LATIF NASSER: Hey, I'm Latif Nasser.

MOLLY WEBSTER: Hi, I'm Molly Webster. And this is Radiolab.

LATIF: And what are we doing today, Molly?

MOLLY: Okay. Well, Latif, remember back in 2009 ...

LATIF: Mm-hmm?
MOLLY: ... before you and I both worked at the show, there was an episode called "Parasites."

LATIF: Oh my God, I love that episode.

MOLLY: It is really one of my favorites. And in that episode, we talk about this tiny, maybe creepy little worm called a hookworm.

LATIF: That's right.

MOLLY: You remember it.

LATIF: Yeah! I mean, it hooked into my brain. Like, the ...

MOLLY: The hookworm hooked into your brain?

LATIF: It's the story of that one guy, and then there's the final scene where he's walking through the ...

MOLLY: Oh, wait. Okay, wait, wait, wait. You don't actually have to—don't say what the final scene is.

LATIF: Okay.

MOLLY: Because what we're gonna do here is I'm gonna play this—the hookworms chunk of that episode.

LATIF: Okay.

MOLLY: And then I have an update, a 20-year-later hookworm and human medical update.

LATIF: VH1 Behind the Music: Where Is the Hookworm Now?

MOLLY: [laughs] Yes. Where is the hookworm and where is the human?

LATIF: Okay, great.

MOLLY: It—this whole episode, it introduced this idea that this thing that we think is, like, the biggest, scariest, grossest pest of all time ...

LATIF: Yeah.

MOLLY: ... maybe they're not as gross as you think.

LATIF: Yeah.

MOLLY: And now 20 years later, people are saying maybe they're really not as gross as you think.

LATIF: Love it.

MOLLY: 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.

LATIF: Ooh! That, as you know, is one I'm particularly interested in.

MOLLY: Yeah, that's ...

LATIF: But—well, yeah, I'm sold. I would like to hear more.

MOLLY: Okay, great. So I'm gonna 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.

LATIF: Okay, great!

[RADIOLAB INTRO]

JAD ABUMRAD: Hello, I'm Jad Abumrad.

ROBERT KRULWICH: And I'm Robert Krulwich.

JAD: This is Radiolab. Our topic today ...

ROBERT: Parasites

JAD: Parasites.

ROBERT: Now we've met them that are nice. And we've met them when they're not so nice.

JAD: I don't know that we've met any nice ones, really.

ROBERT: We haven't? I thought—I thought that ...

JAD: Oh the blood-flukes!

ROBERT: Yeah!

JAD: Oh! Yeah, they were pretty nice. They were nice.

ROBERT: 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 ...

JAD: Invisible.

ROBERT: Invisible and sort of off stage. But when you back off a little bit and consider them, you know, and the effects that they have on the world.

JAD: They are actually these powerful sculptors of monumental narrative.

ROBERT: Well, there was these little guys telling very big stories.

JAD: In fact, here's an example: Recently, I went to visit a guy named Dickson Despommier up at 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.

MOLLY: 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.

DICKSON DESPOMMIER: The story I love telling the most is how we eradicated hookworm.

JAD: The story begins in 1908.

DICKSON DESPOMMIER: John D. Rockefeller, Sr.

JAD: A really, really rich guy is sitting in his New York office. And he's thinking ...

DICKSON DESPOMMIER: How can I make more money selling something to the South?

JAD: 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 ...

DICKSON DESPOMMIER: Would just get off their butts and get going.

JAD: Problem was, they weren't. They weren't getting off their butts.

DICKSON DESPOMMIER: The farms were not operational. The economic engine was turned off.

JAD: The economy was in the toilet.

JAD: And so John D. Rockefeller wanted to know why.

JAD: Why aren't they producing more?

DICKSON DESPOMMIER: Yep. What's happened to their economic engine?

JAD: So he thought ...

DICKSON DESPOMMIER: I know. I'll form a commission.

JAD: Yeah.

DICKSON DESPOMMIER: So he sat 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—they don't behave like we do."

JAD: What does that mean?

DICKSON DESPOMMIER: They are slow. [laughs] Not mentally. They're slow, physically. They're pale. I'll give you an example. You remember the movie Deliverance?

JAD: Sure.

DICKSON DESPOMMIER: Okay. Remember that little guy that played the banjo?

JAD: I remember the other scene that we all remember that we're not gonna talk about.

DICKSON DESPOMMIER: 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.

JAD: Sickly pale?

