Hi, I'm Aaron Welsh and this is This Podcast Will Kill You.

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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 nineteen forties, but it is a growing and deadly one.

The WHO estimates that in twenty nineteen, antimicrobial resistance directly led to one point two seven million deaths and contributed to four point nine to five million deaths around the globe.

Nearly five million deaths due in part to antimicrobial resistance.

That's more death than HIV, tuberculosis, and malaria combined.

What's more is that these numbers are 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 bacteria phases to treat antibiotic resistant infections.

Many of us, such as those of us here in North America or Western Europe, may have learned about phase 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 Strathti 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 phagias are found and administered, and learn of the profound promise a hold for the global problem of antimicrobial resistance today.

This book will have you marveling at this forgotten cure and grateful for those who did not let it slip into permanent obscurity.

I have always been such a fan of phage therapy and it was a joy to chat with Lena and learn more about its history and current developments in the field.

I am so excited to share this conversation with you all, so let's just take a quick break and get into it.

Lena, thank you so much for taking the time to chat with me today.

Thank you for having me here.

I'm very excited to talk about all things phages.

Let's start at the very beginning.

What are bacteria phases 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 phagies are different.

Phagies don't have the right biological equipment to afflict humans.

They can only attack bacteria, and that's why they call bacteria phagis.

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 for one bacteria.

They're very peaky at what they eat, and that makes bacteria phagis 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 bacteria phages into the bladder for people who are dealing with recurring UTIs.

You can also administer them intraveniously nowadays, but it's more complicated because those firm relations 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 phases 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 phases?

So phages?

You can 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 phage is 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 phases 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 they just found will work, and that's how they know that they've got a phage full.

Let's say you know this strain of color, or this strain of discent theory, 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 phases?

And then what is the purification process like?

Or maybe why is the purification process so important?

The way it works is that first you grow your bacteria, which is very easy.

Most bacteria is fairly easy to grow.

You just put a bunch of like meat scraps, you cook basically a bullion, and you see this bullion with bacteria and they just love it.

They're so happy there.

They procreate, they grow, and once they have enough there, you inoculate the proof with phages, and phages set to work and they attack the 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 of drinking them, you can actually skip that step.

Historically, it works just fine.

What gets tricky is that if you want to give it somebody intravenously, you don't want all these bacterial debris in there because your immune system is going to react to that bacterial debris and taxins and whatnot and it may go into shock and pure fying.

Well, it sounds kind of simple, but it's not because you need all just sophisticated equipment.

Basically, you need special certifugures that spin very fast, and they managed to separate phages from everything else and that's how you get you 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 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?

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 buy all this investigational new drug application, these 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 phases and antibiotics in terms of, you know, in an ideal world where phase 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 phases.

Probably.

I think at least at this point, it looks like antibiotics would still be our first line of defense, and that's because it's just so easy to use them.

As I mentioned, with phages, you need to know what particular infectious organism you are infected with.

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 you're intibiotics work in the meantime, you golden.

You don't need anything.

However, if you antibiotics don't work anymore, that's when you will need a phage or multiple phages.

I think antibiotics are still going to be our first line of defense for a while.

The interesting thing about antibiotics and phages and how like, you know, the pros and cons.

You know, antibiotics are static molecules that we synthesize by chemical reaction or some other means, and they're static.

They don't evolve, and bacteria are amazing at various mechanisms of resistance that they just evolve, you know, from one day to the next, all sorts of tricks.

You know.

Some of them developed these pumps they spit on 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 out coats.

If you'd like.

So, antibiotics can stick to some manage evens surround themselves, like in the protective ink that also destroys antibiotic molecules.

So when we run into these 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 a resistance 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 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.

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 phases evolve with or in response to bacteria, they are, as you describe in your book, an infectious cure.

So someone receiving phase therapy can spread those phases 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 phasis can be contagious too.

And I think we'll get into history and phage therapy in a little bit.

But the first person who realized that phagius as cure can be contagious was one of the early phage therapy adopters, Felix Theyrell, who's trying to stop an outbreak of salmonella in chickens in France, and he realized that as soon as one chicken would get a bacteria phage he gave this salmonella, the entire coup would recover because they'll pack 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 cure and then you're done.

That's it.

That's so cool.

I'd love to get into the history now of bacteria fish therapy, and I think it is it's surprising to a lot of people who are used to using antibiotics and used to having antibiotics be the frontline of you know, bacterial infections to realize that not only fish 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 discussies of bacteria facis.

So the year is nineteen seventeen, and two things are happening almost at the same time and two different parts of the planet.

There is Felex Terrell in Paris working at the Pastoral Institute, which is like the holy grail of science medical science at the time, and he is both near a biologist and a medical doctor, which was very common at the time.

