Speaker 1: There's a question. I've been waiting a long time to
Speaker 1: ask you phage or phage?
Speaker 2: I say phage. Some people say fage.
Speaker 1: Faj Come on, get the fuj out of here. What
Speaker 1: is it?
Speaker 2: I think phage and phage are so similar that we
Speaker 2: can work with that. It's Greek for killer or to
Speaker 2: sort of eat.
Speaker 1: But in English. Yeah, so you're saying, you say phage
Speaker 1: rhymes with.
Speaker 2: Age, I say phage.
Speaker 1: I'm talking with Tom Ireland. He is a science journalist
Speaker 1: who just wrote a book called The Good Virus, and
Speaker 1: it is all about phages. Phages are these amazing viruses
Speaker 1: that have sort of flown under the radar since they
Speaker 1: were discovered in the first part of the twentieth century.
Speaker 1: Phages also known as bacteria phages are viruses that kill bacteria,
Speaker 1: and that is a very useful trait if you need
Speaker 1: to kill bacteria that are making someone really sick. And
Speaker 1: in fact, Tom told me people are now turning to
Speaker 1: phages to try to treat infections that can't be cured
Speaker 1: with antibiotics.
Speaker 2: I think this year is the year that it all changes,
Speaker 2: because the crisis of drug resistance is so acute and
Speaker 2: so scary. Now that we have to take it seriously.
Speaker 2: So the World Economic Forum this year named phage therapy
Speaker 2: in their top ten Emerging technologies for twenty twenty three.
Speaker 2: You know, we're not just guessing and throwing viruses into
Speaker 2: people with bloodstream anymore. This is a kind of modern
Speaker 2: phage therapy two point zero, and there's some real momentum
Speaker 2: building behind the idea.
Speaker 1: Now, we spend a lot of time on this show
Speaker 1: talking about viruses that are bad for humans, Viruses that
Speaker 1: make us sick, viruses that have killed hundreds of millions
Speaker 1: of people. Today, for the season finale, we bring you
Speaker 1: a shocking twist show about viruses that are good for people,
Speaker 1: Viruses that help us fight disease. We'll hear the story
Speaker 1: of one of the first scientists to study phages. He
Speaker 1: was kind of a genius, but also he was kind
Speaker 1: of shady. And then we'll talk to a scientist who
Speaker 1: collects phages in lakes and sewage plants and then uses
Speaker 1: them to treat patients with life threatening infections that cannot
Speaker 1: be treated with antibiotics. I'm Jacob Goldstein. This is incubation
Speaker 1: in the world on planet Earth right now. How many
Speaker 1: phages not kinds of phages, but phages.
Speaker 2: So there's a number that goes around a lot. It's
Speaker 2: a very rough calculation, but it's ten with thirty one
Speaker 2: zeros after it. One way of thinking of that is
Speaker 2: a trillion phages for every grain of sand on the planet.
Speaker 2: So just just crazy numbers.
Speaker 1: I don't know what to do with that. You said
Speaker 1: a trillion for every grain of sand. That's like a
Speaker 1: come on kind of number, right, I mean, I guess
Speaker 1: one way to think of it is like we actually
Speaker 1: live on phage planet. Like we think we're the main
Speaker 1: thing going on on the planet, but maybe we aren't.
Speaker 2: Yeah, life is evolved in a soup of viruses, and
Speaker 2: most of those viruses are phages. And if a kind
Speaker 2: of alien life form was to just pluck a random
Speaker 2: bit of the Earth and look for life, they would
Speaker 2: probably find phages and nothing else, you know, if they
Speaker 2: just took a random bit of sea water.
Speaker 3: Huh.
Speaker 1: So we've been talking about phages at this sort of
Speaker 1: macro level, big picture level at a more micro level,
Speaker 1: like what's a phage look like? I know they're very small,
Speaker 1: but if you look really closely, what to look like?
Speaker 2: So one of the reasons I'm so interested in phages.
