You’ve probably heard about “zombie ants”: ants that become zombie-like when infected by a certain parasitic fungus. Like many parasites, some fungi can control the behavior of their hosts, and they do this to increase their own fitness, affecting the host’s morphology and behavior to make it more likely that the parasite will pass its genes to the next generation. This is simple natural selection operating on the parasite, but doing so in a way that captivates and fascinates both biologists and laypeople. How can a fungus or worm take over a larger animal and make it do its “will”? (I’m speaking in biological shorthand here.)
One of the iconic examples of such parasitism involves those zombie ants. When a carpenter ant is infected by the parasitic fungus Ophiocoryceps unilateralis (henceforth, “the parasite”), the ant’s behavior eventually changes. The parasite enters the ant through the cuticle, and then begins to grow. After 16-25 days, the fungus makes the ant climb a plant (they nest in the ground), move to a conspicuous location on a plant, and then bite down hard on a plant vein, affixing itself firmly to the vegetation. The ant dies, and the fungus grows a stalk out of the ant, ready to disperse its spores to the ground, where the infection and life cycle will resume when the fungus is encountered by the next unlucky ant.
Here’s what the dead ants with the parasite growing out of them look like:
Another photo:
Clearly, the fungus is somehow manipulating the ant’s behavior to facilitate reproduction of the parasite. But how does it do this?
We don’t know exactly in any case (though there are a fair number of cases), but it must involve either growth of the parasite inside the host or chemical manipulation of a host(or both)—presumably in ways that affect the host’s brain. After all, if the brain isn’t affected, how can you modify the host’s behavior?
We now have a better, but still incomplete, idea of what’s going on with zombie ants from work described in a new paper in PNAS by Maridel Fredericksen et al. (reference at bottom and free access; pdf here). What the authors did was infect carpenter ants (Camponotus castaneus) in the laboratory with the “zombie-making” O. unilateralis fungus (as well as with a control fungus that doesn’t create zombie ants but does kill them). Then right when at the crucial moment when ant bites down on the plant, they microdissect that infected ant to see where the fungus was.
This latter procedure was a tour de force, for it involved a complex series of manipulations on a very tiny creature. The ant was dissected tiny bit by tiny bit, and then each bit was treated with immunofluorescent stain that could distinguish between fungus tissue and ant tissue. The authors then developed a computer program to look at the microscopic sections and put them together. This procedure, called “deep learning”, is a huge improvement over it being done by hand—the usual technique. As Gizmodo notes:
Using electron microscopes, the researchers created 3D visualizations to determine location, abundance, and activity of the fungi inside the bodies of the ants. Slices of tissue were taken at a resolution of 50 nanometers, which were captured using a machine that could repeat the slicing and imaging process at a rate of 2,000 times over a 24-hour period. To parse this hideous amount of data, the researchers turned to artificial intelligence, whereby a machine-learning algorithm was taught to differentiate between fungal and ant cells. This allowed the researchers to determine how much of the insect was still ant, and how much of it was converted into the externalized fungus.
What they found was surprising:
1.) First, there was no fungus in the ant’s brain, though it was present throughout the body. This really was a surprise, as everyone expected that the fungus would glom onto the ant’s brain, and that was the way it controlled its behavior. Instead, there was fungus everywhere else in the ant, especially in the muscles. (That was true of the “control” fungus, too, but, surprisingly, the paper gives no information about whether the control fungus was found in the ant’s brain).
Here’s part of a figure showing the ant’s brain (stained in green), and the nearby fungus (red); scale bar is 20 microns. There are a few fungal tracheae in the brain (arrowheads) but nowhere near the degree of intermixing of brain and fungus cells seen in muscles, and there are no fungal hyphae (the filaments of the fungus that conduct and transfer nutrients) in the brain at all, whereas they’re deep into the muscle (see below).
2.) The fungus formed a connecting network of hyphae that attached to and penetrated the ant’s muscles. Here’s an example of the networks of fungi (yellow) surrounding the ant’s muscles (red) from the paper:
What is the fungus doing infiltrating the muscle and forming a network that ramifies widely throughout the ant’s body? The authors posit, and this seems likely, that the fungal hyphae are sucking nutrients from the ant’s muscles and transferring them to other fungal cells not touching the muscles. This may be how the fungus feeds itself and grows throughout the ant. Muscles are rich in mitochondria, which give the ant energy reserves and are good food for the fungus. The authors also observed severe atrophy of the muscle probably connected with the fungal invasion. This muscle infiltration and formation of networks was not seen in the control fungus.