And so he's dealing with patients who have dysentery.

And again this is before antibiotics.

You've got dysentery, you might be dead very shortly, and so people are dying.

But one of his patients recovers, and he figures this has to be something in his stomach that helped him recover.

So he starts looking at two this person stool samples, and he realizes that there is no dysentery bacteria in there anymore.

So he's like something skilling it.

So let's try this.

He takes like these stool samples and in locum lads other bacteria samples new with it, and Lloyd behold, Dysenteria bacteria dies there too, and in the next one and the next one.

But he can't see what it is because phagies are much smaller than bacteria, and at the time they could see bacteria under the microscope but not phagis.

In fact, that took an electronic microscope of nineteen thirty 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 at the same time out there in the country of Georgia, in Pilisi, which by the way is a beautiful city and at the time it was called the Paris of these really interesting dichotomy.

There is another scientist, the Georgian scientist Giorgi Alaiyava, who is a little bit younger, not as experienced, but just came back home from the front lights of World War One, which just ended where he tended to, you know, six soldiers who had cholera and dysentery and whatnot, and he is looking into presence of cholera in the city water in the river where everybody gets the water from, and 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 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 color there anymore, which doesn't make any sense.

Color doesn't die a 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 onto something, but he can't figure out what is he onto.

Fast forward a few more months.

He has to go to Paris to study at the Pastor's Institute how to you know, make vaccines and other meta since 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 Drell's the scientific role 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 destroyed didn't theory.

No, it also doesn't fit into the established immunity theory you know at the time.

So basically, at that moment, Dyrell is a laughing stock.

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

So Eliella walks into Fastero's intitude and right in the middle of all this and he goes, I've seen that too, and they're like, all right, another one.

But here where the character differences come into place.

Drell was kind of a prickly character, and he spoke his mind and probably made a fair mind out of it as in his life.

And Elia was exactly the opposite.

He was absolute charmor like people.

He could sweet talk anybody into anything.

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 started 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.

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 truth thing, are we seeing what we actually think we're seeing?

And then how soon after that was how can we use this then to help cure infectious disease?

Yeah, so fairly soon.

I think it was nineteen nineteen I five, 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 challenge child like recovered in twenty four hours.

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

And I think the next really big breakthrough was in nineteen twenty five when the rail managed to cure a couple of cases of bubonic plague.

What sort of was the turning point for the medical community then reconsidering phases 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's sort of like slow happened over like the next maybe few years, like after nineteen nineteen.

But I think if if the nineteen twenty five when Durrell cured Bogonic 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 boguonic plague.

You got it, you died.

I mean, it's almost 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 the bonic plague, and he had phages that he brought from India where he eyes related it from rats.

Your rats could 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 recover it.

And that was just like nothing, you know, short of a miracle.

Oh my gosh.

I mean to then go from you know, laughing stock to cure of bubonic plague, this like very fear disease.

That is, that's incredible.

And then we go from that to a whole institute being created for the explicit reason to study phasianes.

Can you tell me a little bit about this institute?

So Eliava and Durrell became not just like lifelong friends but also lifelong collaborators.

And so Aliama had this really grand idea of building a bacteria of age research center and a treatment center in Bilisi, in Georgia.

And at the time he had a fair amount of money because Stalin, who was Georgia and himself, was willing to throw a bunch of money into his home state, especially for things like medicine, because healthy populations means strong umpire, and he was building strong umpire.

So the plans for the institute were approved, and you know, there was a crazy amount of money, even like, you know, several millions, which god knows how much it would be in today's money, but it was.

It was a very turbulent time in history, in particular in the history of the Soviet Union, because Stalin was very paranoid about keeping his grip on the country, keeping his power, and he wasn't tolerating any dissent, and Eliyaba, like many brilliant people, was known to speak his mind, and eventually that cut out with him, so he was arrested and tortured, like really really brillly tortured.

I was able to find some of the introgation 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 one day they would want him to say that he was working with the French intelligence, the next day was 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 Phage's as medicines survived because there was really nothing else at the time, and it basically stayed in Beliezi, like in the time capsule of sorts, and it was used through all of the years of Soviet power.

This huge loss that the Phage therapy field faced, you know, how was that immediately felt?

And then what were some of the long term implications of that In let's say, like the decade or so that followed Eliava's death.

So the diga that followed in Aliava's this was really it was a really difficult decade because we kind of like get into World War two, right, So what happened in late thirties in America is that phage therapy in the West basically fell out of favor, and for really interesting reasons.

For no fault of phages, it was mostly because it was kind of misused.