Speaker 2: Is that actually extraordinary looking things? And there was some
Speaker 2: discussion in the phage community that the lunar landers were
Speaker 2: actually based on a certain type of phage. I was
Speaker 2: never able to confirm that, but they have a remarkably
Speaker 2: similar structure, and they look almost like kind of tiny
Speaker 2: robotic nano machines or spiders. They're weirdly angular. So they
Speaker 2: have this twenty sided head which looks quite sinister, which
Speaker 2: contains all of the DNA. Then they have this long
Speaker 2: tail which actually acts like a kind of molecular syringe
Speaker 2: which can inject the genes from the head into the bacteria.
Speaker 2: And then they have these kind of spider like little
Speaker 2: legs which they use to land on the surface of
Speaker 2: the bacteria and bind to it. There's this head that
Speaker 2: has the payload in whether that's astronauts or genes, and
Speaker 2: then the landing legs. And then once once the phage
Speaker 2: is landed and injects the DNA, and it essentially hijacks
Speaker 2: the bacteria and turns it into a virus factory.
Speaker 3: Amazing.
Speaker 1: You know, viruses are generally thought of as bad, and
Speaker 1: it is sort of delightful to encounter this large universe
Speaker 1: of helpful viruses, like I'm very happy to be discovering
Speaker 1: these good viruses.
Speaker 2: Yeah, and they vastly outnumber the ones that we fear
Speaker 2: and hate. It's really interesting that the idea of using
Speaker 2: them to kill bacteria and kill the bacteria that caused
Speaker 2: disease is not new at all. You know, they were
Speaker 2: being used in medicine decades before the first real antibiotic, penicillin.
Speaker 2: They were being used in the twenties and the thirties,
Speaker 2: and this idea of using them as allies as medicines
Speaker 2: is becoming you know, it's being taken really seriously again. Yeah.
Speaker 3: Right.
Speaker 1: That goes back to the early part of the twentieth century.
Speaker 1: And there is this key figure who you write a
Speaker 1: lot about in your book. Really interesting story. So tell
Speaker 1: me about him. Tell me about Felix Durell.
Speaker 2: So, Felix Durel's fascinating character, a real maverick. He's kind
Speaker 2: of self taught, volatile, has none of the diplomacy that
Speaker 2: was expected of kind of gentlemen scientists of the early
Speaker 2: twentieth century. There's a dispute about whether he's French or
Speaker 2: Canadian or Belgian because he kept changing his name. He
Speaker 2: didn't really go to college to university. He spent his
Speaker 2: teenage years traveling around Europe. He moved over to Canada,
Speaker 2: declared himself a microbiologist. He was commissioned by the Canadian
Speaker 2: government to make whiskey from maple syrup, which maybe the
Speaker 2: most Canadian thing I've ever heard. And then he had
Speaker 2: this period of kind of conducting completely wild, lawless science
Speaker 2: as an infectious disease doctor in Mexico and Watemala, where
Speaker 2: he was really given free reign to do what he wanted.
Speaker 2: So a really unconventional background, very brash and terrible diplomacy,
Speaker 2: you know. So he made lots of enemies. People were
Speaker 2: very suspicious of him, and he was just, you know,
Speaker 2: just the ultimate kind of outcast, I suppose in a
Speaker 2: very important scientific field.
Speaker 1: How does Dourell make his discovery about features.
Speaker 2: In the nineteen tens, He essentially stumbles across this amazing
Speaker 2: of observation, which is that he has plates of bacteria
Speaker 2: that he's working on. It's called a lawn of bacteria.
Speaker 2: It doesn't look like much, but it's kind of opaque
Speaker 2: and milky, and that means all of your bacteria is
Speaker 2: growing nicely on whatever medium. You've given it to grow on.
Speaker 2: And he starts noticing on some of his plates there's
Speaker 2: holes and there's literally nothing there. Ah, And he takes
Speaker 2: a little touch from the middle of one of these holes,
Speaker 2: and he just which is another plate of completely healthy, uniform,
Speaker 2: milky bacteria. A hole starts growing on that too, And
Speaker 2: then he can do this indefinitely. He can take a
Speaker 2: touch from the hole and touch it on another healthy
Speaker 2: plate of bacteria. The hole starts growing again. So he
Speaker 2: knows this isn't just something that's a kind of antibacterial chemical.