So we have two questions left:
Why does the fungus not infiltrate the brain? We don’t know, but it’s possible that doing that would quickly kill the ant and render it useless for further growth and manipulation of behavior. Further (or in addition), it may be easier to control the ant’s behavior by secreting chemicals into an intact brain than by brute-force physical invasion of the brain. After all, the behavioral manipulation by the fungus is precise: it makes the ant go to a specific exposed position on the plant (see below) and then bite down hard with its mandibles.
So how is the fungus affecting the ant’s behavior? We still don’t know. Clearly the fungal attachment to the muscles is not somehow moving the muscles in a preferred way or controlling the mandibles; rather, the muscle infiltration is a way for the fungus to get the energy it needs to grow and then form the stalk that spreads spores. What is very likely, but remains to be shown, is that the fungus secretes a chemical that somehow affects the intact brain in a way that makes the ant behave like a zombie. The authors do note that metabolite chemicals secreted by the fungus differ when it is near the brain than when it is near the muscle. Not only that, but the behavioral modification is more than just biting: the ant goes to a very specific place before biting, and that directionality somehow has to be produced by the parasite as well. As Wikipedia notes,
An infected ant exhibits irregularly timed full body convulsions that dislodge it to the forest floor. The ant climbs up the stem of a plant and uses its mandibles with abnormal force to secure itself to a leaf vein, leaving dumbbell-shaped marks on it. The ants generally clamp to a leaf’s vein at a mean height of 25.20 ± 2.46 cm above the forest floor, on the northern side of the plant, in an environment with 94–95% humidity and temperatures between 20 and 30 °C (68 and 86 °F). Infections may lead to 20 to 30 dead ants per square meter. “Each time, they are on leaves that are a particular height off the ground and they have bitten into the main vein [of a leaf] before dying.” When the dead ants are moved to other places and positions, further vegetative growth and sporulation either fails to occur or results in undersized and abnormal reproductive structures.]
In other words, the fungus has to direct the dying ant to a specific microenvironment optimal for survival and propagation of the spores.
This adds up to a real tour de force of natural selection: imagine the evolution of a chemical that can make the ant behave in such specific ways! The mind boggles: what were the intermediate steps in the evolution of this kind of host manipulation?
As Matthew emailed me (he found the paper), “What an amazing adaptation of the fungus to make the ant do the things the fungus needs it to do (‘puppet master’ is wrong metaphor because the fungus isn’t the master—natural selection is!)”. It’s stuff like this that keeps the evolutionary biologist—well, at least the ones with imagination—in a constant state of wonder and awe.
Now of course we don’t know the crucial answer: how does the manipulation of behavior actually work. But we know at least that it’s probably chemical rather than physical, and we also know that the parasitic fungus evolved adaptations for sucking nutrients from the ant’s muscles. That’s two steps forward. And the usual ending of scientific papers applies: “More work needs to be done.”
________
M. A. Fredericksen et al. 2017. Three-dimensional visualization and a deep-learning model reveal complex fungal parasite networks in behaviorally manipulated ants. Proc. Nat. Acad. Sci USA.; published ahead of print November 7, 2017, doi:10.1073/pnas.1711673114
Very cool. Excellent work by the researchers. Thanks for the explanation, Jerry. I was wondering if the fungal mycelium was acting as an independent replacement analog for the ant’s nervous system and just stimulating the muscles until it achieved its goal, but apparently not.
Amazing.
Oooh, wish you’d had this post at Halloween!
I just love this! Makes me wonder about human parasites…for example, whether toxoplasmosis (from cats) might actually manipulate human behavior.
Carl Zimmer has a fascinating book about parasites called Parasite Rex.
I think toxoplasmosis mainly operates on mice, making them “voluntary” prey to cats. Humans who pick it up, as I understand it, are a dead-end for the parasite. (My wife has it, passed on to her from her mom in utero.)
I had heard that toxoplasmosis does have an effect in the human brain, in that it encourages risky behaviour. In rats and mice the parasite causes them to be attracted to cat urine, which makes them more likely to be eaten by cats and continue the parasite’s life cycle. In humans, many people killed racing motorcycles, etc. tend to have a lot of the parasite in the same part of the brain as in rats.
