Daniel and Kelly’s Extraordinary Universe - Zombie fish

Episode Date: January 8, 2026

Daniel and Kelly talk about a brain-infecting parasite of California Killifish, and discuss how the parasite might be altering the fish's behavior to its own ends.See omnystudio.com/listener for privacy information.

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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.

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breaking the water surface and creating these super conspicuous ripples on the surface. Or they'll turn on their sides as they scratch their bodies against a rock. As they do this, their silvery bellies reflect the sun and create this quick and vibrant flash of light. Why are they doing this? These fish are bite-sized to the sharks and the predatory birds that sometimes roam these estuaries in search of food. Shouldn't they be trying to look a little less conspicuous? Why are they drawing so much attention to themselves?

Well, it's me speaking, so you've probably guessed that the answer is parasites. Today, we're going to talk about U.Hap Lourkes, California. a brain-infecting parasite of California killifish, which are the silvery fish dancing through the waters in California that we were just talking about. Welcome to Daniel and Kelly's extraordinarily infected universe. Hi, I'm Daniel. I'm Daniel. I'm a particle physicist. assist, and I hope I'm parasite-free. Hello, I'm Kelly Weiner-Smith.

I study exactly what we're talking about today. And I'm okay if I'm harboring a parasite or two, depending on what they are. All right, well, that was actually my question for you, Kelly. Oh. If you had to harbor a parasite, what would be your parasite of choice? Oh, all right. Well, so I probably have some Demodex mites on my face. I'm okay with that.

They, you know, they might not count as a parasite, depending on, you know, what they're doing on the given day. Are those the ones that living? your pores and climb out and there was uncertainty about whether or not they had anuses or if they just exploded when they got filled up. That's right, but they do have anuses. Science figured that out recently. Way to go, science. What's better that they're taking a dump on your face or they're exploding on your face? I don't know. I don't feel great about either option. Yeah, I think in the end, you know, the waste ends up on your face either way. So Daniel almost spit his coffee out there.

It's just great. How do you know we're talking about biology? Because if poop on your face in the first five minutes. That's right. This is a Kelly led episode. I don't know that we'll get to cannibalism today, though. So that's too bad. We'll see. Yeah.

I'll do my best to bring us there. Yeah. Okay. All right. I guess I wouldn't be too upset if I had one or two pinworms. I wouldn't mind having a small load of pinworms because they probably wouldn't hurt me that much. Pinworms aren't those the ones that at night crawl out and like make you itch in

uncomfortable places? Yeah. I mean, no parasite is good. right? Like that would defy the definition of parasite. I'm trying to pick something that would be least bad and pinworms are probably it. Although not a lot of adults get penworms. What about you? Oh, man. You're making a lot of gross faces today. I wish we did video. There is no parasite I would be happy with. Yes, absolutely. That was an answer? Yes, that's my answer. It just creeps me out. It just bothers me imagine like something living inside of me, treating me like a cave or like a habitat or something.

Like, no, I would just like, I would get a rusty spoon and dig it out. Okay, hold on. Is this a question of magnitude? Because you have billions of bacteria living in your gut, doing exactly what you just described. Katrina has convinced me that they are part of me. I contain multitudes. I am multitudes. Why can't the Demodex and the pinworms be part of your multitudes? Not invited to the party. No. Okay. No. There's a fuzzy but bright line between the microbial invaders and the non-microbial invaders.

Maybe it's just because I'm married to a microbiologist and not a parasologist. Do you think Zach would be happy having parasites live within him? Absolutely not. But so one of the things that made me interested in microbiome science initially was this idea that there's a connection between, the brain and the gut, and that microbes sometimes release neurotransmitters that can speak to, you know, speak. I'm being super anthropomorphic here, but influence. Influence.

Like, you know, there are nerves that go from your brain to your gut and the neurotransmitters released by those microbes, you know, might be influencing how we feel about certain things. And so I became super interested in this idea that the way that we respond to the world might be influenced by the things that are living inside of us. And my advisor at the University of California Davis, Andy C., who is amazing, I adore him, one day was like, Kelly, have you heard about toxoplasma gondi? It's a parasite that you can get from your cat that changes your behavior.

And in a very early listener questions episode, we talked about like how good the science is, what we know about that, so you can look for that. But that started me on my journey, being like interested in how, parasites impact behavior. And so today we're going to talk about, you know, what I spent a decade. It wasn't supposed to be that long. What I spent a decade working on. And is all the research we're going to talk about today already published? Yes, because my, I think my collaborators would appreciate if the two papers that we haven't quite finished yet were not highlighted on the episode. I don't care, but they are, you know, still hoping to get tenure. So I will, I will not

mention those in press or in prep results. But yeah. I do agree that's super fascinating. And it makes a lot of sense that the things living inside of us don't just live inside of us. They influence us. They change the way our bodies work. And that includes potentially changing our behavior because we are these biological machines and the decisions we make. are not divorced from that, right? They're completely influenced by that. But still, I find it okay to imagine that my microbiome is influencing the decisions I make in the way I perceive the world.

But I do feel hijacked if there's like some critter living inside me that's forcing me to like eat that second donut. Yeah. Well, so I think there's a difference in goal in some cases, you know? So like I would like to think that a lot of your microbiome is in sync with you, you know, the microbiome wants you to thrive so that they can thrive. But for a lot of the systems that I've ended up working in, the host needs to die for the parasite to thrive.