Speaker 2: This has the power of replication. This is growing at
Speaker 2: the expense of the bacteria. So it's a double whammy
Speaker 2: of scientific discovery because he's he's found something that seems
Speaker 2: to be killing bacteria really quickly and really efficiently, all
Speaker 2: at once. He has a suite of theories. He theorizes
Speaker 2: that this is a virus that kills bacteria. He works
Speaker 2: out that they are replicating inside the bacteria and then
Speaker 2: bursting out. He also theorizes that phages are maybe part
Speaker 2: of our immune system, and that when someone spontaneously recovers
Speaker 2: from a disease, perhaps it's phages in our guts or
Speaker 2: in our body that has helped us recover from that disease.
Speaker 2: So as well as being completely groundbreaking, that latter idea
Speaker 2: of them being part of our immune system was kind
Speaker 2: of heretical at the time. You know, it was a
Speaker 2: completely wild and wacky theory.
Speaker 1: This is a moment when there are no antibiotics in
Speaker 1: the world, right, this is the moment when, no matter
Speaker 1: how rich you are, if you get a little infection
Speaker 1: on your foot, you might die from it. Right, truly,
Speaker 1: like there is no way to reliably and safely kill bacteria.
Speaker 1: So like this is a huge, huge thing.
Speaker 2: Yeah, when he presented these ideas to the world, the
Speaker 2: establishment of these huge you know, microbiologists of the time
Speaker 2: they just said, there's no way this is true. I
Speaker 2: think one of them actually said, if this microbe exists,
Speaker 2: I would have found it by now. People just couldn't
Speaker 2: believe that he'd discovered this entirely new form of life
Speaker 2: that had such a powerful potential use in medicine.
Speaker 1: So he has discovered this incredible thing, there's this obvious
Speaker 1: potential for clinical applications, right, how does he try and
Speaker 1: take this idea and actually use it as a treatment.
Speaker 2: Yes, So this is before clinical trials. Felix Drel walks
Speaker 2: into a children's hospital in Paris and says, I have
Speaker 2: a way of treating dysentery, this horrible inflammation of the
Speaker 2: bowels which causes you to essentially have such severe diarrhea
Speaker 2: that you die. And they decide to give a dose
Speaker 2: of phases to two young kids from a particular family
Speaker 2: who've come in with very severe dysentery, and you know,
Speaker 2: they make a full recovery.
Speaker 1: I mean, one question is how often does that happen
Speaker 1: in the absence of treatment?
Speaker 2: Right?
Speaker 1: Like the reason you really want a randomize trial is
Speaker 1: to know is this the treatment, is it in this
Speaker 1: case the phage, or is it just would have happened anyway.
Speaker 2: Exactly So Durrell he tries it on a few more
Speaker 2: kids in this hospital. It's successful. He's essentially selling his
Speaker 2: own cocktails of phages for various different bacterial diseases, and
Speaker 2: he's in this really unusual situation where the establishment microbiologists
Speaker 2: are still suggesting he's wrong, and they don't believe his theory,
Speaker 2: and they're trying to disprove his theory. But he is
Speaker 2: a great salesman of these phage based potions and he
Speaker 2: starts traveling the world and selling them to ministries of
Speaker 2: health and hospital directors, and they don't really care what
Speaker 2: the kind of academics are saying. And within a decade,
Speaker 2: phages are everywhere.
Speaker 1: Does it work? Like? I can't tell? Like he still
Speaker 1: seems shady, Like it could be snake oil.
Speaker 2: I think Felix Drell, who had an understanding of phages
Speaker 2: that was greater than anyone else on the planet. He
Speaker 2: developed a way of actually understanding which strains of bacteria
Speaker 2: were circulating in a given place at a given time,
Speaker 2: and then creating a remedy based on phages that he
Speaker 2: knew could kill those bacteria. As soon as pharmaceutical companies
Speaker 2: got involved and started trying to make products that were
Speaker 2: like mass market products, you know, it was completely hit
Speaker 2: and miss. So there was this complete inconsistency. At the time.