I’d need some evidence there. Certainly it doesn’t map to personal experience.
In humans, it leads to cat posting on facebook.
😎
“An infected ant exhibits irregularly timed full body convulsions that dislodge it to the forest floor.”
If the fungus triggers the convulsion that drops the ant to the ground, then it could be that it just repeats that cycle until the ant happens to clamp onto a leaf with the right conditions. The right conditions then cause the fungus to switch to sporulation mode, which kills the ant, locking it in place.
I am thinking of similarly simple measures. Like an inducement to walk, perhaps by a chemical that creates the equivilant of restless leg syndrome. Once that is released, the course of infection runs at a fairly reproducible pace. By the time the ant succumbs it was induced to walk long enough to be about 25cm off the ground. It then dies in a state of tetany, and that is why it has chomped down on whatever it was climbing on.
I would look for relatively simple things like that first.
I went through Wikipedia to find this paper from 2011, describing the behavior in more detail:
https://bmcecol.biomedcentral.com/articles/10.1186/1472-6785-11-13
There is a nice graph, figure 1, showing the what happened to a group of ants, which I summarize as:
Infected ants drop from the canopy and walk around in drunken stupor, climbing whatever they bump into, mostly small saplings.
Multiple convulsions prior to the bite moment are recorded for most of them. Multiple falls back to the ground are recorded for many of them. Not perfectly guided behavior, in other words.
When conditions are just right, an ant is induced to do a death bite. Then the sporulation process sets in, and the ant is toast.
Good thought. Anything that triggers disorientation might cause the ant to clamp down in response.
The timing is still an interesting question but you’ve at least thought of a mechanism which seems relatively easy to produce.
Thanks for this write up.
I now lay in wait for the Creationist to come along, eagerly arguing that, of course, God made the parasite grow in a creature, leech off its muscle, manipulate its behavoir to ultimately burst out of the head, killing its host. Something tells me that Creationists are perhaps not too eager to argue that case. 😉
I doubt if it would faze them. They’d probably just argue that ant and fungus lived together in perfect harmony until the Fall, at which point the Satanic forces unleashed by Adam & Eve caused the fungus to turn nasty. People who claim that T. rex was originally a vegetarian won’t be put off by a few dead ants.
Good point, I hadn’t considered they also believe “Satan Diddit” at the same time, conveniently.
Oh. Satan. Bugger.
I was just contemplating the potential “Goddidit” argument and reflecting on what a perverse, kinky, bizarro weirdo that would make God. But I must admit I hadn’t thought of the Evil One.
Mind you, if it was Satan – was that the best he could do? He’s supposed to be, like, the Ultimate Evil, and all he can do is fritz around bugging ants?
Pfft!
cr
Not a problem – it just displaces the question by one entity near the top of the Great Chain Of Being. Satan is a creation of God ; Satan does perverse kinky bizarro stuff because God intended him to do it. The fault lies with the God of the bizarro, not with Satan.
It wasn’t God. Or Satan. Maybe it’s because the fungus “knows” how to “decay” things so it’s able to “know” how to “give birth” to the stalk made out of ant brain coming from its head.
The irony of such assertions by the religiously credulous is that the control of a host by a fungal infection is analogous to the infection of a human mind by a self serving and propagating parasite of an information based infection such as religion.
A wild supposition: most of the normal ant’s behavioral sequences are triggered either by hormones or pheromones – for example in several species future queens climb in the vegetation to take off for their nuptial flight, and to bite hard if the nest is attacked is part of the normal defense behavior – and also several hymenopterans cling to twigs with their mandibles to sleep. If a parasitic fungus secretes a substance accidentaly similar to the corresponding ant’s hormone – or pheromone – it will induce the ant to climb and therefore increase its chances to reproduce, even better if the ant is tired and wants to sleep. A good basis for the selection to work on.
Thanks Jerry for sharing this study and your insights, but I want to quibble with your suggestions of the actions of the fungus that imply intent. “Why does the fungus not infiltrate the brain? We don’t know, but it’s possible that doing that would quickly kill the ant and render it useless for further growth and manipulation of behavior. Further (or in addition), it may be easier to control the ant’s behavior by secreting chemicals into an intact brain than by brute-force physical invasion of the brain.”