And so when we're looking at manipulation, which is what I sort of specialized in in grad school, which is an instance where the host behavior is changing in a way that's driven by the parasite, in a way that's usually bad for the host, but good for the parasite, you know, that's very dangerous. different than what you're imagining. But folks might remember that we did a zombie ant episode

a little while back. And what I love about these systems is that often parasites are changing behaviors of their hosts in ways that we couldn't replicate in the lab. And by we, I mean neuroscientists, you know? So like ants, they've got these simple little brains relative to humans, you know? But we still couldn't get the ants to do

these like series of behaviors that this fungus, like operating the ant by, remote control can get the ant to do. And so, you know, through the process of natural selection, this fungus has essentially acquired the ability to control ant behavior. And it, and, you know, in a very anthropomorphic sense, it knows neuroscience better than we do. And so I love these systems as a way to, you know, maybe jumpstart our understanding of how brains work by, like, studying what these parasites have essentially learned about how brains work over evolutionary history. And so I get super excited about, you know, using parasites as tools to understand how

brains work. Although, as we'll discover over the course of this episode, neuroscience baffles me. So I mostly focus on the behavior stuff and then collaborate with neuroscientists. All right. So today we're not talking about the things living in Daniel's gut or toxoplasmiae or zombie ants or any of that kind of stuff. What is the system that you spent 10 years of your life exploring. Oh, man. Okay, so in Baja California and Southern California, in estuaries. So estuaries are areas where the ocean is coming in and there's a freshwater system meeting the ocean. So it's where freshwater and salt water are mixing. These tend to be super productive areas where like baby fish are growing and sharks will come in to eat some food and there's a lot of crabs and stuff

like that. They're super productive systems. They are these tiny little fish. They are silvery. They're you know, like maybe the adults are a bit bigger than the length of your maybe middle finger, but they're not as big as like your whole hand. So they're, you know, somewhere in between. They're pretty small. They're pretty drab. The males will sometimes have some yellow coloration during the breeding season. But in general, they're just like these silvery kind of drab fish. And they're called killifish? Killifish. Not Kellyfish, not killifish, killyfish. What does that mean? I don't know

I don't know Why are they called killy fish You only spent 10 years studying it And never thought Why are they have this silly name Well stuff doesn't always mean stuff You know That was really articulate of me

I don't think it's I don't know that it means anything Oh see It's of uncertain origin But it's likely to have come From the Dutch kill For a small stream Nah

If you say so So these sillily named fish Yeah so actually when I met Zach The person who would eventually become my husband He asked me what I studied And I said, killy fish And he said, you study Kelly fish? And I said, no, no, killy fish

And for a while after that he called me Kelly fish Which was kind of cute. But anyway So these are super abundant fish They're social, so they're, you know, you often find them in big schools. And Kevin Lafferty and Kimo Morris in the 90s, they notice that if you walk around in the estuaries and you look into all of these, like, channels, you see schools of these fish swimming by, but they're really obvious. Like, there are other schools of fish that will swim by, and you sort of like don't really notice them. But when the killy fish swim by, they start doing all of these weird behaviors.

It's like they're dancing through the water. They'll, like, break the surface of the water, and you'll see. these obvious ripples and then there'll be all these flashes of silver because they're shooting forward, they're turning on their sides, they're rubbing against things, they're contorting in the shape of S. They're just doing all of these like really conspicuous behaviors that the other fish species didn't seem to be doing. And then you bring a bunch of fish back into the lab and you survey what's happening in the estuaries and you discover that the California killy fish have a bunch of parasites on their brain, which makes you wonder, is that what's going

on. So is that the reason they began studying this fish? Were they the first people to study this fish? Or is this like a well-known model fish in the community? A bunch of people have studied this fish, but not in relation to the fact that it had a brain-infecting parasite. Because it's a superabundant fish in these super productive ecosystems, people have studied other things about them, like how the heck do these fish survive the fact that when the ocean goes out and the river is still coming in, the salinity goes from like, you know, almost completely fresh water. And then when the ocean comes in, it's almost completely salt water. How do they survive that? But a lot of people hadn't been studying the parasite stuff.

Because I don't know if it's widely appreciated, but in biology we have like these model systems where we don't study things in the wild. We have like a few things that we like grow in the lab and study in detail, you know, mice and fruit flies and all sorts of stuff. And I wonder like what makes an animal suitable to be selected. But these are being studied in the wild, right? So it's because of their interesting behaviors and these fascinating. questions, right? Not because they're quick to grow or they eat something easy or anything. Yeah, right. So I hate these guys. So it turns out. So mummy chugs, which is fungillus heterocletus. I study fungillus parvipinnis, but a closely related species on the opposite coast is very easy to

study in the lab. This is a model species. We've got the genome. We've got a bunch of genetic tools. You can grow them up super easy. But fungillus, part of a penis, you bring into the lab, and it is really hard to keep them from dying, which is crazy, because they live in these environments where the salinity's changing. You'd, like, they survive all of these extremes. You'd think you bring them in the lab where life is easy. They would thrive, and they do not. And I don't know why.

And I, like, literally, years of my PhD was figuring out how to keep them happy in the lab. And that's probably why they're not a model organism, because they're little jerks. You think about them at home at night, and they start dying in the lab. All right. So these guys, Lafferty and Morris, noticed these fascinating behaviors, and they studied these fish. And what did they learn about them? Okay. Well, so they brought the fish into the lab and they were like, oh, my gosh, the brains of these fish are, like, carpeted by this parasite on their brain.

Like, a thousand parasites on the brain of an adult is pretty typical. 8,000 can happen sometimes, too. So there are these tiny little, like, cysts. these tiny little balls, they almost could look like their little glass balls. And this is a trematode parasite. So a trematode parasite that you might have heard of is schistosoma mancini. It causes schistosomyasis. This is a problem in places like Africa. This parasite is also a trematode parasite, not necessarily particularly closely related to that one, but this is the only other trematode you're likely to have heard of. And it has a complex life cycle. And let's go through

the life cycle because it helps you understand why this parasite might want to make the fish behave conspicuously. And this is the life cycle of the fish or of the parasite or the harmonious combination. Of the parasite. All right. And I'm going to start calling the parasite Yuha because Euaplercus Californiansis is way too much to say every time. So, you have. So tell us about Uha's lifestyle. Okay, so Uha accidentally gets consumed

by California horn snails that live in the salt marshes. Bad news for the snails. Hmm. The snails get castrated by the parasite. What? I know.

