Or at least this is the theory proposed in Brain Evolution Through The Lens Of Parasite Manipulation by Marco del Giudice.
The paper starts with an overview of parasite manipulation of host behavior. These are the stories you hear about toxoplasma-infected rats seeking out cats instead of running away from them, or zombie ants climbing stalks of grass so predators will eat them. The parasite secretes chemicals that alter host neurochemistry in ways that make the host get eaten, helping the parasite transfer itself to a new organism.
Along with rats and ants, there is a dizzying variety of other parasite manipulation cases. They include parasitic wasps who hack spiders into forming protective webs for their pupae, parasitic flies that cause bees to journey far from their hive in order to spread fly larva more widely, and parasitic microorganisms that cause mosquitoes to draw less blood from each victim (since that forces the mosquitoes to feed on more victims, and so spread the parasite more widely). Parasitic nematodes make their ant hosts turn red, which causes (extremely stupid?) birds to mistake them for fruit and eat them. Parasitic worms make crickets seek water; as the cricket drowns, the worms escape into the pond and begin the next stage of their life cycle. Even mere viruses can alter behavior; the most famous example is rabies, which hacks dogs, bats, and other mammals into hyperaggressive moods that usually result in them biting someone and transmitting the rabies virus.
Even our friendly gut microbes might be manipulating us. People talk a lot about the “gut-brain axis” and the effect of gut microbes on behavior, as if this is some sort of beautiful symbiotic circle-of-life style thing. But scientists have found that gut microbes trying to colonize fruit flies will hack the flies’ food preferences to get a leg up – for example, a carb-metabolizing microbe will secrete hormones that make the fly want to eat more carbs than fat in order to outcompete its fat-metabolizing rivals for gut real estate; there are already papers speculating that the same processes might affect humans. Read Alcock 2014 and you will never look at food cravings the same way again.
But del Giudice thinks this is just the tip of the iceberg. Throughout evolutionary history, parasites have been trying to manipulate host behavior and hosts have been trying to avoid manipulation, resulting in an eons-long arms race. The equilibrium is what we see today: parasite manipulation is common in insects, rare in higher animals, and overall of limited importance. But in arms race dynamics, the current size of the problem tells you nothing about the amount of resources invested in preventing the problem. There is zero problem with war between Iran and Saudi Arabia right now, but both sides have invested billions of dollars in military supplies to keep their opponent from getting a leg up. In the same way, just because mammals usually avoid parasite behavior manipulation nowdoesn’t mean they aren’t on a constant evolutionary war footing.
So if you’re an animal at constant risk of having your behavior hijacked by parasites, what do you do?
First, you make your biological signaling cascades more complicated. You have multiple redundant systems controlling every part of behavior, and have them interact in ways too complicated for any attacker to figure out. You have them sometimes do the opposite of what it looks like they should do, just to keep enemies on their toes. This situation should sound very familiar to anyone who’s ever studied biology.
Del Giudice compares the neurosignaling of the shrimp-like gammarids (small, simple, frequently hijacked by parasites) to rats (large, complex, hard to hijack). Gammarids have very simple signaling: high serotonin means “slow down”, low serotonin means “speed up”. The helminths that parasitize gammarids secrete serotonin, and the gammarids slow down and get eaten, transferring the parasite to a new host. Biologists can replicate this process; if they inject serotonin into a gammarid, the gammarid will slow down in the same way.
Toxoplasma hijacks rats and makes them fearless enough to approach cats. Dopamine seems to be involved somehow. But researchers injecting dopamine into rats don’t get the same result; in fact, this seems to make rats avoid cats more. Maybe toxoplasma started by increasing dopamine, rats evolved a more complicated signaling code, and toxoplasma cracked the code and now increases dopamine plus other things we don’t understand yet.
Aside from the brain, the immune system is the most important target to secure, so this theory should predict that immune signaling will also be unusually inscrutable. Again, this situation should sound very familiar to anyone who’s ever studied biology.
Second, you have a bunch of feedback loops and flexibility ready to deploy at any kind of trouble. If something makes dopamine levels go up, you decrease the number of dopamine receptors, so that overall dopaminergic neurotransmission is the same as always. If something is making you calmer than normal, you have some other system ready to react by making you more anxious again.
Del Giudice makes the obvious connection to psychopharmacology. Many psychoactive drugs build tolerance quickly: for example, heroin addicts constantly need higher and higher doses to get their “hit”. Further, tolerance builds in a pattern weirdly similar to antibody response – it takes a while to build up a cocaine tolerance, and you lose it over time if you don’t use cocaine, but the body “remembers” the process and a single hit of cocaine years later is sufficient to bring you back up to the highest tolerance level you’ve ever had.
The standard explanation for tolerance is that it’s an attempt to maintain homeostasis against the sort of conditions that can cause natural variation in neurotransmitter levels. I never questioned this before. But why is the body prepared to suddenly have all its serotonin reuptake transporters inhibited? Is that something that frequently happens, out in nature? I guess maybe plant toxins could do that, but then how come the body is prepared to deal with this for months or years?
While not denying the value of these standard explanations, Del Giudice thinks defense against parasite behavior manipulation may also play a role. Remember, gammarids absolutely have parasites that try to increase their serotonin levels as a prelude to getting them killed. Is it that surprising that a lot of different animal lineages would develop a reaction of “If something other than normal cognition has started increasing your serotonin levels, it’s a trap and you need to get them back down again”? Does that explain why SSRIs don’t work for some people, or randomly stop working, or need frequent dose escalation?
