Pod Insights This Podcast Will Kill You Special Episode: Lina Zeldovich & The Living Medicine About this episode The development of antibiotics was one of the greatest turning points in the history of medicine. Bacterial infections that were once death sentences were cured within a matter of days after administration of these lifesaving compounds. But the honeymoon didn’t last long, as resistant bacterial strains emerged and spread. Now, antimicrobial resistance poses one of the greatest threats to global health; frankly, we can’t invent new antibiotics faster than resistance develops. Fortunately, there may be a solution, one that has existed even before antibiotics came on the scene: phage therapy, the use of bacteriophages to treat bacterial infections. In The Living Medicine: How a Lifesaving Cure Was Nearly Lost—and Why It Will Rescue Us When Antibiotics Fail https://bookshop.org/a/3175/9781250283382, author Lina Zeldovich https://linazeldovich.com/ takes readers through the incredible and long-forgotten story of phage therapy and the doctors who developed it. Tune in to learn how phage therapy, after almost being relegated to a footnote in the history of medicine, is reemerging as a possible solution to the deadly problem of antimicrobial resistance.
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Transcript 0:01 Speaker 00 This is Exactly Right.
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0:38 Speaker 00 Hey, I'm Niall Rogers. This fall, I'll be driving across the country, meeting some of today's coolest and most fascinating artists. We'll explore the stories before the moments that changed everything. Because every musician remembers the moment where it all began. Experience Before the Moment, a Lincoln Original Series on the iHeartRadio app, YouTube, or wherever you get your podcasts.
1:53 Speaker 02 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, thispodcastwillkillyou.com.
2:36 Speaker 02 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 the 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
3:22 Speaker 02 so you never miss a new episode drop. All right, 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 due in part to antimicrobial resistance. That's more deaths than HIV, tuberculosis, and malaria combined.
4:07 Speaker 02 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.
4:40 Speaker 02 In this week's episode, I am joined by journalist and author Lina Zeldovich 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
5:21 Speaker 02 featured Stephanie Strathde 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, Zeldovich takes readers through the history of phage therapy, where we get to meet the visionary researchers that championed this treatment, discover how
6:04 Speaker 02 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.
7:00 Speaker 02 Lina, thank you so much for taking the time to chat with me today.
7:04 Speaker 03 Thank you for having me here. I'm very excited to talk about all things phages.
7:08 Speaker 02 Let's start at the very beginning. What are bacteriophages and what is phage therapy? Like, what does it mean if someone is receiving phage therapy?
7:17 Speaker 03 So, 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. So, phages are different. Phages don't have the right biological equipment to afflict humans. They can only attack bacteria, and that's why they're called bacteriophages. They prey on bacteria out there in nature, and they've been doing this for millions of years, kind of evolving alongside each other. Typically, it's like one phage per one bacteria. They're very picky at what they eat. And that makes bacteriophages our friends. So, basically, an enemy of my enemy is my friend.
7:58 Speaker 03 So, we can use these amazing creatures as alternatives to antibiotics when antibiotics don't work. And there are different ways of administering, you know, phage therapy. But basically, you either drink them for intestinal diseases, or you put them on skin or wounds. And there are some trials out there that inject bacteriophages 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 formulations must be clean from all sorts of things that may trigger your immune system to go haywire.
8:38 Speaker 02 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, you know, how people go through this process. Where do you find phages?
8:54 Speaker 03 So, phages, you find phages everywhere. There are out there in soil, in water, in the air, in sewage, on rotten fruit. Just, they're basically everywhere. In 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 you test them on what bacteria, phages they just found will work. And that's how they know that they've got a phage for, let's say, you know, this strain of cholera
9:40 Speaker 03 or this strain of dysentery or this strain of something else.
9:43 Speaker 02 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?
10:00 Speaker 03 The way it works is that first, you grow your bacteria, which is very easy. Most, most bacteria is fairly easy to grow. You just put a bunch of like meat scraps, you cook basically a bouillon. And you see this bouillon with bacteria and they just love it. They, they, they, they're so happy there, they procreate, they grow. And once you have enough there, you inoculate the brood with phages. And phages set to work and they attack this bacteria. The way they work is that they get into bacterial cells, they multiply inside them, they burst bacterial cell open. And once you have almost no bacteria there, you know you have a lot of phages.
10:42 Speaker 03 And that's when the purification step comes in. And 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 to 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 you're purifying, well, it sounds kind of simple, but it's not because you need like ultra sophisticated equipment. Basically, you need special certifuges that spin very fast and they like manage to like separate phages from everything else and that's how you get your clean phages.
11:25 Speaker 03 Again, I said, it sounds very simple, but the right equipment for that, because we're dealing with like super tiny structures, that only became available fairly recently.
11:37 Speaker 02 I'm trying to imagine the timeline for this and and I know that it can be very different depending on in the US, you know, 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? Like, do we have to be reactionary or can we be proactive?
11:59 Speaker 03 So I think we still approach this on a per case basis. If if a team of doctors wants to treat a patient that is 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.
12:18 Speaker 02 It's such an incredibly like an obvious solution to what is growing to be an increasingly a huge problem, you know, antibiotic resistance. And I want to kind of get into the differences between phages and antibiotics in terms of, you know, in 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?
12:50 Speaker 03 Probably. I think at least at this point, it looks like antibiotics would still be our like 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.
13:30 Speaker 03 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. Uh, they're static. They don't evolve.
13:55 Speaker 04 Hmm.
13:56 Speaker 03 And bacteria are amazing at various mechanisms of resistance that they just evolve. 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 outer coats, if you'd like, so antibiotics can stick to. And 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.
14:40 Speaker 03 So even if a bacteria develops a 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 that, at the, at the level of this microorganism, it can happen very fast.
14:56 Speaker 02 Let's take a quick break, and when we get back, there's still so much to discuss.
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16:00 Speaker 00 Hey, it's Niall Rogers, host of Before the Moment, a Lincoln original series. I'm driving across the country, meeting some of today's most fascinating artists. We're exploring the stories before the moment that changed everything. This week, I'm joined by Miguel.
16:18 Speaker 05 Man, I'm a Black and Mexican kid from San Pedro, and I grew up in Inglewood as well. I never liked to be boxed in. Both of my parents colored outside of the line. I mean, even them being together at the time in L.A. was just not typical. And so I think that has always been a part of my DNA. There's a defiant something in me that feels like what we get to do with what we're given that's greater than us is to maybe connect people to ideas that they wouldn't naturally, you know, connect to. That's really me. I'm just kind of like defiant with love, though.
16:54 Speaker 00 Experience Before the Moment, a Lincoln original series on the iHeartRadio app, YouTube, or wherever you get your podcasts.
17:19 Speaker 02 Welcome back, everyone. I've been chatting with Lina Zeldovich 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.
17:48 Speaker 03 It's, I mean, for me, 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 phage therapy uh in a little bit, but the first person who realized that you know, phages as a cure can be contagious was one of the early phage therapy adopters, Felix Dierel, who was trying to stop an outbreak of Salmonella in France, in chickens, in France. And he realized that as soon as one chicken would get um a bacteriophage against this Salmonella, the entire coop would recover because they all peck at each other's feces.
18:32 Speaker 03 So it would just spread through all of them. And suddenly, they would be not sick anymore.
18:37 Speaker 02 That's amazing. I mean, also talk about like, then you just have to get one chicken, uh, the phage therapy cure, and then you're done. That's it.
18:45 Speaker 03 Yeah.
18:45 Speaker 02 Uh, 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 front line of, um, 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?
19:13 Speaker 03 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 Dierel in Paris, working at the Pasteur Institute, which is like the holy grail of science, medical science at the time. Um, and he's both a biologist and, 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, you know, very shortly. And so, you know, people are dying, but one of his patients recovers. And he figures this has to be something in his stomach that helped him recover.
