Your Friendly Neighborhood Hookworms

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Hey, I'm Latif Nasser. Hi, I'm Molly Webster and this is Radio Lab. And what are we doing today, Molly? OK, well, Latif. Remember back in 2009, before you and I both worked at the show, there was an episode called Parasites. Oh my God, love that episode. It is really one of my favorites. And in that episode, we talk about this tiny, maybe creepy little worm called a hook worm. That's right. You remember it. Yeah, I mean, it like hooked into my brain. Like the hook worm hooked into your brain. It's the story of that one guy and then there's the final scene where he's walking through the. Oh, wait, OK, wait, wait, you don't actually have to. Don't don't say what the final scene is, because what we're going to do here is I'm going to play this the hookworms chunk of that episode. OK, and then I have an update. A 20 year later, hookworm and human medical update. VH1 behind the music. Where is the hookworm now? Yes. Where is the hookworm and where is the human? OK, great. This whole episode, it introduced this idea that this thing that we think is like the biggest, scariest, grossest pest of all time. Yeah. Maybe they're not as gross as you think. Yeah. And now 20 years later, people are saying maybe they're really not as gross as you think. Love it. And there's just like all this cool new research about hookworms in the human body. And specifically one very important type of disease, autoimmune disorders. That, as you know, is one I'm particularly interested in. But, well, yeah, I'm sold. I would like to hear more. OK, great. So I'm going to play the original hookworm segment just so we all know what's going on. And then we'll jump into an update in about 20 minutes. OK, great. Yeah, wait, you're the thing. OK. All right. OK. All right. You're listening to Radio Lab. Radio Lab. From WNYC. Six. Yep. Rewind. Hello, I'm Chad Abumram. And I'm Robert Krillwich. This is Radio Lab, our topic today. Parasites. Parasites. Now, we've met them, they're nice, and we've met them, but they're not so nice. I don't know that we've met any nice ones, really. Oh, we haven't? I thought that. Oh, they're all flukes. Yeah. They were pretty nice. Yeah, they were nice. So now the question is, let's just talk about scale. I mean, for the most part, they're irritating and little, and they seem kind of... Invisible. Invisible and sort of offstage. Yeah. But when you back off a little bit and consider them, you know, in the effects that they have on the world... They're actually these powerful sculptors of monumental narrative. In other words, these are little guys telling very big stories. In fact, here's an example. Recently, I went to visit a guy named Dixon Despamye. But Columbia University, he's a parasitologist and, well, he does a bunch of different things. We ended up talking about... Well, he told me this crazy story. Okay. Molly jumping in here really quick. This next part of the story, which has to do with Rockefeller, think of it like those stories that has been told so many times. It starts to become like a tall tale. It's a living myth. So the facts are a little blurry, but the idea is right. Here we go. The story I love telling the most is how we eradicated hookworm. The story begins in 1908. John D. Rockefeller, Sr. Ridley Wich Guy is sitting in his New York office and he's thinking... How can I make more money selling something to the South? Yeah, I've got all this money, got all these resources. I just need a new market. And in terms of new markets, the South was pretty much untapped. If only those damn Southerners. Just get off their butts and get going. Problem was, they weren't. They weren't getting off their butts. The farms were not operational. The economic engine was turned off. The economy was in the toilet. And so John D. Rockefeller wanted to know why. Why aren't they producing more? Yep. What's happened to their economic engine? So he thought... I know, all form a commission. Yeah. So he sat down a bunch of economists and sociologists and people like that on the original Rockefeller commission. They did everything a commission could possibly do to try to find out why these Southern gentlemen were not rising to the occasion. And they came back with the following conclusion. Well, we don't exactly know what's wrong, but we think that these people are sick from something because they don't behave like we do. What does that mean? They are slow. Not mentally. They're slow physically. They're pale. I'll give you an example. Remember the movie Deliverance? Sure. OK. Remember that little guy that played the banjo? I remember the other scene that we all read. Yeah. We're not going to talk about that. No, we're not. No, we're not. But if you can recall what that little banjo player looked like. Little wiry looking guy, but he looked old. Sickly pale. Yeah. Sickly pale and yet an adult. Well, what do you know? I was like, that is not a description of all Southerners. No. It was a description of one teeny corner in a palace. No, but what the commission did say about a lot of these Southern people that they encountered is that a lot of them, they just don't look right. They look weak. They look when they look kind of when, when, when, when, when, when. They were one. Pale, lethargic. It's interesting. When or when? When. You choose. So