Special Episode: Lina Zeldovich & The Living Medicine

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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.

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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.

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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.

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 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 featured Stephanie Strathdee 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 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 bacteriophages and what is phage therapy?

Like, what does it mean if someone is receiving phage therapy?

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 call it 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.

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 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, you know, how people go through this process.

Where do you find phages?

So phages, you find phages everywhere.

There are out there in soil, in water, in the air, in sewage, on rotten fruit, just 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 cholera 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 uh most bacteria is fairly easy to grow you just put a bunch of like meat scraps you cook uh basically a bullion and you see this bullion 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 um 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 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 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 it somebody intravenously you don't want all this bacterial debris in there because your immune system is going to react to that you know bacterial debris and toxins and whatnot and it may go into shock

and you know purifying well sounds kind of simple but it's not because you need 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.

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.

I'm trying to imagine the timeline for this.

And I know that it can be very different depending on in the U.S.

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 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 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.

It's such an incredibly like an obvious solution to what is growing to be an increasingly 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 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 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.

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 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 don't evolve.

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, they 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.

Some manage even surround themselves 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 resistant to our 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 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

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Welcome back, everyone.

I've been chatting with Lena 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.

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 a cure can be contagious was one of the early phage therapy adopters, Félix Therrell, who was trying to stop an outbreak of salmonella in

chickens in France.

And he realized that as soon as one chicken would get a bacteriophage against the salmonella, the entire coupe would recover because they all peck at each other's species.

So it 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 that put the phage therapy cure, and then you're done.

That's it.

Yeah.

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, 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 Félix Durrell in Paris working at the Pasteur Institute, which is like the holy grail of science, medical science at the time.

And he's both neurobiologist 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

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.

So he starts looking into

this person's tool 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 like these two samples and inoculates other dysentery bacteria samples

with it.

And lo and behold, dysenteria 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 the 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 Tpilisi, 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 I, which just ended,

where he tended to to sick soldiers who had cholera and dysentery and whatnot.

And he is looking into the 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.

Like he has to go somewhere.

He locks 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 color 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 color does it again same result he knows he's on to something but he can't figure out what is he on to

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 other other medicines, because that's, again, at the time where that's where everybody went to study.

He goes to Paris and he walks into this really heated debate.

So Durrell's,

the scientific world did not welcome Durrell's finding.

peacefully

because it really to them it didn't make sense.

You know, you're talking about invisible destroyers that destroy disinterry.

No, it also doesn't fit into the established immunity theory

at the time.

So basically at that moment, Tyrrell is a laughingstock.

And at the moment, he's out there in the countryside dealing with chicken salmonella.

So Eliyahu walks into Fastor's Institute 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 were the character differences come into play.

So Tyrrell was kind of a prickly character.

He spoke his mind and probably made a fair amount of enemies in his life.

And Eliyah was exactly the opposite.

He was this absolute charmer.

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 and 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 your 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, okay, you know, first there's just 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?

Yeah, so

fairly soon, 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, and the child recovered in 24 hours.

I think there were like a few other children they drank pizzin theory phages.

And I think the next really big breakthrough was in 1925 when Durrell 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 these guys' head 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?

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 Durrell cured bubonic plague, was probably a really, really big turning point because everybody like immediately paid attention.

I mean, there was no cure from the bubonic plague.

You got it, you died.

I mean, it's almost, it depopulated Europe in the Middle Ages.

So, and Durrell was stationed in some port city in Egypt, and a couple of sailors fell in with chronic 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, you know, made these new phage concoctions and he treated the sailors with phages and they recovered.

And that was just like.

nothing

short of a miracle.

Oh my gosh.

I mean, to then go from laughing stock to cure of bubonic plague, this like very fear disease, 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 Eliyah and Durrell became not just like lifelong friends, but also lifelong collaborators.

And so Eliyah 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 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 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 right um but it was it was a very you know turbulent time um in in in history in particular in the history of the soviet union because stalin was very paranoid about you know keeping his grip on the country uh keeping his power and he wasn't tolerating any dissent and aliyaba like many brilliant people was known to speak his 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 of the 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.