The paper starts with an overview of parasite manipulation of host behavior. These are the stories you hear about toxoplasma-infected rats seeking out cats instead of running away from them, or zombie ants climbing stalks of grass so predators will eat them. The parasite secretes chemicals that alter host neurochemistry in ways that make the host get eaten, helping the parasite transfer itself to a new organism.
Along with rats and ants, there is a dizzying variety of other parasite manipulation cases. They include parasitic wasps who hack spiders into forming protective webs for their pupae, parasitic flies that cause bees to journey far from their hive in order to spread fly larva more widely, and parasitic microorganisms that cause mosquitoes to draw less blood from each victim (since that forces the mosquitoes to feed on more victims, and so spread the parasite more widely). Parasitic nematodes make their ant hosts turn red, which causes (extremely stupid?) birds to mistake them for fruit and eat them. Parasitic worms make crickets seek water; as the cricket drowns, the worms escape into the pond and begin the next stage of their life cycle. Even mere viruses can alter behavior; the most famous example is rabies, which hacks dogs, bats, and other mammals into hyperaggressive moods that usually result in them biting someone and transmitting the rabies virus.
Even our friendly gut microbes might be manipulating us. People talk a lot about the “gut-brain axis” and the effect of gut microbes on behavior, as if this is some sort of beautiful symbiotic circle-of-life style thing. But scientists have found that gut microbes trying to colonize fruit flies will hack the flies’ food preferences to get a leg up – for example, a carb-metabolizing microbe will secrete hormones that make the fly want to eat more carbs than fat in order to outcompete its fat-metabolizing rivals for gut real estate; there are already papers speculating that the same processes might affect humans. Read Alcock 2014 and you will never look at food cravings the same way again.
But del Giudice thinks this is just the tip of the iceberg. Throughout evolutionary history, parasites have been trying to manipulate host behavior and hosts have been trying to avoid manipulation, resulting in an eons-long arms race. The equilibrium is what we see today: parasite manipulation is common in insects, rare in higher animals, and overall of limited importance. But in arms race dynamics, the current size of the problem tells you nothing about the amount of resources invested in preventing the problem. There is zero problem with war between Iran and Saudi Arabia right now, but both sides have invested billions of dollars in military supplies to keep their opponent from getting a leg up. In the same way, just because mammals usually avoid parasite behavior manipulation nowdoesn’t mean they aren’t on a constant evolutionary war footing.
So if you’re an animal at constant risk of having your behavior hijacked by parasites, what do you do?
First, you make your biological signaling cascades more complicated. You have multiple redundant systems controlling every part of behavior, and have them interact in ways too complicated for any attacker to figure out. You have them sometimes do the opposite of what it looks like they should do, just to keep enemies on their toes. This situation should sound very familiar to anyone who’s ever studied biology.
Del Giudice compares the neurosignaling of the shrimp-like gammarids (small, simple, frequently hijacked by parasites) to rats (large, complex, hard to hijack). Gammarids have very simple signaling: high serotonin means “slow down”, low serotonin means “speed up”. The helminths that parasitize gammarids secrete serotonin, and the gammarids slow down and get eaten, transferring the parasite to a new host. Biologists can replicate this process; if they inject serotonin into a gammarid, the gammarid will slow down in the same way.
Toxoplasma hijacks rats and makes them fearless enough to approach cats. Dopamine seems to be involved somehow. But researchers injecting dopamine into rats don’t get the same result; in fact, this seems to make rats avoid cats more. Maybe toxoplasma started by increasing dopamine, rats evolved a more complicated signaling code, and toxoplasma cracked the code and now increases dopamine plus other things we don’t understand yet.
Aside from the brain, the immune system is the most important target to secure, so this theory should predict that immune signaling will also be unusually inscrutable. Again, this situation should sound very familiar to anyone who’s ever studied biology.
Second, you have a bunch of feedback loops and flexibility ready to deploy at any kind of trouble. If something makes dopamine levels go up, you decrease the number of dopamine receptors, so that overall dopaminergic neurotransmission is the same as always. If something is making you calmer than normal, you have some other system ready to react by making you more anxious again.
Del Giudice makes the obvious connection to psychopharmacology. Many psychoactive drugs build tolerance quickly: for example, heroin addicts constantly need higher and higher doses to get their “hit”. Further, tolerance builds in a pattern weirdly similar to antibody response – it takes a while to build up a cocaine tolerance, and you lose it over time if you don’t use cocaine, but the body “remembers” the process and a single hit of cocaine years later is sufficient to bring you back up to the highest tolerance level you’ve ever had.
The standard explanation for tolerance is that it’s an attempt to maintain homeostasis against the sort of conditions that can cause natural variation in neurotransmitter levels. I never questioned this before. But why is the body prepared to suddenly have all its serotonin reuptake transporters inhibited? Is that something that frequently happens, out in nature? I guess maybe plant toxins could do that, but then how come the body is prepared to deal with this for months or years?
While not denying the value of these standard explanations, Del Giudice thinks defense against parasite behavior manipulation may also play a role. Remember, gammarids absolutely have parasites that try to increase their serotonin levels as a prelude to getting them killed. Is it that surprising that a lot of different animal lineages would develop a reaction of “If something other than normal cognition has started increasing your serotonin levels, it’s a trap and you need to get them back down again”? Does that explain why SSRIs don’t work for some people, or randomly stop working, or need frequent dose escalation?
by Scott Alexander, Slate Star Codex | Read more:
