Antibiotic Apocalypse

12:07Soren Wheeler:Can't just be me blathering. Let's move. All right. All right. So this is Stephanie Strathdee.

12:13Avir Mitra:Yeah.

12:13Soren Wheeler:She's an infectious disease epidemiologist at University of California, San Diego. But here, she's just going on vacation with her husband, Tom, to Egypt.

12:23Avir Mitra:We ended up going at a time when there had been a terrorist attack in Sharmul 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. And then we'd had this lovely seafood tower for dinner, and we're looking at the stars. It 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.

13:07Soren Wheeler: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.

13:19Avir Mitra:Well, 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.

13:51Soren Wheeler:How 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.

14:07Avir Mitra:I have a chart of all the different antibiotics that it was resistant to right off the top. And I call those the gorillacillins that are the heavy-duty antibiotics that have to be infused into the patient and that have a lot of toxic side effects. He 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.

14:45Soren Wheeler:This is probably a dumb question, but emotionally, what are you going through at this time?

14:52Avir Mitra:Well, 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, so 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?

15:34Avir Mitra:I mean, yeah, it's crazy just to think about what she said that this was a bacteria that she was plating with just gloves and then it's become this thing that we can do nothing about.

15:44Soren Wheeler: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. I 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 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.

16:20Soren Wheeler:Like what is really going on here?

16:22Avir Mitra:Well, I mean, so now that we've got you at sort of like a little bit out of doctor mode and 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.

16:40Soren Wheeler: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...

16:47Avir Mitra:Or us and bacteria. Or us and bacteria, yes, yes.

16:50Soren Wheeler:I forgot I was human. Us, team us, I promise I'm human. We're on this side. Think 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.

17:27Avir Mitra:I got to say, it raises the question, which is sort of like, how in the hell are we losing?

17:31Soren Wheeler:No, 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.

17:47Avir Mitra:And what, like?

17:48Soren Wheeler:I mean, sure, we have all this stuff, you know, but they can actually just evolve better than we can at a very fundamental level.

17:56Avir Mitra:Well, explain how something can evolve, like because they got like the faster lifespan, they mutate easier. Like what, how do you evolve better?

18:05Soren Wheeler:I could describe it, but I'd rather kind of just show you.

18:08Avir Mitra:Yeah, let's do it.

18:08Soren Wheeler: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. We're going to watch evolution happen. Let's pretend you guys are all humans. And me, Dr. Mitra, I'm going to try to kill everyone in this room. The way I'm doing it is by...

18:26Avir Mitra:This is, by the way, not a typical public radio tactic.

18:30Soren Wheeler:Right. It's an aggressive donation request. Or else. Yeah.

18:35Avir Mitra:No. Okay, all right. The only way out is if you donate.

18:38Soren Wheeler: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, and 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?

19:19Soren Wheeler:Well, 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.

19:30Avir Mitra:You get the idea. We get the idea.

19:34Soren Wheeler:Then maybe that special miracle of birth will happen.

19:37Avir Mitra:Yeah, so that's human evolution. We've got to wait a while, but that's just evolution.

19:43Soren Wheeler:That's evolution, but it's a specific type of evolution, really. It's called vertical gene transfer. Vertical, like down the generation. Like her 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.

20:04Avir Mitra:So at this point in the show, Avir put up a picture right behind us on stage. It 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.

20:20Soren Wheeler:It's a different thing. This doesn't look like Danielle at all, actually. But it turns out— More like a date. that was unrecognizable. 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.

20:43Avir Mitra:And they're shooting genes, I assume?

20:46Soren Wheeler: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.

20:52Avir Mitra:Wow, that's pretty cool.

20:54Soren Wheeler:So that's the sex pill. 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 pill. So I need to pick someone in the audience. I'm going to pick, what's your name? Rich. Rich, the bacteria, you 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.

21:26Avir Mitra:This is getting weird, yeah.

21:27Soren Wheeler: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.