It's crazy. Chemically or like surgically? Uh, I mean, are we losing bits of the body here or are they just becoming deactivated? Well, okay, so all of the gonads inside, I'm not quite sure how you're imagining this,

but the gonads are all... You don't want to know how I'm imagining it. Yeah, no, I, I didn't ask you to explain it. And so the gonads are inside of the snail. All of the gonad tissue ends up being taken up by parasite tissue. So the parasites start replicating, replicating, replicating, replicating, replicating, and they produce a stage that will swim out from the snail to go off in search of fish.

This is nightmare fuel already, Kelly. And these snails can still live for like a decade or more with this parasite. And when the tide comes in in the summer, up to 2,000 of the free swimming stages of this parasite can emerge from the snail to go off and search a fish. It's crazy. And, okay, parasites have social lives. All right. So, look, I'm going to be honest, everybody. This is going to be a little bit of a ranty episode because I love this parasite.

And I've just spent a decade, like, falling in love with its weirdness. FYI, this warning is 15 minutes too late, Kelly. Guys, and Daniel tried to get me on track before the start of this episode. He's like, Kelly, I can tell you're going to get rantey. Let's focus. And here I am being like, sorry, Daniel. All right, rant away. Really quick.

Okay, so once you're inside of a snail and you've taken control of a gonad, there are other trematodes that would like to come in and usurp the gonad that you're living in. And so you have Luricus Californiansis and other trematode species out in the estuary, make a stage called a soldier. And the soldier is essentially just like a giant mouth that patrols the snail. And if another stage comes in, it will go, at this stage in their life, they're essentially just giant bags of fluid. And so it will like try to pop the other bags of fluid so that they can't come in and

take control of the snail gonad. And so anyway, they've got reproductive stages that are like making this free swimming stage of the parasite, reproducing, reproducing, and then they're making a bunch of soldiers that are patrolling the snail to keep. everything safe. It's just absolutely amazing to me that there's this like... Grand battle for the snail gonad. Exactly. Yes. Incredible.

And so these parasites are working together. They're like cooperating with each other against the snail and against competing parasites. Yes, but they're also, they're reproducing asexually, so they're like all clones. So it's like the exact same individual clone, clone, clone, clone, clone, clone, but some of them

look like soldiers. Some of them look like reproductives. But like if you were to sequence them, genetically they're all like the same. All right. So it's like the snail gonad hive mind. That sounds like the title of a book I'd like to read. Sure, yeah, or the book I'd like to write. And so, all right, when the tide comes in in the summers, when the water is nice and warm, thousands of these parasites leave the snail.

And each one of them has a very low probability of finding the fish. And they only live for like 24 hours. They're like little sacks of energy and they're going to run out real fast. But if they do encounter the fish, we think what happens is they, they're burrow through the fish's skin, they find a nerve and they follow that nerve up to the fish's brain. And then they go on top of the brain and they form a cyst on the brain. So they're not in the brain tissue. They're like resting on top of the brain. And why do they want to be on top of the brain? Ah, there's a couple different ideas there. So one of the ideas, and this was like a

very early idea, is that if you're on top of the brain, you're kind of protected from the immune response because if the brain's immune system overreacts, then that could be really bad for the fish. That could kill the fish. The fish could start swimming on its side. Then it could get eaten by another fish. And so by being in an area where the host can't allow the immune system to attack too strongly, you sort of increase your odds of survival. But it could also be because it's a pretty good place if you're going to be trying to manipulate behavior. That's a good location from which to do that. Yeah, that makes sense. And so there are multiple of these parasites crawling up the fish nerve to the brain. Are they all working in tandem like they did in the snail gonad? Or are they

now fighting each other for who gets to like ratatouille drive this fish? That's a great question. So hard to say, we think that they are working together because usually you see signs of competition between parasites. But when we studied this, we saw some evidence that they were cooperating. And so the way that we measured this was we looked at the volume of the parasites as the density of parasites increased. So usually what you see is that as you get more and more parasites crammed into the same size of a space, they start getting smaller. And that's probably because they're competing for food resources. But what we saw was that the more parasites you got crammed onto the brain of a fish, the bigger the parasites seemed to get. Because they're cooperating. Yeah, which suggested to us

maybe they're secreting some compound that suppresses the immune system or they're creating some compound that manipulates behavior. And the more of them that are present, the less each one needs to create in order to accomplish the same goal. So even though they're not identical, they can still cooperate. Maybe. So these were fish that were caught in the wild. This was just an observational study. So this is indirect evidence that maybe they are cooperating. And we didn't see the same thing happening when we looked at trematodes that were. living in their liver. So it looks like, you know, maybe there's some cooperation happening.

We don't know for sure. All right. These ideas have parasited my brain, and they are now ratituting me to suggest that we should take a break so everybody can go off and cleanse their mind from snail gonads. And when we'll come back, we'll discover what these parasites do to these poor little killyfish. 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 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. Hey, everyone, it's Ed Helms. And I'm Cal Penn, and we are the hosts of Earsay, the Audible and IHeart Audio Book Club. This week on the podcast, I am talking to film and TV critic, radio and podcast host, and Harry Potter superfan Rihanna Dillon to discuss Audible's full cast adaptation of Harry Potter and the Sorcerer's Stone.

