Daniel and Kelly’s Extraordinary Universe - How do parasites evade our immune system? (featuring Dr. John Hawdon)

Episode Date: November 11, 2025

Daniel and Kelly chat with Dr. John Hawdon about how parasites like hookworm, malaria, and schistosomes hide from our immune system.See omnystudio.com/listener for privacy information.

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Upgrade to smooth, high-quality streaming with Intel Wi-Fi 6E and maximize game performance with enhanced overclocking. Win the tech search. Power up at Lenovo.com. On the podcast Health Stuff, we are tackling all the health questions that keep you up at night. I'm Dr. Priyanko Wally, a double board certified physician. And I'm Hurricane Dibolu, a comedian and someone who once Googled, Do I have scurvy at 3 a.m?

And on our show, we're talking about health in a different way, like our episode where we look at diabetes. In the United States, I mean, 50% of Americans are pre-diabetic. How preventable is type 2? Extremely. Listen to Health Stuff on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. Hi, Kyle. Could you draw up a quick document with the basic business plan? Just one page as a Google Doc and send me the link. Thanks. Hey, just finished drawing up that quick one page business plan for you. Here's the link. But there was no link. There was no business plan. I hadn't programmed Kyle to be able to do that yet. I'm Evan Ratliff here with a story of entrepreneurship in the AI age. Listen to Zyatlin.

attempt to build a real startup run by fake people. Check out the second season of my podcast, Shell Game, on the IHeart Radio app or wherever you get your podcasts. And she said, Johnny, the kids didn't come home last night. Along the central Texas plains, teens are dying, suicides that don't make sense, strange accidents, and brutal murders. In what seems to be, a plot ripped straight out of Breaking Bad. drugs, alcohol, trafficking of people.

There are people out there that absolutely know what happened. Listen to paper ghosts, the Texas teen murders, on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Howdy friends? Just a heads up that we're talking about parasites again. And as you're probably aware of by now, that can get pretty gross. Also, it's kind of upsetting to hear about parasite life cycles and the effects of parasites on our health. I get that. Today, we're going to be talking about malaria, chistosomiasis, and hookworm.

So decide if those are topics you are prepared to hear about. All right, here we go. According to the World Health Organization, in 2023, about 263 million people were infected by malaria, of which 597,000 passed away from this disease. Most of these deaths happened in Africa, and 76% of the deaths were children under five. You might remember from a past episode that we were able to create a vaccine for smallpox and that that vaccine was used to wipe smallpox off the face of the planet, saving humanity from this ancient scourge.

And yes, thanks to all who wrote in, I pronounce the word correctly now. We also have vaccines for other bacterial and viral infections like polio, chickenpox, human papilloma virus, COVID-19, measles, mumps, etc. With the exception of some tricky viruses like HIV which hide in our immune cells, we've had a lot of success making vaccines for viral and bacterial infections. And we know that our immune systems attack big stuff, as well as the little stuff like bacteria and viruses. In a past episode, we talked about how our immune systems will attack entire organs following a transplant.

So why do our immune systems seem to do. such a crummy job of attacking parasites in our bodies, things like nematodes. And why is it so hard to make vaccines to give our immune system a leg up on these invaders? We've been working on malaria vaccines for a really long time, but only recently have two malaria vaccines become widely available in areas in Africa where malaria is prevalent. That's good news, but why did it take so long? And why don't we have a vaccine for hookworms yet? Remember hookworms, those dirt worms we talked about a few months back?

Yeah, those guys. There are many parasitic diseases that have proven stubbornly difficult to control with vaccines. And so today we're going to talk to Dr. John Hodden, a molecular biologist and parasitologist who's going to help us understand why it's so darn hard to make vaccines against parasites. Welcome to Daniel and Kelly's Extraordinary Universe. Hi, I'm Daniel. I'm a particle physicist, and I'm excited to be talking about all sorts of icky invaders today. Hello, I'm Kelly Wiener-Smith, and I always love talking about icky invaders, although with all the required sensitivity for the pain and suffering that these parasites cause. But anyway, I study parasites and space, and today we're talking about my first love, parasitology.

Your first love. Something I love about science is how excited. did people get about their funny little, tiny little niche. You know, you're going to meet somebody who's, like, amazed at the hairs on spider's legs or somebody else who, like, can't stop thinking about how, you know, the mantle flows and how rocks form. And, like, these nerds get so excited about their little niche. It's wonderful, right? That's why we know so much about the universe and spider legs and rocks and parasites because

people get weirdly excited about stuff. My friend Ashley Smyth refers to this as a limitless human curiosity. Yes. Because I was asking her about like, oh, why do parasitologists sometimes infect themselves with the parasites that they study? Isn't it weird that we do that? And she was like, Kelly, that's our limitless human curiosity. And I was like, okay. I totally love that about humanity.

I mean, curiosity is something deep about being human. Actually, I wonder if it is just about being human or if, you know, aliens are curious about the universe also if that's something that's, really is universal. But today, unfortunately, we're not talking about aliens. We're talking about critters so gross that invade you that it almost feels like they are alien. And today we invited on the show, my friend John, he's going to be talking about three different kinds of parasites. And specifically, we invited John on the show because we had two listener questions that felt somewhat out of my expertise, even though I'm a parasite person. And so I knew the guy to invite on the show. So let's go ahead and listen to the two questions from listening.

before we bring John on. Hi, Daniel and Kelly. This is David from the San Francisco Bay Area, and this question is for Kelly. What makes developing a vaccine for parasitic infections so difficult? It seems like progress has been only recent and incremental with some experimental vaccines

for hookworm, and the one approved malaria vaccine is not very efficacious. So what gives? And this topic is at least tangentially related to what I do for a living, which is working on a new platform to produce RNA therapeutics, so I'm especially interested in what you have to say.

