Antibiotic Apocalypse

Intro

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0:25Wait, you're listening. Okay. All right. Okay. All right. You're listening to Radio Lab. Radio Lab. From WNYC. See? Yeah.

Avir Mitra Introduction

0:45Hi, everybody.

0:49Thank you for coming out tonight. Welcome to our home station, WNYC. Hey, I'm Latif Nasser, here with our executive editor, Soren Wheeler. Hello, Latif. The only one with the key to the executive bathroom, Radio Lab's executive bathroom. I've never been in there myself, but the reason I've pulled Soren out of the executive bathroom here onto the mic is because a little while back here in New York City. Welcome to our home turf at the green space here.

1:20You got on stage to do a little live show. I did. It's true. It's true. We are doing a live taping of a thing that we've been playing around with lately. This was the latest in a series of shows that we've been doing with our favorite and only ER doctor reporter, Avir Mitra. Right. You may have heard the one I was on stage with him for about CPR. Right. Or the one Lulu did with him about breast milk. Right. And so this time we were like, every once in a while, it's nice to give you some air to air you out a little bit.

1:52Let me out of the closet. Yeah, that's right. And because tonight is a live taping, we will be keeping it loose. We will have some audience interaction. We will have some live guests who can come up. And part of the reason it was so fun, this one, was because you're an editor and you were just editing him in real time, like tweaking, adjusting. You're dialing it in. You're like, OK, we're done with this. Let's move on. Yeah. Yeah. It's sort of funny. Like you can hear this is what Soren does behind the scenes anyway. I mean, we were actually trying to keep it loose, you know, like not dialing it in.

2:24Too much and a little bit of a seat of the pants kind of thing.

Antibiotic Resistance

2:27But also, you know, the show, what the show was about was antibiotic resistance, which. Sexiest topic. It was. The funny thing about that is it was something that I sort of knew about quite a bit. You know, like we get pitches about it. We've done shows about it. You know, I think more generally, all of us sort of like catch some passing news bit about it here or there once every couple of years and then move on with our lives. But Aver, in his position as a doctor. Yeah. He was able to make it so much more visceral and honestly, a little bit more terrifying.

3:04But at the same time, because he reported it out and looked in all these places and tried to figure out what was going on. He also, I think by the end, gave me for sure. I mean, hopefully all of us like a sort of a different and maybe even hopeful way of looking at it. Mm hmm. Well, let's play it. Okay.

3:29Here you go. So help me welcome out Dr. Aver Mitra. Hey, hey. Thank you. Thank you, guys. Wow. A lot of people. I love that. I got to say that every story you've ever brought me, I feel like, starts at your job. Like somebody walks through your doors at the ER with some, I don't know, injury or disease or what have you. That is what today is kind of about. But as I was thinking about it, I kind of realized it goes back even further than that.

Avir's Father's Experience

4:03It goes back to 2006, this thing that happened with my dad, actually. Your dad is a doctor, right? Yeah. Yeah, he's a doctor. My mom's a doctor. My grandmom's a doctor. But at the time, I didn't want to be a doctor. I just wanted to be like a rock star. That was my dream. You went to med school. Then you decided you don't want to be in med school. You want to be a musician. And being an old, practical man as I am, I knew that's not going to work. I told you a thousand times that the difference between a large pizza and a musician, which pizza, large pizza feeds a family.

4:40Bold to let this room laugh at you like that. That's why I go to therapy. Fair share. But the point is, at this time in my life, I was going every day to band practice, hanging out with my buddies, staying up until five in the morning. Meanwhile, my dad is waking up early. He's going to work at a hospital. And he was seeing this sort of interesting change take place. We have been seeing infected hand patients, hand infection patients, coming all the time to us with various reasons.

5:14It could be a small scratch. It could be a pin puncture. And we were treating them basically with a 48 hours worth of antibiotic, IV antibiotic, or PO antibiotic. And it used to get resolved easily.

MRSA Infection

5:27And then suddenly we started to see these patients who were not really getting better within that short period of time. So we said, that doesn't make any sense. Why is it so that we're seeing so many patients? And we started doing some culture for each and every patient who came into the emergency room on a routine basis. So he's doing this at work. And he sort of comes up with this idea like, let's do a research project about this. Let's see what's going on. So he turns to me because, you know, English isn't his first language. He doesn't know how to use a computer. I'm a pretty smart kid.

5:58So he's like, why don't I get you to help me write this paper? You are the only person who has absolutely nothing going on at that stage with the music, etc. Instead of sitting idle, I thought if I keep you busy doing some medical papers later on, if you ever plan to reapply, these papers might help the guys who are looking at your application saying, he's not a complete derelict. Well, I wasn't sitting idle because I was doing music at that time. It's a derelict in the sense you're doing music.

6:30I do feel like I should step in and let you all know, Avir was a little bit of a legit rock star. I mean, you had a record. You had gig. You were on Conan O'Brien. That's true. That's true. But this was later, right? At the time, I was broke. I was living in the basement. It was not a good look. I get it. But anyway, back to the topic. What we found in this paper is that these patients were coming in with infections. The bacteria was MRSA. Oh, sure. I feel like MRSA is like the late 90s news super hospital bug. Yeah.