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the sort of the seminal work on this. What did they find initially about how these parasites affected the behavior of these fish? Yeah, but in order to understand the results of the Lafrey and Morris study, you need to understand where the parasites have to get after they're in the fish. Oh, wait, the fish is not the end of the cycle? There's more. There's more. There's more.

The nightmare continues, people. It does. It does. Okay, so, all right, so you've got like a bunch of parasites on the brains of the fish. But actually, the last host that the parasite needs to get to are predatory birds. And so once a California killy fish gets eaten by a predatory bird, the digestive juices in the predatory bird start breaking down the fish. that breaks down the cysts that the parasites are in. The parasites break out of the cysts.

They find love. They find a mate. They produce eggs. So being eaten by the bird is bad for the fish, but good for the parasite. Exactly. Yes, the parasite cannot complete its life cycle unless the fish gets eaten by a bird. And if the fish gets eaten by a shark, that's bad for the parasites. They have to get eaten in a certain way.

There are wrong ways to get eaten and right ways to get eaten. I got to say these parasites are bad engineers. This whole thing is every time I hear about a parasite life cycle, it's some ridiculously complicated Rube Goldberg machine where everything has to go just right. Yeah, well, in another episode we should talk about the evolution of these life cycles because we think that they came about because like, you know, so say it started at the snail and you got the parasites that leave the snail and maybe they were going off in search of another snail, the idea is that so many of them were getting eaten by fish, it made more sense to capture fish

as a host in your life cycle than to, you know, just keep getting eaten by fish and in this way complexity arose. So, you know, this complexity might be better than what was happening before. It's also the kind of example that makes me just like sort of squish up my eyebrows when somebody says, nature is so obviously designed because I'm like, nobody would design this. This is a mess. This is a mess. It really is. It's wild. All right. So now they're happy that they're in these birds and they've killed these poor killy fish by feeding them to these. birds, then what happens? Okay. And then when the bird poops, they poop the parasite eggs out into the salt marsh where the snails accidentally eat the eggs and the cycle starts again. So that is

the life cycle. Oh my gosh. Wow. All right. So it really is a loop. It really is a loop. Snails eat them. They grow in the gonads. Then they crawl up the fish into the brain, influence the fish, get eaten by birds. And then the birds poop them out and they're eaten by snails. And the cycle continues. Yes. Right. Okay. So Kevin Lafferty and Kimo Morris were out in the estuaries in Southern California, and they were looking at these California killyfish populations, which they knew they had a bunch of parasites on their brains, and they saw these fish just like doing all of these weird conspicuous behaviors. And they knew that this parasite had to get to birds next. So they thought to themselves, are all of those

weird behaviors that the fish are doing, things that they're doing to try to draw the attention of the predatory birds so that the predatory birds will eat the, fish that are behaving conspicuously. So they went to a population that doesn't have the parasite so that they could get naturally uninfected fish. Are there populations that don't have the parasite? Yes. Why is that? So there's populations that have the parasite and populations that don't. And they differ in actually kind of a lot of ways. So the way you get a population that doesn't have the parasite usually is that the population becomes landlocked in some way. So for example, on the campus of the University of California

Santa Barbara, there is a lagoon that has California killy fish in it and because it isn't tidily influenced or maybe for some other reason I don't know a lot about snails but for whatever reason there's not snails in there. And so this environment doesn't have the snails without the snails, you don't get the parasite,

you don't get the life cycle. But you also don't have tides, which means the fish aren't like, you know, going out into the ocean sometimes. They're not coming, like the whole system is different in a bunch of ways. And so these fish differ not only in that they don't have the parasite, they also differ in a lot of like their daily activities,

the predators that they encounter, blah, blah, blah, blah. And immediately this makes me wonder if they're a good control sample, right? Because they're different, not just in the fact that they don't have the parasite, but in all these other ways. And somebody out there might be thinking, that's bad science. But my reaction is like, well, this is where the experimental science comes in, right, in understanding those differences and can you drive? draw conclusions and what can you do to quantify your uncertainties about them? So what kind of

conclusions could they draw from this other sample of slightly different fish? Well, so they were very clear about the limitations in the study. They, you know, they pointed out it's a different population. It differs for a variety of reasons. This should be the start of our studies in this system, not the end of our studies in this system. But I'm going to tell you about the rest of the study that they did. And then I'm going to tell you that like two decades later, I did the follow-up work to address this problem. As is often the case, the nuance is lost and the bigger story sort of dominates the lore. Yeah, I'm going to jump ahead a little bit and tell you that this paper has been cited over 700 times

and continues to clock a bunch of citations. And my paper, that was the boring study that was like super painstaking, is not getting anywhere near that many citations. But anyway, it's still interesting and you're going to have to listen to. to it, everybody. Thank you. So. All right. So they got fish from a population without the parasites. Yeah. They got fish from a population that had the parasites. But they also had a bunch of other parasites because the fish in these systems, they're not just infected by the parasite on their brain. They're infected by, you know, something like seven other trematode parasites as well.

Oh my God. Yeah. They're just like riddled with parasites. Lousy with parasites. All right. So they brought them into the lab. And what they noticed was that, you know, they noticed, was that. the fish that had parasites on their brain were doing about three to four fold more conspicuous behaviors than the fish from the population without the parasites. So they were doing these conspicuous behaviors a lot more often. And then they set up enclosures in a lagoon where the fish would be out in these enclosures and predatory birds could wade in and eat whatever fish they wanted and then come back out again. And then after about 50% of the fish had been eaten or something. They went out and they looked to see which fish had been eaten and which

fish were left behind. So these enclosures paint me a picture of them. I was imagining first that they're like sectioned off various parts of the lagoon. But are these things open from the top? Why did the birds have to wade in? So these were along the shoreline and it was a net that sort of went out from the shoreline, traveled along the shoreline and then came back to the shoreline. So it had like three netted sides and they did that twice. And one side they covered so that they could just measure how often the fish were just sort of like escaping from the net. And then the fish could either just sort of drop from the top in, if they wanted, or they could walk along the beach and wade in along that way.