DICKSON DESPOMMIER: Yeah, sickly pale and yet an adult.

ROBERT: Well, wait a second. Wait a second. That is not a description of all Southerners, it's a description of one teeny corner.

JAD: No. No, but what the commission did say about a lot of the Southern people that they encountered is that a lot of them, they just don't look right. They look weak. They look wane. They look kind of—wane? Wan?

ROBERT: Wane.

JAD: Wane?

ROBERT: They were wane.

JAD: Pale, lethargic.

ROBERT: It's interesting—wane or wan?

JAD: Wane.

ROBERT: You choose.

JAD: So the thought was maybe these Southerners had some kind of laziness disease. This is really what a lot of folks thought. Then one member on the committee suggested to Rockefeller, "You know what? Perhaps these people are anemic."

DICKSON DESPOMMIER: "Anemic? They're—they're anemic, 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.

JAD: Next thing you know, Rockefeller puts together another commission ...

DICKSON DESPOMMIER: 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.

JAD: And this seemed to be a clue. The incidence of anemia was linked somehow to the soil, maybe—bum bum bum!

ROBERT: Yes?

JAD: Something was in the soil.

DICKSON DESPOMMIER: That's correct. So somehow they hit upon this idea of looking for hookworm.

JAD: The hookworm!

DICKSON DESPOMMIER: The hookworm!

JAD: So they thought, "All right, let's run some tests."

DICKSON DESPOMMIER: When they did, big time. They discovered hookworm big time. So the anemia is due to hookworm.

JAD: Now the question became how are the 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 gonna 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 ...

DICKSON DESPOMMIER: "I defecate over there. See that tree over there? That's where I defecate. So I defecate over there, but I live over here."

JAD: Okay, so then the investigators asked the next question, "When you go to that tree and do it, do you—do you wear any shoes?" Most of them said no.

DICKSON DESPOMMIER: Barefoot just like everybody else, because it's comfortable.

JAD: So clearly, these worms are in the feces that are landing near the tree and are somehow getting into people's feet the next time they come to use the tree, but no one intentionally steps in their own—you know—no one does that. Which meant ...

DICKSON DESPOMMIER: Oh my goodness! Oh my goodness, it can crawl. Right. So let's find out how far it can crawl.

JAD: So what they did, these researchers, is they built a sandbox, and then they took some hookworm-infested stool ...

DICKSON DESPOMMIER: And put it right in the middle. Then every day, we will 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 were three feet. "I can't believe it! They're crawling a long way!" Day four, they crawl to four feet.

JAD: What about day five?

DICKSON DESPOMMIER: I am allowed to ask. And what about day five?

JAD: Five feet?

DICKSON DESPOMMIER: No.

JAD: No? Four feet?

DICKSON DESPOMMIER: That's it. So how in the world could you deal with this problem when these worms can crawl—they can crawl four feet. It doesn't matter where you defecate, they're gonna crawl away from that, and within a four foot radius of that stool sample, you're gonna 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.

JAD: Because if the worms can only make it four feet, well then that's two feet past the point where they die.

DICKSON DESPOMMIER: We call that the outhouse. [laughs] And in fact, Rockefeller got his wish. The South did rise again.

JAD: That sounds too easy to me, though. You're telling me that an understanding of hookworm, which created the outhouse removed the quote, "Southern laziness disease," and they did rise?

DICKSON DESPOMMIER: They did.

JAD: And you bring that all back to the hookworm?

DICKSON DESPOMMIER: I do.

JAD: Really?

DICKSON DESPOMMIER: No, I bring it back to sanitation.

JAD: Now to be fair, you can find plenty of other reasons why the South rose again.

ROBERT: Air conditioning and highways and universities.

JAD: Right.

ROBERT: And stuff like that.

JAD: 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 [bleep] there were all of these unintended consequences.

DICKSON DESPOMMIER: Salmonella disappeared. Histolytica disappeared. Shigella disappeared. Cholera disappeared. Giardia disappeared. Cryptosporidium. Anything that's associated with parasites in feces disappeared. Every time we build outhouses and people use them religiously, guess what? Their kids can stay in school longer. They could learn more. They got ahead faster.

JAD: Dickson Despommier is a Professor of Public Health and Environmental Health Sciences in Microbiology at Columbia University.

ROBERT: Can they make longer titles at that university?

JAD: He literally wrote the book on parasites.

ROBERT: The book is called Parasitic Diseases. You know it very well. It's soon to be a major motion picture and it's now in its fourth edition.

JAD: In its fourth edition.

ROBERT: 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—are you there?

PAT WALTERS: Yeah, I'm here, Robert.

ROBERT: So tell us a little bit about this fellow—what's his name, exactly?

PAT: His name is Jasper Lawrence.

JASPER LAWRENCE: That's right, Jasper Lawrence.

ROBERT: So where's he from?

PAT: He actually grew up in England, he grew up in this little farm in the southwest corner of England. 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.

JASPER LAWRENCE: 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.

PAT: But it was nothing debilitating.

JASPER LAWRENCE: They were just allergies.

PAT: And so, you know, he, just like most other people who have allergies just learned to deal with it.

JASPER LAWRENCE: You know, you live with it.

PAT: But ...

JASPER LAWRENCE: What changed for me in my late 20s, early 30s was my asthma. At 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.

PAT: I think someone with allergies, starting a landscaping business, that seems kind of unexpected.

JASPER LAWRENCE: "Stupid" is actually the word for it. And within six months or a year ...

PAT: He starts to notice ...

JASPER LAWRENCE: This really weird barking cough.

PAT: Was there anything particular that brought this on?

JASPER LAWRENCE: No, it was just sitting and breathing. Cats certainly didn't help.

PAT: Right.

JASPER LAWRENCE: 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 Singulair 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.

PAT: And he decides in the summer of 2004 to take a vacation.

PAT: You made this visit to England.

JASPER LAWRENCE: 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, and I stayed on the internet until perhaps two in the morning. I didn't stop.

PAT: And he's reading and reading.

JASPER LAWRENCE: And the work of all these researchers.

PAT: One study after the next.

JASPER LAWRENCE: In Japan. Epidemiological studies in Africa. Animal models in multiple sclerosis. This enormous weight of evidence ...

PAT: 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.

ROBERT: Hookworm?

PAT: Yeah, hookworms.

JASPER LAWRENCE: Yeah, I learned that asthma was 50 percent less likely in someone who had a hookworm infection.

PAT: So this sort of just like hits you?

JASPER LAWRENCE: Oh yeah.

PAT: What did you think when you—when you read that?

JASPER LAWRENCE: Oh, I immediately was determined to obtain hookworm immediately. I couldn't wait.

PAT: So hookworms are these very tiny worms the size of a little hair, but if you take a microscope and use zoom way in, they have this big circular mouth brimming full of pointy teeth.

ROBERT: Oh!

PAT: Very scary to 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.

ROBERT: This guy wants hookworms in his intestines?

PAT: Absolutely.

PAT: And so did you just google it?

JASPER LAWRENCE: Yeah, hook—hookworms for sale. I mean, you know, someone's got to be selling them, but no—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 gonna have to go to the tropics.

PAT: So fast forward a little. Jasper is in Cameroon, along the coast.

JASPER LAWRENCE: Quite literally, and figuratively the armpit of Africa.

PAT: He's 200 miles north of the equator. It's extremely hot. He finds a guy to drive them around. And so he and his driver would go to a village ...

JASPER LAWRENCE: Get out of the car ...

PAT: Walk up to these villagers and ask them if they could see the latrine.

JASPER LAWRENCE: 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—I almost couldn't do it. It was—it must have been 110 degrees that day, 100 percent humidity. And the stench and the noise from the insects, it was so repulsive and so disgusting.

PAT: How many villages' latrines do you think you visited?

JASPER LAWRENCE: Between 30 and 40.

PAT: Jasper spent two weeks there, walking around in village latrines, and then he flew home.

ROBERT: Hmm.

JASPER LAWRENCE: 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, that was such a good day. I got into my car and I started driving. And I had the window down, and 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 phlegm was gonna 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.

ROBERT: What is the hookworm doing? Do you know?

PAT: Well, so the immune system that we learned about in elementary school is all about, like, these attack cells that go after foreign invaders and destroy them.

ROBERT: Right.

PAT: And that's a big important part of the immune system. But 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. There are, like, 80 of these diseases.

ROBERT: Eighty!

PAT: 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.

ROBERT: So these are like lullaby cells?

PAT: Exactly. What lots and lots of scientists think, Joel Weinstock ...

JOEL WEINSTOCK: Joel Weinstock, Tufts Medical Center.

PAT: ... and dozens of others, is that over ...

JOEL WEINSTOCK: Thousands and thousands of years ...

