The Return of the Puppet Masters by Carl Zimmer

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http://loom.corante.com/archives/2006/01/17/the_return_of_the_puppet_masters.php

 

The Loom

 

 

January 17, 2006

The Return of the Puppet Masters

 

 

Posted by Carl Zimmer

 

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,

sheddding 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 offpsring.

 

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.

 

 

Update 2/9: link to new PRSL paper fixed.

 

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