The fungus known as Ohio cortceps may be the most famous fungus in pop culture right now.

I know it's a lobar, but still it's pretty cool.

The Girl with All the Gifts, The Last of Us and a host of other books, movies, and video games feature this behavior manipulating fungal pathogen.

But what does it really do?

How do the zombie ants behave?

And what do we know about how the fungus hijacks ant behavior?

And Yes, at the end of the episode, I'll speculate on whether Ofio coort aceps could jump from ants to humans hijacking or behavior along the way.

Welcome to Daniel and Kelly's Manipulated Universe.

Hi.

I'm Daniel.

I'm a particle physicist, and I like to think of myself as a fun guy.

You know, Daniel, you have made that joke before.

It's too good?

It is, It is good, It's good.

I'm Kelly Wider Smith, and I'm a fun gal.

And today we're talking about how funguses make us friends, or make us more fun no, or make us whact weird and climbed to the tops of.

Things or something else entirely Yes, how ants get manipulated by a fungal pathogen, but probably well, wait till the end, we'll see what we think about people.

I do like the idea that some of our weird behavior can be attributed to some part of us that's not really part of us.

You know, that you can say, oh, that's just the fungus in my brain.

Yeah.

Absolutely.

So.

When I started my PhD, I was studying why organisms behave the way they do, so I was into animal behavior and I came across the Toxoplasma Gandhi literature, where that parasite that lives in our brains is a sociated with weird behaviors.

And I got absolutely hooked on this idea that not all of our behaviors are attributable to our decisions, that maybe it's like a group effort the person who we end up being, and that you know, the microbes in our gut influence our behavior and the parasites in our brain influence our behavior.

And I find this topic totally fascinating.

But in some sense that's frame because it tells you, oh, it don't make all my decisions.

In another sense that's terrifying because it's like, oh my gosh, I don't make all my decisions, and Katrina would probably be like, no, that is who you are.

Your microbes are part of you.

Yeah, No, I tind of agree with that take.

But one thing that I think is fun is that one of the big names in the field that studies how Toxoplasma gandhia impacts human behavior, his name is Yaroslav Flagger.

Apologies for my you know, forever bad pronunciations.

He got into this because he was like, you know, I act kind of weird, sort of like not like other people.

I wonder if I have a brain infecting parasite.

And he gave himself a test and he did, and this set him off on the path of like wondering about how toxoplasmosis is associated with human behavior.

It's an interesting question.

Is it possible to have a fungus in your brain that makes you eat cookies too late at night?

Can I blame that on somebody?

Daniel?

That is you?

No, that's you, Daniel, that's you.

And just for clarification, Toxoplasma gandhia is not a fungus, but there are a variety of different parasites that can live in human brains.

Unfortunately, so if I do have a parasite, it's probably, like Daniel, stop eating cookies.

Those are bad for you and bad for us.

Yeah.

Maybe, Wow, I'm overruling them.

I don't know that cookie consumption as an implication of brain parasites has been studied thoroughly, So I don't want to go on the record.

It's so easy to get to the edge of knowledge in biology.

Wow.

Yeah, we're not asking the right questions.

Why does mainstream biology want to shut this question down?

Kelly hmm.

Yeah, I don't know, Daniel, not a great question, But you know, what is a great question?

Give us a transition?

Yeah, what is a great question is the question we asked our listeners.

What was that?

That was?

What is summit disease?

And if you would like to answer questions for us, send us at an email at questions at Danielinkelly dot org and we'll add you to our list.

So let's hear what our listeners had to say in response to what is summit disease?

Summit disease is an affliction that occurs when you can't stop hiking to the top of mountains, and it causes you to neglect the rest of your life.

I think it's a brain disorder that makes you way at dead bodies on the way up Nepalese mountains.

The sickness individuals get when they are at a high altitude and climbing mountains, for example.

I think you're referring to high altitude sickness.

Mountain climbers, when they go up above a certain elevation, can get lack of oxygen, pulmonary edema, cerebral edema, et cetera.

No bueno, this is a disease a similar to OCD.

You have to walk around adding things together.

I could be mistaken, but I believe it is when an avid climber gets the impulsive need to tell the people around them all of the mountains that they have summitted.

It seems like summer disease could be when I go on top of a mountain and my fingers swell up and I get tired.

Easier except for way way worse.

Summit disease is when you, after a really long climb, get to the summit, and then the mountain gods invade your brain make you do bad stuff.

I don't know.

When you reach the summit of a mountain and you can't stop throwing up because you're so sick of looking at mountains.

I think that's when you're hiking and you've each an altitude or an elevation where the air gets dinner and you start to get headaches and funauseous and stuff like that.

So I also would have guessed something that happens to you at the top of Mount Everest.

Yeah, that is a totally reasonable answer.

We have a very smart audience, but actually this is something that happens to insects and not to humans.

And I'll also note that I laughed out loud at the uh you have to walk around adding things together.

It took me a second to put that together and be like, oh, some it some it adding, and I laughed out loud.

So anyway, thank you for that moment of revelation there.

Well, I love this opportunity to dig into the real science that's sort of underlying some Hollywood myths.

You know, there are these fun stories you hear sometimes in science fiction, but often these are inspired by actual and really fascinating on their own stories of what's going on out there in nature.

So tell us, Kelly, what is the story that inspires all these Hollywood tropes?