PAT: Hookworms almost developed in tandem with the human immune system.

JOEL WEINSTOCK: Co-evolution. Parasites living within your body, your immune system changes.

PAT: So you got to a point where the hookworms could survive safely.

JOEL WEINSTOCK: The worm gets a home, there's food coming down the food pipe. And in return ...

PAT: The human immune system gains some kind of ...

JOEL WEINSTOCK: Some form of ...

PAT: ... positive regulatory ...

JOEL WEINSTOCK: advantage.

PAT: So that if you had this glitch where your immune systems started attacking your own body, the presence of the hookworms will keep things ...

JOEL WEINSTOCK: Controlled. And that's the gift: you do something for the worm, the worm does something for you.

ROBERT: So 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 ...

PAT: Yeah, this is called ...

JOEL WEINSTOCK: They call it the hygiene hypothesis.

ROBERT: The hygiene hypothesis: that we're not dirty enough.

PAT: Too clean.

JASPER LAWRENCE: We function like rain forests. 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.

JOEL WEINSTOCK: Now I don't want to leave the impression that hygiene is bad for you. People can't go back to living in filth, kids playing in sewage by the riverbank, but in improving our hygiene, we are also excluding organisms that may be important for making us well.

ROBERT: So then what does Jasper do about all this?

PAT: He decides to start a business selling hookworm to people.

ROBERT: What?

PAT: You can call him up and he will literally FedEx a dose of hookworms to your door.

ROBERT: How ...?

JAD: Sorry, if I can just break in for a second. Pat ...

PAT: Hi, Jad.

JAD: Where does he get the hookworm from?

PAT: This is weird. [laughs] Jasper gets the hookworm from himself.

PAT: Could you describe how you go about getting hookworm from your stool into one of your patients?

JASPER LAWRENCE: Well, it's a very easy organism to work with. 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've repeatedly washed 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 and 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.

ROBERT: Wait, is this a safe thing to do?

PAT: Jasper—Jasper has done tons and tons of research, but he's not a doctor. The treatment is not approved by the FDA.

ROBERT: That's why I wonder, is there any serious sort of double-blind study, trying to figure out whether some safe delivery of hookworm might make sense?

PAT: Yes. And so one of the guys who was sort of a pioneer in this hookworm research is David Pritchard.

DAVID PRITCHARD: I'm Professor David Pritchard.

PAT: An immunologist and parasitologist ...

DAVID PRITCHARD: 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 the therapeutic benefit results from infection with worms.

PAT: So Pritchard infected himself pretty much just to make sure that it was safe.

DAVID PRITCHARD: 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 that 10 worms were tolerated.

PAT: But Pritchard when he did this proof of safety study actually gave himself 50 hookworms.

ROBERT: Oh!

PAT: Which put him out of commission for a while.

DAVID PRITCHARD: Well, I felt pretty bad. I mean, pain in the gut, really, you know, you can feel them, because they are biting on your tissues.

PAT: 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.

DAVID PRITCHARD: If you have too many, you—you lose quite a bit of blood to these parasites.

JASPER LAWRENCE: Well, you know, if you take too many hookworm—which you're not going to—if you come to us, the worst thing you're gonna 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.

PAT: Jasper has kind of just gone for it. You know, it's a very sort of like cowboy move.

JASPER LAWRENCE: To the scientific community, I think they believe that I'm premature ...

JOEL WEINSTOCK: It's not FDA approved.

JASPER LAWRENCE: ... in offering this to the public.

JOEL WEINSTOCK: You don't know what it is, you don't know its purity. It's not safe.

PAT: But I've talked to several clients who have 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.

PAT: Like, how many people do you think that you have infected?

JASPER LAWRENCE: It's about 85 right now.

PAT: How is business? Is it everything ...?

JASPER LAWRENCE: 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.

PAT: The way he sees it, people are scared.

JASPER LAWRENCE: Well, they're the people who are coming from the 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 sakes, 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?

LATIF: Okay, okay, okay. Okay, so ...

MOLLY: So that's it.

LATIF: So—so wait, but—okay.

MOLLY: Yeah, maybe the—maybe the question is: Latif, you have talked about this on the show. You have an autoimmune disorder.

LATIF: Yes.

MOLLY: Crohn's disease.

LATIF: Crohn's disease.

MOLLY: Okay.

LATIF: Yeah.

MOLLY: You've heard this piece. Are you scared of a little worm?

LATIF: I mean, I am intrigued. I am—I don't know whether to be scared. If there are clinical trials ...