21:37Avir Mitra:Just to explain, by the way, we actually handed out glow sticks to everybody in the audience as they came in the door.

21:43Soren Wheeler:Only Rich, the special bacteria. You can go ahead and turn on that glow stick for us. And hold it up.

21:48Avir Mitra:Yeah, can I wave it around? Let's see it.

21:49Soren Wheeler: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 get tapped, you can turn on your glow stick and you can tap people around you.

22:11Avir Mitra:Yeah, when you get tapped, also spread the tap.

22:13Soren Wheeler:And let's see how long it takes for this trait to spread everywhere. Okay? On my count. Ready? Three, two, one, go.

22:24Soren Wheeler:Okay. Hold him up so we can see him. Let's see this happen.

22:28Avir Mitra:So, Avir and I are standing on stage in the dark, and it was actually pretty cool to watch this happen. You could sort of see Rich's light spread to the next person, and at first it was actually pretty slow and sort of halting.

22:41Soren Wheeler:These guys are still dying over here. They're struggling.

22:44Avir Mitra:But then it started to spread pretty quickly. It took a little while to get over to different sections.

22:50Soren Wheeler:The VIP section is all time.

22:52Avir Mitra:But really, once it got going, it went fast.

22:54Soren Wheeler:Amazing.

22:55Avir Mitra:And suddenly the whole theater was sort of like a sea of little wiggling lights.

22:59Soren Wheeler:All right, nice. Let's bring the house lights up. Give yourselves a round of applause. That was actually really cool. That was great. That was really amazing to watch. These are great bacteria. That was so good.

23:12Avir Mitra:Everybody give yourself a round of applause.

23:16Soren Wheeler:So 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.

23:27Avir Mitra: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. Give me some time. I want you to take your time, but...

23:37Soren Wheeler:Right. Exactly. So, you know, you 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. Per person. Per person.

23:50Avir Mitra:So that's me 30 trillion, you 30 trillion, 30 trillion, 30 trillion.

23:53Soren Wheeler: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.

24:06Avir Mitra:So what we're up against is like terrifying numbers of blazingly fast and nimble tiny little enemies.

24:14Soren Wheeler:Exactly. It really is like our brains versus their sex pillus. And their sex pillus is winning, basically.

24:23Avir Mitra:Well, okay, but this is actually where I was hoping that our brains might come back in. Because, okay, sex pillus and trait tricks and we do a drug, they figure out a way around it. But then we come up with a new drug.

24:34Soren Wheeler: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. We just don't anymore.

24:48Avir Mitra:Why is there not – there's zero new antibiotics since 19-whatever that is. Why?

24:53Soren Wheeler: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. 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.

25:19Avir Mitra:So that means that you then are literally just sitting around using the same drugs over and over again. And meanwhile, every time you use one, the bacteria has a chance to train up on it and figure a way around it. Yeah.

25:32Soren Wheeler: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 and obviously that number's about to get a lot bigger too do you remember when

26:07Avir Mitra: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 gonna have to be a ray

26:17Soren Wheeler:of hope and i'm thinking now i had this okay okay so with some prodding avir did eventually talk

26:24Avir Mitra:about how they're dealing with the rise of antibiotic resistance in hospitals.

26:28Soren Wheeler:We have 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 all these protocols we've got to follow.

26:37Avir Mitra:Basically making sure that they don't use antibiotics in a way that gives the bacteria a chance to evolve or resist the drug and then pass that resistance along.

26:46Soren Wheeler: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.

26:59Avir Mitra: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. And that will all come right after this quick break. Stick around. When the economic news gets to be a bit much. Listen to The Indicator from Planet Money. We're here for you, like your friends trying to figure out all the most confusing parts. One story, one idea, every day. All in 10 minutes or less. The Indicator from Planet Money, your friendly economic sidekick. From NPR.

27:43Avir Mitra:This 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.

28:06Soren Wheeler:Like, 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.

28:22Avir Mitra: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.