Well, So let's start with what is summit disease.

And Summit disease is a thing that happens to a lot of different insects that are infected by fungus or by viruses.

And the deal is that either the fungus or the virus gets an insect to climb high, and then it gets the insect to stay there instead of like coming down for the night.

And then they like cling in some way and they stay up high and from that location they then die and they rain infectious particles down on their other insects below.

They like explode.

Uh you know, explode might be over selling it a little, but like, so, for example, there's a virus that infects caterpillars, and caterpillars go up during the day to like eat leaves, and then at night they usually come down and they like hide.

But this when they're infected by this virus, they climb up and they stay there and then they die and they sort of liquefy and they rain virus particles down on the caterpillars that are below.

They drip guey infected caterpillar down they do.

Yeah, what a weather forecast that's oh yeah, cloudy with the chance of virus soup caterpillar bits.

That's right, gross, But this also happens.

There are like quote unquote zombie flies that are infected by a fungus and they'll climb up and they'll even like they'll climb up and then they'll spread their wings out to the side so that when they die, the fungus can come out of their back and their wings don't get in the way.

And that one does it sort of like shoots like cannonballs out of their back down at the like flies below.

And so, oh my gosh, this is a pretty common strategy you see in viruses and fungus that infect insects that want to go on to infect more insects.

It's fascinating because you say it does this so that this other thing happens, which implies that there's some sort of high level decision making.

But I know it's all like low level mechanistic blind evolution.

So I'm curious to hear how all that comes together and how the whole process comes together.

You know, it's one of these examples of like a complicated thing where you need lots of pieces all together to accrue the benefit, which always makes me wonder how it came together in the intermediate stages.

Yeah, and this is why the zombie ant system is one of my favorite systems to study.

So this phenomenon where some parasite or pathogen hijacks the behavior of its host so that the host is doing something that benefits the parasite, we call this manipulation, and it's really tempting, and we've talked about this in other episodes.

It's really tempting when you see a host behaving weirdly to be like, oh, that's a manipulation that must benefit the parasite in some way.

But while it's easy to come up with a story, it's harder to test that.

And every once in a while we'll have a story where it sounds like the pathogen was benefiting, but when you look into it, it's not so.

Mosquitos when they're infected by malaria, right after they get infected by malaria, they bite less, and there's a period where after the mosquito takes a blood meal that has malaria, that malaria is sort of maturing and can't transmit yet.

So if the mosquito took a blood meal and got slept by a hand, then the malaria would die, and so that wouldn't be good.

You know, in a very anthropomorphic way, the malaria quote unquote doesn't want the mosquito to get killed or to take blood meals at that point.

While it's still developing and preparing.

That's right.

But once it's ready, once it's in the mosquito salivary glands and could transmit to a human, those mosquitos start biting even more.

So this was thought of as manipulation.

The parasite is protecting the mosquito and itself until it can transmit, and then once it transmits, it gets the mosquito to bite a lot more.

And that really sounds like it would be good for the mosquito.

It's a good story, it's a great story.

But it turns out that if you activate the mosquito's immune response by for example, killing bacteria and then putting those dead bacteria into the mosquito, it will do the same thing.

Even though it doesn't benefit that bacteria.

That's right.

Where Yeah, the bacteria are dead, they're just making the mosquito's immune system activate, and this is what the mosquito does.

So it could be like when the mosquito's immune system is activated, it just kind of wants to hunker down.

It's not as fast, it's feeling kind of crummy.

It's just taking a nap before it's ready to go again.

And so that's probably not manipulation.

It doesn't look like the malaria is doing that.

That's something that's driven by the mosquito.

Could still be in response to the malaria.

Right when it gets infected, it does this, and the malaria can benefit from it.

You're just saying it's not something that the malaria has specifically engineered to benefit itself.

It's something the mosquito is already doing or would otherwise have done.

Fascinating exactly.

Yeah, So trying to figure out who's driving the change in the behavior and how it actually benefits is much harder than coming up with the initial story.

Yeah, and so what I love about the zombie ants is that this system has been studied in quite a bit of detail, and so we're actually starting to nail down the various pieces of what's happening here.

Well, that reminds me of our conversation with Capo hen and when we were talking about science and storytelling and how much of science is storytelling is saying this happens because of that, because of this other thing, and sometimes the statistics or the mechanics of it don't always support that.

It's just we are trying to extract stories because stories make sense to us.

Yeah, and I think sometimes we get a little carried away with our stories and we don't necessarily have facts to support every piece of the story.

And so this system is nice because almost every piece of the story has been dug into to some degree.

All right, then carry us away to a story, Kelly tell us about manipulation of ants.

Okay, you are a little ant walking around on the forest floor.

Unbeknownst to you, you have stepped on a fungal spore.

The fungus gets in between the cuticles and invades the body.

Wait, I'm a little ant and I have cuticles still exoskeleton.

I think they call that cuticle.

I don't study ants.

Man.

What's the name of my aunt?

Am I Dantiel?

Yes, yes, you're Danchel.

Walking around the forest with my little cuticles.

Okay, so poor Danchel has picked up a fungus.

Danchel doesn't realize that he's infected.

Actually, if you're a forger, you're probably a female.

So this anyway, this is not working great.

But anyway, so the little ants, the little ant has gotten infected, doesn't realize it.

