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Jaroslav Flegr: A manipulation hypothesis

Brain parasite influences human behavior, Czech scientist says

Posted: February 28, 2007

By Paul Voosen

Rats are perceptive little devils, switched on to any change in their environment, be it a dropped piece of cheese or the patter of a tabby cat. But, according to recent research, cats may have an unexpected ally in this eternal battle of Tom and Jerry: the protozoan parasite Toxoplasma gondii.

Scientists have proven that this parasite, when nestled into the brains of otherwise normal rats, slows reaction times and causes “an almost suicidal attraction to cats,” says Joanne Webster, a British scientist who led the research.

Why would Toxoplasma want its rat hosts eaten by cats? It’s the natural drive to multiply: While Toxoplasma can live in many animals, it can only reproduce in cat intestines. So, over the eons, some scientists say, Toxoplasma has evolved the ability to influence its host, improving the parasite’s odds of returning to a cat.

The possibility that a parasite could evolve such a talent is called the manipulation hypothesis, and it’s controversial even when applied to rats. But, according to one Czech scientist, Toxoplasma doesn’t stop there. He has met another victim of manipulation, and it is us.

For the past 15 years, Jaroslav Flegr, 48, an evolutionary biologist in the department of parasitology at Charles University, has led a sometimes quixotic quest to prove that Toxoplasma — one of the world’s most common parasites, infecting some 30 percent of the Czech population and a higher percentage than that worldwide — is pulling primeval levers in our brains, a backseat driver directing our moods, warmth and ability to trust.

He says this quite calmly in a delicate voice as he sits in his basement office on a recent afternoon, its walls lined perilously high with strained bookshelves. In the best of scientific traditions, his carrot-colored hair sprouts wildly from his head, resembling a stretched-out wire brush. Next door in his lab, students wait to leech information from him during his office hours.

“Most people never learn they are infected,” he says, because initial symptoms from toxoplasmosis, as Toxoplasma gondii infections are called, resemble a low-grade flu; detection comes through a simple blood test. After a few weeks, the malaise tails off as the parasite goes latent, lodging for the long term: Once you contract toxoplasmosis, it’s with you for life. No big deal, scientists say, since latent infection is asymptomatic — harmless.

But, since Flegr returned to Charles University, his alma mater, from the Czech Academy of Sciences and started his research in 1992, he has been skeptical of the conventional wisdom. And he is now convinced it is wrong.

“We know now that these changes between infected and Toxoplasma-free subjects are real and concern not only personality,” he says, “but real behavior.”

Flegr’s research is gaining some acceptance in the scientific community, bolstered by testing on rodents and interest from U.S. schizophrenia researchers.

“He is very much a pioneer in this area, looking at possible personality changes,” says E. Fuller Torrey, a prominent American psychologist who is studying links between schizophrenia and toxoplasmosis.

“I don’t know anyone else in the world doing what’s he’s doing,” Torrey says. “I admire him for it. It sounds crazy, but, when you look at it, you really become a believer.”

Social studies

It has long been thought that toxoplasmosis could illustrate the manipulation hypothesis in lower animals, Flegr says, but he had a hunch that even humans could be susceptible. And, as it turned out, it was far more affordable to research that idea than it would have been to study toxoplasmosis in animals.

“Animals are very expensive,” he says. “It’s necessary to feed them and so on. So I decided to study the manipulation hypothesis on our students. We have a lot of them. They keep and feed themselves.” And, since the parasite is so common, Flegr knew a percentage would be infected.

Flegr’s students would have contracted toxoplasmosis in two ways: Eating raw or undercooked meat — particularly lamb, pork or rabbit — or swallowing cat feces, which contain hardened versions of the parasite that can survive for years in the soil. And yes, this does happen: Think unwashed vegetables or playing in sandboxes as a kid. The food-hygiene connection is why countries such as France and Germany have infection rates nearing 50 percent.

Once you ingest the parasite, it crosses the lining of your intestines and begins invading cells, creating cysts that allow it to feast on cholesterol, amino acids and lipids. It can invade almost any cell that has a nucleus, and it hooks rides in the bloodstream that bring it to muscles and the brain, where it settles for its latent phase, says Keith Joiner, a doctor at the University of Arizona who studies the parasite.

For the first 10 years of his studies, Flegr was not researching the physical mechanisms of Toxoplasma — again, expensive — but rather drawing on resources from the social sciences. He had students fill out 40-minute personality questionnaires, comparing their answers to infection rates for any correlation. He had some positive results, which he replicated in subsequent surveys.