People didn't necessarily know how to grow phages properly, and even when they did, pagies didn't always work.

And that happens too.

Sometimes pages don't work for exama, they don't work for hives, they don't work for allergies or herpies or whatever.

But some companies advertised pages for this health issues, and of course fages 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 late nineteen thirties, and they decreed that pages aren't really trustworthy enough to use this 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, pensila became the answer.

You know.

At the same time, though, in the Soviet Union, phases were being used at a larger scale than they had been previously.

Can you tell me about some of the prophylactic use of phases during World War Two in Stalingrad?

Yeah, that is like one of my favorite topics because it's just so mind buggling and it's like so unknown, right.

Yeah, and the prophilactic use of phasias, I had no idea.

I always thought of it as a treatment, not a prophylactic.

Yeah, it's amazing.

So we're now into nineteen forty two and the Nazis forces are closing and on stalin Grad, like the Soviet strengthhold on the Vulgar.

We were named after Stalin, So that's so many things are a tie to this CD you know, like first it bears Stalin's name.

Second, siss 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 Stalar is absolutely brutal.

Neither side can afford to lose the city, and so sometime in summer, the Moscow hears some rumors about cholera cases among the German troops, and at first they're very happy to hear that, because okay, well that's good.

And then they realize that no, it's not good because cholera doesn't care, doesn't care about front lines, but it's on one side to oil beyond the other.

And they realize they've got this whole city that they bombed out to smooth the rings with like sewage broken you know, water means broken.

And they realize it's going to be a disaster, and so they send a woman there.

Her name is Zinaida Yrmuliva, and she's one of the leading Soviet biologists on microbiologists at the time, on a tiny plane that manages to somehow evade the German bombers and actually learn there.

And she comes with this tiny little bag of phages, and she hears that color 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 it's phage Arsenal on a train, and the train goes to Stalingrad and it never makes it because it gets bummed out to smooth rains.

And she goes, Okay, we'll have to grow phages here.

We've got vulgar right there.

There's got to be cholera in there, and their phages will be in there, and of course they are.

So they take these 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 prefiloxies the entire city on a daily basis.

I think she wrote in her so 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.

I mean, it's such an incredible story, and like you said, it's such a profound demonstration of the power of phases.

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 phasis 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 and I think that there actually was some medical collaboration during World War two, and there were some European American scientists who were working with Zinaida Uni world, but more so on antibiotics than than phagis.

And I think they just didn't think that pages were realistic enough that they were like really useful.

I don't know why it didn't happen.

Part of it could have been just like the general mistrust that just never took off.

Let's take a quick break here, we'll be back before you know it.

Welcome back, everyone.

I'm here chatting with 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 the West and the Soviet Union, and how that sort of led to one pursuing antibiotics and the other pursuing phases.

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 more.

In particular, by the end of nineteen thirties, the trust in phages kind of dropped, and I think people that are genuinely 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.

It was easy and cheaper than growing this phoinichy crete with you know, peaky appetites whose biology sides still didn't fully understand, and physicians agreed.

At the time, a large percentage of American doctors were private practitioners, and many worked from their home offices, and they weren't attached to any bacteriological laboratories or hospitals.

They didn't necessarily have you know, test labs, let alone like complex facilities to synthesize pages.

There in those settings, the easy, ready to use medications that had a long shelf life and killed a white spectrum of drums 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 went over phages.

In the Soviet Union, however, medicine was a state endeavor, so a family couldn't start a company to grow phages to 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 wars made patient seekert, they could be declared the enemy of the people and that was it.

So consequently, Soviet sciences had like a very different medical paradigm.

Western medics embraced stability in life in laws in drugs.

But the Soviet medics STYG just learned to exist in this ever shifting landscape.

You know, if peniculin was mass produced today, it didn't mean that the factor will still be there tomorrow.

The rowing ingredients could vanish, the inventor could be arrested.

So Soviet medics just uced whatever they have in a given day.

They hadn't tabiotics, good, don't have antibiotics all right, let's go to the nearest river of phages.

Wow.

Yeah, that's a fascinating lens to think about, sort of the differences in what drives innovation and what drives accessibility to equipment, all of that.

And so when antibiotic resistance started to show up in around the world, which it did, you know, very soon after penicillin was started to be widely used.

How did phage therapy?

How was that used in the Soviet Union to treat resistant infections.

Yeah, that's a great question.

Like basically, if antibiotic stuff working, there was always a phage.

I mean, Spelici kind of remained a center of all sorts 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 SPILICI maintain sort of like 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 these new samples to the lapse and they would see, is this bacteria evolving resistance to our phages?

Oops, it is okay, time to find a better phage.

Let's go out to the river.