7:01MRSA was like a typical bacteria that had become resistant. And it was a thing that had already existed. But it was the type of bug, the type of infection you could get if you were super sick. You're in the hospital for months and you're getting all these meds. It's like, but what this paper found is that people were coming in off the street who had like never been in a hospital. Kid falls off a skateboard. Cut. He's got MRSA. So what we found is that actually this bacteria that lived in one place, it's sort of like escaped. It doesn't stay limited to that patient or that limited to that facility.

7:32It essentially escapes and then it becomes a risk factor for the general population. So yeah, you know, I had that experience. I wrote up this paper and I didn't think much of it because I was like, whatever, I'm in a band. But eventually, you know, I go to med school. Now 10 years go by and now I'm actually showing up in the ER as a resident. And at this point, you know, MRSA is just like a common thing. Probably three or four of you have MRSA here. It's like just a thing that people have. But I wasn't worried about it because we had a drug called vancomycin, which can treat

8:03MRSA. So it's not like incurable. So now I'm working in the ER. A year goes by and then it's weird.

Vancomycin Resistance

8:08All of a sudden, I start seeing patients who have resistance to vancomycin. So now the vancomycin isn't working. It's like, okay, so at least we have a class of antibiotics called carbapenems, a little bit more rare, but I can use those drugs for those patients. But you have a backup. Yeah, I have that backup. I can use it. But then another year goes by and then I'm starting to see patients that are resistant to the carbapenems. That's not working anymore. And so then at that point, I have to go to this drug colistin, which is like just this

8:40crazy old drug that I don't even want to use. It's got a bunch of side effects. And basically, I feel like I'm being backed into a corner all of a sudden. It's just this simple infection. And now it's like I have to do all this stuff and I have no choice. I got to say, like, as we've been talking about this, like, obviously, I've known about antibiotic resistance and I'm sure many of us here have. But like, how long have you been a doctor? 10 years? 10 years. It's like, I'm not that that's not a lot, but it's not a lot. Yeah. And I feel like, you know, you in that short time, you have been sitting there literally

9:13watching drugs that you could use slip away. I mean, it's sort of like the pace of it. Like while we've all been distracted by presidential politics or maybe a pandemic like this has been happening right in front of your eyes. Yeah. No, it honestly is terrifying to like go up to work and see this happen. I don't know. It's just scary because it's like if we don't have antibiotics, like we're not really doctors. Like you can't get a surgery if you don't have antibiotics. You can't get a C-section. Like you're basically useless without these drugs, you know?

9:47And that's why I kind of start to have these nightmares where it's like, am I just everything I know about medicine? Is it just this like little bubble that we're living in? What do you mean by like little bubble? What I mean is like, okay, let's zoom way, way out. All right. For hundreds of thousands of years, we've been human beings and we've been fighting bacteria.

Evolution of Bacteria

10:08But for like most of that time, we have been losing. Like just think about it. Like back in the day, you get a little simple UTI, like you die. Have sex with the wrong person, you get disfigured for life. You catch a little cold, it turns into a pneumonia. I mean, basically you got to move somewhere like Arizona, try your best, or you probably just die. Like that is the way the world has always been until not that long ago. Like less than a hundred years ago, Alexander Fleming, he basically just observed that fungi

10:43were producing a chemical that was killing bacteria. So he basically just isolated that chemical. So that's penicillin, right? That's penicillin. And like everything we've done since then has been a variation on that theme. We tweak it a little bit here, find a different fungus there, but it's the same idea. And it's basically this idea that has allowed like civilization as I guess we all know it to exist. Like that's how we've won wars. That's how we live in a city. That's how we're all in this room together. And like people aren't dying, you know, everything we do is just based on kind of this idea.

11:18And that is the bubble that you feel like is bursting? That's the like hundred year bubble. I mean, does that mean that you actually feel like, what are we looking at in the five, 10 years that there are bugs out there that no drug works on? Well, maybe I can like share a story. Yeah. All right. As your editor, I recommend you do. I know. Can't just be me blathering. Let's move. All right. All right. So this is Stephanie Strathde. Yeah. She's an infectious disease epidemiologist at University of California, San Diego.

11:52But here she's just going on vacation with her husband, Tom, to Egypt. We ended up going at a time when there had been a terrorist attack in Sharm el-Sheikh a couple of weeks prior. So all of the people from the West had canceled and we were the only one on this cruise ship. So it was really kind of a ghostly experience. I remember standing at the front of the boat doing one of those Titanic things like, and then we'd had this lovely seafood tower for dinner and we're looking at the stars.

12:22It was really romantic. And then all of a sudden, Tom started to turn a bit green and he was losing his stomach contents all night. So I called a doctor to the ship and the doctor first gave him an intravenous antibiotic and some fluids and said, oh, he'll be right as rain by dinner. And he wasn't. He was worse. So they get off the ship at this point. They go to a clinic in Egypt where they're trying some other medicines. It's not working. So they actually ship him to a bigger hospital in Germany.

