mind-controlling cats?

originally posted by Carl Zimmer to the Loom on January 17, 2006:

The Return of the Puppet Masters

Are brain parasites altering the personalities of three billion people? The question emerged a few years ago, and it shows no signs of going away.

I first encountered this idea while working on my book Parasite Rex. I was investigating the remarkable ability parasites have to manipulate the behavior of their hosts. The lancet fluke Dicrocoelium dendriticum, for example, forces its ant host to clamp itself to the tip of grass blades, where a grazing mammal might eat it. It's in the fluke's interest to get eaten, because only by getting into the gut of a sheep or some other grazer can it complete its life cycle. Another fluke, Euhaplorchis californiensis, causes infected fish to shimmy and jump, greatly increasing the chance that wading birds will grab them.

Those parasites were weird enough, but then I got to know Toxoplasma gondii. This single-celled parasite lives in the guts of cats, shedding eggs that can be picked up by rats and other animals that can just so happen be eaten by cats. Toxoplasma forms cysts throughout its intermediate host's body, including the brain. And yet a Toxoplasma-ridden rat is perfectly healthy. That makes good sense for the parasite, since a cat would not be particularly interested in eating a dead rat. But scientists at Oxford discovered that the parasite changes the rats in one subtle but vital way.

The scientists studied the rats in a six-foot by six-foot outdoor enclosure. They used bricks to turn it into a maze of paths and cells. In each corner of the enclosure they put a nest box along with a bowl of food and water. On each the nests they added a few drops of a particular odor. On one they added the scent of fresh straw bedding, on another the bedding from a rat's nests, on another the scent of rabbit urine, on another, the urine of a cat. When they set healthy rats loose in the enclosure, the animals rooted around curiously and investigated the nests. But when they came across the cat odor, they shied away and never returned to that corner. This was no surprise: the odor of a cat triggers a sudden shift in the chemistry of rat brains that brings on intense anxiety. (When researchers test anti-anxiety drugs on rats, they use a whiff of cat urine to make them panic.) The anxiety attack made the healthy rats shy away from the odor and in general makes them leery of investigating new things. Better to lie low and stay alive.

Then the researchers put Toxoplasma-carrying rats in the enclosure. Rats carrying the parasite are for the most part indistinguishable from healthy ones. They can compete for mates just as well and have no trouble feeding themselves. The only difference, the researchers found, is that they are more likely to get themselves killed. The scent of a cat in the enclosure didn't make them anxious, and they went about their business as if nothing was bothering them. They would explore around the odor at least as often as they did anywhere else in the enclosure. In some cases, they even took a special interest in the spot and came back to it over and over again.

The scientists speculated that Toxoplasma was secreted some substance that was altering the patterns of brain activity in the rats. This manipulation likely evolved through natural selection, since parasites that were more likely to end up in cats would leave more offpspring.

The Oxford scientists knew that humans can be hosts to Toxoplasma, too. People can become infected by its eggs by handling soil or kitty litter. For most people, the infection causes no harm. Only if a person's immune system is weak does Toxoplasma grow uncontrollably. That's why pregnant women are advised not to handle kitty litter, and why toxoplasmosis is a serious risk for people with AIDS. Otherwise, the parasite lives quietly in people's bodies (and brains). It's estimated that about half of all people on Earth are infected with Toxoplasma.

Given that human and rat brains have a lot of similarities (they share the same basic anatomy and use the same neurotransmitters), a question naturally arose: if Toxoplasma can alter the behavior of a rat, could it alter a human? Obviously, this manipulation would not do the parasite any good as an adaptation, since it's pretty rare for a human to be devoured by a cat. But it could still have an effect.

Some scientists believe that Toxoplasma changes the personality of its human hosts, bringing different shifts to men and women. Parasitologist Jaroslav Flegr of Charles University in Prague administered psychological questionnaires to people infected with Toxoplasma and controls. Those infected, he found, show a small, but statistically significant, tendency to be more self-reproaching and insecure. Paradoxically, infected women, on average, tend to be more outgoing and warmhearted than controls, while infected men tend to be more jealous and suspicious.

It's controversial work, disputed by many. But it attracted the attention of E. Fuller Torrey of the Stanley Medical Research Institute in Bethesda, Maryland. Torrey and his colleagues had noticed some intriguing links between Toxoplasma and schizophrenia. Infection with the parasite has been associated with damage to a certain class of neurons (astrocytes). So has schizophrenia. Pregnant women with high levels of Toxoplasma antibodies in their blood were more likely to give birth to children who would later develop schizophrenia. Torrey lays out more links in this 2003 paper. While none is a smoking gun, they are certainly food for thought. It's conceivable that exposure to Toxoplasma causes subtle changes in most people's personality, but in a small minority, it has more devastating effects.

A year later, Torrey and his colleagues discovered one more fascinating link. They raised human cells in Petri dishes and infected them with Toxoplasma. Then they dosed the cells with a variety of drugs used to treat schizophrenia. Several of the drugs--most notably haloperidol--blocked the growth of the parasite.

So Fuller and the Oxford scientists joined forces to find an answer to the next logical question: can drugs used to treat schizophrenia help a parasite-crazed rat? They now report their results in the Proceedings of the Royal Society of London (press release). They ran the original tests on 49 more rats. Once again, parasitized rats lost their healthy fear of cats. Then the researchers treated the rats with haloperidol and several other anti-psychotic drugs. They found that the drugs made the rats more scared. They also found that the antipsychotics were as effective as pyrimethamine, a drug that is specifically used to eliminate Toxoplasma.

There's plenty left to do to turn these results into a full-blown explanation of parasites and personalities. For example, what is Toxoplasma releasing into brains to manipulate its hosts? And how does that substance give rise to schizophrenia in some humans? And even if the hypothesis does hold up, it would only account for some cases of schizophrenia, while the cause of others would remain undiscovered. But still...the idea that parasites are tinkering with humanity's personality--perhaps even giving rise to cultural diversity--is taking over my head like a bad case of Toxoplasma.