Speaker 2: People didn't understand phages well enough, and so phages got
Speaker 2: this reputation as being inconsistent, which they really struggled to
Speaker 2: shake off until antibiotics came along.
Speaker 1: So let's talk about that. So antibiotics come along in
Speaker 1: the what nineteen thirties, nineteen forties, Ah, what does the
Speaker 1: rise of antibiotics mean for phage therapy.
Speaker 2: Penicillin was discovered, it was you know, it really was
Speaker 2: a miracle drug. You know, you could mass produce it.
Speaker 2: Doctors knew that if a bacterial disease was one of
Speaker 2: these forty different types of bacteria, if it was caused
Speaker 2: by those bacteria, then penicillin was good for it. And
Speaker 2: so really that phage therapy started to look logistically very
Speaker 2: difficult to administer. You know, you've got to match the
Speaker 2: phage to the bacteria, or you've got to create a
Speaker 2: cocktail of different phages. It just all of a sudden
Speaker 2: seemed like a kind of wild and old fashioned and
Speaker 2: backwards way to treat bacterial infections. And in the West,
Speaker 2: at least, the idea of using phages was like, rah,
Speaker 2: forget it.
Speaker 1: So what's the end of the story of Felix Durell.
Speaker 2: Well, it's not a happy ending for him. Really. He
Speaker 2: died without any kind of acknowledgment of his work. He
Speaker 2: was actually nominated for the Nobel Prize about thirty times
Speaker 2: but never won it. He was a genius in his
Speaker 2: own way and really set the ball rolling for this
Speaker 2: idea of using phages to treat bacterial infections.
Speaker 1: So let's talk about the present. Antibiotics are amazing, but
Speaker 1: bacteria are constantly evolving to resist antibiotics. Ken phages help
Speaker 1: us with intibiotic resistance.
Speaker 2: Yeah, they absolutely can. I mean, it's as I've said,
Speaker 2: it's not straightforward. This is very different to having a
Speaker 2: pharmaceutical chemical that we can use on millions of people.
Speaker 2: There is lab work involved with each case, and you're
Speaker 2: talking about treating people with a living, evolving thing, often
Speaker 2: that's been found in a kind of river or a sewer.
Speaker 2: So there's just huge numbers of like logistical and regulatory
Speaker 2: challenges around this. But you know, they have been evolving
Speaker 2: for billions of years to kill bacteria. They are amazingly
Speaker 2: good at it, and there are countless examples now of
Speaker 2: phage therapy being used to save the life of people
Speaker 2: who have infections that are resistant to every known antibiotic
Speaker 2: in the cabinet.
Speaker 1: Tom Ireland's book is called The Good Virus, The Amazing
Speaker 1: Story and Forgotten Promise of the Phage. We'll be back
Speaker 1: in just a minute to talk to a scientist who
Speaker 1: is using phages to treat disease. Now. In the first
Speaker 1: half of today's show, Tom Ireland talked about how phage
Speaker 1: therapy is being used today to treat people who have
Speaker 1: antibiotic resistant infections. In the second half of today's show,
Speaker 1: I'm going to talk with one of the few researchers
Speaker 1: in the country who is actually doing this work. His
Speaker 1: name is Ben Chan. He's a research scientist in ecology
Speaker 1: and evolutionary biology at Yale. How did you come to
Speaker 1: be a phage guy? How to get into phages?
Speaker 4: Back in grad school I studied amphibian biology. I studied
Speaker 4: parental care behavior of poison dart frogs.
Speaker 3: And you got to do this.
Speaker 4: Amazing field work in amazing places and loved it. And
Speaker 4: there was this fungal disease that's driving amphibian decline.
Speaker 3: And what I really.
Speaker 4: Wanted to do is I wanted to engineer the skin
Speaker 4: microbiome of these poisoned dart frogs by making the bacteria
Speaker 4: produce anti fungals so that they'd be resistant to this disease.
Speaker 4: And I was like, that's how I'm going to save,
Speaker 4: you know, frogs, And I wanted to do so with
Speaker 4: a phage. Actually, I was going to engineer these bacteria
Speaker 4: with phage.
Speaker 1: Ben told me he couldn't get funding for his save
Speaker 1: the Frog's idea. But he wanted to continue his work,
Speaker 1: and in twenty thirteen he started working at a lab
Speaker 1: at Yale where he finds and studies phages. And it
Speaker 1: was there that Ben connected with the surgeon at Yale
Speaker 1: New Haven Hospital. The surgeon told him about this one
Speaker 1: really challenging case.
Speaker 4: So this guy had and aneurysm on his A order. Right,
Speaker 4: the vessels weaken, and when that's a vessel in the body, like,
Speaker 4: if that thing explodes, that's really bad news, right, especially
Speaker 4: the A order, which is like the largest vessel. So
Speaker 4: they you know, bring him into surgery. They cut out
Speaker 4: that piece and replace it with a plastic piece. And
Speaker 4: then it turns out that got infected somehow, So he's
Speaker 4: got this artificial graft onto his heart and then there's
Speaker 4: like pseudomonius bacteria growing on it.
Speaker 1: So to be clear, he has this infection in a
Speaker 1: place you really don't want an infection. Yeah, it's a
Speaker 1: bacterial infection, So great, give him antibiotics. They give him antibiotics.
Speaker 4: What happens, it sort of just suppresses it at best, right,
Speaker 4: So it won't go away with antibiotics, but you can,
Speaker 4: you know, prevent it more or less from killing you,
Speaker 4: I guess, but it's like a slow battle that eventually
Speaker 4: you're gonna lose, and so they're kind of out options.
Speaker 1: So this patient has is infected with this bacteria that
Speaker 1: you can't wipe out with antibiotics. So how does that work?
Speaker 1: How does the bacteria survive the antibiotics?
Speaker 4: Yeah, So there's a few ways that bacteria can survive
Speaker 4: antibiotic exposure.
Speaker 1: Right.
Speaker 4: They can either have an enzyme that chops up the
Speaker 4: antibiotic before it does its job, or they can decrease permeability.
Speaker 4: And then there's this other way, which is called antibiotic eflux,
Speaker 4: where it's the antibiotic gets into the cell and could
Speaker 4: otherwise function and kill the bacteria. But there are these
Speaker 4: special pumps that the bacteria have that recognize antibiotics and
Speaker 4: other sort of toxins and then they pump it out
Speaker 4: before it can do what it's meant to do.
Speaker 3: That's rad yeah, the way they're so smart, right, the yeah.
Speaker 1: And so that's what's going on in this case. Right,
Speaker 1: The bacteria inside this guy has a pump. So you
Speaker 1: give him antibiotics, it goes into the bacteria and the
Speaker 1: bacteria pumps it back out.
Speaker 4: Yeah, and so our natural response would be like, okay,
Speaker 4: let's just throw more antibiotics there, right, And when you
Speaker 4: do that, it makes them make more pumps, right.
Speaker 3: So there it's a tough arms race.
Speaker 1: It's the kind of antibiotic versus pathogen arms.
Speaker 3: Race, yeah, exactly.
Speaker 4: And the more you get in, eventually you're going to
Speaker 4: start seeing some side effects.
Speaker 2: Right.
Speaker 4: You can only put so much chemical in someone before
Speaker 4: there's there's problems.
Speaker 1: Yeah, And what is your idea when you show up?
Speaker 4: So I just was like, well, why don't we try
Speaker 4: to use you know, a bacteria phage, which is a
Speaker 4: virus of bacteria to try and kill this infection because
Speaker 4: it's independent of antibiotic resistance, right, And that's not like
Speaker 4: my idea. Right, They've been doing this since they found
Speaker 4: bacteria phages, or they've been trying it. But I was like,
Speaker 4: you know, it's been years since we've actually done this
Speaker 4: seriously in the United States. Maybe we should, Maybe this
Speaker 4: would be a good case to try it. And so
Speaker 4: the surgeon was like, perfect, let's try it.