Anyway, keep up the great work both of you, and Daniel, I forgive you for your chemistry phobia. Cheers. I got my master's degree in the late 70s. At that time, there are three theories on how systems evaded immune system. My advisor's theory was called molecular mimicry. Although it was over 40 years ago, I remember it well because for the final exam, we had eight hours to answer two questions, one of which was to name the three current theories of how the treatment hose evades immune system and which one do you agree with and why. Of course, I chose my advisor's theory, but after receiving my master's degree, I lost track of the issue since I got my

doctorate in different but related subject. My question is, what advances have been made and have any conclusions been made pertaining to their evasion of the host immune system? And if so, it will lead to a practical subject such as tissue transplantation. All right, these are awesome questions. And thank you to everybody who writes to us with your questions. We really do love to hear from you. If you have questions about comets or about malaria or about parasites or about whatever you have limitless curiosity about, please do send them to us. We'd love to hear from you questions at danielandkelly.org. All right.

And without any further ado, let's bring my friend John on the show to answer these listener questions. Dr. John Hodden is a parasitologist and molecular biologist at the George Washington School of Medicine and Health Sciences. He was previously the president of both the American Society of Parasitologists and the Helmithological Society of Washington. He's done some really fantastic work on hookworms, which you'll remember are one of the dirtworms or geo-helmints that we talked about in a prior episode. And we're very lucky to have him come on the show to talk to us about parasites and vaccines. Welcome to the show, John. Thank you. My pleasure.

We're excited. You're here. I'm excited to be here. You sound really excited, John. Okay. So let's start with hookworms. So we did have a whole episode on the soil geohelments, which we called dirtworms. But just to remind everybody, can you talk about the life cycle of hookworms?

Sure. So hookworms live as male and female worms in the intestinal tract of various mammalian hosts. And they get together and have their little party and the female legs that are been fertilized and they pass out into feces. They spend a period in the ground where they hatch and they develop through two mults to a third stage larvae or L3 that's infective for the next host. And then the next host gets infected by either coming into skin contact with the infective larvae or in some cases, like in dog hookworms, for instance, by ingestion of the larvae. We're talking about eating poop. Well, yeah. As I tell my students, you know, when you get one of these fecal oral diseases, it means you ate a tiny little bit of poop.

Yeah, poop to mouth. So once they get into your host blotty, if they go through. the skin, they undergo a migration that takes them into the circulatory system to the lungs where they break out in the bronchials and they crawl up your bronchial tree to the trachea, to your mouth where they're swallowed and then are carried to the small intestine where they will resume the development and molt to the adult stage. If they enter orally, they don't need to leave the intestine and they can develop directly to the adult stage. And they're called hookworms because they bite onto the wall of your intestine and hook in?

That's a common misconception. All right. Correct. It's actually because of the way the worms appear, they can't see me. I'm doing this for the camera, but do a little bend, but yeah, so there's a little bend in them that makes it look like a hook. Like if you have gotten some from inside an animal and you put them in a dish, or even And if you're looking at the surface of an infected small intestine, they will appear to be bent. You said if you're looking at a dish of them, like, you mean you're at a restaurant and somebody serves you like a hookworm salad or something?

Alamode. Al-a-comode? Sorry. We love potty humor, us parasitologists. All right, I don't want to get us too far off track, but I have to ask, when the worms crawl up your tracheon into your mouth, do people feel that? I think I asked our mutual friend Jimmy who got infected with hookworms as part of an experiment, and he said he did not at any point feel the hookworms crawling in his mouth. What's the deal there, John? Well, he's the expert on that. I have never been infected. But my understanding is

you don't notice it. Okay. Right. So you'll swallow them with food or with saliva or whatever. Gross and amazing. Oh, my God. Well, they're clean by the time they run through your body. Sure. All right. So with a lot of infections like chicken pot, You get it once, and then you have lifelong immunity. So why doesn't that happen with hookworms? Like, why can't you give everybody one hookworm? And then for the rest of their life, they never have to worry about getting hookworm. Boy, life would be a lot easier if you could do that.

Yeah. Hookworms are, like most parasites, are very good at evading the immune system. And they can do this actively or passively, primarily actively. They release molecules, most of which are unknown, that alter the immune response. to be a favorable environment for them to survive. The human hookworms, notably, you never really get a sterile immunity to them. You can be reinfected over your entire lifetime. Dog hookworm, for instance, the second infection never takes as well as the first.

And the older the dog gets, the less likely it is to get a heavy infection of worms. So, okay, so wait, dogs mount an immune response better than humans. What, do we understand why that's different? No. Okay. But there's a, independently, there's an age-associated resistance in dog hookworms so that the older the dog gets, the less likely it is to get a heavy infection. This thought, you don't see this in any of the human species, to our knowledge. I mean, you can get infected as a kid and you can infect it as an elderly person with Nicator Americanaus, for instance, and you're going to, you'll still be infected.

Got it. And just a quick reminder for folks that Nicator Americanaus is a species of hookworm. But microscopically, like, what's the issue? The hookworm has got to be a foreign body. Doesn't the immune system identify it as foreign and attack it? The way it does, if you, like, get a splinter or get an organ donation, what's the obstacle for the immune system? Have these hookworms evolved to, like, look like human flesh?