12:53Well, he was in an ICU in Frankfurt, where they have some of the best gastroenterologists in the world. But when the culture came back, the doctor said, I've got some terrible news. This is the worst bacteria on the planet. It's Acinetobacter bomanii. And I went, what? And when he said it again, I realized, wait a second. This was an organism that I used to plate on my Petri dishes back at the University of Toronto when I was a student in the 1980s. And all we needed was the lab coat and gloves back then.

13:24How can this be the worst bacteria on the planet? So despite all this treatment, he's getting all these antibiotics. He is getting worse and worse. At this point, he's on a breathing machine. He's getting sicker. So they package him up and send him back home to the University of California, San Diego, the ICU there. I have a chart of all the different antibiotics that it was resistant to right off the top. And I call those the gorilacillins that are the heavy-duty antibiotics that have to be infused into the patient and that have a lot of toxic side effects.

13:55He was on all of those in a cocktail, but there was no other alternative. In fact, we didn't even know if these antibiotics were going to do anything. And I pointed to a whole bunch of them on the wall. And the doctor said, you know, there's nothing that will kill this thing. I said, well, then why are we treating him with all of these antibiotics? And they said, because we don't know what else to do.

14:19This is probably a dumb question, but emotionally, what are you going through at this time?

14:26Well, I felt like it was God's cruel joke that here I am, an infectious disease epidemiologist, and I had no idea that antimicrobial resistance had gotten this bad over the last few decades. That an organism, a wimpy bacteria, as one of the doctors called it, that has acquired these superpowers and is now, like, killing my husband? Like, what? Like, how can this be? How can an infection that you acquire on vacation to a guy who's, you know,

14:57so healthy that he was crawling backwards down into a pyramid one day, and then two days later, he's fighting for his life? Like, this just doesn't happen, does it? I mean, it is, yeah, it's crazy just to think about, like, what she said, that she was, this was a bacteria that she was plating with just gloves, and then it's become this thing that we can do nothing about. Yeah. Yeah, it's scary, man. I mean, like, look, and this was 10 years ago that this happened. I'm showing up to work, and I'm seeing cases like this where no antibiotic works.

15:27I got to mix and mingle different antibiotics to try our best, and I don't know, it's just a scary feeling because I feel like I'm watching a world war that's happening basically right under our noses, and, you know, we're not really paying attention to it. And then somehow, like, I'm at the front lines of this, and I'm like, how did this happen to me? Like, why am I here? I guess that's why I wanted to come here and talk today because I wanted to sort of zoom out and take a big picture of, like, okay, there's this global war. Like, what is really going on here? Well, I mean, so now that we've got you at sort of, like, a little bit out of doctor mode

15:59and into maybe reporter or investigative looker mode, like, back me up a little bit because you talk about it as a world war. Yeah. Like, give me the layout of, you know, unpack that metaphor for me a bit. Like, what's the battlefield? Who are the combatants? Okay. Walk me up to it. Yeah, so we could start with sort of who is this battle between, right? Because you got us and humans, and on the one side— Or us and bacteria. Or us and bacteria, yes, yeah. I forgot I was human. Us. Team us. I promise I'm human. We're on this side.

16:30Think about what we have, right? Like, we're composed of trillions of cells. We have, like, huge brains. We have all these muscles. We have fancy degrees. We have chat GPT. We have everything. And on the other side, we have bacteria that are, like, single-celled organisms. They don't go to school. They don't know how to read. They don't have brains. They don't even have a single neuron. They don't have any muscles. Like, they, you know, just put them in the air, and they'll probably just die. I got to say, it raises the question, which is sort of like, how in the hell are we losing?

17:04No, I know. That's exactly what I think about. And yet, I'm sitting at work and watching us lose it, and that's where I get to thinking. And I don't know. I've grown to have a respect for these guys because I'm like, I actually fundamentally think that they're, like, better than us. I really do. And what, like—

Horizontal Gene Transfer

17:21I mean, sure, we have all this stuff, you know, but they can actually just evolve better than we can at a very fundamental level. Well, explain how something can evolve, like, because they got, like, they've a faster lifespan. They mutate easy a year. Like, what—how do you evolve better? I could describe it, but I'd rather kind of just show you. Yeah, let's do it. But you guys have to be involved. All right, let's some crowd participation. All right, I'm going to set up a hypothetical scenario here where we're going to watch evolution happen. And let's pretend you guys are all humans.

17:52And me, Dr. Mitra, I'm going to try to kill everyone in this room. The way I'm doing it is by— This is, by the way, not a typical public radio— Right, right. —tactic. Right. It's an aggressive donation request, you know. Right. Or else. Yeah. No. Okay, all right. The only way out is if you donate. No, I'm going to seal all the windows, everything, and just suck all the oxygen out of the room. So you all are going to suffocate to death. I'm sorry. I know some of you guys. I apologize. But—

18:22And I need a volunteer. I need one volunteer, ideally a single person. All right. What's your name? Danielle. Danielle. So sucking out all the oxygen in the room, everybody dying. We got that. But Danielle, she didn't even know this. She has a random mutation where she can hold her breath for 20 minutes. So while everybody else dies, you're going to live. So let's think about, like, from an evolutionary perspective, if we want this trait, ability to hold your breath, to spread, how's that going to happen?

18:52Well, Danielle has to go on some dates, meet someone that she's into. We don't need a doctor to tell us what has to happen. Right, right. You get the idea. We get the idea. Then maybe that special miracle of birth will happen. Yeah. So that's human evolution. We've got to wait a while, but that's just human. That's just evolution. That's evolution. But it's a specific type of evolution, really. It's called vertical gene transfer.

19:23Vertical, like down the generation. Like birth genes pass down to the children and grandchildren. They go down the generational tree. So while Danielle has to have sex, bacteria have a sex pillus. So at this point in the show, Avir put up a picture right behind us on stage and had these, like, two gray blobs. It's kind of a grainy picture. And there's this tube just, like, shooting out from one of them, connecting it to the other one on the other side.

19:53It's a different thing. This doesn't look like Danielle at all, actually. But it turns out— More like a date. Yeah, no. Exactly. About a billion years ago, bacteria evolved this crazy trick where they're able to just generate a tube out of their bodies and just suck into the bacteria next to them. It doesn't even have to be the same species. They can just create a tube and connect to the person next to them. And they're shooting genes, I assume? So they make this tube, and then they can make a copy of some of their genes and just send them over to the person next to them.

20:26Wow. That's pretty cool. So that's the sex pillus. And so I kind of want to use this now as an example. Okay, so we're going to try the same scenario again. Instead of you guys being humans, now you're all bacteria. Okay, you all have a sex pillus. So I need to pick someone in the audience. I'm going to pick—what's your name? Rich. Rich. Rich, the bacteria.

20:46You have a special mutation. Let me explain. In this scenario, all you need to live is light. Okay, that's what you need is bacteria. So let's go ahead and turn all the house lights down. And as these are turning down, you guys are all slowly dying. This is getting weird, yeah. But Rich, the bacteria, has a special mutation. He didn't even know he had it. He has the ability to make his own light. So, Rich, please tell me that you have a little glow stick. Just to explain, by the way, we actually handed out glow sticks to everybody in the audience as they came in the door. But— Only, Rich, the special bacteria.

21:18You can go ahead and turn on that glow stick for us. And hold it up. Yeah, kind of wave it around. Let's see it. All right. So using the sex— It's just like, no one's ever been to a rave, I guess. All right. So, Rich, anyone you tap on the shoulder can then turn on their glow stick. Don't do it yet. Don't do it yet. We're going to time this. Okay? And then once you, you know, once you get tapped, you can turn on your glow stick and you can tap people around you. Yeah, when you get tapped, also spread the tap. And let's see how long it takes for this trait to spread everywhere.

21:50Okay? On my count. Ready? Three, two, one, go.

21:57Okay. Hold him up so we can see him. Let's see this happen. Don't turn on your glow— So, Avir and I are standing on stage in the dark, and it was actually pretty cool to watch this happen. You can sort of see Rich's light spread to the next person and the next— And at first, it was actually pretty slow and sort of halting. These guys are still dying over here. They're struggling. But then it started to, like, spread pretty quickly. It took a little while to get, like, over to different sections. This is the VIP section is all dying over here. But really, once it got going, it went fast.

22:28Amazing. And suddenly, the whole theater was sort of like a sea of little wiggling lights. All right. Nice. Let's bring the house lights up. Give yourselves a round of applause. That was actually really cool.

22:39That was great. That was really amazing to watch. You guys are great bacteria. That was so good. Everybody, give yourself a round of applause.

22:49So, what you just witnessed is actually horizontal gene transfer, right? So, while humans have to pass genes down, you guys can pass genes horizontally. You could just pass them to each other. Meanwhile, I think Danielle is still, like, trying to find that date. Right. She's not so sure about the last date she went on. There's going to be some time. I mean, I want you to take your time, but— Right. Exactly. So, you know, you've got to think about that. Look at how fast that spread. And now you take into account that for every single human being on Earth, there are 30 trillion bacteria, okay?

23:22Per person. Per person. So, that's me 30 trillion, you 30 trillion, 30 trillion, 30 trillion. Exactly. It's just unbelievable. There's universes of bacteria for every single human being, and all it takes is for, like, one mutation to happen in one of those bacteria, and then that trait is going to spread like wildfire. So, what we're up against is, like, terrifying numbers of blazingly fast and nimble tiny little enemies. Exactly. It really is, like, our brains versus their sex pillows.

23:53And their sex pillows is winning, basically. Well, okay. But this is actually where I was hoping that our brains might come back in because, okay, sex pillows and trait tricks, and we do a drug, they figure out a way around it. But then we come up with a new drug. Well, that's the idea. Problem is, like, we haven't really been coming up with new antibiotics. We sort of fell off a cliff. Like, we haven't come up with a new antibiotic, a significant one, since, like, 1980. No. We just don't anymore. Why is there not – there's zero new antibiotics since 19, whatever that is.

24:25Yeah. Why? It's mostly, like, an economic issue. You know, you think about how much money it costs to do all these trials to invent a drug. That's going to cost you, like, a billion dollars. So, that's a lot if we all have to chip in on that, you know. And you're going to do all this to make a drug. It might work. And if it does, bacteria, just in a matter of, like, two, three years, they're going to figure out a way around it. So, it's just kind of like a money-losing proposition for pharmaceutical companies. So, they're just not going to do it. So, that means that you, then, are literally just sitting around using the same drugs over and over again.