So the death from above swooping down to gobble your lunch is still an option. Yep, still an option. Okay. And so what they found was that the fish that had more parasites were more likely to be eaten. And the way they inferred that was when they did the dissections afterwards. they would have expected to see, you know, something like 10 fish with 1,000 parasites on their brain, but they didn't see any fish with 1,000 parasites on their brain. Most of the fish that were left had very few parasites on their brain.

And so they end up concluding that the more parasites you have on the brain, the more conspicuous behaviors you do, and the more likely you are to be eaten by predatory birds. And I feel like that's a story I've heard before, that parasites manipulate host behavior, makes it more likely for them to be eaten. Was this like the first time that had been observed in detail? Was this a new story just in this animal or more broadly? This was not the first time, like, you know, since the 70s, I think people had been talking about this. But this was one of the first times it had been well studied in a vertebrate

and one of the first times there was a really elegant experiment that showed that not only was the parasite associated with the behavior that seemed intuitively like it really should be increasing risk for the host but also then they showed that like, yeah, the predatory birds are actually eating the infected fish. The authors were like really good about explaining all of the caveats, like all of the limitations of the study. And like this paper got me, you know, I spent the next decade following up on this paper. I found this study super exciting.

And I moved to Santa Barbara for two years to like study underneath the lab that did this work. Wow. Yeah. This is like a now classic example of manipulation. And in their first paper, do they come up with a causal mechanism to explain this? Or is it more just correlational? More parasites means more behavior. And therefore we're inferring that the parasites are.

causing the behavior. It's correlational. Yeah. And so there's another parasite that they quantify that is living in the liver. And they look for correlations between this liver trematode and conspicuous behaviors as well. And they find some correlations, but the correlations are stronger with the brain parasite. And so they hypothesized that from its location in the brain, this parasite is probably hijacking behavior. And so there's probably something about being in the brain that helps the parasite do that. But, you know, since they hadn't actually done experiments on mechanisms, they, you know, leave that to future work. And their postdoc Jenny Shaw actually would go ahead and follow up on that, which we will talk about a little bit later.

In the grand tradition of leaving the hard questions to future work, as we all do in our papers. Ooh, that's important weakness in my study. I'm going to say that's future work. Yeah, well, you know, you can't do everything all at once. No, you certainly can't. I do that all the But I guess that leaves us open to the possibility that the parasites are not causing this behavior, but there's some third unknown thing, which is causing both the parasites and the behavior, for example, which would induce a correlation as well. Yes, right. Okay. So first of all, there's the problem of them coming from different populations, and the population's differing in a lot of ways. Second, there's the problem that not all of the parasites in the wild fish were quantified.

It could be some other parasite or some combination of parasites that were causing the problem. problem. And so this is not an ideal study design as noted by the authors. Ideally, what you'd want to do is, you know, get fish from a population that has like an evolutionary history with the parasite, bring them into the lab, like maybe hatch them in the lab, grow them up in the lab, infect some of them with the parasite. And a lot of folks, when they infect fish with parasites, they'll infect them like once with like 5,000 parasites, where, is actually when they're in nature, they start acquiring parasites, like almost as soon as they hatch and they acquire like two or three every day. And you can imagine a brain would respond very differently to like getting like slammed with 5,000 parasites in one day, you know, relative to picking up a few every day. So yeah, ideally you'd hatch fish in a lab, infect them a little bit every day, leave some fish as controls where they don't get infected, and then observe how their behaviors change over time. And that gives us a more direct answer to

this question because we're inducing the effect so we're not open to the possibility that something else is causing both the parasite and the behavior. That's right. All right. So let's take a break. And when we come back, we'll hear all about Kelly's painstaking slog through through the questions of the killy fish. 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 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. Hey everyone, it's Ed Helms. And I'm Cal Penn, and we are the hosts of Earsay, the Audible and I Heart Audio Book Club. This week on the podcast, I am talking to film and TV critic, radio and podcast host, and Harry Potter super fan, Rihanna Dillon, to discuss Audible's full cast adaptation of Harry Potter and the Sorcerer's Stone. What moments in this audiobook capture the feeling of the Mesauch? magical world best for you, or just stood out the most? I always loved reading about the Quidditch matches, and I think the audio really gets it

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with the Brad versus Everyone podcast, hosted by me, Brad Palumbo. Every day of the week, I bring you on a wild ride through the most delulu takes on the internet, criticizing the extremes of both sides from an independent perspective. Join in on the insanity and listen to the Brad versus. Everyone Podcasts on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. All right, we're back, and we've sort of set up the question now. We understand what the killy fish is and the life cycle of this parasite, what people had studied, the sort of click-bitty result that's gotten a lot of attention.

And now Kelly, as is her want, is going to pour. cold water all over all that understanding. Since you said clickbait, you know, Kevin Lafferty, one of the authors is a good friend of mine. So, you know, I don't feel like he clickbaited it. He was very clear about the limitations, but it took off and had a life of its own. Right. No, it sounds like they were responsible and clear about the limitations and didn't overstate their conclusions. Yes, perfect. Thank you. Okay. But as is often the case, if you have nuance in your paper, that's sometimes overlooked in the coverage. Yes. Even if it's not the author's fault. Yeah. Yes. Right. That absolutely happened.