There's a couple problems. First of all, there's no good way to get rid of a large organism like a hookworm. It's also in the gut, which is a little bit harder to. to deal with too. So you get what's called a weep and sweep reaction where you get a lot of secretion of liquid of water and things into the gut that cause it to be flushed out. And you don't see that in hookworm, then it's probably due to them suppressing that and turning the immune reaction into one that they can tolerate. And it basically becomes a tradeoff because if the host puts enough evolutionary effort into getting rid of worms, they could do it, but it would be costly for them

to do it. So in general, you come to this equilibrium where the number of worms is not really a big, has a large effect on the host. Now, there's exceptions to that. Some people get really high-level infections that are dangerous. But for the most part, the host and a worm seem to come to an agreement where they kind of limit the damage, right? And it's just negotiation down on a molecular level, really, between the immune system and the molecules that the worm produces. If the hookworms and our immune system have essentially like come to a standstill, a standoff, why do we need a vaccine for hookworms if our immune system has decided this isn't worth fighting off? Did I say we needed one? Okay. All right. So put yourself in the shoes of one of one of

the people who are working on a vaccine for hookworms? What would they say for why we need a hookworm vaccine? I mean, I want a vaccine. I don't want to get hookworm. This sounds gross. Please give me a vaccine. You know, there used to be hookworm in the United States. And the reason you don't get hookworm here is because toilets, right? Once you've separated people from their waste, you break the life cycle and you don't have transmission anymore. In places where it's too poor to have sewers in sanitation like this. There's some need or desire to vaccinate, especially kids, so that they can minimize the effects of the infection. So it's thought that if you periodically deworm or if you vaccinated, you would improve growth and development. You would

improve school performance and all these other economic indicators later in life that people would make more money and this sort of thing. And there are some evidence for that, but there's also contradictory evidence that that would really happen. Again, in the most cases, even children aren't infected with dangerous levels of hookworm, right? But there is a small population, a group of the population that is highly susceptible to worms, called wormy people, basically. And for it's either genetics or sometimes it's exposure, you know, behavioral things. like that that increase exposure. I can't tell because of your deadpan delivery if you're joking or if scientists really call them wormy people. Oh no, they do. They do. There's an article about this

famous article by a man named Stoll, I believe, it said, this wormy world. And the people are called wormy because they tend to get more worms. And it's that small, that group there that's going to have the pathology and everything. And I guess the question of skeptics of vaccines is, is it worth the investment to get to this small population with a vaccine, to target that small population with a vaccine. Or would the money be better spent either targeted treatment of this group of people, identifying them and then treating them, which is also expensive, but probably not as expensive as a vaccine, or just improving sanitation in general in these places. And essentially, the only places that ever really controlled these dirtworms were places that

economically grew out of it. For instance, Japan, South Korea, the United States, Europe, all these places basically built toilets and economically developed their way out of these parasites, these infections. Can I ask a question about that? I have a toilet-related question. Sure. We get this a lot. You're saying that the presence of toilets basically separates people from their waste, and that breaks the cycle. And that makes sense to me, except that I live with a microbiologist. And she refers to toilets as fecal tornadoes because when you flush, there's like a spray of microscopic poop, basically. And she does all these studies that show that if you live with people long enough, your microbiomes all sink because you're basically breathing and eating

each other's poop particles in the air. It's very romantic, let me tell you, to be married to a microbiologist. And so how do I understand that at the same time as understanding that we've broken the hookworm life cycle? Are these hookworm larva too small to like take a ride on the fecal? tornadoes? Is that the issue? I don't know, but your fecal tornado is only going to have the eggs, which are not infectious, right? It takes three or four days in a tropical temperature in order to develop to that effective stage. So unless you're leaving your poof sitting in the toilet for a few days, and then I'm not even sure they would develop then. And then you did your fecal tornado.

I see. But, you know, I mean, why do we have an immune system? It's for things like fecal tornadoes, right? It's probably good for you to stimulate your immune system. A lot of life lessons here today on the podcast. I try to help the humans. Wormy or not. Yeah.

All right. So you said that hookworms release chemicals that sort of trick the immune system into not responding to it. So how do we have any hope of creating a vaccine against it? What have people tried so far? Well, I don't know how much of this I should say, but there is some promising results with vaccines now. And they seem to target antigens that aren't normally seen by the body and are involved in feeding, for instance, like gut proteins in the worm that will block feeding.

Whether these pan out eventually to be vaccines is not clear, but in some early studies, they seem to be promising. Is an antigen something your immune system produces? No, that's an antibody. So then what's an antigen? Well, it's what your immune system recognizes to react to, produce an antibody or to... It's a thing that triggers the immune response. Exactly. Okay.

To be honest, I thought, man, this isn't going to work. And sometimes I think it even surprised the people who do the experiments that it worked because, you know, these are hard organisms to kill. They're big. And they have all these chemical defenses. The more we learn about them, the more there are. There are multiple overlying mechanisms to subvert. the immune system. So, yeah, it is a daunting prospect. And one argument I've always had is that

we jumped into making vaccines before we knew enough about the worm, that a lot of the money that went into early investment into the vaccines would have been much better learning some basic biology about the worms. And we're starting to know more about what they release, but we still don't know how they affect the immune system. So maybe had we waited a little longer, we would have had better antigens to use for the vaccine. But again, that money could also been spent to build sustainable toilets in developing countries, which is something I had advocated for earlier in my career. Well, it sounds like you have fundamental criticisms of this whole program, and yet you're the president of the American Society of Parasotologists. Why don't you

have more influence? Why aren't they listening to you, John? Former president. Because Well, there are people with bigger voices than me involved in this, the WHO and various people there. There's a lot of money in trying to develop this. I don't want to be a cynic and say, well, this is how they make their money or whatever. This is what they truly believe and they're advocates for it, right? And they have a larger voice than I do in this. I don't think it's, you know, the money spent on the vaccine. You know, we did learn some things from that.