19:55 Speaker 03 So he start looking at to uh this person's stool samples. And he realizes that there is no dysentery bacteria in there anymore. So he's like, hmm, something's killing it. So let's try this. He takes like these stool samples and inoculates all the dysentery bacteria samples, you know, with, with it. And lo and behold, dysentery bacteria dies there too. And then the next one, and 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 nineteen thirty to actually see any virus.
20:36 Speaker 03 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. Yeah. There is another scientist, a Georgian scientist, Georgi Aliyeva, 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, um, where he tended to, you know, seek soldiers who had cholera and dysentery and whatnot. And he is looking into presence of cholera in the city water,
21:20 Speaker 03 in, in, in the river where everybody gets the water from. And, you know, 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. Like 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.
22:00 Speaker 03 Uh, fast forward a few more months, he has to go to Paris to study at the Pasteur's Institute, how to, you know, make vaccines and, and other medicines. Cause that's, again, at the time, that's where everybody went to study. He goes to Paris and he walks into this really heated debate. So Dirrell's, the scientific world did not welcome Dirrell's findings peacefully. Because it really, to them, it didn't make sense. You know, we're talking about invisible destroyers that, you know, destroy this and theory. No, it also doesn't fit into the established immunity theory, you know, at the time. So basically, at that moment, Dirrell is a laughing stock.
22:44 Speaker 03 And at the moment, he's out there in the countryside dealing with chicken salmonella. So Eliela walks into, and right in the middle of all this, and he goes, I've seen that too.
22:58 Speaker 03 And they're like, all right, another one. But here were the character differences coming to play. Dirrell was kind of a prickly character. He spoke his mind and probably made a fair amount of enemies in his life. And Eliela was exactly the opposite. He was this absolute charmer, like people, he could sweet talk anybody into anything.
23:20 Speaker 03 When I, 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 experiments? And 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.
23:46 Speaker 02 Yeah, and so is that when like the scientific or medical implications of these findings? It was not only like, okay, you know, first there's this ground truthing. 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?
24:07 Speaker 03 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, you know, drank phages and they showed that nothing happened. And then they gave these phages to a very sick child, and the child like recovered in 24 hours. I think there were like a few other children, they drank this and theory phages.
24:39 Speaker 03 And I think the next really big breakthrough was in 1925, when Darrel managed to cure a couple of cases of bubonic plague.
24:49 Speaker 02 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' heads where they're just coming and they're talking about nothing. And they're like, oh, here comes another one. At what point did that transition happen?
25:09 Speaker 03 I think it sort of like slowly happened over like the next maybe few years, like after 1919. But I think if if the 1925, when Darrel 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 it depopulated Europe in the Middle Ages. So and and Darrel was stationed in some port city in in Egypt. And a couple of sailors fell in with 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.
25:55 Speaker 03 So he, you know, made this new phage concoctions. And he treated the sailors with phages and they recovered. And that was just like nothing, you know, short of a miracle.
26:07 Speaker 02 Oh, my gosh. I mean, to then go from, you know, laughing stock to cure of bubonic plague, this like very feared disease, that is, that's incredible. And and then we 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?
26:27 Speaker 03 So Eliava and Darrel became not just like lifelong friends, but also lifelong collaborators.
26:35 Speaker 03 And so Eliava had this really grand idea of building a bacteria phage 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 Georgian himself, was willing to throw a bunch of money into his home state, especially for things like medicine, because healthy populations means a strong empire, and he was building a strong empire. So the plans for the institute were approved and yeah, there was a crazy amount of money given, like you know, several millions, which God knows how much it would be in today's money.
27:16 Speaker 02 Right.
27:16 Speaker 03 Um, but it was, it was a very turbulent time um in, in, in history, in particular in the history of the Soviet Union, because Stalin was very paranoid about keeping his grip on the country, uh, keeping his power, and he wasn't tolerating any dissent. And Eliyahu, like many brilliant people, was known to speak his mind, and eventually that caught up with him. Um, so he was arrested and tortured, like really, really brutally tortured. I, 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.
28:01 Speaker 03 Like, you know, one day they would want him to say that he was working with French intelligence, the next day was the British intelligence, but the end result was that he was killed. And um, 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.
28:26 Speaker 02 Mm hmm.
28:27 Speaker 03 And, and it like basically stayed in Belisi, like in a time capsule of sorts, and it was used through all of the years of Soviet power.
28:37 Speaker 02 This huge loss that the phage therapy field faced, you know, how, how was that immediately felt? And then what were some of the long-term implications of that in, let's say, like the, the decade or so that followed Eliyahu's death?
28:52 Speaker 03 So the decade that followed Eliyahu's death was really, was a really difficult decade, because we kind of like get into World War Two, right? Um, so what happened in late thirties in, in America is that the phage therapy in the West basically fell out of favor, and for really interesting reasons.
29:14 Speaker 03 For no fault of, you know, phages. Uh, 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.
29:37 Speaker 02 Right.
29:37 Speaker 03 Or herpes or whatever, but some companies had advertised phages for this uh, uh, you know, health issues and of course, phages did nothing to those undermining, you know, people's people's trust and, and, and physicians' trust. And so all that prompted some prominent American physicians to examine medical literature in late nineteen thirties. And they decreed 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.
30:13 Speaker 02 Yeah, penicillin became the answer and then.
30:16 Speaker 03 The answer, yeah, penicillin became the answer.
30:19 Speaker 02 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 Two in Stalingrad?
30:32 Speaker 03 Yeah, that is like one of my favorite topics because it's just so mind boggling and it's like so unknown, right?
30:38 Speaker 02 Yeah, and the prophylactic use of phages, I, I had no idea. I always thought of it as a treatment, not a prophylactic. Yeah, it's amazing.
30:46 Speaker 03 So we're now into nineteen forty-two and the Nazi forces are closing in on Stalingrad, like the Soviet stronghold on the Volga River named after Stalin. So there's so many things are uh, uh, 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 Stalingrad is absolutely brutal. Neither side can afford to lose the city.
31:24 Speaker 06 Hmm.
31:25 Speaker 03 And so sometime in summer, the Moscow hears some rumors about cholera cases among the German troops. And at first, they they're very happy to hear that because, okay, wow, that's that's good. And then they realize that, no, it's not good because cholera doesn't care.
31:42 Speaker 06 Right.
31:43 Speaker 03 Doesn't care about front lines. If it's on that one side, tomorrow will be on the other. And they realize they've got this whole city that they bombed out to smithereens with like sewage broken, you know, water mains broken, and they they realize it's going to be a disaster. And so they send a woman there. Uh, her name is Zinaida Yermolova, and she's one of the leading Soviet biologists, um, microbiologists at the time, on a tiny plane that manages to somehow evade the German bombers and actually land there. And and and she comes with this tiny little bag of phages. And and she hears that cholera's already arrived, and she knows that she doesn't have enough phages. So she calls Moscow and says, we need more phages.
32:27 Speaker 03 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. Oof. And she goes, okay, we'll have to grow phages here. We've got polga right there. There's gotta 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, you know, bombing can destroy them. And in that, in those basements, they grow enough phages to basically give for prophylaxis the entire city um on a daily basis.
33:08 Speaker 03 I think she wrote in her memoirs that fifty thousand people took this bacteria phage 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.
33:28 Speaker 02 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?
34:06 Speaker 03 Yeah, it's a very good point. I mean, yeah, not all secrets were shared. And I think that there actually was some medical collaboration during World War II. And there were some European and American scientists who were working with Zainayda Yermol, but more so on antibiotics than than phages. And I think they just didn't think the phages were realistic enough, that they were like, 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.
34:43 Speaker 02 Let's take a quick break here. We'll be back before you know it.