Okay. So working with Ryan Heckenger and Oathen Overly, we decided that we were going to try to do a bit of a better design to try to nail down exactly what this brain infecting parasite was doing. And so what we did was we went out to an estuary. And during the full moon, when the killy fish breed over the summer, we went out there and we said, excuse me, Mr. and Mrs. Killifish, may we please have some gametes? Wait, why did the killyfish only breed during the full moon? I mean, I get it's romantic. But, like, this system was complicated enough without you having to introduce, like, astronomical coincidences. I don't know. It would have been great if we could have got out there more often. But it's synced up to the moon. All right. So there's some werewolf connection here we don't know about. That's right. That's right. But I was, like, six months pregnant at the time. And so we were, like, you know, very gently getting the fish to release their gametes into a bucket for us so that we could fertilize eggs. And I was trying really hard to not puke into the gamete bucket as like so many science moms before me have had to try to avoid doing. So you're pleasuring these fish by hand to get them to produce these gametes.

That's not how I'd put it. But all right. This is the glamorous work of science. This is a glamorous work of ecology. But so we were able to actually hatch a bunch of fish in the lab. And then we went out and we collected snails. And we figured out which snails were infected by you. huh? And you can get them to repeatedly give you the same, you know, genotypes of the parasites over and over and over again. But we collected a bunch of the snails so we could get a bunch of different genotypes of the parasites. We kept those snails in the lab. Unfortunately, we had to get snails from like one estuary down. We had hoped to get everything from the same estuary. That's a long story. But anyway, so we were able to get our parasites, able to get our fish. They were hatched. And then twice a week, every week, we did.

controlled infections in their tanks. Wow. And so we would like extract some parasites. We would put it in a vial. We would slowly lower the vial into the tank and we'd leave it in there overnight. So they slowly built up infections. And at one point we went out into the wild and we collected wild fish and we were able to confirm that we had about the same number of parasites in our fish as you found in the wild

fish at the same time. So we had sort of mimicked what was happening in the wild, which was a ton of work. Good for us. And again, the goal of mimicking what's happening in the wild is to have a little bit more control over it. And you have some fish with the parasites and some fish without the parasites to get a better understanding of like the actual mechanism here. Well, yeah. And because if we eventually want them to have like 2,000 parasites on their brain like they would have in the wild, we didn't want to slam them with 2,000 parasites all at once because that could kill them. And so we were trying to sort of slowly build it up so that what was happening in the wild was also happening in the lab. And so we did that.

We did have a slightly higher density because our fish didn't grow quite as fast as the wild fish. We don't know why. That's annoying. Why won't biology just obey my commands? Right? I know. I know. And so anyway, then we measured the behavior of the fish at three, seven, and eight months of age.

and we found out that, like, there were a bunch of different conspicuous behaviors that we were measuring. The effect that was the most pronounced was that the fish that had parasites on their brain darted about twice as much as the control fish. So that was the main effect. I thought the main effect was going to be scratching.

Because to me, the most obvious conspicuous behavior when you're standing on the shoreline is when they flip on their sides and the sun reflects off of their belly, that really draws my attention. But the behavior that seems to be impacted is what we call darting. So this is when a fish sort of like out of nowhere, it will shoot forward really quick, like something really scared it.

And then it's like it forgot that it was afraid and it just goes back to its normal behavior. And it's really weird. So darting is a behavior that fish often use when a predator is around. But when they dart, they're darting like behind a piece of vegetation or they're like darting into like a turbid zone. Like, you know, there's like a plume of sand and they're darting into the middle so that they can hide. It's very strange to see a fish dart forward and then immediately resume normal movement. And so the idea here is that if they dart forward, they draw the attention of the predatory bird. And then if they're not hiding afterwards, they're very easy to like hone in on.

Maybe. We haven't actually like done videos to show that that's exactly what's happening. And so there were some categories of behavior you were looking for, scratching, darting, et cetera. How did you come up with these categories? Is there a possibility that there's some kind of categories? category of behavior that the fish are doing that different between the two populations that you didn't think to observe? Yeah. So first of all, in Lafferty and Morris's paper, they watched the fish for a long time. They came up with, like, any category of weird behavior that they could think of. That's called like an ethogram where you watch for a long time and you, you know, take notes on any behaviors that you think are relevant. But it feels a little subjective, right?

Yes. Behavior. Exactly. Yes. It is sort of subjective. I'll actually be very interested in what AI does to this field. Because if you can have computers analyzing everything about behavior at some, you know, is a computer able to analyze behavior in a way that's different and maybe less subjective than how human eyes do? And there's some programs now that analyze behaviors that weren't available when I was doing it. No, it's still going to be biased just in a way you don't understand as well. Yeah. No, you might be right. So anyway, so I looked at, their ethogram, what behaviors they thought were important. And then I watched also and looked to see if I was seeing something different. And I've also watched fish from a couple of different estuaries. So this is not the only study I've done with these fish.

And so I've spent a lot of time staring at fish. The glamorous work of science. That's right. That's right. Maybe I haven't captured all the important behaviors, but I feel like I have. All right. And so you saw this darting effect. So compare or contrast that with the original.

in the earlier paper. Less strong. So before, they didn't see that darting was the behavior most strongly associated with this brain-infecting parasites. And they saw that behaviors were like four times more pronounced in their infected fish. So we're seeing a different behavior most strongly impacted by the parasite and a lower magnitude. And we don't know if that's because it was a different population that we were looking at.

It could be because the wild fish in the other study had a whole community of parasites and a lot of those community of parasites also go to predatory birds. Maybe each of those parasites are like manipulating a different part of the behavior or they're all sharing the cost of manipulating. There's a lot

of different reasons, but at the end of the day, what I found was that the effect is a little bit more complicated and a little bit smaller than what had been found before. So no one cites my work. Exactly. But this was the exact goal of this study is to tease this apart and try to understand more specifically what is the effect of this parasite.