So it's not money wasted in that case. And if they get a vaccine, I think it may be useful in certain situations. But then you get into the question of, do you want to kill all the worms, right? I mean, there's a whole group of people in this country and around the world who think having a few worms is actually beneficial for your immune system. And there's a lot of, there's an absence, let's say, or a dearth of information about how parisies, and their hosts have co-evolved and, you know, does this effect on the immune system that allows the hookworm to live? How does that affect other parasites and other diseases? And if you take that component away, what are you going to do these other diseases? Some people think that

that's why the West has this large number of autoimmune diseases like, you know, lupus and MS and all kind of things, because they've taken away some of the regulatory we're getting now into the hygiene hypothesis, but they've taken away the early exposure to things our old friends like parasites that have trained our immune system to not react to the little things and to only react to the big things that are dangerous.

And you take that away and now you've got an entire arm of your immune system which is designed to fight worms is now looking for something to do and it picks on, you know, starts going after self-antigens and things like that. So these are all questions that we don't really know enough about. So jumping into deworming and vaccinating the entire world may lead us to places we don't necessarily want to go.

We could end up nostalgic for the time when we had worms. We could. Some of us are. All right. Well, in a future episode, I think we'll do a whole hour on the hygiene hypothesis because I find this topic absolutely fascinating. So wait for that in the future, folks. And in the meantime, let's take a break. And when we get back, we'll talk about parasite number two, the schistosomes.

upgrade to smooth high-quality streaming with Intel Wi-Fi 6E and maximize game performance with enhanced overclocking. Win the tech search. Power up at Lenovo.com. Lenovo, Lenovo. On the podcast Health Stuff, we are tackling all the health questions that keep you up at night. Yes, I'm Dr. Priyanka Wally, a double board certified physician. And I'm Hurricane Dibolu, a comedian and someone who once Googled,

Do I have scurvy at 3 a.m? On health stuff, we're talking about health in a different way. It's not only about what we can do to improve our health, but also what our health says about us and the way we're living. Like our episode where we look at diabetes. In the United States, I mean, 50% of Americans are pre-diabetic. How preventable is type 2? Extremely.

Or our in-depth analysis of how incredible mangoes are. Oh, it's hard to explain to the rest of the world that, like, Your mangoes are fine because mangoes are incredible, but, like, you don't even know. You don't know. You don't know. It's going to be a fun ride. So tune in. Listen to Health Stuff on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

Hi, Kyle. Could you draw up a quick document with the basic business plan? Just one page as a Google Doc. And send me the link. Thanks. Hey, just finished drawing up that quick one-page business plan for you. Here's the link. But there was no link.

there was no business plan. It's not his fault. I hadn't programmed Kyle to be able to do that yet. My name is Evan Ratliff. I decided to create Kyle, my AI co-founder, after hearing a lot of stuff like this from OpenAI CEO Sam Aldman. There's this betting pool for the first year

that there's a one-person, a billion-dollar company, which would have been like unimaginable without AI and now will happen. I got to thinking, could I be that one person? I'd made AI agents before for my award-winning podcast, Shell Game. This season on Shell Game, I'm trying to build a real company with a real product run by fake people. Oh, hey, Evan.

Good to have you join us. I found some really interesting data on adoption rates for AI agents and small to medium businesses. Listen to Shell Game on the IHeart Radio app or wherever you get your podcasts. She said, Johnny, the kids didn't come home last night. Along the central Texas plains, teens are dying. Suicides that don't make sense. strange accidents, and brutal murders. In what seems to be, a plot ripped straight out of Breaking Bad.

Drugs, alcohol, trafficking of people. There are people out there that absolutely know what happened. Listen to paper ghosts, the Texas teen murders, on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. All right, and we're back, and now we are talking about the schistosomes. They cause a disease called schistosomyasis, and they're quite nasty parasites. And Daniel's laughing at me. Why are you laughing?

I'm laughing because we just went from the ones you get, if you eat poop, to ones called schistow, which, you know, has some sort of resonance with other words we shouldn't say on the podcast. So tell me, is this another poop-related parasite? John? Indirectly. Indirectly. Its life cycle is a little bit different for a couple of reasons. The adults live in the bloodstream and the eggs come out in the feces. But let's just start with the feces and the eggs come out.

They have to get into water. And when they get into water, they hatch and they get a small larval stage that now is on the hunt for a snail. And in the case of schistosomes, the snail is. very particular. It has to be a particular species. They find it, they penetrate into it, and then they do several generations of asexual reproduction. And what this does is it builds up the number of the next stage, which is called a circaria. And this is the stage and it's going to infect people. So in order to get schistosome, you have to have contact with water that has had both feces and a right species of snail. And if you do, the schistosomal swim,

and it will penetrate into your skin, and then it will undergo a migration. It goes, it pretty much hits all the highlights in the body. It goes to the liver, it goes to the lungs. And eventually, they come back to the liver and they pair up as a male and a female, and they move up into the vessels. And depending on a species, it's either the vessels of the large intestine, small intestine, or the bladder. And here, the male and the female live in what's called But in copulo forever, the male has a body that's split, hence the name Shisto, Soma, split body. And the female nestles in there and is mating essentially all the time with the male. And then they release their eggs into the bloodstream that then undergo a remarkable journey to get out of the bloodstream.