28:28Soren Wheeler:It's reasonable but actually 70 % of all the antibiotics given are given to animals.

28:35Avir Mitra: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. So basically cows and pigs and chickens are getting four times the amount of antibiotics that we humans are getting.

28:53Soren Wheeler: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.

29:05Avir Mitra:This is not like just if they get sick.

29:09Soren Wheeler: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.

29:21Avir Mitra:So Avere 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?

29:46Soren Wheeler:So he designs a study, and like all good studies, it involves poop. It's like a common theme in Radiolab, I feel like.

29:53Avir Mitra:Yes, it comes up a lot.

29:54Soren Wheeler: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. So we cultured all this poo and then we analyzed the data. And the one thing that popped out like really strong was gentamicin resistance.

30:35Soren Wheeler: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. Then 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.

31:14Soren Wheeler: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. But 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.

31:34Avir Mitra: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.

31:43Soren Wheeler: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. They 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. 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.

32:17Avir Mitra:Really. Do you remember when like 10 minutes ago, I was like, can we do like, do the turn to hope? thing?

32:25Soren Wheeler:No, 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 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.

32:42Avir Mitra:Well, but so then what, I mean, okay, what's your next move? Like you're going to call up big chicken?

32:46Soren Wheeler:Well, I did the radio lab thing. Yes. That's actually exactly what I started emailing people I was doing. I was Tyson Chicken, and they weren't into me. But 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, 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.

33:25Avir Mitra:Bruce. 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 a veer 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 specifically for chickens.

34:03Avir Mitra: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. And 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?

34:59Avir Mitra: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 chickens. 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?

35:40Avir Mitra:Inject it into the egg with a vaccine to keep the vaccine clean as you vaccinate. You 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. Every 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.

36:28Soren Wheeler:And it helps their gut stay healthy through all the challenges. So we were putting antibiotics in the feed for that. 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 antibiotics. So then they decide to like change the feed.

36:54Avir Mitra: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. 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, is 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, but. 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.

37:33Avir Mitra: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 a 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.

38:18Avir Mitra:Chickens like to do three things. They like to climb, they like to perch, and they like to hide. And 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 anything other than treating sick flocks. Yeah. Thank you for the chicken, and thank you for coming up here and talking to us.

39:04Avir Mitra:All right, everybody.

39:09Avir Mitra: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 um it's delightful other than the fact that we are eventually going to slaughter and eat them right and i gotta say you know like also to take in consideration just what like the overall the animal industry is doing should we be doing it the climate of course like yeah yeah yeah exactly

39:37Soren Wheeler:it's like there you know there's a lot of problems with eating meat in general you know you could 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. And 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.

40:08Soren Wheeler:What we do to them comes back to us. I don't know.

40:10Avir Mitra:Yeah.

40:10Soren Wheeler:It's kind of an interesting proof of concept. I'm into it.

40:13Avir Mitra: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, is even that any kind of decisive move on our part or are we?

40:36Soren Wheeler:The 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.

40:58Avir Mitra:All right, good.

40:58Soren Wheeler: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.

41:06Avir Mitra:Who went with her husband, Tom, and the Tom gets sick and okay. Exactly. So one day the doctors came to me and said, you know, Steph, you realize that Tom's on life support, right? Right. 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. I'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?

41:52Avir Mitra:And that moment was just like, I can't believe this is happening. You know, when you have your advanced directives and you sit down with your partner and you write a will. And he had said to me, hey, if I'm ever brain dead, please pull the plug. But this situation, it was his brain that was alive. It 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, 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, Steph. How is he going to communicate?

42:29Avir Mitra:I said, well, 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 if 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.

43:12Avir Mitra: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? I'm not a doctor. I mean, the question in the room here, for me at least, is what did she do next?

43:29Soren Wheeler:Yeah, well, we can ask her. Stephanie, come on up.

43:34Avir Mitra:All right, we will get Steph's story and what happens to her and Tom next. right after this quick break.