24:59And meanwhile, every time you use one, the bacteria has a chance to train up on it and figure a way around it. Yeah. And that's how, like, a little trickle of bacterial resistance that's always been around, it's, like, turning into an avalanche. It's scary. I talked to the WHO. There's a whole chapter of the WHO dedicated to this. And they told me that currently, as of today, one in six infections is resistant to the antibiotic that used to work for it. Like, you have to use something else. And currently, today, a million people a year are dying from infections that they used to survive, like, a couple years ago.

25:36And obviously, that number's about to get a lot bigger, too. Do you remember when you were pitching me this story? And I said, well, you can't just leave these people depressed and desidue. No, I know. And you remember I said, like, there's somewhere there's going to have to be a ray of hope. And I'm thinking, now is? I had this. Okay, okay. So, with some prodding, Avir did eventually talk about how they're dealing with the rise of antibiotic resistance in hospitals. Like, we have, like, committees that are filled with annoying people that will email me if I do something wrong, or they pull me into a Zoom meeting, or there's, like, all these, like, protocols we gotta follow.

26:11Basically making sure that they don't use antibiotics in a way that give the bacteria a chance to evolve or resist the drug and then pass that resistance along. You know, we want to treat things only if there's really an infection and then really kill everything. Like, you know, we don't want there to be, like, any survivors that can live to tell the tale of what happened. But, Avir, he did have a little bit more darkness that he wanted to stare at. Although I promise it does eventually lead us to a more hopeful space, eventually.

26:44And that will all come right after this quick break. Stick around.

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28:54This is Radio Lab. I'm Soren Wheeler. And we are back on stage with Dr. Avir Mitra, who is giving us his frontline view of what he calls a world war between us and bacteria. And at this point in the show, Avir told us that as he was reporting all of this out, he realized it wasn't just a problem with him giving antibiotics to a patient in the hospital.

Antibiotic Use in Animals

29:16Like, we also give them to animals. I don't know why that never occurred to me. But if I had to ask you, like, of all the antibiotics given in the U.S., what percentage would you say go to humans versus animals? I don't know. I feel like it's one of those things where I'm supposed to guess bigger than I would think. But I have no idea. Half. I don't know. It's reasonable. But actually, 70% of all the antibiotics given are given to animals. Another way of putting that is that every year here in the U.S., we humans take about seven pounds of antibiotics, whereas farm animals are given 30 million pounds every year.

29:57So basically, cows and pigs and chickens are getting four times the amount of antibiotics that we humans are getting. Yeah. I had no idea. Wow. They're basically just mixing their food with antibiotics. They mix the water. They're drinking water with antibiotics. They, like, spray it on the ground. They inject them with antibiotics. It's just like a real— So this is not, like, just if they get sick? No, no, no. This isn't just if they get sick. It's just very willy-nilly. In many cases, these are the same antibiotics that we use, treating, like, the same infections that we get.

30:32So Avir ended up talking to a scientist, a guy named Lance Price. He's the founding director of the Antibiotic Resistance Action Center at George Washington University. But before he was that, he was researching this exact problem, the use of antibiotics on farms. And the thing that he was specifically trying to figure out was, what effect could the use of all these antibiotics on farm animals have on us? So he designs a study, and like all good studies, it involves poop.

31:02It's, like, a common theme in Radiolab, I feel like, right? Yes, it comes up a lot. So he designs this study. All right. So what he does, he decides to study the poop of chicken catchers, the person who goes around the chicken farm and picks up the chickens by their necks with their hands and throws them in the chicken truck when they're, like, ready to get harvested, basically. So they're touching a lot of chickens. So what he does is he measures the bacteria in the poop of these chicken catchers versus the bacteria in the poop of, like, regular people like, you know, you and I.

31:32So we cultured all this poo, and then we analyzed the data. And the one thing that popped out, like, really strong was gentamicin resistance. And so it turned out that the chicken catchers had 32 times the risk for carrying gentamicin-resistant E. coli as their peers. So basically, these chickens, before they even hatched, they would poke a hole in the egg and inject that egg with gentamicin.

32:04Then the chickens would grow up. They're being fed gentamicin, like, left, right, center. And so the E. coli that live in the gentamicin were eventually learning from this, becoming resistant to the gentamicin. Those bacteria were jumping from the chickens onto the hands of the chicken catchers, into the mouths of the chicken catchers, enough to the degree where they're literally shitting out resistant bacteria. And look, if you're an epidemiologist and you get three times the difference, you're doing cartwheels down the hall, right? So you're like, I found something. Look at this. It's miraculous.

32:35But this was 32 times. And I just said, we've got to be doing something wrong, right? So we looked at the numbers over and over, and it was clean. So the person handling a chicken is 32 times more likely to have a resistant form of E. coli in their bodies than someone who's not handling a chicken. Yeah, exactly. And then they find out that, okay, these chicken catchers are going home. That resistant bacteria is getting into their children. Then they find that those bacteria are spreading through the schools of the children.