Yes. And so the answer is that on its own, this parasite is not doing everything that the original guy saw. That's right. That's right. But so let's dive in a little bit to what we know about how the parasite might be doing this. Yeah. The first thing you usually wonder when you discover that a infected organism is getting eaten by another organism more often is like, well, is the parasite? Parasite just debilitating it in some way.

Like, is it just making it slower, easier to catch or something? And that doesn't seem to be the case. So first of all, you know, just like observations, if you watch these fish, they've got 8,000 parasites on their brain, man. It's like a carpet. It's so crazy to see all these parasites. But they're not, like, swimming on their sides. They're not having trouble catching their food.

They school normally. Like, they look normal. And my friend Lauren Nadler, who worked on this system as a postage, stock. She stuck them in these little metabolic chambers, and she measured their acute metabolism. So she, like, you know, got them to swim real fast. I don't really know how you do this kind of stuff and fish. This is like what they do to Olympic athletes, right? Treadmills. And, yeah, I don't know how you treadmill a fish. I'm imagining a fish on a treadmill right now. Yeah, yeah. She did a bunch of different things to, like, get their, like, maximum

metabolic rate and their resting metabolic rate and blah, blah. Okay. She fed them red bull and stuff like this. I'm sure she did, yeah. I'm sure she got a protocol and a permit. and all that for that. And what she found, like, using our fish from our lab experiments, where we had, like, hatched them in the lab, infected some, didn't infect others, that the infected fish and the uninfected fish had, like, no difference in metabolism. So it doesn't look like having a bunch of fish on your brain is that energetically expensive. Like, they're pretty efficient at resource extraction when they're on the brain.

They're, like, you know, semi-dormant after they finish growing. So it doesn't seem like it's that. And their body condition is good. If you compare them to uninfected fish, they have, like, their gonads are about the same size because ecologists do gross stuff, like, weigh gonads. And, like, they seem just as good at having babies. They have the same amount of fat reserves. Like, so it doesn't seem like they're making them debilitated in any way that we can measure. Well, what about coming out from the other direction and asking, like, how is the parasite benefiting?

Because that might be the other side of the equation. If the parasite is, like, extracting something specific from the brain or from the fish, then maybe you could understand the impact of losing that on the fish. So, okay, so the idea would be that, like, the parasite is extracting, like, a neurotransmitter or something? I don't know. What is the benefit to the parasite? What do you mean? What is the benefit of the parasite to... Being on the brain.

Like, what is it doing there that's helping it? Yeah, so usually what the parasites do at this stage is they grow a little, and then they can. kind of like they reach, you know, asymptotic growth. They grow and then they stop growing. And I think they mostly stop growing because while they're growing, they're forming a cyst around them. And this cyst protects them from the immune system. And when that cyst finishes growing, they've sort of run out of room to grow. And so that's as big as they're going to get. But presumably they can extract some resources across the cyst wall and maybe even secrete some stuff across the cyst wall. Presumably somebody has looked to see what they all.

are sucking up on the brain. But I don't think we've looked to see if they're like specifically, like I think they're sucking up like nutrients and stuff, but I don't know if they're specifically sucking up like serotonin to try to mess with brain stuff. Because for example, like a tapeworm lives in my gut, eat some of my food, I get less food. So it's easy to understand from the tapeworm's benefit what the impact is on me. I don't know.

I'm not a parasitologist, but it seems like maybe an avenue. So what do we know about how these parasites are influencing these fish? Spoiler alert, we don't know at the end of the day. But we think that what might be happening is that the parasite is making it so that the fish doesn't respond with as much of a stress response as it should. So essentially the parasite is like dampening the stress response. And so here's what we think is happening. So there's a part of the brain in fish that is usually associated.

with the stress response. And when you look at that part of the brain, we see that the typical response to the chemicals in the brain in fish when they're stressed is much lower when the fish has a bunch of parasites in that part of the brain. And so that's got us wondering

if a predatory bird is in the area, for example, is maybe what's happening is that like, uninfected fish would be like, ah, predatory bird, I got to run away. but in a fish that has these parasites are the parasites making the fish be like, eh, no big deal, probably not going to choose me. In fact, actually, I'm going to shoot forward really quick. Oh, look at how cool I am.

And I should say that we have measured these differences in infected and uninfected fish brains, but we have not tied these differences to behavior or tied these differences to like, you know, fish getting eaten by birds more often. So this is just like preliminary observations and how these brains look different. So all that makes sense, except for the part where being less stressed makes them dart more because I thought darting was a response to like, oh, no, I think I'm going to get eaten. Yeah, but so it is a response to, oh, no, I think I'm going to get eaten. But usually it ends in, and so I'm going to hide.

Right. And so, but here it's like, oh, no, I'm going to get, oh, wait, oh, wait, what was I running from? And there's another part of the brain that's associated with locomotion, and you tend to find a high density. of the parasites there. And so I mentioned that, you know, the parasites are sort of like a carpet on the brain. But they're like a carpet, but they also tend to like be a little bit more dense

in two parts of the brain. And one of those parts deals with stress and one of those parts deals with locomotion. And so, you know, again, these are just observations. We haven't linked it to behavior yet. But it could be that like, you know, there's some stimulation of the locomotion part of the brain to get those fish moving,

to get the darts going. And then the part where usually they're like, and now go run and hide is being turned off. So they're moving around, but they're not hiding. Maybe. So these fish are just like more chill. They sound like, of anything, they might be happier. They could be. And so actually, part of how we get funding for this system is we say, you know, look, maybe what the parasite is doing is it's secreting some chemical that is suppressing stress.

maybe there's like a treatment for anxiety or something that we could find by something that's being secreted by this parasite. There could be a novel compound that we could discover with this parasite. Wasn't Ozempic discovered when they were studying like lizard venom or something crazy? You never know. I think he'll a monster venom or something like that. Yeah, you never know. Where the next treatment's going to be found. Your science could change Hollywood.

