intravenously, you don't want all this bacterial debris in there because your immune system is going to react to that. Bacterial debris and toxins and whatnot and it may go into shock. And purifying, well, it sounds kind of simple, but it's not because you need ultra sophisticated equipment. Basically you need special centrifuges that spin very fast and they manage to separate phages from everything else and that's how you get your clean phages. Again, I said it sounds very simple, but the right equipment for that because we're dealing with super tiny structures, that only became available fairly recently. I'm trying to imagine the timeline for this. And I know that it can be very different depending on in the US. Right now I think we're still at that case by case basis. How do we approach this from a non-case by case basis? And what does that timeline look like? Do we have to be reactionary or can we be proactive? So I think we still approach this on a per case basis. If a team of doctors wants to treat a patient who's not responding to antibiotics, they would have to go to the FDA and file this investigational new drug application, in this case phages, and they would receive an approval from the FDA and they would proceed. It's such an incredibly obvious solution to what is growing to be an increasingly huge problem, antibiotic resistance. And I want to kind of get into the differences between phages and antibiotics in terms of, you know, in an ideal world where phage therapy does not have to be approved case by case, and it's more of a routine thing, would there still be cases where antibiotics would be used over phages? Probably. I think at least at this point it looks like antibiotics would still be our first line of defense. And that's because it's just so easy to use them. As I mentioned, with phages you need to know what particular infectious organism you are infected with, and then you would have to go and find a phage for this particular infectious organism. And maybe you would need more than one. So if you have it in your library, that may take hours to days, and if you don't, then it would take days and weeks sometimes. So if your antibiotics work in the meantime, you're golden, you don't need anything. However, if your antibiotics don't work anymore, that's when you will need a phage or multiple phages. I think antibiotics are still going to be our first line of defense for a while. The interesting thing about antibiotics and phages and how, like, you know, the pros and cons, you know, antibiotics are static molecules that we synthesize by chemical reaction or some other means. And they're static, they don't evolve. And bacteria are amazing at various mechanisms of resistance that they just evolved, you know, from one day to the next. All sorts of tricks. You know, some of them develop these pumps that spit antibiotics out once they enter bacterial cells. Others have these molecular scissors, you know, enzymes that literally shred antibiotic molecules to bits. You know, some bacteria have very slippery auto coats, if you'd like, so antibiotics can stick to it. Some manage even surround themselves kind of like in a protective ink that also destroys antibiotic molecules. So when we run into this kind of issues, that's when we need phages because phages evolve alongside antibiotics for a long, long time. So even if a bacteria develops resistance to a phage, the phage will eventually evolve to attack it better. And it doesn't necessarily have to take a long time to evolve because, you know, at the level of this microorganism, it can happen very fast. Let's take a quick break. And when we get back, there's still so much to discuss. People who didn't do what John of God wanted them to do, they usually disappeared. John of God was once Brazil's most famous spiritual healer. But in this limited series podcast, we uncover the darker truth behind his global empire of faith and fear. From exactly right and a Donde Media, this is Too Faced, John of God. Listen on the iHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Welcome back, everyone. I've been chatting with Lena Zeldowicz about her book, The Living Medicine. How a forgotten cure may rescue us when antibiotics fail. Let's get back into things. Not only do phages evolve with or in response to bacteria, they are, as you describe in your book, an infectious cure. So someone receiving phage therapy can spread those phages to another individual as well, which is really just remarkable. It's, I mean, for me, it was also a total eye opener, right? Because we tend to think of diseases as contagious, right? Well, so phages can be contagious too, and I think we'll get into history in the phage therapy in a little bit. But the first person who realized that phages as cure can be contagious was one of the early phage therapy adopters, Felix Therel, who was trying to stop an outbreak of Salmonella in chicken in France. And he realized that as soon as one chicken would get a bacteriophage against the Salmonella, the entire coop would recover because they all packet each other's pieces. So he would just spread through all of them, and suddenly they would be not sick anymore. That's amazing. I mean, also talk about like, then you just have to get one chicken, the phage therapy cure, and then you're done. That's it. That's so cool. I would love to get into the history now of bacteriophage therapy. And I think it is, it's surprising to a lot of people who are used to using antibiotics and used to having antibiotics be the frontline of, you know, bacterial infections to realize that not only phage therapy exists, but that it actually predates the discovery of antibiotics. And so can you take me through sort of the almost simultaneous, I guess, discoveries of bacteriophages? So the year is 1917. And two things are happening almost at the same time in two different