43:45Avir Mitra:When the economic news gets to be a bit much, listen to The Indicator from Planet Money. We're here for you, like your friends, trying to figure out all the most confusing parts. One story, one idea, every day. All in 10 minutes or less. The Indicator from Planet Money, your friendly economic sidekick. From NPR. Hey, it's Radiolab. I'm Soren Wheeler, back on stage with Avir Mitra. And we've been hearing the story of Stephanie Strathie and her husband, who was suffering from a bacterial infection that no antibiotic drugs seem 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.

44:33Avir Mitra:Hey, everybody. I can't believe I'm on my radio lab. I'm geeking out. Thank 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. But, you know, I was his wife, and I wanted him to live. And I thought, okay, 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 experimental treatments that got studied while we were doing clinical trials.

45:18Avir Mitra: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 it freely available. And I entered the keywords, Acinetobacter bomaniae, the superbug that was killing him, alternative treatments, and up popped something called bacteriophage therapy or phage therapy for short. And what is bacteriophage or what's a phage? Bacteriophage are viruses that have naturally evolved to attack bacteria. They're the oldest, most populous organism on the planet and they kill bacteria.

45:59Soren Wheeler:So are you saying just like how I can catch a cold, like a bacteria can catch its own cold type of thing?

46:05Avir Mitra:Well, what was weird is that I learned about bacteriophage when I was a student at the University of Toronto back in 1986. It was just mentioned in class, but I never knew that they had ever been used to treat bacterial infections. But they were discovered before penicillin. It's just that they had been 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 is it like, oh, when you're doing the PubMed Googling, it's like, here's the one to you?

46:48Avir Mitra:Like, 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.

47:22Avir Mitra:Chip Schooley the head of infectious diseases at the time at the University of California, San Diego we found people and even the US Navy who had been sourcing phages from the bilges of ships around the world from like the inside of the underneath the ship 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 stuff from like the farms that Bruce was talking about, that's a perfect place to source phage.

48:03Avir Mitra: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 like... Well, some of these were already samples that were in labs, but literally, yeah. You know, so, you know, I couldn't believe that we were doing this, but, you know, like Tom's in a coma. 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.

48:36Avir Mitra: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. Okay. 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 it. 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.

49:22Avir Mitra:And two to three days later, he was within hours of dying, I was told. He lifted his head off the pillow, opened his eyes, and kissed his daughter's hand. Carly was on shift at that day. and 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.

49:52Avir Mitra:How much do you know about like, I mean, the virus goes in and attacks the bacteria, but like how much do you know about why this is so effective or what's actually happening in there or how this is going down? and like what's actually going on inside the body? Well, 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 a virus synergistic with it? Let me explain this. Okay, so you're a bacteria, okay? Okay. And I'm a phage and a vir is the antibiotic, okay?

50:30Avir Mitra:And we're both trying to kill you, all right? Okay. Why does this keep happening? Typical day at the office. Now, you're a bacteria. So much death. You do not have a brain in this example, okay? 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? You do not want to have to deal with phage. So you decide to take off your shirt. Now, okay. Nobody wants that. I know that this is not that kind of show, people. But your shirt is your slimy biofilm layer. That's your superpower.

51:12Soren Wheeler:It's his resistance, basically, right?

51:14Avir Mitra: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 die. But in doing so, you have made yourself susceptible to the antibiotic. Because he loves nothing more than a shirtless. So he kills you. He gets you. So it's a one-two punch kind of thing. That's right. Or even if one starts to work, you can – but does that mean that like when you use phage therapy, not only do you have a new way of getting at this bug, you've unresistanced it. Like you've dialed back the resistance that it developed over the years of whatever.

51:56Avir Mitra:And now a bacteria can actually be newly susceptible to a drug that it was. So, you know, phage therapy is now going through clinical trials all around the world. Phage is all the rage, people.

52:10Soren Wheeler:She's not going to say this, but actually she is the one setting up all these clinics all over the place. Yes, she is.