That's right. That's right. One of the cool things about studying fish is that if you stick them, in a beaker of water, the steroid hormones, which are things like cortisol, which is associated with your stress response, and things like testosterone and estrogen and stuff like that, they leak across the fish's gills and into the water, and they'll reach an equilibrium. So the concentration in the water is equal to the concentration in the blood. And you have to do some validating work, but you can repeatedly make measurements of hormones in fish without needing

to draw any blood by just putting them in beakers of water. And so I collected cortisol levels from fish repeatedly, and these fish had different levels of parasites on their brain. And we found that the density of parasites on their brain does impact how much cortisol they release. But it wasn't in a nice, predictable way. And this is when I decided I didn't want to work on hormones and neurotransmitters anymore because I had a prediction and I talked to the experts and I was like, it was supposed to be a straight line up, but instead it made a you. And they were like, yeah, this stuff never works out the way we think it's going to. And I was like, I'm done.

I'm done. I'm not doing this anymore. I've had enough snail gonads. I'm moving on. Right. I don't even like pipettes. And so that was it for me. That is one of my fears about biology is that you're doomed to working in complex systems.

You can never really use reductionism and simplify things because everything you're doing is most interesting. in a complex system, which means it might be forever before you actually untangle stuff. It's incredible to me that we've made any progress in biology at all. I have to admit, a lot of my friends are working on these kinds of problems, and I am so glad they are because this is how we, like, get to the bottom of things like, you know, why are parasites becoming resistant to our drugs and so, like, super important questions. I found it really frustrating, and I was like, I can't. I don't think I can keep doing this.

I think something that's not widely enough appreciated about how people end up in the science field they end up in is that you have to be excited about the big questions of the field, but also you have to find the day-to-day work fun. Yeah. And so many fields are fascinating, the questions they ask, but then the day-to-day work is very different. You know, it's like working in a lab pipetting or, you know, making a laser operate well or whatever. And you have to be interested in both sides of it if you're going to spend your life doing it. because it's not every day that you're answering the big questions. Mostly it's the day-to-day work. And so you've got to find that niche where the craft is also fun.

I can't tell you how many days I wanted to hurl that pipette across the lab. I do not enjoy pipetting. I have friends who get in the flow, and I do not. I have no flow. Well, the wonderful thing about humanity is that we're all into different stuff. And so some of us trapes through rainforests and get their socks wet while studying spiders and other people look up at the sky and wonder about all of that. And some people like to pipette.

So because of that, we have a glorious diversity in all of the science stories that we extract from the universe. We do. And if I may. So I hope that work continues in this system because this could be the routes to another treatment for anxiety. Maybe this will be helping me a decade down the road. We can hope. But also, there are other killy fish species in a bunch of estuaries in North America. and there are other U.Aplurcus species

in a bunch of estuaries in North America. So it might be that similar interactions like this are playing out in a bunch of our super productive ecosystems. So this parasite might be impacting, you know, the flow of energy from aquatic systems to terrestrial systems all throughout North America. And we don't understand this very well. And a lot of people are interested in migratory birds.

I think fish are cooler than birds. I'm going to die on that hill. But, you know, bird people, you guys are cool too. And so this kind of stuff matters. And that's some of the excitement of science that you never know around which corner or under which snail go nad is going to be some amazing discovery that really changes the world. And it takes somebody like pushing on a question that seems maybe minor and in a corner, but that like reveals a thread that you can use to unravel our understanding of something much broader. And when you're doing science, you never know. Like, is today the day, I'm going to learn something mind blowing because there have been days like that in the history of science.

We just all hope that one of them is going to happen to us. That's right. Well, thanks for listening to me, Ramble, everybody. I love this parasite. And I thought that was interesting, even without any parasites controlling my brain and telling me what to find interesting. Yay!

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. Hey everyone, it's Ed Helms.

And I'm Cal Penn, and we are the hosts of Earsay, the Audible and I Heart Audiobook Club. This week on the podcast, I am talking to film and TV critic, radio and podcast host, and Harry Potter superfan Rihanna Dillon to discuss Audibles' full cast adaptation of Harry Potter and The Sorcerer's Stone. What moments in this audiobook capture the feeling of the magical world best? for you or just stood out the most. I always loved reading about the Quidditch matches

and I think the audio really gets it because it just plunges you right into the stands. You have the crowd sounds like all around you. It is surround sound especially if you're listening

in headphones. Listen to Earsay, the Audible and IHeart Audio Book Club on the IHeart Radio app or wherever you get your podcasts. When you feel uncomfortable, what do you put on? Biggie.

You put on Biggie when you feel uncomfortable? Because I want to get confident. This is DJ Hester Prynne's Music is Therapy, a new podcast from me, a DJ and licensed therapist, 12 months, 12 areas of your life. Money, love, career, confidence. This isn't just a podcast. It's unconventional therapy for your entire year. Listen to DJ Hester Pryn's Music is Therapy on the IHeartRadio app, Apple Podcast. 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, iHeart radio app or wherever you get your podcasts. The social media trend is slanding some gen Z years in jail. The progressive media darling whose public meltdown got her fired and the massive TikTok boycott against Target

that actually makes no sense. You won't hear about these online stories in the mainstream media, but you can keep up with them and all the other entertaining and outrageous things happening online in media and in politics with the Brad versus Everyone podcast. Listen to the Brad versus Everyone podcast

on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. This is an IHeart podcast, guaranteed human.