the thought was that maybe these Southerners had some kind of laziness disease. This is really what a lot of folks thought. But one member on the committee suggested to Rockefeller, you know what? Perhaps these people are anemic. Anemic. They're anemic, do you say? Yeah, they're anemic. Sounds like a medical problem then. Maybe they're not lazy after all. Maybe they're anemic and maybe they're just weak. Next thing you know, Rockefeller puts together another commission to find out what the basis for the anemia was. And not only did they find anemia, but they found a correlation of the anemia with soil types. That's bizarre. Sandy loamy soils, anemia. Hard-packed clay soils, no anemia. Sandy loamy soils, good farmland, hard-packed clay soils, not such good farmland. So all the rich farmers were anemic and all the poor farmers were doing okay. And this seemed to be a clue. The incidence of anemia was linked somehow to the soil. Maybe, something was in the soil. That's correct. So somehow they hit upon this idea of looking for a hookworm. The hookworm. The hookworm. So they thought, all right, let's run some tests. When they did, big time. They discovered hookworm big time. So the anemia is due to hookworm. Now the question became, how are these Southerners getting the hookworm and giving it to one another? And a pretty good place to start to look for an answer was their feces. Because if these hookworms are in you, they're going to come out of you when you go to the bathroom. So they asked these Southerners, when you guys defecate, where do you do it? Most of them said something like this. I defecate over there. You see that tree over there, that's where I defecate. So I defecate over there, but I live over here. Okay, so then the investigators asked the next question. When you go to that tree and do it, do you wear any shoes? Most of them said no. Barefoot, just like everybody else. Because it's comfortable. So clearly these worms are in the feces that are landing near the tree. They're somehow getting into people's feet the next time they come to use the tree. No one intentionally steps in their own, you know, no one does that. Which meant... Oh my goodness, oh my goodness, it can crawl. Right, so let's find out how far it can crawl. So what they did, these researchers, is they built a sandbox and then they took some hookworm-infested stool and put it right in the middle. Then every day we'll sample from the stool sample out in the sand in all directions and find larvae and find out how far they can travel. How's that sound? So now we have larvae in the stool and they began to crawl away from the stool, seeking a victim. On day one they crawled an entire foot in all directions, but they weren't at two feet. On day two, my God, they're at two feet. At day three, they're at three feet. I can't believe this. They're crawling a long way. Day four, they crawled to four feet. What about day five? I'm allowed to ask that. And what about day five? Five feet? No. No. Four feet. That's it. So how in the world could you deal with this problem when these worms can crawl four feet? It doesn't matter where you defecate. They're going to crawl away from that. And within a four foot radius of that stool sample, you're going to get hookworm unless you do something radical that's never been done before. They devised a scheme for burying the stool sample into the ground six feet deep. Because if the worms can only make it four feet, well then that's two feet past the point where they die. They call that the outhouse. And in fact, Rockefeller got his wish. The South did rise again. That sounds too easy to me though. I mean, you're telling me that an understanding of hookworm, which created the outhouse, removed the quote Southern laziness disease and they did rise? They did. And you bring that all back to the hookworm? I do. Really? No, I bring it back to sanitation. Now, to be fair, you can find plenty of other reasons why the South rose again. There are conditioning and highways and universities and stuff like that. So the hookworm had some help. But what is clear is that when we as a country began to distance ourselves from our own excrement, to put it bluntly, when we stopped walking around in our own sh**, there were all of these unintended consequences. Salmonella disappeared. Iostholitica disappeared. Shigella disappeared. Cholera disappeared. Giardia disappeared. Cryptosporidium. Anything that's associated with parasites in feces disappeared. Every time we built outhouses. And people used them religiously. Guess what? Their kids could stay in school longer. They could learn more. They got a head faster. Dixon de Svamye is a professor of public health and environmental health sciences and microbiology at Columbia University. Can they make longer titles at that university? He literally wrote the book on parasites. The book is called Parasitic Diseases. You know it very well. It's assumed to be a major motion picture. But now, in its fourth edition. In its fourth edition. And while we're on the subject of hookworms and the glorious campaign to deworm America, because this has been a very carefully crafted and intentionally fair program. You have heard the case against hookworms. Now let's turn the coin and say something nice about hookworms. And to begin that discussion, let's go to our reporter Patrick Walters. So Pat, are you there? Yeah, I'm here, Robert. So tell us a little bit about this fellow. What's his name exactly? His name is Jasper Lawrence. That's right, Jasper Lawrence. So where is he from? He actually grew up in England. He grew up in this little farm in the southwest corner of England. And it's important to know, I think before hearing any part of his story, that Jasper has had allergies for pretty much his whole life. On really bad days, my eyes would swell up so much from pollen or airborne allergens that they would feel like they were swelling shut. I could feel my eyes squeaking in my sockets. It was an enormously uncomfortable feeling. But it was nothing debilitating. They were just allergies. So you know, he's just like most other people have allergies, just learn to deal with it. You know, you live with it. What changed for me in my late 20s, early 30s was my asthma. I know that time I was living in Santa Cruz. I was relatively recently married. We had three cats that had been grandfathered in with the relationship. And I started a landscaping business. I really didn't want to work for someone else. I had to pick someone with allergies starting a landscaping business. That seems kind of unexpected. The next stupid is actually the word for it. And within six months or a year. He starts to notice this really weird barking cough. Was there anything particular that brought this on? No, it was just sitting and breathing. Cats certainly didn't help. And during that period, my asthma got much worse very, very quickly. By the time it was 1996, 1997, I was seeing specialists having skin allergen tests and cycling through emergency inhalers, trying singular and all these other drugs that were coming on the market. I was being hospitalized at least a couple of times a year. I mean, I looked terrible. I had dark eyes and pale, waxy skin. I had that allergic look. It was a really bad time. And he decides in the summer of 2004 to take a vacation. And you made this visit to England. Yeah. I took my two daughters back to see my aunt who had raised me. Very early in the visit, I was sitting at her kitchen table and she asked me if I'd seen a BBC documentary about parasites and their connection with things like asthma and allergies, multiple sclerosis. And of course I hadn't. But I went upstairs and got on the internet after lunch. I stayed on the internet until perhaps two in the morning. I didn't stop. And he's reading and reading and the work of all these researchers. One study after the next. Japan epidemiological studies in Africa, animal models, multiple sclerosis. This enormous weight of evidence that in the developing world, people don't really have asthma or allergies. And what he discovers is that behind all of this, to his shock, is hookworms. Hookworm? Yeah, hookworms. Yeah, I learned that asthma was 50% less likely in someone who had a hookworm infection. So this sort of just like hits you. Oh yeah. What did you think when you read that? Oh, I immediately was determined to obtain a hookworm. Immediately. I couldn't wait. So hookworms are these very tiny worms the size of a little hair. But if you take a microscope and you zoom way in, they have this big circular mouth brimming full of pointy teeth. A very scary look at. They have these toothy mouths so that they can burrow up through your feet, ride through your blood and eventually end up down in your gut and start chewing on the inside of your intestines. This guy wants hookworms in his intestines? Absolutely. And so you just Google it? Yeah, hookworms for sale. I mean, you know, someone's got to be selling them. But not nothing. I contacted every laboratory supply company in the world and parasitology research centers and they all said the same thing. No, various flavors of no. And so I came to the conclusion that I was going to have to go to the tropics. So fast forward a little. Jasper is in Cameroon along the coast. It literally and figuratively the armpit of Africa. He's 200 miles north of the equator. It's extremely hot. He finds a guy to drive him around. So he and his driver would go to a village. You get out of the car. Walk up to these villagers and ask them if they could see the latrine. Just an open area of ground, usually with bushes so people can have a little bit of privacy. And I would go over to the area, remove my shoes and start walking. The first time I did that, I almost couldn't do it. It must have been 110 degrees that day, 100% humidity. And the stench and the noise from the insects. It was so repulsive and so disgusting. How many villages of latrines do you think you visited? Between 30 and 40. Jasper spent two weeks there walking around in village latrines and then he flew home. I got back from Africa in early February. So I was looking at allergy season coming up. And the day I realized that I no longer had allergies, it was such a good day. I got into my car and I started driving and I had the window down. I felt the breeze blowing across my face. In the past what that meant was that very quickly my eyes would be itching uncontrollably. Snot and flam was going to be pouring out of every orifice in my face. And it didn't happen. It didn't happen. I just started screaming in the car. I was so, so happy. And I haven't had an asthma attack since I went to Africa. I no longer have allergies. The vast majority of the benefit that I've experienced has come from hookworm. What is the hookworm doing? Do you know? Well so the immune system that we learn about in elementary school is all about these attack cells that go after foreign invaders and destroy them. And that's a big important part of the immune system. If the immune system were allowed to attack and destroy things unchecked, it could kill you. And there are lots of diseases where the primary symptoms are caused by the immune system attacking the body that it's really designed to protect. Allergies and asthma are just two of these. Some of the more serious ones are like type 1 diabetes, multiple sclerosis, Crohn's disease in which the immune system actually starts attacking the inside of the intestines. They're like 80 of these diseases. And so what scientists have found in lots and lots of mouse studies and in some human studies to this point too is that once the hookworms get inside the gut and the immune system actually starts attacking somehow, hookworms actually stimulate these cells, which just quiet things down and tell the attack cells to stop attacking. So these are like lullaby cells? Exactly. What lots and lots of scientists think, Joel Weinstock, and dozens of others, is that over thousands and thousands of years, hookworms almost developed in tandem with the human immune system. Parasites living within your body, your immune system changes. You got to a point where the hookworms could survive safely. Worm gets a home, there's food coming down the food pipe and in return. The human immune system gains some kind of positive regulatory advantage. So that if you had this glitch where your immune system started attacking your own body, the presence of the hookworms would keep things controlled. That's the gift. You do something for the worm, the worm does something for you. So then by that logic, what we in the West, in the richer countries have done stupidly is we have cleaned ourselves up too much and we don't have enough wormies in us. This is called the hygiene hypothesis. The hygiene hypothesis, that we're not dirty enough. Too clean. We function like rainforests, we're ecosystems and we've entirely eliminated a class of organism that co-evolved with us and our genetic predecessors for millions of years. Now I don't want to leave the impression that hygiene is bad for you. People can't go back to living and filth, kids playing and sewage by the river bank, but in improving our hygiene, we are also excluding organisms that may be important for making as well. So then what does Jasper do about all this? He decides to start a business selling hookworm to people. What? You can call him up and he will literally FedEx a dose of hookworms to your door. How? I'll give you a second. Pat. Hi, Jan. Where does he get the hookworm from? This is weird. Jasper gets the hookworm from himself. Could you describe how you go about getting hookworm from your stool into one of your patients? Well, it's a very easy organism to work with it. It just, it gets up and it walks out of it. So it doesn't take an enormous amount of work to separate it from the feces. And then having done that, I repeatedly wash them in solutions of antibiotics to make sure that anything that could live on them is killed. People contact us, we'll have them complete a questionnaire, submit a recent blood test, then we'll ship them a dose and all the materials and equipment and the instructions necessary to infect themselves. Do we just, is this a safe thing to do? Jasper has done tons and tons of research, but he's not a doctor. The treatment is not approved by the FDA. That's what I wonder. Is there any serious sort of double blind study trying to figure out whether some safe delivery of hookworm might make sense? Yes. So one of the guys who was sort of a pioneer in this hookworm research is David Pritchard. I'm Professor David Pritchard. Immunologist and parasitologist at the University of Nottingham where I study parasites and the wound healing properties of maggots. So we've now got two safety trials under our belts, but we've yet to conduct the trials to show that therapeutic benefit results from infection with worms. So Pritchard infected himself pretty much just to make sure that it was safe. What we did was 10 of us in the lab took worms at different doses. We were either given 10, 25, 50 or 100 worms and then we had to report on the symptoms. And on the back of that study we determined the 10 worms were tolerated. But Pritchard, when he did this proof of safety study, actually gave himself 50 hookworms, which put him out of commission for a while. Well, I felt pretty bad. I mean, pain in the gut really. You know, you could feel them because they are biting on your tissues. I mean, if you have too many hookworms, they can cause things like diarrhea and the most serious side effect and the side effect that makes them sort of a public health enemy is that they can give you anemia. If you have too many, you lose quite a bit of blood to these parasites. Well, you know, if you take too many hookworms, which you're not going to, if you come to us, the worst thing you're going to get is anemia. But it's not like you wake up one morning and you're drained of blood. Very slow to develop and it's very easy to deal with. Desperate's kind of just gone for it. You know, it's a very sort of like cowboy move. To the scientific community, I think they believe that I'm premature. It's not FDA-approved in offering this to the public. You don't know what it is. You don't know it's purity. It's not safe. I've talked to several clients who had really severe allergies and asthma. They say they've just achieved these great results. And Jasper also says he's seen success with a few multiple sclerosis patients and several Crohn's disease patients too. Like, how many people do you think that you have infected? That's about 85 right now. How is business? Is it everything that? Business is adequate, but I honestly don't know why I don't wake up in the morning with my front garden 20 deep with people with ulcerative colitis, Crohn's disease, allergies. I just don't know why I'm not completely buried. The way he sees it, people are scared. Well, there are the people who are coming from a point of view of what they learned in kindergarten about clean drinking water and sewers. To them, worms and parasites are so repulsive that there's nothing good to be said about them. But I can make you better. It's simple. It's cheap. I mean, for God's sake, these organisms fall out my rear end every day, a half a million at a time. The raw material is human excrement, for God's sake. All people have to do is open their minds. Are you really that scared of a little worm? Okay, okay, okay, okay. So that's it. So wait, but okay. Yeah, maybe the question is, lettiff, you have talked about this on the show. You have an autoimmune disorder. Yes. Crohn's disease. Crohn's disease. Okay, you've heard this piece. Are you scared of a little worm? I mean, I am intrigued. I don't know whether to be scared. If there are clinical trials that can help tell me whether to be scared or not of this worm, that's what I want to know. All right. I am going to tell you about a clinical trial and then you can tell me what you think. Okay. But after the break. All right. Oh, after the break. After the break. After the break. Let's do it. After the break. It's a clinical trial. I'm ready. I'm excited. Okay. Great. 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Sign up and get 10% off at betterhelp.com slash radiolab. That's better, H-E-L-P dot com slash radiolab. As the day wraps up, get this scoop on what's been happening with Here's the Scoop, a new podcast from NBC News with meteor host Yasmin Vasugian. We'll take a deep dive into the day's top stories with NBC News's trusted journalist. It's a fresh take that's sharp, thoughtful, and it's informative, bringing you closer to the headlines and conversations that are shaping our world. From the front page to the zeitgeist, here's the scoop from NBC News. Listen daily or ever you get your podcasts. Lettiff, we are back from break and we left you at are you scared of a little worm? And I was like, maybe, maybe, I don't know. Let's do some actual clinical trials. And that is what like, okay, so that episode was done in 2009. Right. And so I want to fast forward to today. There have been a number of clinical trials. Okay, so what happened? Okay, so hi. Hey, how are you? I talked to this researcher. Dr. Paul Jackaman. Paul Jackaman. Senior research fellow at the Australian Institute of Tropical Health and Medicine. And he's basically trying to do like the next iteration of. Jasper. Of like Jasper, but like with with actual scientific studies and stuff. Okay, yeah. Yeah, trying to understand the potential beneficial effects of worms in people. So one of the things that he's been studying is. Treating people who are at risk of type two diabetes with hookworms. Hmm. So type two diabetes, that's the diabetes you typically get later in life. Yeah. What made you pick diabetes? It sort of came on the back of research which started in the 2010s where people went into regions of the world where parasitic worms are really common. And what they found is that there's a correlation between something like type two diabetes and the presence or lack of worms. Huh. Yeah. So basically. So what Paul and his team did is basically they took people who are at risk for type two diabetes and they gave them hookworms. How do they give it to them? How do they take them? Do you like slurp it down like a little piece of spaghetti? No. You know, people think where they're going to enroll. They're going to have to swallow a worm or swallow worm eggs, et cetera. So. It's actually much worse. Okay. I don't know. It could be much better than that. Basically, in order to do our research. The first step of the process is they have folks who work in their lab. These what called worm farms. Volunteers. Who've consented to have a small number of worms. Living inside of them. Oh, wow. Yes. Exactly. The only way you can't culture them. You can't just get them and freeze them. Really? Yeah. So, basically, that's one of the limitations about working with these worms. You actually have to maintain a scent we call them worm farms. So, like hazard pay for that? Like what? Do they get a bonus? No, I think they're just very generous volunteers. Brave and dedicated volunteers. And so that if we want to do our research, we say, hey, generous volunteer. Can you give me a sample of your stool? Okay. Because what happens in these people in the worm farms is the hookworms inside of them will mate. And they can produce the females can produce tens of thousands of eggs every day, which are released eventually in the poo. Huh. And so they poop. We get the poo sample. Add charcoal to it. Which reduces the smell. And then we spread it onto the Petri dish. They leave the Petri dish and sort of like kind of a humid tropical environment. Okay. It sits there for a week. And over the course of that week. These tiny hookworm eggs start to hatch. And emerging from them are these microscopic teeny tiny baby worms. Fairly visible to the naked eye. And very quickly, Paul and his team hit them with like a strong disinfectant to clean them. Then we can basically look down the microscope. We just one by one pick the wriggly worms, put them into a little tube. And then what they do is they put the worms on a bandaid, essentially. Uh-huh. And they take that bandaid and they put it on the skin of the patients that are enrolled in the clinical trial. But not even on a cut. Just anywhere on the skin. Just anywhere on the skin. And then we sort of sit with them for about five minutes because participants start to get this tingling sensation. Because what happens is these baby worms on the bandaid start to release an enzyme. Which the grade tissue. Which basically melts your skin so that they can start to burrow into your skin. And as they enter your skin, then your skin just closes up behind them. The tunnel closes. And then the worm makes their way down through your skin into the lymphatics. Your lymphatic system. So if you think of the inside of your body as a water park, as one does. The lymphatic system is like the lazy river. Sure, yeah, yeah. So these baby hook worms go through the skin cells, fall into this like little lymphatic river. Then they float along through your lymph system. I kind of maybe picture them with, I don't know, cozies of non-alcoholic beer. Because they are babies on their little tube. That's funny. And they're floating downstream. They float along. And they get to what is known as your lymphatic duct. Which is kind of right by your collar bone. And once they get there, they get shot out of the lymphstream into your bloodstream. And once they're going into the blood, they're cruising around like on a water slide. They go from your collar bone towards the center of your chest. Where they catch this huge slide that sends them into your heart. And then your heart shoots them out onto another big slide. That slide starts splitting and branching and splitting and branching. And as it does, the slide is getting smaller and smaller and smaller until... Yeah. These little baby worms get stuck. They get trapped inside a super tiny blood vessel. Because they're too big. Yeah, they're too big for the blood vessel. So they get stuck there. And they journey in. But Paul says... That's the cue. To again release an enzyme that starts to melt away the walls of the blood vessel. Whoa. Just enough. They can wriggle their way through and then pop out on the other side of this blood vessel and into your lungs. And then what they do is they crawl. They crawl up through the lung, all the airways. Like a rock climber. Boop, boop, boop, boop, boop, boop. Up your trachea. So they're almost in your throat. And then unknowingly. One day you will cough. Which will dislodge these worms from your trachea up into this little free space in your throat. Where I like to think that they will do backwards unresolved. And then after you cough, you usually swallow. So yeah, you'll swallow them. You swallow the worms. Oh my God. At which point they will shoot down your esophagus into your stomach. Oh my God. And then once it's... Oh, but it's like, why wouldn't you just feed it to people then? Well, like why do this whole crazy... Well, because this whole process from skin to gut takes about two to three weeks. And during that process, the worm is maturing. Got it. And so it's actually developing in such a way that it can survive in your stomach. I see. So it's like this is how it develops. Exactly. So it's a really fascinating life cycle. They can survive the stomach acid and then they sort of make their home in the upper, just beyond the stomach there. And they're up a small intestine. And once they're in the small intestine, they've got these sort of quite violent looking teeth. They will bite and clamp onto you. And they very fairly delicately just sort of suck the blood. And this is where something sort of amazing happens, which is for the next two weeks, your body's going to have this really intense reaction. So where the worm is biting down on your intestinal wall, it's going to get inflamed. There's like an open sore where the worm is sucking and your body is going to freak out and try and flush the hookworm out. So you're going to have diarrhea. You're going to feel sick. And then it's all going to stop. You're going to feel fine. And Paul says this is most likely because right around this time, the hookworm has reached full adulthood. And we've we've actually, in some of our clinical trials, taken a camera and we've had a look in the gut, at regions of the gut where the worm has been feeding. And, you know, there's might be one little small red spot there where next to a worm, but everywhere else, I think there's this rapid healing. The worm might actually be releasing factors that promote, you know, wound healing, for example. Really? Yeah, absolutely. It's in their best interest to basically feed and heal the