parts of the planet. There is Felix de Rell in Paris working at the Pasteur Institute, which is like the Holy Grail of science, medical science at the time. And he's both a biologist and a medical doctor, which was very common at the time. And so he's dealing with patients who have dysentery. And again, this is before antibiotics, you got dysentery, you might be dead in very shortly. And so people are dying, but one of his patients recovers and he figures this has to be something in his stomach that helped him recover. So he starts looking at these person's stool samples and he realizes that there is no dysentery bacteria in there anymore. So he's like, something's killing it. So let's try this. He takes these stool samples and it accumulates other dysentery bacteria samples with it. And lo and behold, dysentery bacteria dies there too. And in the next one, in the next one, but he can't see what it is because phages are much smaller than bacteria. And at the time they could see bacteria under the microscope, but not phages. In fact, that took an electronic microscope of 1930s to actually see any virus. So he goes, well, I think I discovered a parasite of microbes that is so small that we can't see it. It's invisible, but I know it's there and he publishes a paper on it. At the same time, out there in the country of Georgia, in Tbilisi, which by the way is a beautiful city and at the time was called the Paris of the East. Really interesting dichotomy. There is another scientist, a Georgian scientist, Georgi Aliyava, who is a little bit younger, not as experienced, but just came back home from the front lights of World War One, which just ended where he tended to seek soldiers who had cholera and dysentery and whatnot. And he is looking into presence of cholera in the city water, in the river where everybody gets the water from. And lo and behold, cholera is there and he sees it and that's not good news. He's looking at it through his microscope and something interferes. He has to go somewhere. He lacks his lab and comes back to it like a day or two later and he's looking at the same samples of water and there's no cholera there anymore, which doesn't make any sense. Cholera doesn't die that quickly. So he goes back to the river, brings back water, repeats the same experience, same result. After a few hours, no cholera. Does it again? Same result. He knows he's on to something, but he can't figure out what is he on to. Fast forward a few more months, he has to go to Paris to study at the Pasteur Institute how to make vaccines and other medicines, because that's again at the time where everybody went to study. He goes to Paris and he walks into this really heated debate. So the scientific world did not welcome Derels finding peacefully because to them it didn't make sense. You're talking about invisible destroyers that destroy this theory. No, it also doesn't fit into the established immunity theory at the time. So basically at that moment, Derels is a laughing stock and at the moment he's out there in the countryside dealing with chicken salmonella. So Elieva walks into Pasteur Institute and right in the middle of all this and he goes, I've seen that too. And they're like, all right, another one. But here where the character differences come into play, Derels was kind of a prickly character. He spoke his mind and probably made a fair amount of enemies in his life. And Elieva was exactly the opposite. He was this absolute charm. He could sweet talk anybody into anything. When I was reading his family's diary, it literally sounded like when he talked about science it sounded like poetry. And he spoke fluent French because he studied in Geneva. So he went to the Institute director said, can I repeat the experiment? And so of course he talked him into it and he repeated the experiments and he showed that basically the same results. And that was kind of like maybe like that's that's where the things begin to turn a little bit. Yeah. And so is that when like the scientific or medical implications of these findings, it was not only like, OK, you know, first there's this ground truth thing. Are we seeing what we actually think we're seeing? And then how soon after that was how can we use this then to help cure infectious disease? Yeah. So fairly soon. I think it was 1919 if I am not mistaken, when they first tried phages on the very first patient, like a very sick child. First the medics themselves drank phages and they showed that nothing happened. And then they gave this phages to a very sick child, a child recovered in 24 hours. I think there were like a few other children. They drank his and 30 phages. And I think the next really big breakthrough was in 1925 when the rail managed to cure a couple of cases of bubonic plague. What sort of was the turning point for the medical community then reconsidering phages as a viable thing and as something that is not just, you know, in in these guys head where they're just like, coming and they're talking about nothing and they're like, oh, here comes another one. At what point did that transition happen? I think it sort of like slowly happened over like the next maybe few years, like after 1919. But I think if the 1925 when they're out cured bubonic plague was probably a really, really big turning point. Because everybody like immediately paid attention. I mean, there was no cure of them from the bubonic plague. You got it, you died. I mean, it's almost depopulated Europe in the Middle Ages. So and Dorel was stationed in some port city in Egypt and a couple of sailors fell in with the bubonic plague. And he had phages that he brought from India where he isolated it from rats. You know, rats can carry the plague but not die from it. So he made this new phage concoctions and he treated the sailors with phages and they recover it. And that was just like nothing short of a