This is ridiculous. I mean, it just seems so implausible, like step after step after step, and then you got a snail and it's got to do this and you've got to go swimming. But my specific question is when you're swimming and the thing crawls through your skin, how big is this thing? Is this something you notice or just like are you in swimming? You have no idea and now it's inside you. Yeah, I don't think you notice it. It's pretty tiny. And why did they have to be snail asexuals? Like, why do they have to do this thing inside the snail? Why can't they just do it themselves in the water? Well, they first of all will need something to feed on when they basically will feed on the snail. And it absorbs nutrients.

from the snail and makes all these new stages, these circaria. The purpose of this is that this allows them to go from a single mere acidium, it's called, that infects the snail into thousands of these circaria that's going to affect the next host. And what that does is it increases the odds of infection by putting more of these infective stages in the environment. If the mere acidium just tried to infect the host directly, even if it developed to the infective stage, the odds of that happening are pretty low. But the more of these infected stages

you can put into the environment, the higher the odds are that one or more of them is going to get into the next toast. And in the case, the cystocomes, you need a male and a female circaria to get in. So the snail is like a schisto amplifier or something. It's just like, wow. That's exactly what it is. Crazy. It's kind of ingenious. You know, the snail goes around, just grazing and collecting more food and that energy goes towards making more parasites. And so the parasites are getting like a buffet for doing nothing once they establish in the snail. This is a pretty gruesome parasite in the host, though. It causes a lot of problems. And it's not because of the worm, which is relatively tiny and living in the blood vessels.

It's because of the eggs. So this mechanism that gets the eggs out is really elegant, but it's very inefficient. So a vast majority of the eggs don't get out. They end up in the liver. And they form what are called granulomas when the host reacts to them. And that's where the damage comes from are these granulomas in the liver and other organs as well. Well, that was going to be my question. The hookworm we were talking about was mostly in the gut and there was some sort of negotiation you can hang out there because it's difficult for us to attack you anyway. But these guys are all over. I hear them being in the blood. They're in the bladder. They're in the liver. So the immune system does respond to them. It forms these glastelomas. Granulomas? Yes. Thank you.

Why doesn't it get rid of them? Well, the worms in the blood are pretty much untouched, and they have a bunch of immunovasive mechanisms as well, which is sort of similar to the hookworm, but different mechanisms. The eggs, on the other hand, they alter the immune system to make what's called a TH2 response, which is when you get a whole bunch of cells will come in and they'll surround the egg and form this granuloma, and then they will slowly move it through the tissue, right? And eventually, they'll come to the bladder wall or the intestinal wall, and they will just basically dump the egg out, but they often get stuck.

So you'll have these eggs stuck in the bladder wall. All this depends on the species. Where it is, is it in the bladder? Is it in a larger small intestine? But in any case, you'll get them stuck in the wall of those organs as well as in the liver. And then they're constantly releasing antigens that are pulling more cells in.

And these granulomas can get very big and then start impacting the function of the tissue that they're in. And you get fibrosis in the liver, and schistosomiasis can be really nasty disease. It's probably the most pathogenic of the worms that infect humans. I thought I heard, and remind me if I'm wrong, I thought there were some areas where the kind of schistosome that they have is near the bladder and the granulomas build up in the bladder, and every once in a while, like, the males will get it so much that they will start

to bleed along with the, you know, with the females of the certain. age, and it's almost like a right of passage. So many kids get this, that blood in your urine is just something you expect for both sexes. Is that still the case, John? Yeah, that's called schistosome, hematobium. It's found exclusively in Africa. And yeah, it will cause, because these granulomas move into the bladder wall, they cause it to erode, and then you will get blood in the urine. And there's some evidence that I think they're pretty convinced now that schistosome, as well, some of these other trematodes can cause cancer as well, including bladder cancer in that case. Man.

Because of over years and years of this erosion occurring and the body responding to it and the eggs releasing these antigens that it could result in cancer. Well, that sounds like something we should vaccinate against. Yes. I would be in favor of that, I think. I think schistocystomiasis is one that we can do without. It's going to be just as hard, though, to make a vaccine. Again, they have some promising candidates, but we're still a long way away from actually using a vaccine.

Again, it's a sanitation thing, right? In this case, if you keep your feces away from water, you're not going to have a problem. Snail control is possible, but it's difficult. It's expensive. We see some promise with introducing predators that actually eat the snails in some areas, West Africa that have done this. and they've seen, you know, you can combine it with chemotherapy and snail control, and you could see a huge decrease in the prevalence in the schistosome infections. But step one, you said, was keep your feces away from water.

But in the previous segment, we were talking about toilets, and that's like the basic operating principles, like turn your poop into sewage, right? Right. How do you do both at once? Well, as long as you don't have snails in your sewage, you're going to be okay. And plus, people generally, I mean, if you're talking about Western sewage, systems, you've kept away from the sewage the entire time. The water, you know, goes through sewage treatment plant and gets treated and converted back into usable water. So, you know,

you're still breaking the transmission in that case, right? Remember, you need water and snails. This sounds like a particularly tricky problem because you've got like the adults that hide from the immune system. And then you've got the eggs that as they pass through the body definitely do not seem to be good at hiding from the immune system, and the immune system responds, and that's what causes the problem for people. So it seems to me that if you made a vaccine, you'd need to be careful to not make the problem with the eggs worse, because now your immune system is over-responding. Yeah, I think you would have to stop it before they got to the egg-producing adults, and you would have to make your vaccine against the stages that

are penetrating into the host. Do we understand how the adults are hiding from the immune system? Right. So they do several things. First of all, they will actually take host molecules and bind them to their cuticle so that then the host immune system doesn't see it as foreign. I mean, that's amazing. Yeah. Like, can we just sit on that for a second? That's like taking, like, you know, taking the skin off of a human and putting it on themselves or something. Wow. That's amazing. They hide with our own material. It's a wolf and sheep's clothing. Yeah. But that's not all. Go on. They also make what's molecular mimicry. They will make molecules that are very similar to molecules in the host, like a hormone, for instance.

