Like most scientists, I attend professional meetings every now and then, and I recently returned from the annual meeting of something called the Society for Neuroscience, an organization of most of Earth’s brain researchers. Now, this is one of the more intellectually assaultive experiences that you can imagine. For one thing, there’s about twenty-eight thousand of us science nerds jammed into one convention center, and this begins to feel pretty nutty after a while—for an entire week, go into any restaurant, elevator, bathroom, and the folks standing next to you will be having some animated discussion about squid axons. Then there’s finding out about the science itself. The meeting has fourteen thousand lectures and posters, a completely overwhelming amount of information. And of the subset of those posters that are essential for you to check, a bunch you never get to see because of the enthusiastic crowds in front of them, another turns out to be in some language you don’t even recognize, and then there’s the critical poster that reports every experiment you planned to do for the next five years. And amid this all, there’s this shared realization that despite the zillions of us slaving away at the subject, we still know squat about how the brain works.
My own low point came one afternoon as I sat on the steps of the convention center, bludgeoned by all this information and a general sense of ignorance. My eyes focused on a stagnant, murky puddle of water by the curb, and I realized that some microscopic bug festering in that puddle probably knew more about the brain than all of us neuroscientists combined.
My demoralized insight was prompted by a recent, extraordinary paper about how certain parasites control the brain of their host. Most of us know that bacteria, protozoans, and viruses have astonishingly sophisticated ways of using animal bodies for their own purposes. They hijack our cells, our energy, and our lifestyles so they can thrive. As one example of their cleverness, some viruses go latent in the bodies of mammals and just wait there, biding their time. When does it make sense for them to come out of latency, to activate and replicate? When the mammal’s immune system is suppressed, not at its best. When are immune systems suppressed? During stress. Contained in the DNA of these viruses are detectors that are activated by stress hormones. So get good and stressed by a chronic illness, starvation, a string of final exams, and these viruses know it, come roaring out of latency to replicate while your immune system is at its worst. And suddenly you get that herpes cold-sore flare-up. Then there are tropical protozoans like trypanosomes that invade your body and defeat you because every few weeks they’re able to switch the identifying fingerprint of proteins on their cell surfaces, just as your immune system was about to recognize and attack them. Or then there are blood flukes like schistosomes, which don’t even bother switching identities. Instead, they steal yours—cloaking themselves in your own identifying cell-surface proteins, so that they are immunologically invisible.
But in many ways, the most dazzling and fiendish thing that such parasites have evolved—and the subject that occupied my musings that day—is their ability to change a host’s behavior for their own ends. Some textbook examples involve ectoparasites, organisms that colonize the surface of the body. For instance, certain mites of the genus Antennophorus ride on the backs of ants and, by stroking an ant’s mouthparts, can trigger a reflex that culminates in the ant’s disgorging food for the mite to feed on. A species of pinworm of the genus Syphacia lays eggs on a rodent’s skin, the eggs secrete a substance that causes itchiness, the rodent grooms the itchy spot with its teeth, the eggs get ingested, and once inside the rodent they happily hatch.
Bizarre as these examples are, things get even stranger when considering the ways that parasites manipulate our behavior from inside us. Some examples involve parasites with sequential hosts—they go through one life stage inside the body of some intermediate host, then reproduce or replicate inside the body of a definitive host. The challenge is to move from the former to the latter host. So the parasite may damage the muscles of an intermediate host, blind it, parasitize the host’s food, forcing it to concentrate on foraging instead of looking over its shoulder—all ways to increase the likelihood of the intermediate host, along with the parasite inside, winding up in the predator who is the definitive host.
Things get even weirder when considering parasites that alter the function of the nervous system itself. Sometimes, this is done indirectly, by manipulating hormones that affect the nervous system. There are barnacles (Sacculina granifera), a form of crustacean, that attach to male sand crabs and secrete a feminizing hormone that induces maternal behavior. The zombified crabs then migrate out to sea with brooding females and make depressions in the sand ideal for dispersing larvae. The males, naturally, won’t be releasing any. But the barnacles will. And if the barnacle infects a female, it induces the same maternal behavior—after atrophying the female’s ovaries, a practice called parasitic castration.
The ultimate, though, is when a parasite gets into the brain itself. These are microscopic, mostly viruses, rather than relatively gargantuan creatures like mites, pinworms, and barnacles. Once one of these tiny parasites is inside the brain, it remains fairly sheltered from immune attack, and it can go to work diverting neural machinery to its own advantage.
The rabies virus is one such parasite. There are lots of ways rabies could have evolved to move between hosts. The virus didn’t have to go anywhere near the brain itself. It could have developed a trick similar to the one employed by the agents that cause nose colds—namely, to irritate the nerve endings in your nasal passages, causing you to sneeze and spritz viral replicates all over the person sitting in front of you at the movies. Or the virus could have evolved an ability to induce an insatiable desire to lick someone, thereby passing on virus shed into the saliva. Instead, as we all know, rabies can cause its host to become aggressive so the virus can jump into another host via saliva that gets into the wounds.
Just think about this. Scads of neurobiologists study the neural basis of aggression—the pathways in the brain that are involved, the relevant neurotransmitters, the interactions between genes and environment, modulation by hormones, and so on. There are conferences on the subject, doctoral theses, petty academic squabbles, nasty tenure disputes, the works—while all along the rabies virus “knows” just which neurons to infect to make someone rabid.