MOLLY: Okay.

LATIF: ... that can help tell me whether to be scared or not of this worm ...

MOLLY: All right.

LATIF: ... that's what I want to know.

MOLLY: All right. Well then, I am gonna tell you about a clinical trial, and then you can tell me what you think.

LATIF: Okay.

MOLLY: But after the break.

LATIF: All right. Oh, after the break. All right.

MOLLY: After the break.

LATIF: Let's do it.

MOLLY: A clinical trial.

LATIF: I'm more—I'm ready. I'm excited.

MOLLY: Okay.

LATIF: Great.

MOLLY: Latif, we are back from break.

LATIF: Yeah.

MOLLY: And we left you at, "Are you scared of a little worm?"

LATIF: And I was like, maybe? Maybe? I don't know. Let's do some actual clinical trials.

MOLLY: And that is what, like—okay so that episode was done in 2009.

LATIF: Right.

MOLLY: And so I want to fast forward to today. There have been a number of clinical trials.

LATIF: Oh, this is great. So excited. Okay, so what happened?

MOLLY: Okay, so ...

MOLLY: Hi!

PAUL GIACOMIN: Hey, how are you?

MOLLY: ... I talked to this researcher.

PAUL GIACOMIN: Dr. Paul Giacomin.

MOLLY: Paul Giacomin.

PAUL GIACOMIN: Senior research fellow at the Australian Institute of Tropical Health and Medicine.

MOLLY: And he's basically trying to do, like, the next iteration of, like, Jasper. But, like, with actual scientific studies and stuff.

LATIF: Okay. Yeah.

PAUL GIACOMIN: Yeah. Trying to understand the potential beneficial effects of worms in people.

MOLLY: So one of the things that he's been studying is ...

PAUL GIACOMIN: Treating people who are at risk of type 2 diabetes with hookworms.

LATIF: Hmm!

MOLLY: So type 2 diabetes, that's the diabetes that you typically get later in life.

LATIF: Yeah.

MOLLY: What made you pick diabetes?

PAUL GIACOMIN: 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.

MOLLY: And what they found is that there is a correlation between something like type 2 diabetes and the presence or lack of worms.

LATIF: Huh!

PAUL GIACOMIN: Yeah, so basically ...

MOLLY: So what Paul and his team did is basically they took people who are at risk for type 2 diabetes and they gave them hookworms.

LATIF: How do they give it to them? How do they take them? Do you, like, slurp it down like a little piece of spaghetti?

MOLLY: No. No.

PAUL GIACOMIN: You know, people think when they enroll, they're gonna have to swallow a worm or swallow worm eggs et cetera. So ...

MOLLY: It's actually much worse.

LATIF: [laughs] Okay.

MOLLY: Or I don't know, it could be much better than that.

PAUL GIACOMIN: Basically, in order to do our research ...

MOLLY: The first step of the process is they have folks who work in their lab.

PAUL GIACOMIN: These are called worm farms.

MOLLY: Volunteers.

PAUL GIACOMIN: Who have consented to have a small number of worms ...

MOLLY: Living inside of them.

LATIF: Oh wow!

PAUL GIACOMIN: Yes, exactly. It's the only way. You can't culture them. You can't just get them and freeze them.

MOLLY: Really?

PAUL GIACOMIN: Yeah. So that's one of the limitations about working with these worms. You actually have to maintain, essent—we call them worm farms.

LATIF: Is there, like, hazard pay for that? Like what—do they get a bonus?

MOLLY: No, I think they're just very generous volunteers.

PAUL GIACOMIN: Brave and dedicated volunteers, and so that if we want to do our research, we say, "Hey, generous volunteer ..."

MOLLY: "Can you give me a sample of your stool?"

LATIF: Okay.

MOLLY: Because what happens in these people, in the worm farms, is the hookworms inside of them will mate ...

PAUL GIACOMIN: And they can produce, the females can produce tens of thousands of eggs every day, which are released eventually in the poo.

LATIF: Huh!

MOLLY: And so they poop.

PAUL GIACOMIN: We get the poo sample.

MOLLY: Add charcoal to it.

PAUL GIACOMIN: Which reduces the smell. And then we spread it onto the Petri dish.

MOLLY: They leave the Petri dish in sort of like kind of a humid, tropical environment.

LATIF: Okay.

MOLLY: It sits there for a week.

PAUL GIACOMIN: And over the course of that week ...