I suspect that you don’t really think the fungus is acting to avoid the ants premature death, or that it seeks to drive the ant like a cowboy drives a horse. Perhaps we could suspect that the growth of the fungus on the muscles causes the muscles to release (or inhibit the release of) chemical or electrical transmitters that reach the brain causing, unintentionally but beneficially, the ant to move. Also, I would speculate that the ants may be driven toward the strongest source of a pheromone rather than a specific altitude with a range of temperatures. Maybe even driven toward the source of that pheromone in order to bite into it and collect it.
Whatever the mechanism, I agree that the evolutionary path to reach this state is amazing!
Addressed:
My error – thanks Matt.
There are many examples of predators and parasites keeping their prey alive, but consuming nonvital parts, so they can use it to keep growing. So your claim that I don’t really think what I said is wrong. Yes, what I said I regard as a real possibility. And yes, the fungus has evolved, in all likelihood, to “drive the ant like a cowboy drives a horse.” This is what natural selection on the fungus does, and I see no alternative explanation.
What an important clarification. I suppose many of us first encountered this example in the writings of Daniel Dennett.
Yes, he did talk about zombie ants. As I recall, Dennett told the story of a fluke infecting an ant’s brain. It could be that the fluke uses different mechanisms.
The highly-acclaimed video-game The Last Of Us has you navigating a Cormac McCarthy-esque post-apocalypse ravaged by a variant of the cordyceps parasite that actually takes over human beings and changes their behaviour(it doesn’t make the affected humans climb plants and then collapse though, as that would make for a pretty rubbish in-game enemy).
Anyone wishing to use this as an example of “intelligent design”, will need to add “sadistic”.
Fantastic read! Thanks!
As for the seeming precision in getting the ant to place themselves at the specific temperature and humidity that is optimal to the fungus– I suggest that there is a fairly straightforward explanation. It could be that the ants are induced to die by the time they arrive at those settings, and the fungus secondarily evolved to be optimally productive under those conditions.
But why would infected ants tend to die in particular areas of relative humidity AND spatial directions?
Fascinating. I love the science posts, even if I can’t contribute much to the discussion.
I think I first heard about/saw cordyceps on Planet Earth, or maybe a different Attenborough shows.
Splitting hairs? The third photo down looks more like a dolichoderine Dolichoderus (Hypoclinea) than the formicine Camponotus. Something near D. validus or D. bispinosus. Perhaps an “ant person” could comment and set me straight? Ants of all kinds are attacked by these fungi, but few attack as viciously as Dolichoderus can.
The inevitable xkcd cartoon:
Mycology
That’s great!
Brilliant!
I guess we’re lucky there are no parasitic fungi that can do that sort of thing to us – imagine what that would be like – to be puppetted around …
Maybe this is how we can account for Trump’s presidency!
Keith: Are you absolutely sure we are not “puppetted around”? Or are you just being sarcastic?
We’re not coopted by other living things. I have no problem with being “integrated causally with the universe”. But if I had a brain-(or muscle-)altering parasite, I think that would be worse. Why? Because it probably *feels* worse, as we are used to our sense of agency.
After reading Daniel Dennett’s account of the ant, it occurred to me that humans with STDs should, in principle, exhibit behaviour likely to spread their STD. I was delighted to read in ‘The Man Who Mistook His Wife For a Hat’ an account of an elderly lady who had been rescued from a brothel many years previously by her husband. When young she had been infected by syphilis. In late life, she commented to her doctor that she was ‘feeling frisky’, shortly after which she became aware that her syphilis had resurfaced. Puppets!
STDs should, in principle, lead their hosts to behaviour which spreads them faster.
If they’ve adapted to their human hosts. If they’re a trivial branch of a species which normally lives on another species and only recently has come into infecting humans (eg through domestication or increased contact), with the main part of the population not being affected by the minor infection rate in humans.
It’s the old argument about allopatric speciation versus geographical isolation, but translated to a context of various host species taking the role of islands, or whichever geographic feature you want to use.
Consider the ecological space of Simian Immunodeficiency Viruses – for millions of years they bumbled along in various African simians, occasionally colonising a new “island/species”, then around 1957 on made a leap (by blood contact, or sexual contact, or whatever) into this new population of less hairy simians with fair transmissivity and a huge interconnected population. Cue HIV.