They'll then get processed by the host enzymes and act as a suppressor of the immune response. Do we know how all of this elaborate machinery evolved? Do we have any idea of the history here? Is it like, do you need all these pieces together to survive? Can you, like, do it one step at a time and refine it? How does it work? How does it evolve? Incrementally.

And ones that add more and more. more mechanisms probably are better at survival. So you might have one of these things initially and that lets more of them survive and then you will get the mutations for the other things that occur and they just pile up to have a whole suite of things that is really efficient at inhibiting the immune system. So each of these tricks is helpful. None of them are absolutely necessary. And so as you evolve, you develop more and more tricks to sort of optimize survival in the host. Wow. Impressive. I know this episode is isn't about the history of Kelly, but when I read about this in Carl Zimmer's book, Parasite Rex,

this was like literally a turning point in my life. I had gone from being like parasites, oh, they're just kind of gross, to being like, holy cow, it's like amazing the way they've managed to hide inside of our bodies. And like, it totally changed the way I looked at parasites and like literally altered the course of my life. So anyway, it infected your mind. It infected my mind. And now we got to share it with everybody. And so I'm very excited. Wait, no, this is the intellectual version of the snail amplification. It goes into Kelly's brain, just dates for a while. She gets a podcast, and then she spreads it to the whole community.

Through John. John is my snail, and I am the parasite, and this has gone too far. Okay, so let's, oh, can I play on the word schistow, like take a break? Can we split for a second? Nope, not clever enough. All right. Daniel, do you have something? In case anybody needs to take a break and have a schist, go ahead and we'll be back in a minute to talk about another parasite.

Ah, poop-related jokes. Love it. beyond performance with Intel Core Ultra processors for the next era of gaming. Upgrade to smooth high-quality streaming with Intel Wi-Fi 6E and maximize game performance with enhanced overclocking. Win the tech search.

Power up at Lenovo.com. Lenovo. On the podcast Health Stuff, we are tackling all the health questions that keep you up at night. Yes, I'm Dr. Priyanko Wally, a double board certified physician. And I'm Hurricane Dibolu,

a comedian and someone who once Googled, do I have scurvy at 3 a.m. On health stuff, we're talking about health in a different way. It's not only about what we can do to improve our health, but also what our health says about us and the way we're living. Like our episode where we look at diabetes. In the United States, I mean, 50% of Americans are pre-diabetic. How preventable is type 2?

Extremely. Or our in-depth analysis of how incredible mangoes are. Oh, it's hard to explain to the rest of the world that, like, your mangoes are fine because mangoes are incredible, but, like, you don't even know. You don't know. You don't know. It's going to be a fun ride. So tune in.

Listen to health stuff on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. Hi, Kyle. Could you draw up a quick document with the basic business plan? Just one page as a Google Doc and send me the link. Thanks. Hey, just finished drawing up that quick one page. business plan for you. Here's the link. But there was no link. There was no business plan. It's not his fault. I hadn't programmed Kyle to be able to do that yet. My name is Evan Ratliff. I decided to

create Kyle, my AI co-founder, after hearing a lot of stuff like this from OpenAI CEO Sam Aldman. There's this betting pool for the first year that there's a one person, billion dollar company, which would have been like unimaginable without AI and now will happen. I got to thinking, could I be that one person? I'd made AI agents before for my my award-winning podcast, Shell Game. This season on Shell Game, I'm trying to build a real company with a real product run by fake people. Oh, hey, Evan. Good to have you join us.

I found some really interesting data on adoption rates for AI agents and small to medium businesses. Listen to Shell Game on the IHeart Radio app or wherever you get your podcasts. She said, Johnny, the kids didn't come home last night. Along the central Texas plains, teens are dying. suicides that don't make sense, strange accidents, and brutal murders. In what seems to be, a plot ripped straight out of Breaking Bad. Drugs, alcohol, trafficking of people. There are people out there that absolutely know what happened.

Listen to paper ghosts, the Texas teen murders, on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. And we're back, and we are going to start with John's snail-related joke that he queued up during the break for us. Oh, wait, did you just say that this might not be appropriate for the show? No, this one's fine. Okay. This one's fine.