wounds in their environment. So the really cool thing is, is that when this hookworm reaches adulthood and it's bit onto you and it's making this hole in your intestine, it can actually release a protein or maybe many proteins to heal the wound at the same time. So you're not left with this gaping wound in your stomach. And then it's also producing other proteins that are quieting the immune system. Because your immune system could, it could just unleash an enormous attack on these worms. But that would obviously the worm does not want that. So it has these little proteins at sucrease that tells your immune system, shh, be quiet. And you heard about this in our last episode. And I think this is what Jasper also sort of suspected was happening. There was something overall from the hookworms, quieting the immune system. I feel like you've kind of reframed this whole thing for me. So now it's become less like a story of a human clinical trial and more of a story of like mission impossible on a worm scale. Like I'm like, how can this thing like vault over this, but then say the right words to this person that they'll leave them alone. And then and then climb up and then it's like it's crazy. And then use their little blaster to like melt this thing so they can walk through this wall. It's like crazy. It's like a crazy thing that they're doing. But here's the thing, Latif, when Paul and his team got to the end of this two year trial with people who are at risk for type two diabetes. The people who were treated with the hookworms had things like reduced like glucose levels. They had dramatically reduced insulin resistance levels, lost a little bit of weight. And some of these people who were considered pre-diabetic were no longer pre-diabetic. Oh, wow. So some people were cured effectively. Yeah, basically. Well, when you look at the placebo people who got no worms, they went on to continue having high insulin resistance, glucose, no weight loss. So it was really the first causal clinical evidence that the worms were having a benefit on metabolic health. Then at the end of the trial, the end of the two years, the people who had the hookworms inside of them, they have the option to just get rid of the worms. Like you can take an over the counter deworming medication and they'll be gone the next day. Paul says that the end of this two year study, almost everyone kept their worms. Wow. They were happy at the end. They wanted to basically live with their worms. They were happy with them. And this is universal. Every clinical trial, almost universally at the end of a clinical trial, people are happy with their worms. Do you think the happiness is emotional or do you think the happiness is like they actually feel different? Yeah, exactly. So there's two things. One of them they might think, well, it's not doing them any harm. So let's just keep them. And the other thing is we've, you know, in our two most recent clinical trials, which were placebo controlled. So these trials were looking at celiacs disease. Yeah. We asked people to do a quality of life and mood and wellbeing survey. And in both clinical trials, we had this really interesting improvement in well being and mood and sleeping quality. Wait, really? We saw in the people with the with the worm treatment and the placebos, we didn't see it. I can't explain it, but, you know, the data was there and it's really compelling. And there is like. What a weird thing, right? I know. So one, well, here's the thing. I'm going to break that down for you, which is like one of the things we're all talking about right now is our microbiome. Right. It's like, what is the tiny stuff living inside of us like viruses and bacteria that's actually helping us? Right. One of the things Paul was talking about is like, well, there's also a microbiome. You know, the microbiome, the organisms that you can see within naked eye, these worms that can, you know, somehow live for up to a decade or even longer. Within our gut, the immune system should really have recognized these worms and kick them out because there's such a big insult on the body. But Paul says it could be that when these worms, when they reach adulthood in your gut, when they start making the proteins that quiet your immune system, that actually suppresses the immune system. So the immune system doesn't kill it. Yeah. And that also means that then the immune system is like not reacting as strongly to some other things. So this is where the whole autoimmune thing gets into play because in autoimmune diseases, as you know, your own immune system is attacking you. Right. And if you've got a worm inside of you telling the immune system like, hey, you can chill out, I'm kind of part of you. Yeah. Don't attack me. Yeah. Yeah. Yeah. Then overall, it's just the immune system is not going to attack you. I just, you know. This is the thing that's really confusing to me is why. We've left you more confused. No, because like why would like this is something that we need seemingly to regulate our own kind of internal army, right? Like it's like, why would we outsource this very crucial part of ourselves? Like, like, you mean outsource? Like outsource, like the worms are not us. Like if they're if they're helping regulate. We would outsource it because they because they're helping like we would outsource it because it's beneficial. Like