MOLLY: These tiny hookworm eggs start to hatch. And emerging from them are these ...

PAUL GIACOMIN: Microscopic ...

MOLLY: ... teeny, tiny baby worms.

PAUL GIACOMIN: Barely visible to the naked eye.

MOLLY: And very quickly, Paul and his team hit them ...

PAUL GIACOMIN: With like a strong disinfectant.

MOLLY: To clean them.

PAUL GIACOMIN: Then we can basically look down the microscope, and we just one by one pick the wriggly worms, put them into a little tube ...

MOLLY: And then what they do is they put the worms on a Band-Aid, essentially.

LATIF: Uh-huh?

MOLLY: And they take that Band-Aid, and they put it on the skin of the patients that are enrolled in the clinical trial.

LATIF: But not even on a cut, just anywhere on the skin?

MOLLY: Just anywhere on the skin.

PAUL GIACOMIN: And then we sort of sit with them for about five minutes because participants start to get this tingling sensation.

MOLLY: Because what happens is these baby worms on the Band-Aid start to release an enzyme.

PAUL GIACOMIN: Which degrades tissue.

MOLLY: Which basically melts your skin so that they can start to burrow.

LATIF: Agh!

MOLLY: Into your skin. And as they enter your skin, then your skin just closes up behind them.

LATIF: Hmm.

MOLLY: The tunnel closes, and then the worm makes their way down through your skin into ...

PAUL GIACOMIN: The lymphatics.

MOLLY: ... your lymphatic system. So if you think of the inside of your body as a water park ...

LATIF: Uh-huh?

MOLLY: ... as one does, the lymphatic system is like the lazy river.

LATIF: Sure. Yeah, yeah, yeah.

MOLLY: So these baby hookworms 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.

LATIF: That's funny.

MOLLY: And they're floating downstream.

LATIF: Uh-huh?

MOLLY: They float along, and they get to what is known as your lymphatic duct, which is kind of right by your collarbone. And once they get there, they get shot out of the lymph stream into your bloodstream.

PAUL GIACOMIN: And once they're gone into the blood, they're cruising around like on a waterslide.

MOLLY: They go from your collarbone towards the center of your chest, where they catch this huge slide that sends them into your heart, and then your heart—thud, thud, thud— 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 ...

LATIF: Yeah?

MOLLY: ... these little baby worms get stuck. They get trapped inside of a super tiny blood vessel.

LATIF: Because they're too big.

MOLLY: Yeah, they're too big for the blood vessel, so they get stuck there.

PAUL GIACOMIN: And their journey ends.

MOLLY: But, Paul says ...

PAUL GIACOMIN: That's their cue ...

MOLLY: To again release an enzyme that starts to melt away the walls of the blood vessel.

LATIF: Whoa!

MOLLY: Just enough that they can wriggle their way through and then pop out on the other side of this blood vessel and into your lungs.

PAUL GIACOMIN: And then what they do is they crawl ...

MOLLY: They crawl ...

PAUL GIACOMIN: ... up through the lung, all the airways.

MOLLY: Like a rock climber—boop, boop, boop, boop, boop.

LATIF: Agh!

PAUL GIACOMIN: Up your trachea.

MOLLY: So they're almost in your throat.

PAUL GIACOMIN: And then unknowingly ...

MOLLY: 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 a backwards somersault. And then after you cough, you usually swallow.

PAUL GIACOMIN: So yeah, you'll swallow them.

MOLLY: You swallow the worms.

LATIF: Oh my God!

MOLLY: Ahh! At which point they will shoot down your esophagus, into your stomach.

LATIF: Oh my God!

MOLLY: And then ...

LATIF: Why wouldn't you just—oh, but it's like, why wouldn't you just feed it to people, then? Like, why do this whole crazy ...?

MOLLY: Well, because this whole process from skin to gut takes about two to three weeks, and during that process, the worm is maturing.

LATIF: Got it.

MOLLY: And so it's actually developing in such a way that it can survive in your stomach.

LATIF: I see. So it's like this is how it develops.

MOLLY: Exactly.
PAUL GIACOMIN: 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 in their upper small intestine.

MOLLY: And once they're in the small intestine ...

PAUL GIACOMIN: They've got these sort of quite violent-looking teeth.

MOLLY: They will bite and clamp onto you.

PAUL GIACOMIN: And they very fairly delicately just sort of suck the blood.

MOLLY: And this is where something sort of amazing happens, which is for the next two weeks, your body is gonna have this really intense reaction.