So I tell this in my class. So this guy goes to a Halloween party, a costume party, and he's got this girl draped over his show. older. And he goes in and the host says, hey, how are you doing? And you're great and everything. He says, uh, are you a costume? He goes, yeah, this is my costume. I was, well, what's with the girl? And I said, well, that's Michelle. Oh, Michelle, he's a snail? Is that? Okay. I think I left out the snail part. We got there, though, as a team. As a team we got to the end. So, Yeah, sorry I blew the joke. So malaria has some tricky ways of evading the immune system,

but we're going to start with the malaria life cycle and get to the immune system stuff in a second. And I've always found the malaria life cycle to be super confusing. It has a bunch of stages. All the stages have similar and kind of hard to remember names. So I'm going to give a super simplified version of the life cycle that I think will be sufficient for the discussion we're about to have. All right. So when a mosquito bites a person who's already infected by malaria, the parasite goes to the mosquito's gut and it starts to replicate. So after that, it moves to the mosquito's salivary glands. And that's right, mosquitoes have salivary glands. I don't know why that's surprising to me. But anyway, when a mosquito bites a person, the parasites are injected by the mosquito into the human body. The stage of the parasite that gets released into a person is called a sports. sporozoite. This is the only stage we're going to name. So just remember, the sporazoite is the early stage in humans. From there, the parasite moves on to the liver and does some replicating. After that,

it moves on to our red blood cells. When a parasite gets into the red blood cell, it's able to sneak proteins through the surface of the red blood cell, and those proteins stick onto the surface of the red blood cell. This helps the parasite hide from the immune system, and I'm sure John's going to tell us more about this later. All right. So the parasite is living in the red blood cell and it's eating the hemoglobin in the cell. And as you might remember from our past conversation about synthetic blood, hemoglobin is the protein in your red blood cell that helps your cells carry oxygen to different parts of the body. So the parasite is hiding in the red blood cell and chowin down on the hemoglobin. It's replicating while it's in the red blood cell and every like 24 to 48

hours, the red blood cell will burst open and these newly released stages will go off to search for new red blood cells to infect. So that red blood cell cycle will start again. Over time, a lot of the red blood cells get infected this way. So you're regularly losing your red blood cells, which can result in anemia and your body gets poisoned when these red blood cells burst open and all of the stuff that used to be in the red blood cells is now like in circulation and And that's not good. Plus, when the red blood cells burst, there's suddenly loads of new parasites in the circulation, and the immune system goes nuts.

You get chills, you get fevers, et cetera. And the parasite is bad for a lot of other reasons, some of which I'm sure John is going to tell us about in a few moments here. And all of this, I'll note, is particularly dangerous for children or for adults who have never been exposed to malaria before, like travelers, for example. And does it use the mosquito just as a way to get from one body to another? Or is this something that happens inside the mosquito, like snail amplification? Oh, yeah.

Very important part of the life cycle happens in the snail. So there is an amplification in number, plus there is also sex or recombination occurring in the mosquito. So we can definitely blame the mosquito for part of this. Absolutely. Good. And, you know, you blame the female mosquitoes because they're the only ones to take a blood meal. Hmm. I don't like where this is going.

So I'm broadly anti-mosquito, female, male, I don't care. I'm not sexist about it. You know, it doesn't work without the male, so they're partially involved, but they're not the ones that are fighting you. Yeah, exactly. Blame them all. I'm broadly anti-dipterin. So dipterins are flies and mosquitoes. I'm not a big fan of any of them.

But anyway, so inside the body of us, we get these cycles where they live in our red blood cells. They replicate, and then they burst out of our red blood cells. and then they go back into red blood cells. So it seems like when they're in red blood cells, I can imagine it would be harder for our immune system to find them because they're like hiding in our cells. They have evolved ways to transport things across their membrane, across the vacuole membrane,

to be displayed on the red cell membrane. And one of the things that they display is a molecule called, in the case of plasmonium-fellciporum, which is the most dangerous one, erythracidic membrane protein one, or as I call it, P-FMP one. And P-FMP-1 then is expressed on the surface of this cell. So there is an immune reaction that develops against this P-FMP-1 molecule. And the P-FMP is interesting because it is able to bind to receptors in the blood

vessels, the veins of the host. And it basically takes those out of circuit. right? So they're bound to the inner vessels, right, of your larger veins and everything. And they just sit there so they're not being circulated through the spleen, which would recognize the red cells as being deformed and would take them out of circulation. So that's one way they avoid the physical destruction associated with the spleen. And they'll sit there and they'll do their replication bound to these vessels. And that's also a major cause of the pathology, because when they bind to the small vessels like in the brain or in the placenta, in the kidney.

This is where you get this micro occlusion of the capillaries and you get decreased oxygenation and then you get the metabolic acidosis. And these are the kind of things that cause the big problems with malaria. I'm not 100% sure I understand. Let me see if I can explain it back and if I'm right. So I think what you're saying is that the red blood cells, they end up with the stuff that sticks out of the cell. It connects them to like the veins or arteries so that they don't go to the spleen whose job is to remove infected or disfigured cells and get rid of them. So they

essentially keep themselves from going to the police station by hanging on in one spot. And if that happens like in your brain or in a placenta, it causes clogs that are bad. Right. And it seems to be particular bad. Like that's one of the major causes is the cerebral malaria, which is the big killer. So then what are the possibilities here for a vaccine since this sounds pretty bad and we all hate mosquitoes and nobody wants this stuff in your brain? Yeah, that's a good question. So I think most of the success for the vaccines has been against the sporesalite. If you have an immune response to sporezoid when it gets into the skin, that can stop the infection right there. And there are some promising vaccines, some that have actually been used.

or in use that maybe give you 60% protection or so. I'll take it. Yeah, it's kind of what a flu vaccine does too. Yeah, so there are some promising ones and there may be more in the future because it put a lot of effort into this vaccine development for malaria. And definitely it would be a good thing. You just need to prevent people from dying because as they live there, they're going to build up this natural immunity that occurs over time.

time, and then it won't be an issue anymore. But it would be important for kids and also for travelers, like if you're going into Africa and you've never had malaria, then that would be very useful to have a vaccine or for the military or something like that. So there's definitely a need for vaccine here. We're getting closer, I think. There are, like I said, several have been deployed. So it's promising, I think, more so, I think, than with the worms at this point. Oh, yeah, we never said what kind of an organism malaria is. So the first example we talked about was a nematode. The second one was a trematode. And malaria is a protozoan. Protist.