33:06They later find out that if you're driving behind that chicken truck, carrying chickens, those bacteria are getting off of the truck, in through your air vents, and landing in the cars behind them, onto the people behind it. Like, it's like, it's truly insane. And then when you really just sit back and think about it, like, then these chickens go die. They get packaged up with the bacteria in them, and they get sent to, like, all of our houses, really. Do you remember when, like, 10 minutes ago, I was like, can we, like, do the turn to hope thing?

33:36No, I know, I know. But, like, look, this is, to me, this is exciting. This is good. Because, like, I'm spending my whole life in the ER, like, trying to be super anal. Like, no, you're not getting into zithromycin. Like, I'm not giving you a Z-Pak. But really, like, this is where the real battle is happening. I've been on the wrong battlefront the whole time. Well, but so then what, I mean, okay, what's your next move? Like, you're going to call up Big Chicken? Well, I did the Radiolab thing. Yes, that's actually exactly what I started emailing people I was doing. I was trying to do the Radiolab thing. So I emailed Tyson Chicken, and they weren't into me.

34:09But I kept looking, I kept looking. Eventually, I was able to find one guy who is a higher up at a chicken company. Big deal guy. Okay. And he actually agreed to talk to me. Great. So let's bring him up. This is Bruce Stewart-Brown. He's the chief medical officer at Purdue Chicken.

34:36Bruce. Nice to see everybody. Thank you for coming. Thank you. Thank you for agreeing to talk about this. I want to just break in and say that I actually had figured that this was going to be the point in his reporting where Avir would hit a wall. And so it really felt like a sort of strange but very cool opportunity to sit down and talk to somebody who's on the inside of one of the biggest chicken producers in the country. Yeah. So I'm a veterinarian, and I started at Purdue in 1998 as a field veterinarian and just kind of getting used to how commercial chicken was raised and the process of being a veterinarian

35:12specifically for chickens. And in 2002, we got in a room together and talked about the fact that concerns around antibiotic use had hit the radar for us. And that means that people were calling in or writing and saying, look, I heard you guys use a lot of antibiotics in chickens. And they wondered why. And in this meeting, then, Jim produced a third-generation CEO, chairman of the company at the time.

35:49And Jim is going, first of all, tell me why we use all those antibiotics. And then second, tell me how we can not use all those antibiotics. Let's make it a project and start now. Let me ask you, at that moment in time when the big cheese has showed up and said, we're going to do this, what's your reaction? I'm going, oh, my man, we have got to change everything. If you just pulled out the antibiotics, you are likely going to have to treat quite a few

36:22chickens. And that's not right. That's not a great thing. So what do you end up doing to make up, if you're going to take the antibiotics out, what do you have to do to make up for that? First thing is you have to redefine clean. You have to decide, in our case, that we thought this egg was clean. It's got to be cleaner. So there's four ways chicken companies were using antibiotics, including us. One is it was going in every egg as a virus. Like injected into the egg? Injected into the egg with a vaccine to keep the vaccine clean as you vaccinate.

36:57You have this tremendous opportunity in chicken to vaccinate the embryo. It's amazing, honestly, that you can get the vaccine started, you know, in an embryo. But you do poke a hole in the egg. And the egg did come out of the rear end of a hen, which is the same place, you know, manure comes out of. So it can be dirty. And the idea was keep it clean with the antibiotic. Okay, that's the first. So cleaning chicken cloaca is step number one. Yeah, well, but the other parts were there was antibiotics in the feed.

37:31Every bite of feed from day old had an antibiotic in it in those days, even though they weren't sick, just in case they might be. And it helps their gut stay healthy through all the challenges. So we were putting antibiotics in the feed for that. Then when I went down to the farm, I'm seeing that the things they used to feed these birds were other animal parts. And so that gives them gastrointestinal illnesses because it's like, you know, kind of gross food. And so then they got to use the antibiotics.

38:02So then they decide to like change the feed. Yeah, we had to change. We had to look at the feed a whole new way. Take the antibiotics out, take the animal byproducts out because those are irritants. We put in probiotics, good bacteria, things that help the digestive tract of a chicken operate optimally. Same thing, you know, you're probably all familiar with the good bug thing. It's really big. So is this all like, is it, you're going along.

38:32Is it working? Does it seem like you're getting somewhere? I don't know. Maybe there's some other things you had to do too. Yeah, well, we did have to work on the chicken house and the change in feed, the change in approach to feed was a big deal. The cleaner eggs was a big deal. But changing the way you care for chickens became the thing. So raise these chickens in a way that even if nobody cared, you used antibiotics, you wouldn't use them. The whole thing became about caring for chickens in a way that you'd never, let a chicken be

39:04a chicken, put things in the chicken house so they can get up off the floor, let them exercise, put some windows in the chicken houses, back in the chicken house. The traditional industrial chicken house has zero windows and it's all artificial light. Put some windows back in, expand the floor space to something above the floor. Chickens like to do three things. They like to climb, they like to perch, and they like to hide.

39:35And in a traditional chicken house, they don't get to do much of any of that. And so get that back in there. Take the stressors away from the way you raise chickens as much as you can and learn all the time. Can I get you to like, I mean, over how long did this take and maybe where did you land? Where are we at now? 2016, we were done. Wait, does done means what? All the antibiotics were out of the feed, out of the eggs, not using any antibiotics for

40:05anything other than treating sick flocks. Yeah.