LATIF: Uh-huh?
MOLLY: So where the worm is biting down on your intestinal wall, it's gonna get inflamed. There's like an open sore where the worm is sucking. And your body is going to freak out and try to flush the hookworm out. So you're gonna have diarrhea, you're gonna feel sick, and then it's all gonna stop. You're gonna feel fine. And Paul says this is most likely because right around this time the hookworm has reached full adulthood.

PAUL GIACOMIN: And we've—we've actually, in some of our clinical trials, have taken a camera and we've had a look in the gut at regions of the gut where the worms have been feeding. And, you know, there might be one little small red spot there right 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.

MOLLY: Really?

PAUL GIACOMIN: Yeah, absolutely. It's in their best interest to basically feed and heal the wounds in their environment.

MOLLY: 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.

PAUL GIACOMIN: Because your immune system could—it could just unleash an enormous, you know, attack on these worms ...

MOLLY: But obviously the worm does not want that.

LATIF: Yeah.

MOLLY: And so it has these little proteins that it secretes 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.

LATIF: 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 climb up the dah dah dah. 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.

MOLLY: 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 2 diabetes ...

PAUL GIACOMIN: The people who were treated with the hookworms had things like reduced blood glucose levels. They had dramatically reduced insulin resistance levels. Lost a little bit of weight.

MOLLY: And some of these people who were considered pre-diabetic were no longer pre-diabetic.

LATIF: Oh wow! So some people were cured, effectively.

MOLLY: Yeah, basically.

PAUL GIACOMIN: Well, when you look at the placebo people, who got no worms ...

MOLLY: They went on to continue having high insulin resistance, glucose ...

LATIF: All the problems. Yep.

MOLLY: ... no weight loss.

PAUL GIACOMIN: So it was really the first causal, clinical evidence that the worms were having a benefit on metabolic health.

MOLLY: Then at the end of the trial, at the end of the two years, the people who had the hookworms inside of them?

LATIF: Mm-hmm?

MOLLY: They had the option to just get rid of the worms. Like, you can take over-the-counter deworming medication and they'll be gone the next day.

LATIF: Yeah.

MOLLY: Paul says at the end of this two-year study, almost everyone kept their worms.

LATIF: Wow!

PAUL GIACOMIN: 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.

MOLLY: Do you think the happiness is emotional, or do you think the happiness is like they actually feel different?

PAUL GIACOMIN: Yeah, exactly. So there's two things. One of them, they might think, well, it's not doing me 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 ...

MOLLY: So these were trials looking at celiac's disease.

LATIF: Yeah?

PAUL GIACOMIN: 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 wellbeing and mood and sleeping quality.

MOLLY: Wait, really?

PAUL GIACOMIN: That we saw in the people 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.

LATIF: Huh!

MOLLY: And there is, like ...

LATIF: What a weird thing, right?

MOLLY: I know. So one of—well, here's the thing. I'm gonna break that down for you, which is like one of the things we're all talking about right now is our microbiome.

LATIF: Right.

MOLLY: Right? It's like, what is the tiny stuff living inside of us? Like, viruses and bacteria that's actually helping us.

LATIF: Right.

MOLLY: One of the things Paul was talking about is like, well, there's also a macrobiome.

PAUL GIACOMIN: You know, the macrobiome, the organisms that you can see with your naked eye, these worms that can somehow live for up to a decade or even longer within our gut. You know, the immune system should really have recognized these worms and kicked them out because they're such a big insult on the body.

MOLLY: But Paul says it could be that when these worms, when they reached 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.

LATIF: Yeah.

MOLLY: 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.

LATIF: Right.

MOLLY: 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, like, don't attack me ...

LATIF: Well, this—yeah. Yeah, yeah, yeah, yes.

MOLLY: Then overall it's just the immune system's not gonna attack you. [laughs]

LATIF: I just—this is—the thing that's really confusing to me is why ...

MOLLY: We've left you more confused.

LATIF: No, because like, why would—like, this is something that we need, seemingly, to regulate our own kind of internal army, right?

MOLLY: Mm-hmm?

LATIF: Like it's like, why would we outsource this very crucial part of ourselves?

MOLLY: What do you mean, outsource?

LATIF: Like, outsource. Like, the worms are not us. Like, if they're—if they're helping regulate ...

MOLLY: We would outsource it because they—because they're helping. We would outsource it because it's beneficial. Like, you have to imagine, like, we've been living with worms for millions of years.