It goes back to its nest.

The nest mates don't seem to realize that it's infected either.

But a couple weeks after it initially gets infected, it starts walking out of the nest.

And this nest is up in a tree, and it starts rumbling down.

We call it a drunk walk.

So it sort of starts stumbling down the tree and then it walks along the forest floor and it climbs up a stalk and this is in the tropics.

It climbs up a stalk or a stem of something to about twenty plus or minus two centimeters.

This is happening at solar noon and on the north northwest side of the plant.

It goes underneath a leaf, bites down with its mandibles.

These are like the pinsy mouth parts it has, and then it will never move again and it dies.

Wow.

So it has to go all the way down the tree just to find the stalk to climb up.

Yes, yep, just to find the stock to climb up.

Fascinating.

And then the ant dies and a stalk comes out of the side of its neck and it forms a ball at the sort of like top ish part of the stalk, and then fungal spores rained down on the forest floor and the cycle starts again.

The stalk is not from the plant, it's some like weird fungal thing.

Yeah, it's the fungus makes it so the fungus, now that the ant is dead, it starts using all of the ant's internal body parts and converting it into fungus and makes this stalk that rains fungal spores down, and the cycle starts again.

This sounds like a science fiction horror movie.

You're telling me this is happening on our planet all the time.

Oh my it is.

And okay, so what blows my mind is that that is so specific.

Like one of one of Zach's gripes about me as a human being is that I am really bad at estimating distances, and like He'll be like, well, what's you know?

Do it about two feet from here, and I'll be like, I have no idea what you mean, Like, I just I can't do that.

Whereas this fungus by remote control is getting the ant to about twenty five centimeters plus or minus like two and a half centimeters.

I think earlier I said it was twenty but it's more like twenty five, which is very specific.

And so how does that happen.

We're gonna get to our best guess right now at how that happens a little bit later in the show.

But it's amazingly specific.

Wow.

But now it's worth mentioning that.

Okay, that is a story from O fio cordus steps unilateralis And just to complete the.

Loop, it rains it down on the forest floor and then the next ant can come along and pick it up in there goals and that's how it completes the cycle.

Danchel, the she ants does pick up dante l Yeah, Dantel, that's right, picks up the fungus and the cycle starts again.

Wow, all right, okay, And so the name of this fungus is some crazy Latin phrase.

Yeah.

So Ofio cordyceps unilateralis.

The unilaterallysis refers to the fact that the stalk comes out of one side of the ant's head.

And so opio coortceps is a genus.

So there's a lot of different fungus species that are very closely related, and they infect different ant species, so they seem to specialize on different species.

So there's actually a bunch of ants all over the world that are infected by this fungus in slightly different ways.

So the story isn't the same for all of them.

The story I gave you is a story that I'd initially read for Ophagio Cordyceps unilateralis infecting an ant species in the tropics.

But yeah, there's a lot of this happening in our world, and.

Within this species of ant and this species of fungus.

You're saying, there's not a lot of variation in the behavior of ants.

They like basically all do the same march to death and then brain.

Explosion, brain explosion or you.

Know, fungal stock extrusion or what.

Yeah.

Yeah, So we are going to talk about how they differ a little bit.

The details can differ depending on where you are, but the story is generally the same.

That they find a way to be up above the areas where the foragers usually go so that they can rain the spores back down.

Again.

Wow, amazing, So tell us how it works.

So first, I want to note we call these zombie ants, and I often get people in the field grumpy with me for calling them zombies because they're like people are gonna think they come back from the dead.

Dear listener, I don't think that you think that ants come back from the dead.

But just to be clear, the zombie ants do not come back from the dead.

They are their behavior is getting hijacked while they're alive, and then they die in a very particular position that benefits the fungus.

So you're saying they're not zombies because the ants haven't died.

They're just in some sort of like controlled state where they're not really acting the way they would if they were normal ants.

They're like drunk or they're hallucinating or something.

Something like that, and yet it looks like their circadian rhythms are getting messed with.

So Terarissa de Becker's lab has looked at how a big part of the manipulation seems to be them doing kind of normal behaviors but at abnormal times.

So that seems to me a very technical definition of zombie.

I mean, if humans, for example, were infected by something which made them stagger around and want to eat brains, but weren't technically dead, would you be there being like, excuse me, you're not a zombie.

Sir, No, Because I love fiction in all of its forms, and as long as the rules are consistent in the world that's created, I don't care.

So when I use the word zombie, I basically just mean an organism where a significant amount of its behaviors seem to be under the control of another critter, and those behaviors are good for the parasite but usually bad for the host.

All right, well, let's take a break because I definitely need one, and come back and hear all about the details of how this fungus controls this an.

Okay, we're back, and we're talking about the name of a fungus that I cannot pronounce but is amazingly adept at manipulating ants.

This is a really nice like turn of the tables.

Usually I'm the one who can't pronounce things.

We've got to do more episodes with like complex latinate names.

But okay, So one of the first things I think is so amazing about this system is that it evades the social immune system that ants have.

So ants are very genetically related to one another, and they work together for this common goal of like helping the queen create more offspring and stuff like that.

And they have complex fractional relationships, right, It's not just like you have kids that are half you.

You're like related by a quarter or a sixth or a third or something complicated.

Right.

I think it's like three quarters.