40:10Thank you for the chicken. And thank you for coming up here and talking to us. All right, everybody. That, I mean, it is actually imagining, imagining the chicken leaving its well-lit coop to go out to its little sort of playground exercise area with maybe a like probiotic parfait in hand. Yeah. It's delightful. Other than the fact that we are eventually going to slaughter and eat them. Right. And I got to say, you know, like also to take in consideration just what like the overall

40:41the animal industry is doing, should we be doing it, the climate? Of course. Like, yeah. Yeah, yeah, exactly. It's like there, you know, there's a lot of problems with eating meat in general. You know, you can think about climate change. You can think about ethics. And this doesn't solve all of that, but certainly in just a proof of concept, you know, to me it's interesting, like the antibiotics were sort of masking cruel treatment towards these animals. Like you can treat them however you want, but if you pump them with enough antibiotics, they live.

41:11And once you remove those antibiotics, all of a sudden you're sort of seeing the truth of what you're doing. And if you treat them better, they're healthier, you're healthier. What we do to them comes back to us. I don't know. It's kind of an interesting proof of concept. I'm into it. Yeah, I guess I'm just like back thinking about the war because like, let's say that everybody went full Bruce and there's maybe a cow Bruce and a pig Bruce and, but even then, like, yeah, like given the way you've described what's going on globally, I mean, is even that any kind of decisive move on our part or are we?

41:47The way I see it, everything that Bruce is doing, that's sort of playing great defense, right? Like, let's stop training these guys to get better. But I agree. You know, at some point we have to go on offense, like any good war. And so I do have one more story I want to share with you guys that kind of takes us there. And honestly, I think this is the part that gives me really the most hope, the most excitement. All right, good. But to get there, we're going to have to go back to like a dark place. It's been the theme of the night, but we got to go back to Stephanie Strathdee. Who went with her husband, Tom, and the Tom gets sick and, okay.

42:20Exactly. So one day the doctors came to me and said, you know, Steph, you realize that Tom's on life support, right? His, he's on a ventilator to keep his lungs working. He's on three medications called pressers to keep his heart working. And now his kidneys are blinking on and off. So that's the trifecta where we stop talking about organs that are having problems working. We're talking about whole systems, whole body systems.

42:51I'm like, okay, okay. Like speak to me. And they said, well, do you want to start kidney dialysis? And so what they were really asking me is, do I want to pull the plug? And that moment was just like, I can't believe this is happening. You know, when you have your advanced directives and you, you know, you sit down with your partner and you write a will and, you know, he had said to me, hey, you know, if I'm ever like brain dead, please like, you know, pull the plug. But this situation, it was his brain that was alive.

43:23It was his body that was dying. And I had no idea what he would want me to do. So the doctors are looking at me and they're saying, okay, you know, what do you want to do? And I said, okay, I think we should ask Tom what he wants to do. And then I said, well, he's in a coma stuff. Like, how is he going to communicate? I said, well, you know, let's see. Let's just see. So I had this conversation with Tom that you just never think that you're going to have to have with somebody. And I said, hey, honey, I am. I know you're fighting really hard and you have to be really tired, but I need to know

43:58if you want to live. And if you want to live, I need you to tell me by squeezing my hand and I will leave no stone unturned. And I remember that moment like it was just yesterday. I still get chills just talking about it. I waited for a whole minute and I thought, oh my God, he's not going to squeeze my hand. And then all of a sudden he squeezed really hard. And I thought, oh yeah, like, you know, I pumped my little blue gloved fist in the air. And then I thought, oh crap, like, what am I going to do now?

44:31I'm not a doctor.

44:35I mean, the question in the room here, for me at least, is what did she do next? Yeah, well, we can ask her.

44:44Stephanie, come on up. All right, we will get Steph's story and what happens to her and Tom next. Right after this quick break.

Phage Therapy

44:57On this week's On the Media, I spoke to the MAGA warrior who ended up defending the Federal Emergency Management Agency against the administration's assault. He proceeded to berate me over the fact that the media got a hold of a story and was running a topic that they felt was too sensitive and not fit for public domain. The topic was abolishing FEMA. Correct. You don't want to miss this one. Tune in to On the Media from WNYC. Find On the Media wherever you get your podcasts. Hey, it's Radiolab.

45:29I'm Soren Wheeler, back on stage with Avir Mitra. And we'd been hearing the story of Stephanie Strathie and her husband who was suffering from a bacterial infection that no antibiotic drugs seemed to be able to treat. And at this point in the show, we actually got Stephanie up on stage to share with all of us what exactly she had to do next. Hey, everybody. I can't believe I'm on my radio lab. I'm geeking out.

46:00Thank you for coming. I'm going to just go in with the first one. The big question that we're all left with, I think. What do you do next? Well, I was terrified. I mean, some of the top infectious disease physicians are at University of California, San Diego. They were our colleagues caring for Tom. And but, you know, I was his wife and I wanted him to live. And I thought, OK, like if he dies, I want to know that I did my very, very best. So I'm an AIDS researcher by training, and I learned as an AIDS researcher that there are

46:34experimental treatments that got studied while we were doing clinical trials, and there should be some experimental treatments that we could use to save Tom. So I hit the research. I went on PubMed, which is a search engine that the National Library of Medicine makes that freely available. And I entered the keywords, Acinetobacter bomaniae, the superbug that was killing him, alternative treatments. And up pops something called bacteriophage therapy, or phage therapy for short. And what is bacteriophage, or what's a phage?