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35:46 Speaker 00 Hey, it's Niall Rogers, host of Before the Moment, a Lincoln original series. I'm driving across the country, meeting some of today's most fascinating artists. We're exploring the stories before the moment that changed everything. This week, I'm joined by my friend, John Ledge. How does music actually enter your mind?
36:08 Speaker 07 I'm not sure why or how the music comes to me, but I think people who love music and write music, our brains are just filled with music.
36:18 Speaker 00 Right.
36:18 Speaker 07 Like, we have listened to so much music, we've been a part of so much music. I think of the story that I want to tell, the mood that I want to create with the music, start playing chords, see where they lead me.
36:29 Speaker 00 Sometimes, I'm just not even thinking about music, right? And I hear this little thing, and I go, oh, that could be this.
36:39 Speaker 07 You know, you just have to be ready for when the inspiration hits.
36:42 Speaker 00 And it comes. Experience Before the Moment, a Lincoln original series on the iHeart Radio app, YouTube, or wherever you get your podcasts.
37:07 Speaker 02 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.
37:42 Speaker 03 In America, in the West, I should say, and in America, probably more in particular, by the end of nineteen thirties, the trust in phages kind of dropped. And I think people generally thought of them with suspicions. Even the companies that manufactured phages in nineteen thirties, by nineteen forties, they switched to antibiotics in the post-war era. Synthesizing molecules that worked consistently the same way was easy and cheaper than growing these finicky creatures with 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
38:27 Speaker 03 worked from their home offices, and they weren't attached to any bacteriological borders or hospitals. They didn't necessarily have 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 killed a wide spectrum of germs were bound to win, which is what happened. I mean, they offered all of these 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.
39:10 Speaker 03 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. 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. Yeah. So. Consequently, Soviet scientists had like a very different medical paradigm. Western medics embrace stability in life, in laws, and in drugs.
39:49 Speaker 03 But the Soviet medics, 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 would still be there tomorrow. The raw ingredients could vanish, the inventor could be arrested. So Soviet medics just used whatever they had on the given day. They had antibiotics, good. Don't have antibiotics, all right, let's go to the nearest river, find some phages.
40:17 Speaker 02 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?
40:45 Speaker 03 Yeah, that's, that's a great question. Like, basically, if antibiotics stopped working, there was always a phage. I mean, Spelisi kind of remained a center of all sorts of phages, but there were other towns in the Soviet Union that, you know, 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 Spelisi 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.
41:26 Speaker 03 And by updating, I mean, they would continuously gather samples, bacterial samples from all over the country. And they would bring these, these new samples to the labs, and they would see, you know, is this bacteria evolving resistance to our phages? Oh, 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.
41:55 Speaker 02 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 phage for that. As you describe in your book, there's this incredible moment where, a specific meeting, where the knowledge of phage therapy is 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 of that story and this
42:38 Speaker 02 kind of reawakening of knowledge about phages in the West?
42:42 Speaker 03 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 postdoctorate 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."
43:26 Speaker 03 I mean, this man, he battled through cancer and chemotherapy and recurring 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 I couldn't find 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, they're like, "What?" And when I was talking to Sandra, and I talked to Sandra so many times for this book,
44:05 Speaker 03 it was just a moment of reckoning. I 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.
44:37 Speaker 02 It, 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?
44:46 Speaker 03 Right.
44:47 Speaker 02 Yeah, it's, it's such a, 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. This like slow momentum growing of interest in phage therapy in the West, in the US. And can you talk about some of the, these major moments that eventually led to people pursuing this as a legitimate field of research with such potential?
45:14 Speaker 03 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, you know, at Durel. Eventually, Sandra kind of like changed his new path a little bit, and he began to work on phages for food safety. So bacterial contamination is, is a huge problem in, 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
45:59 Speaker 03 whatever that kill very specific foodborne pathogens. And they work very well. So it is easier to get an approval from FDA for food safety of food products than medical products, because you know, medical products are for people who are very sick.
46:16 Speaker 04 Right.