Like you're way more closely related than like, you know, my brother and I would be, for example, typical siblings, and so they're like, you know, pretty close to you genetically.

And so this tends to result in what look like ultruistic behaviors.

And so if one of the ants comes into the colony and is clearly infected with something, the nest has a like social immune response where other nestmates will be like, oh, you can't bring that in here, man, and they will in some cases kill that ant and then go put it in like a graveyard somewhere far away from the nest so that it can't infect the rest of the.

Nest based just on the behavior.

It's not like it's giving off some pheromones or something.

I think in a lot of cases we don't know exactly how the nest mats can tell.

It's probably some combination of behaviors.

And then ants are a species that in particular tends to communicate a lot with chemical cues.

So it could be that they sort of smell or whatever taste and nestmate and they're like, no, that's it's weird.

We're kicking you out, Daniel.

You taste funny.

We're killing you.

Yeah, that's right, that's right, Daniel.

It's not how your forehead is supposed to taste.

And I licked it and now you can't live here anymore.

Danchel, danchel.

And so anyway, so usually when an infected nest mate comes back, it gets picked up on and they get killed and kicked out.

Brutal but fair.

Brutal but fair.

And this is a pathogen that you would want to put a stop to.

So you know, if they don't capture this individual and kill it, it is going to create essentially like a stock of infectious propagules nearby.

So anyway, there should be selective pressure for this part.

And so how does it evade this selective pressure?

Why can't the other ants tell?

So we don't have a great handle on why the other ants can't tell.

Part of it seems to be that in at least some systems.

So I'm going to be talking about this system like every system acts the same way, but just sort of like with the tartar grades.

Some questions have been asked in one ophiocordycep species infecting one ant species.

Some questions been asked in other systems, but we're going to mix and match for the purpose of this show.

But there's the disclaimer.

So some ants, the timing of their behavior changes and they interact with nestmates less often, and so part of the story might be that instead of just like blindly going into the nest and then getting found out, these ants that are infected are avoiding nest mates so they never get found out, they never get their forehead licked, and so so they're able to escape in that way.

It could also be like the scent of the fungus is being masked in some way, but through mechanisms we don't understand, it manages to evade the social immunity of the nest.

Wow.

Amazing, Yeah, pretty cool.

All right, So now you've got this ant that's infected.

It's nest mates haven't killed it like they probably should have, and then at some point it's does that Drunkard's walk, and we don't really understand why that drunkard's walk happens.

But there is a chemical that's produced by the ant that is associated with something that causes like staggering and seizures and other insects.

And so we think that it's going out there and it's starting to do this staggering thing because of some chemicals produced by the fungus.

It gets down to the forest floor, and now the interesting question is how does it know where to go?

So this is the Summit disease part.

It starts climbing up, but we're trying to figure out how does it know where to stop?

How does it know where a good spot is.

Well, it's very confusing to me that the behavior is so complex that it includes climbing down and then climbing up, Like I could see it somehow is pulling on some lever inside the brain to make it go up, to make it go down, but to make it go down and then up like that's really amazing.

That is really amazing.

I mean, I think part of the selection pressure there.

And this is just me telling a story.

I haven't I don't know that we've tested this, but if the ant had gone down, it's probably one going down a big trunk, and they tend to attach to like thin stems, and we'll get into that in a second.

But also if it just kind of clung in an area where foraging ants would be going up and down.

Anyway, if a four ant sees a dead ant with a stalk coming out of its neck, that it is going to throw over into the trash can, and so that would be the end for the fungus too.

So that tells us why that strategy, the simpler strategy wouldn't work of just like clinging to the tree.

But it leaves us still impressed with this complex strategy of climbing down and then climbing up.

Right, And so let me go ahead and jump ahead a little bit to the benefit of climbing back up again.

So there's been an experiment done where they took ants that had like settled in at a particular location and they cut the leaf off that the ant was on and they moved it up.

And when you move it up, the temperature and the humidity are no longer good for the fungus, and the fungus can't make that stalk and it can't make the infectious propagules that rain down on the other foragers, and so there is this like kind of narrow band that the fungus needs to be in in order to complete its development.

And so you know, it takes some work to find exactly the right spot.

And it's fascinating to me to imagine all the evolutionary dead ends.

You know, ants that just went down and never climbed up, ants that climbed up the tree instead and didn't propagate.

It's incredible that this whole thing came together.

Yeah, yeah, it really is well, and I'm sure that a lot of times when researchers go out to study this kind of stuff, like you know, if you're too low, then spiders and other scavengers come along and they'll eat the zombie ant.

And so there's probably some instances where the ant dies and the wrong spot, but the researchers never find it because something is eating it and it's gone.

So you know, you do the best you can with the data you've got.

So tell us about this climbing up.

How does it know where to stop that it gets this right height?

Like, do we understand the mechanisms for how it knows how high it is.

It's not like doing GPS or something.

So we think it's queuing in on light, which is amazing to me because it's inside the body of an ant, and so how is it getting information about light?

So what they did was they found what's called ant graveyards, So the ants tend to accumulate in certain areas of the and so they're like, Okay, we know this is an area that's good because the fungus have chosen to be here before.

And then they put a little bit of a light shade over the zombie graveyard and so now that area is getting a little bit less light than it was getting before.