Speaker 1: Okay, So the surgeon's on board. What do you do
Speaker 1: from there?
Speaker 4: The first thing is we get the isolate, so the
Speaker 4: clinical lab guy here in the hospital was like, Okay,
Speaker 4: here's your plate of bacteria. So we take this bacteria
Speaker 4: back to the lab and we need to make sure
Speaker 4: that we have a phase that can kill the bacteria.
Speaker 3: Right, ok So we've got this like, you know, fridge
Speaker 3: full of phage.
Speaker 1: And the fridge full of phages, like all different phages, Yeah,
Speaker 1: more or less. How many different phages.
Speaker 3: Do you have.
Speaker 4: Within an order of magnitude one thousand, a thousand?
Speaker 1: So how do you come to have a fridge with
Speaker 1: a thousand?
Speaker 3: Yeah?
Speaker 1: Different kinds of phage.
Speaker 4: Yeah, so you know, regular trips to the sewage treatment
Speaker 4: plant or you know, we're collecting from rivers, our ocean,
Speaker 4: water lakes. We have all different phages for all different
Speaker 4: bacteria because they're really really host specific. So it's not
Speaker 4: like I can take any Coli phage and try to
Speaker 4: kill Staph aureus with it or something. We had sort
Speaker 4: of built up this library of Pseudomonus phages and we
Speaker 4: took his sample and we basically tested all these phages
Speaker 4: on his bacteria I see which ones would kill it.
Speaker 4: And so we had phages and we've had one that
Speaker 4: was I think slightly biased, really cool and that the
Speaker 4: receptor binding site. So what the phage use is to
Speaker 4: grab onto the bacteria and recognize it was this eflux
Speaker 4: pump that we were talking about.
Speaker 3: Huh.
Speaker 4: So you know it in a sea of pseudomonas, not
Speaker 4: all of them have these eflux pumps, and so the
Speaker 4: phage is like looking for just those guys.
Speaker 1: So specifically, this phage, this particular phase that you're optimistic about,
Speaker 1: is actually targeting the thing that allows some of the
Speaker 1: bacteria to resist the antibiotics exactly. So this phage is
Speaker 1: sort of optimal to use in combination with antibiotics. Yeah, right,
Speaker 1: because either the bacteria has a pump and is therefore
Speaker 1: antibiotic resistant but targeted by the phage, or it doesn't
Speaker 1: have a pump, in which case the antibiotics will kill
Speaker 1: it exactly.
Speaker 3: Yep.
Speaker 1: It's a great theory, yeah theory.
Speaker 4: Yeah, yeah, but that's what we had to go with, right.
Speaker 4: It was this this theory and that like the thinking
Speaker 4: that the phage it could either it could kill all
Speaker 4: the bacteria, right and that would be a great out
Speaker 4: come for this guy, or it could kill a lot
Speaker 4: of them and then they could evolve resistance, which would
Speaker 4: not be ideal. But it'd be antibiotic ex sensitive, so
Speaker 4: maybe a win. And we tested it in the lab
Speaker 4: and everything looked great. So I brought this data to
Speaker 4: the surgeon. I was like, look, it seems like it's
Speaker 4: pretty good at what it does. And then he's like, well,
Speaker 4: let's try it cuz you mean, what else we need
Speaker 4: to do? So, you know, it gets the FDA on
Speaker 4: the phone and like, okay, here's a few things you
Speaker 4: need to do to make sure that you're not going
Speaker 4: to like do harm. So we did those quality control
Speaker 4: things and then then they're like, okay, cool'll do it.
Speaker 4: So we had the FDA, the institution, everyone was on board,
Speaker 4: and then all we had to do was the actual procedure.
Speaker 1: So once you get the approval, you've got a patient
Speaker 1: out in the world. You've got this one kind of
Speaker 1: phage yeap, how do you get it into the guy?
Speaker 4: Yeah, so it's like a little clear vial. It's a
Speaker 4: clean phage only solution. And then we brought that from
Speaker 4: the fridge over to the hospital. I just in like
Speaker 4: a little foam cooler, and then we go to the
Speaker 4: operating room where they had had this guy sedated and ready,
Speaker 4: and then the surgeons there, he's like, Okay, we're gonna
Speaker 4: do this. One of the nurses is like, okay, do
Speaker 4: you guys need the like the crash cart.