What he found was that people with toxoplasmosis demonstrated subtle changes in their personalities, which increased with the time of infection. Strangely, the parasite seems to have opposite effects on men and women.

“Infected women become more trusting and men less so,” he says. “Most changes are connected to trust. … Infected women are more warmhearted and have more social contacts,” while men become asocial loners.

Flegr is aware of the problems that can come with personality tests. “At first it wasn’t clear whether people getting infected had similar personality types” and that made them more likely to get infected — asocial men may not wash their hands, or warmhearted women are more likely to have cats, for example. But, he says, later studies prove that toxoplasmosis indeed causes the changes.

Because of serious skepticism, Flegr says, “it was very difficult to publish our studies.”

“Humans are not at all interested in thinking that something like a protozoa can get in your brain and alter your behavior,” says Torrey, the American psychologist. “We’re still in the end of the Freudian era. … The idea that a parasite could alter the brain is an insult to the human being.”

And some, like Christopher Genovese, a statistician at Carnegie Mellon who has read Flegr’s publications and is intrigued by his work (“Certainly I’ll be thinking about cooking my meat a little better,” he says), thinks Flegr still has a way to go in proving causation. Personality questionnaires, while a fine tool, are “very limited in what they can tell you,” he says. They can simplify and “bring unduly strong conclusions on the nature of personality change.” Flegr’s reaction-time studies are stronger, Genovese says.

Fleger moved on from personality and behavior tests to reaction-time studies on humans after his first decade. Toxoplasmosis had been proven to slow reaction times in lab rats, but Fleger found it affected people the same way.

For one study, Flegr’s team hit the hospitals to look at whether Toxoplasma-infected subjects caused traffic accidents. The results were startling: “We found that infected subjects were 2.65 times more likely to cause accidents, both as the driver and pedestrian.” Recent work in Turkey has replicated the results.

While his more recent studies have a higher credibility, Flegr admits in a paper that “confounding factors” still can’t be ruled out — reckless drivers may make reckless eaters. These questions will continue to dog him until a mechanism, the cause and effect of how Toxoplasma gondii manipulates the brain, is discovered.

‘A black box’

There are proven health risks from toxoplasmosis: The parasite can cripple the minds of fetuses (why pregnant women shouldn’t change kitty litter) and, when the body’s immune system is compromised, the parasite can reactivate and become life-threatening, most commonly in AIDS patients.

Looking at brain scans of these patients, it is clear that “where the parasite has started to remultiply is where it existed before,” says the University of Arizona’s Joiner. “There’s a pattern to this.” Such patterns suggest the infection is targeting portions of the brain, which means it could prompt similar changes in every brain it infects.

Flegr believes toxoplasmosis raises brain dopamine levels, which is connected with the testosterone production and could explain the personality differences between men and women: “It seems the concentration of testosterone in infected men goes up, and in infected women goes down,” he says.

But there is much left to be proven.

“Toxoplasmosis is very much a black box,” Webster says. “It is likely that dopamine is involved. [But] we need to prove mechanisms, and that will require more invasive studies.”

Such studies aren’t simple or cheap and, since you can’t deliberately infect humans with the parasite, different methodologies will have to be discovered, says Joiner.

Flegr plans to study possible mechanisms further, and will also be working with Torrey on his research into possible ties between schizophrenia and toxoplasmosis. In the meantime, Torrey would like to see others verify Flegr’s work.

“I don’t doubt it, but it needs to be replicated,” he says. “And we would fund it. But there’s a lot of resistance to studying this. If you want to become a full professor, you avoid controversial subjects.”

Even if it’s found that the parasite does not manipulate humans, it is imperative that Toxoplasma gondii be better understood. That’s because it’s so widespread, Joiner says: “If there are consequences to human behavior, it will be important to figure out what they are.”

Flegr is Toxoplasma-positive himself. He thinks he contracted it during a year spent studying in Tokyo, the only place he’s lived besides Prague. He doesn’t seem at all concerned about the diagnosis, but he’s convinced that Toxoplasma is altering his own personality, perhaps enhancing his quiet, lone-wolf nature. “But,” he says, “any change is relatively small.”

He smirks at how people will react if he proves beyond a doubt that our behavior is subject in any way to a parasite. Whither free will? It could be a convenient cop-out, in the end.

“People may like this idea,” he says. “They can say, when in the wrong, ‘Oh, it’s not me. It’s toxoplasmosis doing this.’ ”

By Paul Voosen

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