Despite how impressive these viral effects are, there’s still room for improvement. This is because of the parasite’s nonspecificity. If you’re a rabid animal, you might bite one of the few creatures that rabies does not replicate well in, such as a rabbit. So while the behavioral effects of infection of the brain with parasites can be pretty dazzling, if the effects are too broad, that parasite could wind up in a dead-end host.
Which brings us to a beautifully specific case of brain control and the paper I mentioned earlier, by Manuel Berdoy and colleagues at Oxford University. Berdoy and associates study a parasite called Toxoplasma gondii. In a toxoplasmic utopia, life consists of a two-host sequence of rodent and cat. The protozoan gets ingested by a rodent, where it forms cysts throughout the body, particularly the brain. The rodent gets eaten by a cat, where Toxoplasma reproduces. The cat sheds the parasite in the feces, which, in one of those circles of life, is nibbled at by rodents. The whole scenario hinges on specificity, in that cats are the only species in which Toxoplasma can reproduce and be shed. Thus, Toxoplasma wouldn’t want its carrier rodent to get picked off by a hawk, or its cat feces to get ingested by a dung beetle. Mind you, the parasite can infect all sorts of other species; it simply has to wind up in a cat if it wants to reproduce.
This potential to infect other species is the reason why all those “what to do during pregnancy” books advise banning the cat and its litter box from the house and warn pregnant women against gardening if cats are wandering about. If toxoplasma from cat feces gets into a pregnant woman, it can get into the fetus, potentially causing neurological damage.
Thus, well-informed pregnant women get skittish of cats. And the extraordinary trick that Toxoplasma has evolved is to make rodents unskittish of cats. All good rodents avoid cats—a behavior ethologists call a fixed action pattern, in that the rodent doesn’t develop the aversion due to trial and error (since there aren’t likely to be many opportunities to learn from one’s errors around cats). Instead, feline phobia is hardwired. And it is accomplished through olfaction, through pheromones, the chemical odorant signals that animals release. Rodents instinctually shy away from the smell of a cat—even rodents that have never seen a cat in their lives, who are the descendants of hundreds of generations of lab animals. Except for those rodents infected with Toxoplasma. As Berdoy and colleagues showed, rodents selectively lose their aversion to and fear of cat pheromones. Instead, they become attracted to the smell.
Now, this is not some generic case of a parasite messing with the head of the intermediate host and making it scatterbrained and vulnerable. Everything else seems pretty intact in the rodents. The social status of the animal doesn’t change in its dominance hierarchy. It is still interested in mating and thus, de facto, in the pheromones of the opposite sex. It can still distinguish other odors (for example, of itself, or of a perfectly benign bunny). All that happens is that the rodent no longer recoils from cat pheromones and instead gravitates toward them. This is flabbergasting. This is like someone getting infected with a brain parasite that has no effect whatsoever on the person’s thoughts, emotions, SAT scores, or television preferences, but, to complete its life cycle, generates an irresistible urge to go to the zoo, scale a fence, and French-kiss the pissiest-looking polar bear. A parasite-induced fatal attraction, as Berdoy’s team noted in the title of its paper.
Obviously, more research is needed. I say this not only because that’s obligatory around this point in any article about science, but because this finding is just so intrinsically cool that someone has to figure out how this works. And because—permit me a Stephen Jay Gould moment, if you will—it provides ever more evidence that evolution is amazing. Amazing in ways that are counterintuitive. There is a deeply entrenched idea that evolution is directional and progressive. If you believe this, your thinking goes something like this: invertebrates are more primitive than vertebrates, mammals are the most evolved of vertebrates, primates are the genetically fanciest mammals, and so on until, ultimately, there’s seeming scientific proof for the evolutionary superiority of whatever race, ethnicity, or bowling league you belong to. And it is simply wrong.
So remember, creatures are out there that can control brains (and, in the process, can run circles around neuroscientists). My reflection on a curbside puddle brought me to the opposite conclusion from what Narcissus reached in his watery reflection. We need phylogenetic humility. We are certainly not the most evolved species around, nor the least vulnerable. Nor the cleverest.
NOTES AND FURTHER READING
For a good general overview of the subject, see Moore J, Parasites and the Behavior of Animals (Cambridge: Oxford University Press, 2002).
The amazing Toxoplasma study is reported in Berdoy M, Webster J, and Macdonald D, “Fatal attraction in rats infected with Toxoplasma gondii,” Proceedings of the Royal Society of London, B 267 (2000): 1,591.
Mites riding on the backs of ants, pinworms, itchy rodents, and barnacle-infected crabs, are all discussed in Moore J, Parasites and the Behavior of Animals.
A lot of the essays in this book represent hit-and-run obsessions—for a couple of months, I get crazed about some topic, read endlessly on it, drive my wife to distraction with my monologues on the topic. I eventually write something, getting it out of my system, thereby freeing me to fixate on a next topic. This essay started this way as well. However, that astonishing report about the behavioral effects of Toxoplasma has continued to intrigue me sufficiently so that I recently recruited a superb young scientist, Dr. Ajai Vyas, to my lab to try to figure out what Toxoplasma is doing in the brain of a rodent. Stay tuned.