47:08Bacteriophage are viruses that have naturally evolved to attack bacteria. They're the oldest, most populous organism on the planet, and they kill bacteria. So are you saying just like how, like, I can catch a cold, like a bacteria can catch its own cold type of thing? Yeah. Well, what was weird is that I learned about bacteriophage when I was a student at the University of Toronto back in 1986. Like, it was just mentioned in class, but I never knew that they had ever been used to

47:38treat, like, bacterial infections. But they were discovered before penicillin. It's just that they had been, you know, popularized in the former Soviet Union, and that was seen as kind of Russian medicine and fell out of favor in the West. Okay. So the idea then is that you're going to put a virus into Tom to fight the bacteria. And are there, is it like, oh, when you're doing the PubMed Googling, it's like, here's the one to you?

48:08Like, what are you coming at? Yeah, well, that was the other problem. Well, first I got my colleagues at the University of California, San Diego said, wow, what an interesting and intriguing idea. If you can find phage that are a match for Tom's bacterial isolate, we'll call the FDA and see if they'll give us permission to give it to him on a compassionate basis because he's going to die. But it turns out there's like 10 million, trillion, trillion phages on the planet. Like, that's more than all the stars in the sky. So that was even more daunting. And luckily, I was able to find researchers that agreed to help with the help of Dr. Chip

48:43Schooley, the head of infectious diseases at the time at the University of California, San Diego. You know, we found people and even the U.S. Navy who had been sourcing phages from the bilges of ships around the world. From like the inside of the underneath the ship? Yeah, yeah. Like scraping off viruses? But, you know, the best place to actually go for phage is where there's a lot of bacteria. And you know where there's a lot of bacteria? I feel like this is going back to poop. It's going back to poop. So it turns out that sewage and barnyard waste and duck pond waste, that kind of stuff, the

49:18stuff from like the farms that Bruce was talking about, that's a perfect place to source phage. So within a couple of weeks from my first email asking total strangers for help to the day that we treated Tom with these viruses that attack bacteria, it was only three weeks. Three weeks of people tromping through the sewers and scraping the bottom of Navy boats and like sending... Well, some of these were already samples that were in labs, but literally, yeah. So, you know, I couldn't believe that we were doing this, but, you know, like Tom's in a

49:49coma. I said, you don't believe like we're going to be like pumping like, you know, like purified shit into you to see if you're going to live. Like, it was just like, I can't believe this is my life. But that's essentially what we did. And that was, then, did you say three weeks later? Three weeks. That's all it took. Like, compare that to an antibiotic that takes 10 to 15 years to develop and a price tag of a billion dollars or more. Yeah. But, you know... Okay, so you... So, that's what we did. It was the scariest day of my life, but me and Tom's two daughters said, okay, let's do

50:23it. He's, you know... And is it send it in in an injection, an IV... First, we put them in the catheters in his abdomen because that was the closest to the source of the infection, which was in his gut. And then we injected them and it was a billion phages per dose every two hours. And, um, two to three days later, he, like, he was, like, within hours of dying, I was told, he lifted his head off the pillow, opened his eyes, and kissed his daughter's

50:53hand. Carly was on shift at that day and, um, everybody in the ICU freaked out. There were, like, people cheering. There were people crying. I was crying, too. It was the happiest day of our lives. Wow. Wow. Wow. Wow.

51:11Can you, how much do you know about, like, I mean, the, the, the virus goes in and attacks the bacteria, but, like, how do you, how much do you know about how, why this is so effective or what's actually happening in there or, or how this is going down? Like, what, what's actually going on inside the body? Well, in, in Tom's case, there was something else that was a bit of an opportunistic kind of situation because a couple of the phages were synergistic with one of the antibiotics. What does that mean? How does it, the virus is synergistic with it?

51:43Well, okay, let me, let me explain this. Okay, so you're a bacteria, okay? Okay. And I'm a phage, and, and a vir is the antibiotic, okay? And we're both trying to kill you, all right? Okay? Why does this keep happening? Now, typical day at the office. Now, now, you're a bacteria. So much death. You do not have a brain in this example, okay? Like, I don't know about regular life, but you have to make a genetic decision about who you would rather face, him or me. And I'm scarier than he is, okay?

52:14You do not want to have to deal with phage. So you decide to take off your shirt. Now, okay.

52:22Nobody wants that. I know that this is not that kind of show, people. But, but your shirt is, is, is your slimy biofilm layer. Okay. That's your superpower. It's his resistance, basically, right? Yes. But that's where the receptor for the phage is, is on your shirt. Okay, so if I get rid of my biofilm shirt receptor, you can't attach. That's right. And so I, I die. But in doing so, you have made yourself susceptible to a vir is the antibiotic. Okay. Because he loves nothing more than a shirtless.

52:53So he kills you, he gets you.