Speaker 1: To be clear, that crash card is for if the
Speaker 1: patient's heart stops beating, essentially if they die.
Speaker 4: Yeah, And so I'm like, all right, well, now it's
Speaker 4: like definitely real, like it was real before, but now
Speaker 4: it's like, dude, like, don't screw this up. Then they
Speaker 4: start they're like, okay, so here's what we're gonna do.
Speaker 4: We're gonna take this crazy long needle and we're just
Speaker 4: gonna like jam it way down by the base of
Speaker 4: the air or to The hope was they would take
Speaker 4: this needle and get down into the area like and
Speaker 4: puncture a little area where there was the bacteria. Right,
Speaker 4: So they wanted to get into the spot, rinse it out,
Speaker 4: and then shoot in the phage.
Speaker 3: And that was the dream.
Speaker 4: And they just couldn't puncture this area because there's all
Speaker 4: this scar tissue, and so then they're like, well, we're
Speaker 4: just gonna have to call it because we can't get
Speaker 4: in there, and if we push too hard, you know,
Speaker 4: like stab the guy in the heart.
Speaker 3: So we're stuck. And then this.
Speaker 4: Surgeon was like, okay, so here's what we can do.
Speaker 4: This draining hole here that's draining out of him already.
Speaker 4: What if we just pipe the phage up that hole
Speaker 4: and then it'll track back to the infection site.
Speaker 3: We can try that.
Speaker 4: So he, you know, he calls the pharmacy, gets the
Speaker 4: some antibiotic, mixes it with the phage in the operating
Speaker 4: room in a syringe, and he just like just basically
Speaker 4: pokes it in there and just like shoots it in.
Speaker 1: Shoots it into the hole on the guy's on the
Speaker 1: patient's chest.
Speaker 4: Yeah, So then he covers it up with a bandage
Speaker 4: and he's like, let's see what happens. Right, So they
Speaker 4: close him up and then they discharge him the next
Speaker 4: day and then like I'm like, okay, I wonder if
Speaker 4: it worked. I'm sitting here like everything's fine. Like then
Speaker 4: like it turns into like weeks and I'm like, dude,
Speaker 4: and then uh, the surgeon just emails me like out
Speaker 4: of the boy's like, oh, you'll never guess you turned
Speaker 4: up in my off looks like a million bucks.
Speaker 3: Everything's fine.
Speaker 1: So it worked. So the Finch therapy works.
Speaker 3: Yeah, as far as we can tell.
Speaker 1: Like the infection that had been persisting for years by
Speaker 1: that point, it just went away entirely.
Speaker 4: Yep, yeah, five years and then gone. So he stopped
Speaker 4: antibiotics and then he was fine.
Speaker 1: So this this whole thing happened several years ago, right
Speaker 1: like seven years ago now, and I'm curre's what's happened
Speaker 1: since then? Like, have you still been treating other patients?
Speaker 1: Do you hear from people who were interested in phage therapy?
Speaker 4: So that first case was twenty sixteen, and then we
Speaker 4: treated another seventeen and then like eighteen nineteen, like you
Speaker 4: just went crazy from there. Then things went like extra crazy, right,
Speaker 4: So you get emails all the time from people from
Speaker 4: their physicians, from their loved ones, from whoever who had
Speaker 4: these horrible infections. I mean, you know, like how big
Speaker 4: of a problem antibiotic resistance is, right, You read the
Speaker 4: news and the headlines and stuff, but like I feel
Speaker 4: like it really hits home when someone sends you in
Speaker 4: email that's like, dude, here's my story. I've been on
Speaker 4: these antibiotics constantly. I'm writing you from a hospital on
Speaker 4: my phone right now. This fucking sucks, like like things
Speaker 4: aren't working, and like when you get like after the
Speaker 4: first you know, ten of those, You're like, this is
Speaker 4: like a really serious issue, Like it really hits home
Speaker 4: more when when someone sends you a note like that.