52:18Avir Mitra:At the University of California, San Diego, we do have what became the first dedicated phage therapy center called the Center for Innovative Phage Applications and Therapeutics, or IPATH. So we do provide phage therapy to people that have no... But there's many, many around the world now. And of course, I didn't do this all by myself. I mean, I hear a lot happening, but I also have to wonder a little bit, like, why? Like, I didn't know more about this already. Why Avir wasn't already thinking about this as something he might have to use. Like, why isn't this already happening everywhere? Yeah.

52:51Avir Mitra:Well, you know, when COVID came on the scene, everybody, you know, felt it right away, right? It was a pandemic that hit hard, hit fast. with antimicrobial resistance, it's a slow burn. So you don't really know or feel it unless it hits you in your personal life. Like you're a V, you're an emergency room doctor or you're his dad and you're seeing patients that used to be treatable that aren't treatable anymore. Or you're me, like whose husband is suddenly dying. And we have kind of let this creep up on us. But also with COVID, we had four vaccines or five vaccines developed within a year, right?

53:32Avir Mitra:And so if we had the political will to move phage therapy forward, we could be doing a lot more than we are. So those trials are getting done now, but the pace is not fast enough to overcome the pace at which resistance is spreading. Can I ask you the sort of like embarrassingly typical question that a Radiolab person might ask? With your shirt on, yeah. So in the moment that Tom came back, like, I don't know, talk to me about how that felt. I mean, I feel like there's relief. I heard joy, but is there pride? Like, I don't know. Give me a little bit on that. Well, I think that Tom deserves a lot of credit in this too, because that man had so much resilience to bounce back.

54:17Avir Mitra:And, you know, he had been in the hospital nine months. He'd lost 100 pounds. He lost all of his muscle mass. He had to learn how to walk, how to talk, how to do everything all over again. And now he's the face of evidence-based hope. Yeah. You know? That's an amazing thought. Thank you, Stephanie. Thank you for sharing your story with us. Thank you for being here tonight. Thanks for having me, everybody.

54:46Soren Wheeler:So cool.

54:50Wow.

54:52Avir Mitra:All right, Avir. so we've been through a lot together yeah thanks for coming on this journey of trauma

55:00Soren Wheeler:with me guys, I appreciate it

55:02Avir Mitra:but you know like starting from a place of sort of like seeing this happen in front of your eyes, dealing with it on a day to day pace, turning to try to sort of start to understand it and do the reporter thing or at least the research thing and finding all what you found and sharing all that with us, I guess I am a little bit curious just like where you're at now, like are you still in therapy or?

55:24Soren Wheeler:Yeah, definitely. I mean, you know, I still have a shift tomorrow, so I still got to go to work. You know, I still got to see this stuff, so it's still there. But I guess, I don't know. I mean, thinking about all this stuff makes me think about the whole thing a little bit differently.

55:38Avir Mitra:How so? I mean, okay, let's think about it.

55:41Soren Wheeler:Like when I was first thinking about it, I'm thinking it's humans versus bacteria, you know, and I'm at the middle of this. It's all about me and like that kind of thing. And as I'm thinking about it more, it's like, it's not really, it's humans, bacteria, there's animals, animals probably playing a bigger role than humans. And then if you think about it some more, it's like, wow, all our antibiotics, our whole weaponry comes from fungi because they've been battling bacteria for longer than we've even been around. And now I'm listening to Stephanie. It's like, oh, there's this whole class of viruses that's been fighting bacteria for longer than the fungi have been around.

56:18Soren Wheeler:So I don't know. I guess I'm just looking at the shape of this a little bit differently. It's like, there's a lot of players here. And if anything, we're just like the newest kid on the block.

56:27Avir Mitra:But it does also then feel so much more, it feels like maybe overwhelmingly complex.

56:33Soren Wheeler:Yes, it is. But I don't know, I guess in a weird way, like I'm realizing we're so young as a species, there's so much we don't know. There's so much left to learn. And I don't know. I just think there's hope in that.