Like, you know, one day they would want him to say that he was working with the French intelligence, the next day with the British intelligence.

But 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 and it like basically stayed in Tbilisi 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 Eliyah's death?

So the decade that followed Eliyah's death was really

a difficult decade because we kind of like get into World War II, right?

So what happened in the late 30s in America is that the phage therapy in the West basically fell fell out of favor and for really interesting reasons for no fault of you know 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

new health issues.

And of course, phages did nothing to those, undermining

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 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.

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 Stalingrad?

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 esophagus of

i 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 staling grad like the soviet stranghold on the volga river named after stalin so that so many things are like uh uh 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 caucus 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 is absolutely brutal.

Neither side can afford to lose the city.

And so sometime in summer,

Moscow hears some rumors about cholera cases among the German troops.

And at first they're very happy to hear that because, okay, well,

that's good.

And then they realize that, no, it's not good because cholera doesn't care.

It doesn't care about front lines.

If it's on 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 like sewage broken, you know, water mains broken.

And they realize it's going to be a disaster.

And so they sent a woman there.

Her name is Zinaida Yermuleeva, and she's one of the leading Soviet biologists, microbiologists 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 colour 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 smith rains.

And she goes, okay,

we'll have to grow phages here we've got volga right there there's got to be uh cholera in there and their phages will be in there and of course they are so they you know take the samples and they go on the ground they go into the basements so that your 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 that there actually was some medical collaboration during World War II.

And there were some European and American scientists who were working with Zinaida Yaramoroleva, but more so on antibiotics 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.

Let's take a quick break here.

We'll be back before you know it.

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Welcome back, everyone.

I'm here chatting with Lena 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 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 America,

in the West, I should say, and in America probably more, you know, more in particular,

by the end of 1930s, the trust in phages kind of dropped.

And I think people generally thought of them with suspicions.

Even the companies that manufactured phages in the 1930s, by 1940s, 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 worked from their home offices and they weren't attached to any bacteriological laboratories 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.

And 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 seeker, 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 medics embraced stability.

in life, in laws, and

in drugs, 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 a given day.

They had antibiotics, good.

Don't have antibiotics.

All right, let's go to the nearest river, find some pages.

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 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, Tspilisi 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 Tspilisi 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 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.

To anticipate 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 the specific meeting where the knowledge of phage therapy is brought up in this room in this academic setting and in the U.S., 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 falling apart.

And this Georgian scientist comes from Tpilisi to America for a post-doctorate 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 I just lost a patient to an antibiotic-resistant infection.

I mean, this man, he battled through, you know, 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 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 Glan just gave him that stare, like this, this, this, this stare, 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.

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.

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?

Right.

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, this like slow momentum growing of interest in phage therapy in the West, in the U.S.

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, you know, at Durrell.

Eventually, Tandra kind of like changed his 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 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 an approval from FDA for food safety or food products than medical products because, you know, 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, you know, 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 when one particular person picked up an antibiotic-resistant bacteria, Acinobacter Bermania, 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 Strassi.

And she is a scientist herself.

And they've tried every antibiotic known to science, and none of them worked.

And so it 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, you know, one more antibiotic, and that finally cleared it.

And that was the first time the FDA ever approved an investigation on 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 like big pivoting point,

which kind of brought pages from scientific obscurity back on the front lines.

And since then, a whole bunch of clinical trials were launched.

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 too, 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 FTA didn't necessarily know how to test phages.

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.

change.

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 do you even decide how much phage to give 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, you know, phages now fall under.

And that's 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 U.S.

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, when 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 an emergency 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 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, with 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

you know confident figure that says don't mess with me and it was 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

you know last summer we 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 in a pharmacy and that's what I took but the 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 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.

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.

A huge thank you again to Lena 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, quarantining 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 frontained 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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And thanks to you listeners for listening.

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