46:16 Speaker 03 So I think, I think I was somewhere in the middle of two thousand, the first decade of two thousand was when they get their first approval and then they got, you know, more approval for different type of, uh, you know, phage sprays and they now manufacture quite a few. So you could probably count this as a huge milestone, even though, even though it doesn't appear as huge, but it is because it basically proved that phages were safe, you know, they, they, they didn't cause any harm. And then another big milestone happened a few years down the road, somewhere around twenty sixteen, when one particular person picked up an antibiotic resistant bacteria,
46:58 Speaker 03 Asinabactobamania, 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 co- a couple. The guy's name is Tom Patterson and his wife's name is Stephanie Strasty 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, you know, people uh, in
47:39 Speaker 03 the scientific field, she was able to work with scientists who's, other scientists who studied phages to create uh, 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, you know, one more antibiotic and that, you know, finally cleared it. And that was the first time the FDA ever approved uh, an investigational new drug, phages, for use on humans and it worked. It worked so spectacular because there was nothing else to try.
48:17 Speaker 04 Yeah.
48:17 Speaker 03 And that was a really like big pivoting point. Which kind of brought phages from scientific obscurity back on the frontlines. And since then, a whole bunch of clinical trials were launched.
48:32 Speaker 02 That is one of my favorite stories, The Perfect Predator, which is Stephanie's book. And I, it is so, it is so amazing because it is sort of this, this huge moment that I think raised awareness to, not just within the scientific community, but more broadly about this, 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?
49:17 Speaker 02 Incentivizing research, making people even more aware than they are?
49:23 Speaker 03 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 what, that's how they pass through studies. And that's, and we know they're going to work the same way in, in just about everybody. Phages are tricky because they change.
49:54 Speaker 02 Right.
49:54 Speaker 03 They may change within a person because they multiply, right? So a slightly newer 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 to 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 is a center for biologics evaluation. And that center for biologic evaluation, it regulates products derived from like living
50:37 Speaker 03 sources, for example, flu vaccines, which also change from one season to the next. And so that's where, you know, phages now fall under and that's, that's the department that regulates it.
50:51 Speaker 02 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?
51:16 Speaker 03 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's, 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 the, 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
51:56 Speaker 03 with 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 a grim prediction, 10 million deaths annually by 2050. It's like, it's, 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, to getting this to the finish line sooner rather than later.
52:33 Speaker 02 Yeah, I, I, I hope so. I mean, I, 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, I want to close out the interview by asking you what phages mean to you personally.
52:53 Speaker 03 I've been fascinated with phages probably since I was a kid. Because I was 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 were 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 the letter F that looks like a person who is standing with their arms on their hips, kind of like this very, you know, confident figure that says, "Don't mess with me." And the picture of a phage itself kind of resembled that.
53:36 Speaker 03 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, you know, last summer, the city got a contaminated shipment of grapes and so many kids were sick. And there were not enough antibiotics. And, you know, eventually my grandfather found some antibiotics somewhere in a pharmacy. And 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 liked the phage character as a character.
54:21 Speaker 03 So I brought my colored pencils and I 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 lodged in your head and that was one of those.
54:33 Speaker 02 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.
54:56 Speaker 03 Oh, thank you for inviting me.
55:18 Speaker 02 A huge thank you again to Lina Zeldovich for taking the time to chat with me. I didn't know I could love phage therapy even more, but somehow I do. If you enjoyed today's episode and would like to learn more, check out our website, thispodcastwillkillyou.com, where 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 Rita recipes, show notes and references for all of our episodes, links to merch, our bookshop.org affiliate account, our Goodreads list, a first-hand account
56:00 Speaker 02 form, and music by Blood Mobile. Speaking of which, thank you to Blood Mobile for providing the music for this episode and all of our episodes. Thank you to Liana Scolacci and Tom Bryfogle for our audio mixing, and thanks to you listeners for listening. I hope you liked this episode and are loving being part of the TPWKY Book Club. And a special thank you, as always, to our fantastic patrons. We appreciate your support so very much. Well, until next time, keep washing those hands.
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