And what they found was that if you go back in future weeks, that area doesn't get as many new ants as nearby areas that have more light.

So it looks like the fungus is driving the ants towards areas that have certain amounts of light.

And then they looked there were still some newly infected ants that went into the areas with the shades, and if you followed what was happening with that fungus, overtime, the fungus was less able to produce those stalks and produce I'm just gonna call them baby fungus because no one wants to hear me try to say propagule again.

So less baby fungus gets made in areas where you've got these shades, I see.

And so the ants are using the light as a queue for where to go.

Is the light important in making the baby funguses or is it just like a signal to the fungus of when the ant has crawled up to the right height.

I think that the light is used as a proxy for information about temperature and humidity.

And it could be that the light is important for some way too.

I don't a fungus.

I don't know, but nature's complicated, but it does look like things like temperature and humidity and light are all important for the way the fungus is able to develop.

Wow.

Fascinating.

And this is the part that you see another insects too.

We I talked about those zombie flies and those caterpillars.

This climbing up thing happens in a lot of insects systems.

And then you said they also bite down, they like clamp onto this plant.

Why is that part important?

Is it because the ant's going to die and you want it to stay there.

Yeah, so you want the ant to stay put.

And so in the tropics, what happens is they find a leaf, they crawl along the bottom of the leaf, along the major leaf veanes, and the ants will clamp down with their mandibles.

They've got these pincers and their muscles will like hyper contract, so though like really strongly bite down, and then the ants will never be able to open their mandibles again and they will die there.

Wow.

And so that's how they hold on.

And this is called the death grip.

And one of the things that's interesting is that depending on where you are in the world, the death grip will look a little bit different.

So in the tropics they tend to bite down on leaves, but if you go to like North Carolina, for example, instead of biting down on leaves, they'll bite down on stems, and they'll also wrap their legs around them, and so they'll hold on with their legs and with their pincy parts.

And we think that the reason that they hang out on stems instead of leaves in areas that are farther north like North Carolina, is because in the tropics, leaves really never fall off the trees, or they at least don't have a seasonal pattern of falling off in the winter, whereas farther north, if you bite down on a leaf, you've got until like I don't know, August, September, or October before those leaves start to fall off.

But if you're on the stem, then you can stay up there for longer, raining fire down upon the other ants.

And so it looks like there have been four different instances where you've gotten this evolutionary transition from biting down on leaves to biting down on things like stems.

This is fascinating.

I love these moments in science when you can look at what's going on and unravel it and tell a story.

I remember Hazel summarizing all of science once.

She says, like, stuff happened and we figured out why, And I'm like, yeah, that's pretty much the whole idea.

Yes, So by looking at this pattern of how things evolve differently in different parts of the world where the conditions are slightly different, we start to get a sense for how this all came together.

That's incredible.

Yeah, it's really incredible.

And I got to see one in North Carolina.

I'll put a picture on this online when it comes out.

But we found one in North Carolina, and Andrew Turner found it.

I was out looking for snakes and salamanders.

And Andrew Turner, a friend of mine, was like, is that a zombie at And I freaked out.

Anyone in like a one mile radius probably her me screamed because I didn't think I was going to get to see a zombie ant.

So anyway, I've seen them in North Carolina.

And then Andrew Turner put one in like a resin for me, and so I've got it on my desk and it is my favorite.

And what are we looking at?

We are looking at this is a bit of stem and on the bottom there's an ant that's got its legs wrapped around the stem.

It's biting down with its mandibles.

You can see it's got a big stalk coming out of the side of its head.

The spore that the fungus would come out of is kind of small.

It's hard to see, but it's about maybe three quarters of the way up the stem.

Best thing I own.

You have children too, don't for care.

I don't own them.

You know, they could choose to leave at one point, but this will never leave.

It's a special place in your heart.

It is all right.

So the ant bites down.

And one of the cool things about this, what we call a death grip, is that it leaves a very distinctive mark.

So if you find leaves, you'll see the they've got.

It looks like, you know, like scissors cut on either side of the veins.

And there are forty eight million year old leaf fossils from Germany that have these little scissor cuts in them, and we think that these are like essentially fossil records of behavior showing that like around the time a bunch of the different mammalian species we're sort of evolving into existence, this manipulation was already happening.

And you know, you can't be one hundred percent sure the ants weren't still attached or anything like that, but it's indirect evidence that this is sort of an ancient association and a manipulation that's been going on for longer than humans have been on this planet.

And so when the ant mandibles do this hyper contraction, they make a special sort of pattern that they can't otherwise make because it's just the ant mandible, right, It's not like, how is this pattern different from a normal ant chomp.

So, first of all, a lot of ants don't chomp around leaf veans like this, So you might be thinking about leaf cutter ants, and leaf cutter ants will cut out like chunks of leaves and bring them back to their net so that they can they feed them to fungus, and that they're sort of like a farming situation.

But anyway, ants don't usually just go and like chomp down on leafs around the veins and then do nothing else with it.

I see.

So it's also the location of the chump.

Yeah, it's also the location of the chump.

Wow, amazing, Yeah, pretty cool.

And so you tend to get aggregations in these good parts of the forest where the conditions are good for fungal growth, and so you end up with these ant graveyards where you've got a bunch of these zombified ants hanging on the underside of stems or leaves, raining fungal spores down on their nest mates below.