you have to imagine like we've been living with worms for millions of years. Yeah. And so a worm got inside of us and we probably killed it. And then a worm got inside of us and it probably killed us. Right. And then a worm got inside of us and it lasted a little longer. Yeah. And then we did or did not die. And it's like basically this long term dance between us and the worm. So there's this really interesting truce that's happened throughout evolution where the worm benefits and the host benefits. The worm benefits because it's getting a place to live and some juicy blood to eat for years. And then the host us benefits by not getting sick and dying. But also it's from the potential immune shaping and metabolic shaping powers of the worm. So Paul's lab has shown that people who are given hookworms have fewer symptoms associated with type two diabetes, celiac disease. There's also other studies looking for benefits for people with multiple sclerosis, ulcerative colitis. That's where you get ulcers in your intestines, Crohn's disease, lettif. And in those studies, some people have gone into remission with worms. That's not Paul's lab, but that's other labs. And you know, if they're beneficial and you know, why not turn it into a treatment? But that's kind of the thing, which is that since 2009, when we did that Jasper story, even though there are all these studies showing that hookworms are beneficial, hookworms are still not used as a medication or as a treatment. Yes, there's a lot of hurdles for developing hookworms as a medicinal treatment. Everyone is kind of like, listen, there's so many reasons why people don't want worms. Like they're kind of just gross. But also, I briefly mentioned before, you get the larvae out of people's poo. So making a medicinal product with standardization and decontamination, it's just really hard. Exactly. So at this stage, it's probably never going to be a mainstream treatment. In fact, Jasper, who we had mentioned was selling worms. He and his wife actually fled the US because they were being investigated by the FDA. And so as an answer to this kind of problem of the live worm, what we're seeing is people like Paul, his team, other researchers, they're trying to develop the proteins hookworms produce to heal your gut or quiet your immune system. They're trying to take those proteins, make them in a lab and then put them in a pill form. But no one knows what the timetable for that is. And so for now, you really are just stuck with having to get a hookworm. And there are some sort of more black market where people are actually selling them and you can buy them. But I wouldn't necessarily recommend that for people, partially for the reason because you're paying money for something, which this hasn't really been rigorously tested and it hasn't gone through the regulatory processes that other medications need to go through. And so, yeah, that's where that's where it's at. OK, but OK, I got to go. But my last question is, Molly, should I get a worm? I mean, dude, if I was you and I was in pain, I would try and figure out how to get a worm or get into a clinical trial. Can you fly to Australia and get into one of Paul's? I think that I'll tell you the areas that they're doing it in the big research areas are like the Netherlands, Australia, New Zealand. You got any trips there planned soon? No. My, my. You know, just those lucky people over there, they get worms, you know. Well, you know, you could always do what Jasper did, which is just go walk around in some poop and pick up, you know, hookworms plus roundworms plus tapeworms. You know, that's an option. No, that's not. I'm not going to. I'm not going to roll in human feces. That was a level of desperate you're not at. That's not how desperate I am. OK, well, Australia, it is then. OK, hitting stop. OK, OK, hitting stop. OK, thank you, Molly Webster for the update. You're welcome. Update was produced by Matt Kilty with help from Rebecca Rand. It was edited by Ariane Wack and fact checked by Diane Kelly. And we want to thank Pat Walters, Jad Abumrod, Robert Kowich and the whole 2009 Parasite team that put that episode together. If you want to listen to the entire Parasite episode, you can go check it out on our website. And for everything else, Radio Labby, please subscribe to our totally FDA approved newsletter. All right, we'll be right back in 20 years. No, just next week. Yeah, we'll catch you next week. Bye. Hi, I'm Gabby. I'm from the Bay Area, California, and here are the staff credits. Radio Lab is hosted by Lulu Miller and Lentiff Nasser. Soren Wheeler is our executive editor. Sarah Sandbach is our executive director. Our managing editors, Pat Walters. Dylan Keefe is our director of sound design. Our staff includes Jeremy Bloom, W. Harry Fortuna, David Gable, Maria Paz Gutierrez, Sindhu Naina Sambandhan, Matt Kilty, Mona Madgauker, Alex Nisen, Sara Kari, Natalia Ramirez, Rebecca Rand, Anissa Vizze, Arian Wack, Molly Webster, and Jessica Young, with help from Gabby Santis. Our fact checkers are Diane Kelly, Emily Krieger, Natalie Middleton, Anjali Mercado, and Sophie Samaie. Hey Radio Lab, Michael Tacoma, Washington. Leadership support for Radio Lab Science Programming is provided by the Simons Foundation and the John Templeton Foundation. Foundational support for Radio Lab was provided by the Alfred P. Sloan Foundation.