That literally like went on for years and years and years, and they never stopped.

And they still do that.

To anticipate the future problems and to be able to have that in advance.

And I think that's why I keep thinking about phases as being this proactive approach where you can see almost immediately if you're detecting antibiotic resistance, you can find a phace 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 US and the American scientists have no idea.

They know what bacteria phagias 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 phaseia's in the West.

Sure.

So we're now in the early nineteen nineties when the Soviet Union is falling apart, maybe it's already falling apart.

And this Georgian scientist comes from Pilisi 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 lap and he doesn't look like himself.

So the Georgian his name is Sandra, sees him like that and he asks, you know what happened?

And Glenn says, well, I just lost a patient to an antibiotic resistant infection.

I mean this this man he battled through new cancer and chemotherapy and recurring new cancer and chemotherapy, and he was in his forties, so still fairly young, and and he went through all of this and then at the end he succumbed to an antibiotic resistant infection because I couldn't find an antibiotic to kill this bug that infected him.

And Sandra just went so and the bacteria page didn't work either, and Glunn just gave him that stare like this this this this thy like what And when I was talking to Sandra, and I talked to Sandra so many times for this book, was just a moment of reckoning.

It was just like, oh my god, these people really don't know, like we could treat this in my hometown.

You know.

He came to America because it was the place to do science, and how can this be?

And so he basically took it upon himself to work for the next twenty five thirty years to work with the FDA to convince him 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 phisih 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 US.

And can you talk about some of these major moments that eventually led to people pursuing this as a legitimate field of research with such potential.

So initially, when Sandra and Glenn tried to put together some research proposals to study phigis 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 Dyrell.

Eventually Thunder kind of like changed his new path a little bit and he began to work on phages for food safety.

So bacterial contamination is a huge problem in the food industry, as we all know, like almost every week something is being recalled, right, So his company now makes phage sprays that you spray on letters, meat, sausages, and whatever that kill very specific food porn 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 in medical products for people who are very right.

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 page 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 fijis were safe, you know, 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 Acina bakta bamania while traveling in Egypt with his wife and ended up basically on the brink of death in one of American hospitals.

So this is a really unique couple.

The guy's name is Tom Patterson and his wife's name is Stephanie Trusty, 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 said, I did research, and she's doubled 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 scientists whose 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 warn tabiotic and that you know, finally cleared it.

And that was the first time the FDA ever approved an investigational new drug phages for use on humans.

And it worked.

It worked so spectacular because there was nothing else to try.

Yeah, and that was a really big pivoting point which kind of brought phages from scientific obscurity back on the front lines, and since then a whole bunch of clinical trials were launched.

That is one of my favorite stories, The Perfect Predator, which is Stephanie's book, and it is so 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 and interest.

But there are still some hurdles to overcome, as you mentioned earlier, like FDA approval and also incentivizing research into phage therapy.

What are some of those challenges in terms of, like the logistical side of things, incentivizing research making people even more aware than they are.

I think the original challenge was that years back, the FDA didn't necessarily know how to detest phages like the 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 we know they're going to work the same way in just about everybody.

Phages are tricky because they change.

They may change within a person because they multiply, right, so a slightly 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 side 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 changed from one season to the next, And so that's where phage is now fall under, and that's the department that regulates it.

Yeah, I mean, it seems like there is a promising path forward in terms of getting phage therapy just to redraw some of the standards that we have to not just discard them entirely because of these characteristics that they have.

And so how far away do you think that we are here in the US from phage therapy being like a routine or at least a more widely available option.

That's a great question, and I've asked that question almost everybody, And you know, the best to get is like I don't know, five to ten 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 this book.

The CDC's twenty nineteen reports said that every fifteen minute, someone dies from an antibiotic resistance infection.

So we talked for almost an hour.

That's for people.

The CDC's twenty twenty two reports said that it's gotten worse, and then Newer asked the let's say that by twenty fifty, antibiotic resistance will kill three people every minute.

So like you do the math, and the United Nations says agreement prediction ten million US annually by twenty fifty.

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 finished 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 phagi's probably since I was a kid, because of 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's and it starts with a letter F that looks like a person who is standing with their arms and 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, disent theory, 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 they were not enough on tabiotics, and you know, eventually, my grandfather found some antibiotics somewhere in a pharmacy and that's what I took.

But the study purported that these page 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 page character as a character, so I brought my collared pencils and, like you, color that page character in different colors, and the whole thing just stuck with me and it continues to you know, like some things get lunched in your head, and that was one of those.

I love that story.

What if 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 Zeldovitch for taking the time to chat with me.

I didn't know I could love phage therapy even more, but somehow I do.

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