56:47Avir Mitra:Yeah, I can see that.

56:49Soren Wheeler:Well, I guess before we go, I just wanted to play one more quote because I feel like the show can't end without hearing this. I did talk to Tom and I just wanted you guys to hear him. I asked him if he remembered by any chance that moment where Stephanie squeezed his hand and asked him if he wanted to live.

57:07Avir Mitra:And this is, he's in a coma and she...

57:09Soren Wheeler:Right, at this time he's in a coma. He's completely out of it. He's on the verge of death. And Stephanie asked him, do you want to live? At that moment, I thought I was a snake.

57:24Avir Mitra:In a canyon. Curled up under a bush. And there is a wooden platform that visitors could come and view me from. And they would look down and I would look up. and I could see people through this haze of my milky eyes. It would be hot sometimes, sometimes it was cold. When the night came, I was really alone, disintegrating molecule by molecule, you know, just kind of sinking down bit by bit. my vision because it was blurred by this the milkiness over my eyes i couldn't see her but i could hear her in the distance she said i know you've been through a lot and i know that it's hard and if you want to let go it's okay you can go

58:43Avir Mitra:there was kind of a pause that I had and I realized I was a snake

58:55Avir Mitra:I tried to figure out how to squeeze her hand because I was desperate to squeeze her hand, but I didn't know how without hands. So I thought and thought, and then I thought, well, I'm a snake. I can wrap my body around her hand and squeeze. So that's what I did.

59:44Avir Mitra:Thank you, Avira.

59:46Soren Wheeler:Thank you, guys. Thank you.

59:55Avir Mitra:Of course, also a big thanks to Lance and Tom, who gave us their time and talked to us, and Aver's dad for being willing to throw shade at his son. Well, thank you, Soren, for, you know, being on stage, helping out Aver, pushing him around, editing him in real time, making all that happen. Obviously, I had a lot of fun doing it. A couple quick thanks. Thanks to Tom Philpott, Stephen Roach, Kate Shaw, Carrie McClellan, Alex Wong, and Maren McKinnon. This episode was reported by Avir Mitra. It was produced by Jessica Jung and fact-checked by Natalie Middleton. The live show itself took place at WNYC's Green Space Performance Center.

1:00:39Avir Mitra:And thank you, of course, to the staff there who make those kinds of events work. Also, the folks on the Radiolab team who helped us make it happen, Sarah Sambach, Natalia Ramirez, Anitza Vietza, David Gable, Tanya Chawling, Harry Fortuna, and Jeremy Bloom. I also want to mention that we actually did a first run of this show down in Little Rock, Arkansas. Little Rock Public Radio, the public radio station down there, invited us down to be part of their annual celebration. And it was a ton of fun. So thanks a bunch to Little Rock Public Radio, and in particular to Grace Soufasi, Jonathan Seaborn and Sarah Buford and that's it so we will just go out as we do with most of our live shows by letting one of the listeners from the audience come up and read the Radiolab credits Hi, I'm AJ I'm from Jersey and here are the staff credits.

1:01:32Avir Mitra:Radiolab is hosted by Lulu Miller and Latif Nasser. Soren Wheeler is our executive editor. Sarah Sandback is our executive director. Our managing editor is Pat Walters Dylan Keith is our director of sound design. Our staff includes Jeremy Bloom, W. Harry Fortuna, David Gable, Maria Paz Gutierrez, Sindhu Nyanasambando, Matt Keelty, Mona Madgavkar, Annie McEwen, Alex Neeson, Sarah Carey, Anissa Vietz, Ariane Wack, Molly Webster, and Jessica Young. with help from Rebecca Rand.

1:02:21Avir Mitra:Hi, I'm Daniel from Madrid. Leadership support from Radiolab Science Programming is provided by the Simons Foundation and the John Turbentow Foundation. Fundational support from Radiolab was provided by the Alfred P. Sloan Foundation.

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