Protist. Yeah. Why is it so much harder to make vaccines for parasites than for bacteria and viruses? And so my first question is, is that actually true? I feel like the answer is yes. And then is there a big picture reason for why? Well, okay, it's generally it's true, but think about HIV. I haven't had a vaccine against that yet, right? Yeah. So it's not always easy to do. But I think it's because the immune system seems to be much better able to handle small things, right? You can make an antibody response.

It'll bind to the bacterium or to the viral particle, and then you can get your complement system involved to destroy it. But, you know, the pathogens have ways to get around the immune system as well, right? So your bacteria and your viruses could subvert the immune system too. Wait, I didn't understand that first thing you said, and it reminds me of a big puzzle in physics. You know, you said essentially the immune system is better at attacking small things, but big things are all made out of small things. So why can't it just attack all the small things that a big thing is made out of? It's like the puzzle of like every classical object is made of quantum particles. Why can't we understand it?

I'm not suggesting there's quantum mechanical magic happening here, but what keeps the immune system from attacking each individual cell inside one of these bigger objects? In case of the worms, they all have a cuticle that protects the inner cells from damage, right? In the case of like the hookworms, the immune system is able to go after the small part of the worm, which is the gut, right, that is exposed. It also takes a lot of cells to kill, you know, a bigger worm. It's just harder to do, I think.

And like I said, a lot of the mechanism where the worms involve things like, well, we're just going to flush them out, right? We're not going to try to kill them. We're just going to try to flush them out. Whereas we have cells that will actually ingest viruses and opsonized viruses, at least, and bacteria, right? They recognize the antibody and then they bind to it

and then ingest it and destroy it. Right. So it's a lot easier to do that than it is to try. try to kill a big worm that's got this protective armor around it and is living in the gut, for instance. Yeah, so as a biologist, one of the things I think is super interesting about this conversation is not just how do the parasites evade the immune system, but it's also just that they have such complicated life cycles.

There's so many different places where you could choose to try to protect against parasites. So, you know, for mosquitoes, you can pay for bed nets because the mosquitoes are most active at night and maybe you just keep the mosquitoes from biting. And maybe that's even, you know, better than some of the medicines. Just, you know, if you don't encounter them in the first place, that's helpful. But, you know, all of these systems are evolving. So if you, for example, go after the mosquitoes with pesticides, they evolve resistance. And anyway, it's a very complicated problem.

And all of those complications is sort of what got me interested in parasitology in the first place. Anyway, back to Kelly's origin story. But this has been a fascinating, a fascinating chat. Thanks so much, John, for coming on the show to tell us all about the parasites you study. And the parasites you don't study that I put you on the story. spot to talk about anyway. Well, you know, all these years of teaching, I've learned something. That's excellent.

You've learned how to nail a snail joke or snail it, I guess. Yeah. Well, John, let's save those for another episode. We don't want to overwhelm the audience. Thank you. It was fun. Daniel and Kelly's Extraordinary Universe is produced by IHeart Radio. We would love to hear from you.

We really would. We want to know what questions you have about this extraordinary universe. We want to know your thoughts on recent shows, suggestions for future shows. If you contact us, we will get back to you. We really mean it. We answer every message. Email us at questions at danielandkelly.org. Or you can find us on social media.

We have accounts on X, Instagram, Blue Sky, and on all of those platforms, you can find us at D and K Universe. Don't be shy. Write to us. In the heat of battle, your squad relies on you. Don't let them down. Unlock elite gaming tech at Lenovo.com. Dominate every match with next level speed,

seamless streaming, and performance that won't quit. Push your gameplay beyond performance with Intel Core Ultra processors. For the next era of gaming, upgrade to smooth high-quality streaming with Intel Wi-Fi 6E and maximize game performance with enhanced overclocking. Win the tech search. Power up at Lenovo.com. On the podcast Health Stuff, we are tackling all the health questions that keep you up at night.

I'm Dr. Priyankawali, a double board certified physician. And I'm Hurricane de Bolu, a comedian and someone who once Googled, do I have scurvy at 3 a.m. And on our show, we're talking about health in a different way, like our episode where we look at diabetes. In the United States, I mean, 50% of Americans are pre-diabetic. How preventable is type 2? Extremely. Listen to Health Stuff on the IHeart Radio Act. Apple Podcasts, or wherever you get your podcasts.

Hi, Kyle. Could you draw up a quick document with the basic business plan? Just one page as a Google Doc and send me the link. Thanks. Hey, just finished drawing up that quick one-page business plan for you. Here's the link. But there was no link. There was no business plan.

I hadn't programmed Kyle to be able to do that yet. I'm Evan Ratliff here with a story of entrepreneurship in the AI age. Listen as I attempt to build a real startup run by fake people. Check out the second season of my podcast, Shell Game, on the IHeart Radio app or wherever you get your podcasts. And she said, Johnny, the kids didn't come home last night. Along the central Texas plains, teens are dying. Suicides that don't make sense. Strange accidents and brutal murders.

In what seems to be, a plot ripped straight out of Breaking Bad. Drugs, alcohol, trafficking of people. There are people out there that absolutely know what happened. Listen to paper ghosts, the Texas teen murders, on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. This is an IHeart podcast.