Speaker 1: So where where are we now? Is phage therapy like
Speaker 1: a thing in US medicine? And I just don't hear
Speaker 1: about it because there's a lot I don't hear about.
Speaker 4: It's slowly becoming a thing more with these clinical trials
Speaker 4: going on and like compassionate cases being treated fairly regularly.
Speaker 1: And so in the US at this point, like rough
Speaker 1: order of magnitude estimate how many people a year, say,
Speaker 1: are treated with phage therapy?
Speaker 4: Ooh, within an order of magnitude you know, one hundred,
Speaker 4: one hundred, Yeah, so very small yeah still yeah yeah.
Speaker 1: And you mentioned some clinical trials that are ongoing. I mean,
Speaker 1: is it the kind of thing where if those clinic trials,
Speaker 1: you know, demonstrate safety and efficacy, it'll become a much
Speaker 1: bigger thing. It'll be thousands or tens of thousands of
Speaker 1: people that you're being treated with phage therapy.
Speaker 4: Well, we'll find out. I guess we're sort of finding
Speaker 4: out as we go. But you know, the safety problem
Speaker 4: is it's not an issue I think that's that's got
Speaker 4: a lot of support that they're safe. The efficacy we're
Speaker 4: trying to figure out still, but you know, assuming all
Speaker 4: goes well on these trials, unfortunately, it probably comes down
Speaker 4: to people deciding economically how to make it work.
Speaker 3: Right.
Speaker 1: What are some of the limits of phage therapy.
Speaker 4: You know there are cases in which it hasn't seemed
Speaker 4: to have done anything. The problem with those is that
Speaker 4: they don't often get written up and published, so we
Speaker 4: don't know what we're not doing correctly in a lot
Speaker 4: of these cases, or why it may have failed. But
Speaker 4: that's changing now a little bit.
Speaker 1: Like in this story you told of this one compassionate
Speaker 1: use case, very bespoke, right, and if we want it
Speaker 1: to get to tens of thousands of patients a year
Speaker 1: or thousands of patients a year, even seems like you
Speaker 1: would want it to be less bespoke, You would want
Speaker 1: it to be more industrialized and standardized. Is it possible
Speaker 1: to do that or is the nature of phage therapy
Speaker 1: such that it has to remain you know, very kind
Speaker 1: of artisanal one by one.
Speaker 4: I think it's somewhere in the middle. So it's not
Speaker 4: just me like you know, custom brewing a batch for
Speaker 4: every person that has an infection. So we're past that part.
Speaker 4: But I think it's also not someone just comes in
Speaker 4: and like, here's an injection of phage and you're done.
Speaker 4: But standardization and distribution and all these things are details
Speaker 4: we have to sort of establish. But it's it's definitely doable.
Speaker 4: And the part that I really really love about phage
Speaker 4: therapy is that it it more or less democratizes a
Speaker 4: lot of infection management in that the cost is not crazy,
Speaker 4: the technology is not crazy. I mean there's some meant
Speaker 4: there's some costs, but like any country can do it.
Speaker 1: If things go well, what does phage therapy look like
Speaker 1: five or so years from now?
Speaker 3: I would see it being more readily available.
Speaker 4: I would love to see, you know, people all over
Speaker 4: the world having access and producing their own pages. I
Speaker 4: mean to take a lot of work, but I think
Speaker 4: we could do in five years.
Speaker 3: It was great to talk with you. Thank you for
Speaker 3: your time. Great to talk to you.
Speaker 1: Thanks to my guest today, Tom Ireland and Ben Chan.
Speaker 1: Incubation is a co production of Pushkin Industries and Ruby
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Speaker 1: Markowitz and Amy Gaines McQuaid. Our editors are Julia Barton
Speaker 1: and Karen Shakerjie Mastering by Anne Pope, fact checking by
Speaker 1: Joseph Fridman. Our executive p you Sirs Are Katherine Girardeau
Speaker 1: and Matt Romano. I'm Jacob Goldstein. Thanks for listening.