And does the fungus actually kill the ant or does this sort of death march end up exhausting the ant or why does the ant die?

I don't know if the ant dies, because once it bites down, it can't use its mandibles again.

I don't know if it just eventually dies because it runs out of energy, or if the fungus kills it, but I do know that pretty soon after it bites down, the fungus starts consuming the inside of the ant to make more fungal tissue instead.

And how long is it like spraying propagules.

For That really depends on where you are.

I think in some parts of the world it happens for like just a couple months.

I think in some areas, I think it can happen for like a year.

That really depends on the environment that you're in.

All Right, and let's take a break, and when we come back, we'll hear about how this benefits the fungus and how the ant manages to pull this all off.

Okay, we're back, and we're talking about the death march of zombie ants.

Kelly, tell us why the fungus makes this happen.

Why can't the fungus just find some other friendlier way to spread itself.

I don't know why it doesn't find a friendlier way to do it, but we do know that this method seems to work for the fungus.

As we sort of hinted at earlier.

It's actually pretty easy to move these ants to different places to test out, like where would the best place be for these ants to have settled down, so you can cut off a leaf, And if you move it up too high, as we mentioned earlier, the temperature and humidity and lightning conditions are just not good and the fungus will essentially never be able to produce that stock that makes the spores.

And so that's the end of the line for the fungus.

Not great.

And if you move it down too low, it gets found by scavengers.

And so unlike a lot of other examples where we have a nice story, here we've been able to manipulate the system a little bit and say, you know, look, if you do something different than what we're seeing, the fungus is quite clearly doing less well.

The fungus either gets eaten and killed or it can't make babies.

I'm still sort of amazed that this whole thing works, Like I can imagine a fungus infecting an and and it makes a small change in the ant's behavior, and maybe that benefits it a little bit, But this benefit requires such complex behavior for the antigodam and then across and then up and then bite and all this stuff.

All these pieces have to basically fall into place due to random mutation.

So how do you get all the way to this complex behavior when none of the individual pieces on their own are going to benefit the fungus.

Yeah, that's a great question.

So one thing that's worth noting is that, you know, as we've mentioned earlier, this summoning disease thing happens pretty often.

So it suggests that there's something about insects where it's not too hard to manipulate their ability to go up or stay up.

And so a number of different kinds of parasites and pathogens have found the switch.

I can't say I'm an expert on what that switch is, but there's a couple of different routes to up and stay there.

But you can imagine that this happened, you know, step by step.

So maybe the first thing that happened was that ants that were starting to show signs of being infected by the fungus left the nest so that the nestmates didn't kill them, and maybe they died on the forest floor.

And then there happens to be an ant that climbed up a little bit before it died, and that helped the fungus relative just dying on the floor.

And so you can, you know, imagine how each step could have happened first and then been honed over time.

But this is definitely one of those things where we have to tell a story and we can't be exactly sure what happened in what order.

I mean, maybe what happened first is that the ants that are infected by a fungus would die high up and they'd never go back to their nest.

And maybe the nest stuff came later by some ant that happened to wander back but wasn't discovered for whatever reason.

And so you know, each step there's selective pressure for whatever benefits the fungus more.

But the exact path that this took.

I think the best we can do is speculate.

I see.

But it's plausible to string these complex behaviors together because each individual one already does benefit the fungus.

So that, yeah, that makes sense.

I wonder what in one hundred million years, this fungus will have this ants doing, like, oh, it turns out if they do the macarena before they bite down.

Yeah, yeah, it could be.

I mean I would imagine that, like, as climate is changing across the planet, the exact location where biting down is the most beneficial might change.

So there might be selection to like tinker with exactly where the ants end up so you keep getting the right temperature in humidity, and maybe that will be like you know, you should go to areas with even less light because everything is getting too warm and too hot, and so less light will be a little cooler and the temperatures will be right anyway, So I can imagine that happening.

But part of understanding the steps is probably understanding the mechanisms, because that gives you some insights.

Yeah, like what's going on inside the ant that lets the fungus?

What are these levers that the fungus is pushing?

Yeah, so first let me just talk briefly about how we start answering these questions.

So, as we've discussed, there's a bunch of different steps here that the fungus is doing, and so the answer for how does the fungus manipulate behavior probably differs depending on what step you're talking.

About different ants, different answer.

Do I tell you often enough?

How much I like working with you, Daniel, because I really do.

I'm just going for the easy puns because somebody has to.

I know, the dad jokes, the amazing dad jokes.

So the way that you know, for example, if you're trying to figure out what differs between an ant that gets ignored by its nest mates and an ant that gets dumped, well you can, for example, infect some ants with ofio cordyceps and other ants with a different kind of fungus and send them both into a nest and see how they interact differently with their nest mates, how the nestmates interact differently with them, And then you can look at the different chemical profiles and say, like this one is emitting these chemicals and this one is emitting these chemicals, and then try to figure out, you know, is the fungus is ofio cord aceps producing some chemicals that the other fungus doesn't produce, and then start looking into those as candidates for what's happening there.

Do you need an IRB for these kinds of experiments or can we just experiment willy nilly on ants?

Do ants have any rights?

That's a good question.

So IRBs are almost exclusively for humans, so you don't need an You.

Can't just experiment on dogs and chimps and rats, right, there's some ethics there, yep.

For dogs and chimps and rats, you need an institutional Animal Care and Use Committee protocol and you have to jump through many hoops to make that happen, which which we'll talk about on another episode.

But for invertebrates like ants, you don't need to do those kinds of protocols.

But I will say that everyone who I've ever talked to who works with animals, even just little ants, gets pretty emotionally attached to them, and they do worry about, like how do I euthanize this ant to get my data in the way that will like make it fastest.

And you know, I don't think we really know if ants feel pain or not, but like, if they do, how could we do it so that they'll feel the least amount of pain?

So nobody's just callously grinding up ants.

They're like shedding a tear while grinding up ants.

That's nice.

Yeah, let's move on.

All right, No, but I mean jokes aside.

You're saying that scientists involved understand the costs here in terms of lives and the appearances even of the little ants, and that's nice.

Yes, no, they do, and I think they try to make the ants lives as natural and as nice as possible before these experiments happen.

But so mostly the point I wanted to make was how we do these different comparisons to get a handle on what might be happening.

And the answer is, you know, at very similar time points, you look at ants that are uninfected, ants that are infected by opiel cordyceps, and ants that are infected by other fungus that are bad for the ant, but we don't think they manipulate behavior in any way.

And by looking to see what's happening differently in the bodies and the behavior of the ants in those three different categories, we can start getting some like candidate molecules for you know, this might be the thing that's getting produced by the fungus to change the behavior.

And so they found a lot of stuff that differs, and that's not too surprising because the ants are doing complicated behaviors.

There's a lot of behaviors.

I feel like what we really want as humans is that the answer is there's this one molecule that tells you everything, and that's fascinating, but really it ends up being like hundreds of molecules that are being produced that we think are important in every single different step.

So there's not like a really nice, easy to tell story.

But a couple things that pop out is that interra toxins seem like they're important.

These are toxins that are released by things like bacteria like E.

Coli.

We're not totally sure what the toxin is doing to the ants, but it might be playing a role in breaking down ant muscles at particular times.

So maybe after the ant bites down, those muscles get broken down so the ant can't leave, and that might be what the toxin is doing when it's released at that point.

I think it's great to try to dig into the details and understand the mechanisms to make sure the story that we're telling is the real story, and also because you could discover surprising things when you dig into the details.

But what else could we learn by doing this.

Is there the possibility here of a surprise that we discover, Oh, it's not actually working the way that we expected.

Yeah, So a lot of people think of the behavior manipulating parasites and pathogens as like evolutionary neuroscientists.

So they've been interacting with their host for you know, in this case, it looks like more than forty eight million years, and through the process of natural selection, they've maybe happened upon solutions for changing the ants behavior.

And so by looking to see what is the fungus making, if it's a compound we've never seen before, maybe we've unlocked some tiny piece of the puzzle for how brains work and how you can modify behavior.

And you know, you could imagine maybe if you've got some pest in a field, if you make them all like you know, climb up and stay up and then die, they'll like stop messing with your field.

And so like, whenever we can understand even how insect behavior works, it gives you some extra tools to not just you know, understand how your world works, but also to maybe sort of control some of the negative aspects of like pest organisms.

Wow, so the fungus has been doing neuroscience experiments on the ants for forty eight million years without ever writing a paper and getting their PhD.

That's got to set some kind of record.

They don't have to worry about tenure.

They don't have to get brands, they don't have to write permits and protocols.

It really seems unfair the head start that they've gotten.

But if we study them, then we can sort of extract their secrets and maybe this will help us like jump ahead in our you know, study of neuroscience, which I think is a cool idea.

And so they also found what they call a bioactive compound where they've they've never sort of seen this before, but it looks like another compound that, as we talked about earlier, causes insects to stagger, and so this might explain why they sort of like walk down the tree like they're drunk.

But we think, and this is this is just hypothesizing at this point, we think it might be important in those systems where the ants are clinging to the bottom of stems.

If the ants are feeling like all sort of wobbly and uneven, they might hug down on the stem to hold themselves so they don't fall off of it, and that could be sort of the moment that the fungus kills them, so that they will be really clinging hard to the stem.

And at this point.

This is just a story, and we know that we need to dig into it more.

But that's where we are right now.

So it's complicated.

And do we know like where in the ant the fungus ends up, Like does the ant have a little ant brain and the fungus is sitting on top of it, like cackling maniacally and pulling levers.

Yeah, so this is really neat.

So you know, I've already mentioned that Terissa de Becker's lab has been doing some important work on timing, and they've been working on like chemicals that are produced by the fungus.

David Hughes did some work with collaborators where they scanned ants with an electron microscope, so like very very detailed scans, and they put all of the scans together and what they found was that the fungus is forming a network and it's invading a bunch of different muscles.

And so the way it was described in the popular press was that you could think of it as like the fungus essentially having strings on a puppet, where it could be like pulling up and down, and that might be over selling it a little bit, but one of the things that they thought was interesting was that it doesn't seem to be invading the brain tissue, so it's touching the brain but not going into the brain tissue.

This was made a pretty big deal in the POPSI articles at the time.

I wasn't as impressed with that.

So, like the brain infecting parasite that I studied on fish for my PhD also sat on top of the brain and not inside of it.

And there's some other evidence in the zombieant system that the fungus is kind of protecting the brain.