LATIF: Yeah.

MOLLY: 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.

LATIF: Right.

MOLLY: And then a worm got inside of us and it lasted a little longer, and then we did or did not die. And it's, like, basically this long-term dance between us and the worm.

PAUL GIACOMIN: So there's this really interesting truce that's happened throughout evolution, where the worm benefits and the host benefits.

MOLLY: 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.

PAUL GIACOMIN: But also from the potential immune-shaping and metabolic-shaping powers of the worm.

MOLLY: So Paul's lab has shown that people who are given hookworms have fewer symptoms associated with type 2 diabetes, celiac's disease. There's also other studies looking for benefits for people with multiple sclerosis, ulcerative colitis—that's where you get ulcers on your intestines.

LATIF: Mm-hmm.

MOLLY: Crohn's disease, Latif.

LATIF: Uh-huh?

MOLLY: And in those studies, some people have gone into remission.

LATIF: Wow!

MOLLY: With worms. That's not Paul's lab, but that's other labs.

LATIF: Yeah.

PAUL GIACOMIN: And, you know, if they're beneficial and, you know, why not turn it into a treatment?

MOLLY: 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.

PAUL GIACOMIN: Yes. There's a lot of hurdles for developing hookworms as a medicinal treatment.

MOLLY: Everyone is kind of like, "Listen, there's so many reasons why people don't want worms." Like, they're kind of just gross.

PAUL GIACOMIN: But also, I briefly mentioned before, you get the larvae out of people's poo, so making a medicinal product ...

MOLLY: With standardization and decontamination, it's just really hard.

PAUL GIACOMIN: Exactly. So at this stage, it's probably never gonna be a mainstream treatment.

LATIF: Hmm.

MOLLY: 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.

LATIF: Wow.

MOLLY: 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.

PAUL GIACOMIN: 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 that you're paying money for something which hasn't really been rigorously tested and it hasn't gone through the regulatory processes that other medications need to go through.

MOLLY: And so, yeah, that's where—that's where it's at.

LATIF: Okay, I gotta go, but my last question is: Molly, should I get a worm?

MOLLY: 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?

LATIF: I think that ...

MOLLY: 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?

LATIF: No, but now I'm just, you know—those lucky people over there, they get worms, you know?

MOLLY: 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.

LATIF: No, that's not—I'm not gonna—I'm not gonna roll in human feces.

MOLLY: That's a level of desperate you're not at?

LATIF: That's not how desperate I am.

MOLLY: Okay. Well, Australia it is then. Okay, hitting stop.

LATIF: Okay.

MOLLY: Okay. Hitting—I'm hitting stop.

LATIF: Okay. Thank you, Molly Webster for the update.

MOLLY: You're welcome.

LATIF: This update was produced by Matt Kielty with help from Rebecca Rand. It was edited by Arianne Wack and fact-checked by Diane Kelly.

MOLLY: And we want to thank Pat Walters, Jad Abumrad, Robert Krulwich, 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.

LATIF: And for everything else Radiolab-y, please subscribe to our totally FDA-approved newsletter.

MOLLY: [laughs]

LATIF: All right. We'll be right back.

MOLLY: In 20 years.

LATIF: In 20 years.

MOLLY: No, just next week.

LATIF: Yeah, we'll catch you next week.

MOLLY: Bye!

[LISTENER: Hi, I'm Gabby. I'm from the Bay Area, California, and here are the staff credits. Radiolab is hosted by Lulu Miller and Latif Nasser. Soren Wheeler is our executive editor. Sarah Sandbach is our executive director. Our managing editor is Pat Walters. Dylan Keefe is our director of sound design. Our staff includes: Jeremy Bloom, W. Harry Fortuna, David Gebel, Maria Paz Gutiérrez, Sindhu Gnanasambandan, Matt Kielty, Mona Madgavkar, Alex Neason, Sarah Qari, Natalia Ramirez, Rebecca Rand, Anisa Vietze, Arianne Wack, Molly Webster and Jessica Yung, with help from Gabby Santas. Our fact-checkers are Diane Kelly, Emily Krieger, Natalie Middleton, Angely Mercado and Sophie Samiee.]

[LISTENER: Hey, Radiolab. Michael, Tacoma, Washington. Leadership support for Radiolab's science programming is provided by the Simons Foundation and the John Templeton Foundation. Foundational support for Radiolab was provided by the Alfred P. Sloan Foundation.]

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