miracle. Oh my gosh, I mean, to then go from, you know, laughing stock to cure of bubonic plague, this like very fear disease, that is, that's incredible. And then we go from that to a whole institute being created for the explicit reason to study phages. Can you tell me a little bit about this institute? So Eliava and Dorel became not just like lifelong friends but also lifelong collaborators. And so Eliava had this really grand idea of building a bacteriophage research center and a treatment center in Tbilisi in Georgia. And at the time he had a fair amount of money because Stalin, who was Georgia himself, was willing to throw a bunch of money into his home state, especially for things like medicine because healthy populations means strong empire and he was building strong empire. So the plans for the institute were approved and there was a crazy amount of money given like several millions which God knows how much it would be in today's money. But it was a very turbulent time in history, in particular in the history of the Soviet Union because Stalin was very paranoid about keeping his grip on the country, keeping his power and he wasn't tolerating any dissent. And Eliava, like many brilliant people, was known to speak his mind and eventually that caught up with him. So he was arrested and tortured, like really, really brutally tortured. I was able to find some interrogation manuals and when you looked at it you could literally see how all this was constructed. Like, you know, people who were interrogating him couldn't even decide what they wanted him to say. One day they would want him to say that he was working with the French intelligence and next day was the British intelligence. So the end result was that he was killed and the center never materialized in all the glory that it was envisioned. But the concept of using phages as medicines survived because there was really nothing else at the time. And it basically stayed in Belize like in a time capsule of sorts and it was used through all of the years of Soviet power. This huge loss that the phage therapy field faced, you know, how was that immediately felt? And then what were some of the long term implications of that in, let's say, like the decade or so that followed Eliava's death? So the decade that followed Eliava's death was really, was a really difficult decade because we kind of like get into World War II, right? So what happened in late 30s in America is that the phage therapy in the West basically fell out of favor and for really interesting reasons for no fault of phages. It was mostly because it was kind of misused. People didn't necessarily know how to grow phages properly. And even when they did, phages didn't always work. And that happens too sometimes. Phages don't work for eczema. They don't work for hives. They don't work for allergies or herpes or whatever. But some companies advertised phages for this, you know, health issues. And of course, phages did nothing to those undermining new people's trust and physicians trust. And so all that prompted some prominent American physicians to examine medical literature in the late 1930s and they decree that phages aren't really trustworthy enough to use as medicines except maybe for like very specific things like staff. And then shortly after that, Western medics learned to mass produce antibiotics and that was the end of phages. Yeah, penicillin became the answer. And then the answer, yeah, penicillin became the answer. You know, at the same time, though, in the Soviet Union, phages were being used at a larger scale than they had been previously. Can you tell me about some of the prophylactic use of phages during World War II in Stalin grad? Yeah, that is like one of my favorite topics because it's just so mind-boggling and it's like so unknown, right? Yeah, and the prophylactic use of phages, I had no idea. I always thought of it as a treatment, not a prophylactic. Yeah, it's amazing. So we're now into 1942 and the Nazis forces are closing in on Stalin grad, like the Soviet strengthhold on the Volga river named after Stalin. So there's so many things that are tied to this city. You know, like first, it bears Stalin's name. Second, it sits on the way to the oil field of the Caucasus and whoever gets to keep the oil field will win the war because you need oil to run all this heavy machinery. And so the battle for Stalin was absolutely brutal. Neither side can afford to lose the city. And so sometime in summer, the Moscow hears some rumors about cholera cases among the German troops. And at first, they're very happy to hear that because, OK, well, that's good. And then they realize that, no, it's not good because cholera doesn't care. They don't care about front lines. If it's on that one side, tomorrow it'll be on the other. And they realize they've got this whole city that's bombed out to smithereens with sewage broken, water mains broken, and they realize it's going to be a disaster. And so they sent a woman there. Her name is Zinaida Yermolivayevna and she's one of the leading Soviet biologists, a microbiologist at the time, on a tiny plane that manages to somehow evade the German bombers and actually land there. And she comes with this tiny little bag of phages. And she hears that cholera has already arrived and she knows that she doesn't have enough phages. So she calls Moscow and says, we need more phages. Moscow loads up all its phage arsenal on a train and the train goes to Stalingrad and it never makes it because it gets bombed out to smithereens. And she goes, okay, we'll have to grow phages here. We've got Volga right there. There's got to be cholera in there and their phages will be in there. And of course they are. So they take the samples and they go underground. They go into the basements so that bombing can destroy them. And in that, in those basements, they grow enough phages