So you can imagine that, like if you're inside of the brain, you might just like totally screw up your ride, like it's not gonna do what you want, because you've just totally debilitated it.

And now it's obvious and the other ants can tell.

And so it looks like it's sort of tinkering with the brain without actually like sticking its hands in there.

But it does have its you know, hipha which are like fungal fingers inside the other muscles.

Wow, amazing, and I see something amazing here in the outline.

Tell me about hyper parasites.

Are these like the superhero version of parasites?

Kind of were they bitten by a radioactive spider.

No no, no, no, no, you've watched too many movies, Daniel.

This is true.

Yeah, this is cool.

So you know, you've got this fungus that manipulates ant behavior.

But there are other fungal species that infect opio cordyceps.

So the ant will be like, you know, clinging to a stem, and you'll find fungus that is living on top of Ofio cordyceps and is sapping the o fio cortaceps energy.

It's like fungus inception.

Wait, fungus antception.

Whoa dead jokes galore.

This might be our most dead jokey episode.

Yet I didn't see it coming.

Wow.

So this fungus thought I was pulling the strings, but its strings were being pulled the whole time.

There are so many levels in nature.

I am so glad to be uh where I am so okay.

So I promised at the beginning of the episode that I would answer if Ofio cordyceps could jump to humans and manipulate us, Daniel.

So now I'm going to ask you what is your favorite representation of a fungus that jumps to humans and the ant.

You could just say I don't watch the same shows as 'di Kelly.

I'm not a fan of the zombie genre in general, the violence and the goo and like not a fan.

So yeah, I'm gonna have to leave it to you, all right, Well, okay, I've been really liking The Last of Us lately, but not necessarily because it like hues so closely to what happens in nature, so that one starts by saying, like, yes, I know it seems unlikely that I think they call it cort aceps.

The genus name has changed a little bit, but anyway, yes, it seems unlikely that it could jump to humans, but the way our environment is changing, we can't rule it out or something like that.

And then fast forward decades and humans are infected by the fungus.

I think it is highly unlikely.

Why is that?

Well, okay, so even in nature we talked about at the beginning of the show that each opio cort Aceps species tends to infect and manipulate specific ant species, so they are so specialized that they can't even like manipulate closely related ants.

Like that's too much of a jump.

So maybe like, if you you know how to fly a Sessana.

That doesn't mean that if somebody drops you into like a seven forty seven, you're going to know how to land that thing.

Yes, exactly right, And human brains are so incredibly different than ant brains.

I suppose it's possible that a fungus might be able to eke out an existence in us, but I even think that would be quite a jump.

But if it could, the probability that it would be able to control our behavior in a way that would benefit the fungus seems pretty close to zero.

And I'm not being negative about the movies and TV shows and books that are great and Daniel's missing out.

I think it's great that they created these worlds, and if they're consistent with their rules, I'm on board.

But I'm a person with massive anxiety and it doesn't keep me up at night worrying that ofiocordyceps is going to jump to me or my kids.

Well, I have a theory for how this fungus can jump to humans and benefit itself.

Okay, if you think of this fungus as little neuroscientists, then what you to do It should get humans to help it out.

So if it infects human brains and makes those humans interested in this and puzzle.

So they come along basically acting like colleagues and figuring out like, hey, how does this actually work?

And maybe you can help, like you know, super engineer this fungus to be even more efficient.

I feel like you're in a roundabout way trying to get back to the like it's okay that I eat cookies at night thing, like you know, if the if the fungus benefits from me eating cookies.

But you know what is interesting, So ofio cord accepts Senensis infects I think it's caterpillars, but it infects craters, but instead of having them climb up, it has them burrow into the ground and then the fungal stalk grows out of the ground and like pops up.

Okay, and humans have decided that this is amazing in tea, and so people will actually go out in search of this and they can sell it for a lot of money.

And I think you can even buy this in the United States, like tea with ofio cord accepts senensus in it, and so you know, I don't maybe ofio cordceps senensus jumps to us and makes us want the tea, and so then we'll start big farms where we sort of seed their hosts with the fungus so that they can start growing up and then we can replicate it.

So maybe that'll be the route.

Or maybe that'll just be the story in your Netflix show.

Netflix call us We're ready.

Yeah, you know, I wrote fiction once and I kind of think it was a disaster.

So I don't see me starting a new fictional series.

But if anybody would like scientific input on their own series, I am available.

And she promises not to be completely a wet blanket.

I you know, I don't like to make promises I can't keep.

I'll try to play along, all right, So, just to sort of reiterate, I love this system because we've dug into more of the different pieces in this system than a bunch of other systems.

But there's so much we have left to learn.

And as we mentioned earlier, like we're discovering molecules that we've never seen before.

This might be a way to help us understand how brains work and how we can sort of tinker with behavior.

It might give us some inputs on how to control insect populations.

There's so much cool stuff we might have left to learn as we continue digging into the system.

Amazing and it's incredible what we can learn from like ants and fungus, and sometimes that tells us something deeper about the way brains work.

And so you never know where the next great scientific discovery will come from and who's really pulling your strings?

That's right, But the next great scientific discovery is probably coming from biology.

That's what I think.

As long as it gets into people's heads and makes them listen to the podcast, I'm all for it.

Or it gives Daniel an excuse for eating cookies in the middle of the night.

Chomp, chomp, chomp.

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