That’s studiable, of course.
Is there any evidence that this happens somehow?
We have the confound, needless to say, that there would be already a statistical tendency to promiscuity on the part of someone with an STD.
I’ve always assumed that when a parasite gets its host to do what seems like a complex specific behavior such as this, or when a worm gets an infected cricket jump far into a pond to drown, its by activating sets of sub-routines of the animals normal behavior by releasing specific neurotransmitters into discreet regions of the brain.
For example the ant climbing in grass might be related to its normal nest building behavior when they build flood proof chambers etc. If they could use the fungus to infect ants that either don’t build nests are build them with a very different architecture they might have a very different response to the parasite.
Perhaps they will be working on a fungicide to eliminate this fungus. After all, the ant serves purpose but the fungus only kills. Various forms of fungus are very harmful to plants and animals.
Huh? You want to spray? The Cordyceps fungi are diverse [probably thousands of species, and usually highly host-specific — to a single genus or species group. Not just ants — commonly beetle and lepidoptera larvae among others. A few of the affected species are economic pests, for what that’s worth.]. They don’t attack plants, pets, livsstock, people.
As argued in a Richard Attenborough Planet Earth sequence on cordyceps, the fungi likely contribute to species diversity by density-dependent predation. Overall, that’s a positive for ecosystem health.
Some cordyceps are of economic value — for TCM. Unlike the poor biturong, cordyceps may have contribute some some compounds with pharmacological affect, Though, again, a poor substitute for Viagra.
My offhand guess is they send a chemical signal that makes light more pleasant (or lack of light painful). This would, I think, be a relatively simple biological trigger that causes the ‘climbing’ effect without having to mess much with the brain or directly control the muscles.
There’s probably a number of ways to test this. Here’s just two: (1) observe in nature if the climbing occurs at night. (2) make a lab set up with two identical plants but where one has more access to light, see which the ant prefers.
A similar but ‘opposite stimuli’ fungal strategy might be to alter the ant’s pheromone receptors so that some smell associated with the group (humous, soil, something like that) is painful to them. That would also induce climbing.
Next we need someone to explain this:
Damn auto-play, I meant to post this:
http://www.youtube.com/watch?v=D7r1S6-op8E
This is so fascinating. I wonder if the fungus not being in the ant’s brain has anything to do with the fact that the fungus stalk grows out of the ant’s head. Maybe the fungus uses only the muscles to then use parts of the brain for the stalk. It would be interesting to find out in what way the stalk was made if they could use a similar immunofluorescent stain to determine the ant’s brain and the composition of the stalk. It’s very interesting to think about the ant crawling up to a specific place on the leaf and biting down. I wonder if the ant isn’t as much of a zombie as the ant is like a person suffering from ALS.
It’s not clear to me that these two possibilities are mutually exclusive. If the fungus preferentially extracts nutrients from some muscles but not others, that presumably affects the ant’s motor function in a way that alters its behavior. Why shouldn’t we expect natural selection to fine-tune that alteration to benefit the fungus?
I’m not saying this is the whole story, just that I don’t see why it should be ruled out as part of the story.
“what were the intermediate steps in the evolution of this kind of host manipulation?”
To me this is a less-thorny problem than many other examples of hard-wiring behavior.
There are a huge number of cordyceps and they infect insects in a wide range of habitats. Some hosts [eg, externally-feeding caterpillars] may already be in exposed sites. — The cordyceps may just stop the larva in its tracks — some of these seem to overgrow the host with hyphae, probably tacking it down.
For typically subterranean insects — ants, beetle grubs — behavioral modification can make a huge difference in dispersion of spores. My assumption of the predecessor of this ant parasite simply ‘told’ its host to walk toward the light [positive phototropism] and/or “up [negative geotropism]. Both could easily be hormonally-controlled in the insect. Fine-tuning for optimal height, optimal light, optimal humidity, and adhesion would all be accessible to selective pressures from a very simple behavioral platform.
Thanks for this interesting post.
What a horrible way to die…natural selection is awesome, but cruel.
Where is the intention necessary to the concept of cruelty?
Sub
Zombie ants! I love zombie ants! I don’t understand why it is thought that the fungus controls the brain and not just the muscles though. Can someone please clarify?