to basically give for prophylaxis the entire city on a daily basis. I think she wrote in her memoirs that 50,000 people took this bacteriophage daily and it never before happened in history. And it was so profound that you couldn't leave the city without having a certificate that you took your phages and even bakeries wouldn't give out bread without that paper. I mean, it's such an incredible story. And like you said, it's such a profound demonstration of the power of phages. But also it does make sense considering the larger historical context, how this discovery did not become more widely known and did not sort of make phages be front and center of biomedical research at the time. And I want to kind of talk about that historical context, how this implementation of prophylactic phages didn't happen in a vacuum. There's war as the backdrop. And so can you talk about sort of this larger context and what that meant for the distribution of this information? Yeah, it's a very good point. I mean, yeah, not all secrets were shared. And I think there actually were some medical collaborations during World War II. And there were some European and American scientists who were working with Zinaida Yermoliva, but more so on antibiotics than phages. And I think they just didn't think the phages were realistic enough that they were like really useful. I don't know why it didn't happen. Part of it could have been just like the general mistrust. It just never took off. Let's take a quick break here. We'll be back before you know it. Welcome back, everyone. I'm here chatting with Lina Zeldovich about her book, The Living Medicine. Let's get into some more questions. There was a passage in your book where you talked about sort of these social and cultural and scientific differences between the West and the Soviet Union and how that sort of led to one pursuing antibiotics and the other pursuing phages in terms of, again, kind of like as we talked about this reactive versus proactive approach to medicine and public health. And I was wondering if you could talk a little bit more about that. In the West, I should say, and in America probably more in particular, by the end of 1930s, the trust in phages kind of trapped. And I think people that generally thought of them with suspicions. Even the companies that manufactured phages in 1930s by 1940s, they switched to antibiotics in the post-war era. Synthesizing molecules that work consistently the same way. It was easy and cheaper than growing these finicky creatures with, you know, picky appetites whose biology scientists still didn't fully understand. And physicians agreed at the time a large percentage of American doctors were private practitioners and many worked from their home offices and they weren't attached to any bacteriological laboratories or hospitals. They didn't necessarily have, you know, test labs, let alone like complex facilities to synthesize phages there. In those settings, the easy ready to use medications that had a long shelf life and kill a wide spectrum of germs were bound to win, which is what happened. I mean, they offered all of this advantages, reliable, repeatable, stable, no significant side effects known at the time. They definitely won over phages. In the Soviet Union, however, medicine was a state endeavor. So a family couldn't start a company to grow phages or make penicillin. Medical school graduates couldn't open a private practice. Everybody was applied by the states and all medicines were made at research institutions or like large state owned factories. And that made it harder to produce false advertisements, especially when the director's head was on the line. Right. If their products didn't work or worse made patients sicker, they could be declared the enemy of the people and that was it. So consequently, Soviet scientists had like a very different medical paradigm. Western medicine embraced stability in life, in laws and in drugs, but the Soviet medicine, they just learned to exist in this ever shifting landscape. You know, if penicillin was mass produced today, it didn't mean that the factory was still there tomorrow. The raw ingredients could vanish. The inventor could be arrested. So Soviet medicine used whatever they had on a given day. They had antibiotics. Good. Don't have antibiotics. All right, let's go to the nearest river finds of phages. Wow. Yeah. That's a fascinating lens to think about sort of the differences in what drives innovation and what drives accessibility. To equipment, all of that. And so when antibiotic resistance started to show up in around the world, which it did, you know, very soon after penicillin was started to be widely used. How did phage therapy, how was that used in the Soviet Union to treat resistant infections? Yeah, that's a great question. Like basically, if antibiotics stopped working, there was always a phage. I mean, Tbilisi kind of remained a center of all sorts of phages, but there were other towns in the Soviet Union that produced some phages and they could treat patients with it. What was really interesting to me when I was working on this research is that Tbilisi maintained sort of like a global by the Soviet standards, global library of phages. And not only maintained, but they constantly updated it. And they had literally thousands and thousands of them. And by updating, I mean, they would continuously gather samples, bacterial samples from all over the country and they would bring this new samples to the labs and they would see, you know, is this bacteria evolving resistance to our phages? Oops, it is. Okay, time to find a better phage. Let's go out to the river. That literally like went on for years and years and years and they never stopped and they still do that. To anticipate the future problems and to be able to have that in advance. And I think that's why I keep thinking about phages as being this proactive approach where you can see almost immediately if you're detecting antibiotic resistance, you can find a phase for that. As you describe in your book, there's this incredible moment where the specific meeting where the knowledge of phage therapy is, you know, brought up in this room in this academic setting and in the US and the American scientists have no idea. They know what bacteriophages are, but they have no idea what phage therapy is. I was wondering if you could sort of paint me a picture of that story and this kind of reawakening of knowledge about phages in the West. Sure. So we're now in the early 1990s when the Soviet Union is falling apart, maybe it's already fallen apart. And this Georgian scientist comes from Tbilisi to America for a post-doctored fellowship. And he is working in the laboratory of a fairly well known infectious disease physician, Glenn Morris, at the Maryland School of Medicine. And one day, Glenn Morris, who was an infectious disease physician, a practicing physician, comes to the lab and he doesn't look like himself. So the Georgian, his name is Sandra, sees him like that and he asks, you know, what happened? And Glenn says, well, I just lost a patient to an antibiotic resistant infection. I mean, this man, he battled through cancer and chemotherapy and recurring new cancer and chemotherapy. And he was in his 40s, so still fairly young. And he went through all of this. And then at the end, he succumbed to an antibiotic resistant infection because they couldn't find an antibiotic to kill this bug that infected him. And Sandra just went so, and the bacteriophage didn't work either. And Glenn just gave him that stare like this, this, this, this day like, what? And when I was talking to Sandra, and I talked to Sandra so many times for this book, it was just a moment of reckoning. It was just like, oh my God, these people really don't know? Like, we could treat this in my hometown. You know, he came to America because it was the place to do science and how can this be? And so he basically took it upon himself to work for the next 25, 30 years to work with the FDA to convince them that this was a credible treatment. And if it's done right, it can really save so many lives. I mean, what a moment of shock on both sides. Like, what do you mean phage therapy? What do you mean? What do you mean phage therapy? Like, how do you not know what this is? What is this? Yeah, it's such a mind blowing moment, I think. And then there were several, that was like one turning point. And there seemed to be several turning points. It's like slow momentum growing of interest in phage therapy in the West, in the US. And can you talk about some of these major moments that eventually led to people pursuing this as a legitimate field of research with such potential? So initially, when Sandra and Glenn tried to put together some research proposals to study phages for medical purposes, they wouldn't get any money. And in fact, the entire world would laugh at them just like they laughed back then at DRL. Eventually, Thunder kind of like changed his new path a little bit and he began to work on phages for food safety. So bacterial contamination is a huge problem in the food industry, as we all know. Like almost every week something is being recalled, right? So his company now makes phage sprays that you spray on lettuce, meat, sausages and whatever that kill very specific foodborne pathogens and they work very well. So it is easier to get approval from FDA for food safety or food products than medical products because medical products are for people who are very sick. Right. So I think I think it was somewhere in the middle of 2000, the first decade of 2000 was when they get their first approval and then they got more approval for different type of phage sprays and they now manufacture quite a few. So you could probably count this as a huge milestone. Even though it doesn't appear as huge, but it is because it basically proved that phages were safe. They didn't cause any harm. And then another big milestone happened a few years down the road somewhere around 2016 when one particular person picked up an antibiotic resistant bacteria, Acinobacter bamania while traveling in Egypt with his wife and ended up basically on the brink of death in one of American hospitals. So this is a really unique couple. The guy's name is Tom Patterson and his wife's name is Stephanie Strasse and she is a scientist herself. And they've tried every antibiotic known to science and none of them worked. And so she was basically a question of losing her husband or trying something else. And she sat down and did research and she stumbled upon phage therapy. And because she had enough scientific knowledge and she knew enough people in the scientific field, she was able to work with other scientists who studied phages to create certain cocktails that were able to kill this bacteria in her husband. And in fact, it was like a first round of cocktails, second round of cocktails. And at the end, they also used one more antibiotic and that finally cleared it. And that was the first time the FDA ever approved an investigational new drug phages for use on humans. And it worked. It worked so spectacular because there was nothing else to try. And that was a really big pivoting point which kind of brought phages from scientific obscurity back on the front lines. And since then, a whole bunch of clinical trials are relaunched. That is one of my favorite stories, the perfect predator, which is Stephanie's book. And it is so amazing because it is sort of this huge moment that I think raised awareness to not just within the scientific community, but more broadly about this possible solution and how that then sort of paved the way. You know, if the public wants it, then maybe we should look more into this. And so that, as you said, has led to such a resurgence in interest. But there are still some hurdles to overcome, as you mentioned earlier, like FDA approval and also incentivizing research into phage therapy. What are some of those challenges in terms of like the logistical side of things, incentivizing research, making people even more aware than they are? I think the original challenge was that years back the FDA didn't necessarily know how to test phages. Like, if you think about it, the holy grail of a medicine production is to make sure that medicines don't change, that they're always the same. And that's how they pass through studies. And we know they're going to work the same way in just about everybody. Phages are tricky because they change. They may change within a person because they multiply, right? So a slightly new generation of phages may have slightly different genome. They also, again, multiply, which means you give a person a particular dose, but then there's more phages, more than that dose. And you don't know to what extent they're going to grow. So how do you even decide how much phage to give to anybody? So there was like a lot of challenges like that. But what the FDA is doing now is that so they have two centers. There's a center for drug evaluation and then there's a center for biologics evaluation. And that center for biologic evaluation regulates products derived from like living sources. For example, flu vaccines, which also change from one season to the next. And so that's where phages now fall under and that's the department that regulates it. Yeah, I mean, it seems like there is a promising path forward in terms of getting phage therapy just to redraw some of the standards that we have to not just discard them entirely because of these characteristics that they have. And so how far away do you think that we are here in the US from phage therapy being like a routine or at least a more widely available option? That's a great question. And I've asked that question almost everybody. And, you know, the best you get is like, I don't know, five to 10 years or something. It seems that it's moving a little bit faster in Europe. But I don't think we have a lot of options. And that's why I think it has to go a little bit faster because our antibiotics are losing their punch like way too quickly. You know, when I was working on this book, I first started working on this book, the CDC's 2019 report said that every 15 minutes someone dies from an antibiotic resistant infection. So we talked for almost an hour, those four people. Then CDC's 2022 report said that it's gotten worse. And then newer estimates say that by 2050, antibiotic resistance will kill three people every minute. So like you do the math. And the United Nations has never dreamed of prediction 10 million deaths annually by 2050. It's like it's pretty freaky. So I think it's like necessity is the mother of invention. So I think necessity will just push us to getting this to the finish line sooner rather than later. Yeah, I hope so. I mean, I would love to see a world in which we have alternatives to antibiotics as part of just building a wider toolkit to deal with this growing problem of antibiotic resistance. And I want to close out the interview by asking you what phages mean to you personally. I've been fascinated with phages probably since I was a kid, because I first probably, I don't know, maybe six or seven when I stumbled upon a phage study in one of the scientific magazines that we had at home. A lot of people in my family was scientists. I grew up with all this stuff just kind of like sitting there. And in Russian, the word phage is just three letters. And it starts with a letter F that looks like a person who is standing with their arms on their hips, kind of like this very confident figure that says, don't mess with me. And the picture of a phage itself kind of resembled that. So I started reading that study. And there weren't too many familiar words, but I spotted one that I knew, Dysentery, which I was personally acquainted with because last summer, the city got a contaminated shipment of grapes and so many kids were sick. And there were not enough antibiotics. And eventually my grandfather found some antibiotics somewhere in a pharmacy. That's what I took. But this study purported that these phage creatures could be used as an alternative to antibiotics. And that was just so interesting to me that it sort of stuck with me. And I also like the phage character as a character. So I brought my colored pencils and like, you know, colored that phage character in different colors. And the whole thing just stuck with me and it continues to, you know, like some things get lashed in your head. And that was one of those. I love that story. What a fun, just like this thing that you came across and something about it just stuck with you. That's wonderful. Well, this has been such a fascinating conversation. I've long been a fan of phage therapy and I am just so excited to have read more about it and understand more about the historical context. So thanks again so much for taking the time to chat with me today. Oh, thank you for inviting me. Thank you. I'll post a link to where you can find the living medicine. How a forgotten cure may rescue us when antibiotics fail, as well as a link to Lena's website where you can find her other incredible work. And don't forget, you can check out our website for all sorts of other cool things, including but not limited to transcripts, quarantini and placebo reader recipes, show notes and references for all of our episodes, links to merch, our bookshop.org affiliate account, our Goodreads list, a Fristain account form, and music by Bloodmobile. Speaking of which, thank you to Bloodmobile for providing the music for this episode and all of our episodes. 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