A GAME OF CAT AND MOUSE
http://www.economist.com/sciencetechnology/displayStory.cfm?story_id=16271339
A game of cat and mouse
There is tantalising evidence that a common parasite may affect human behaviour
Jun 3rd 2010 | From The Economist print edition
IF AN alien bug invaded the brains of half the population, hijacked their neurochemistry, altered the way they acted and drove some of them crazy, then you might expect a few excitable headlines to appear in the press. Yet something disturbingly like this may actually be happening without the world noticing.
Toxoplasma gondii is not an alien; it is a relative of that down-to-earth pathogen Plasmodium, the beast that causes malaria. It is common: in some parts of the world as much as 60% of the population is infected with it. And it can harm fetuses and people with AIDS, because in each case their immune systems cannot cope with it. For other people, though, the symptoms are usually no worse than a mild dose of flu. Not much for them to worry about, then. Except that there is a growing body of evidence that some of those people have their behaviour permanently changed.
One reason to suspect this is that a country’s level of Toxoplasma infection seems to be related to the level of neuroticism displayed by its population. Another is that those infected seem to have poor reaction times and are more likely to be involved in road accidents. A third is that they have short attention spans and little interest in seeking out novelty. A fourth, possibly the most worrying, is that those who suffer from schizophrenia are more likely than those who do not to have been exposed to Toxoplasma.
Nor is any of this truly surprising. For, besides humans, Toxoplasma has two normal hosts: rodents and cats. And what it does to rodents is very odd indeed.
Joanne Webster of Imperial College, London, has been studying Toxoplasma for years. Like Plasmodium, which cycles between mosquitoes and man, Toxoplasma cycles between its rodent and feline hosts, living out different phases of its existence in each. In cats, it resides in the wall of the small intestine and passes out of the host in its faeces. These are then picked up by rats and mice (and also by other mammal species, including humans), where they form cysts in brain, liver and muscle tissue. Eventually, if the parasites are lucky, their rodent host is eaten by a cat and the whole cycle starts again.
Unlike Plasmodium, however, which can rely on the natural behaviour of mosquitoes to spread it around, Toxoplasma’s rodent hosts have a strong aversion to helping it into its next home. Which is where, in Dr Webster’s elegant phrase, fatal feline attraction comes in. Rats and mice infected with Toxoplasma start wandering around and drawing attention to themselves—in other words, behaving in ways that will bring them to the attention of cats. They are even, Dr Webster’s work suggests, attracted to the smell of cats.
How these behavioural changes come about was, until recently, obscure. But in 2009 Glenn McConkey of the University of Leeds, in England, analysed Toxoplasma’s DNA. When he compared the results with those of other species, he discovered that two of the bug’s genes encode enzymes involved in the production of a molecule called dopamine. This molecule acts, in animals that have nervous systems, as a chemical messenger between nerve cells. It does not, however, have any known function in single-celled critters. Moreover, dopamine is particularly implicated in schizophrenia. Haloperidol, an antipsychotic drug, works by blocking dopamine receptors.
Intriguingly, Dr Webster has found that haloperidol serves to reverse fatal feline attraction in rats. This suggests the parasite is indeed interfering with the brain’s dopamine system—and thus that it might be doing the same thing in people. Dr McConkey is now making a version of Toxoplasma with the dopamine genes excised, to see if rats infected with this modified bug are protected from the fatal attraction.
The evidence that human toxoplasmosis does more than appears at first sight is, it must be said, quite scattered. But it is intriguing and probably worth following up.
The connection with schizophrenia was originally suggested in the 1950s, but only really took off in 2003, when it was revived by Fuller Torrey of the Stanley Medical Research Institute, near Washington, DC. In collaboration with Bob Yolken of Johns Hopkins University, Dr Fuller discovered that people who suffer from schizophrenia are almost three times more likely than the general population to have antibodies to Toxoplasma.
That does not, of course, prove Toxoplasma causes schizophrenia. As every science student is taught from the beginning, correlation is not causation. It could be that schizophrenics are more susceptible to the infection, or some third, as yet unidentified variable may be involved.
Another interesting correlation has, though, been discovered by Jaroslav Flegr of Charles University in Prague. Dr Flegr has studied several aspects of the Toxoplasma question. In one case he looked at the infection rate of people involved in road accidents. Both drivers and pedestrians who had been in accidents were almost three times more likely to be infected than comparable individuals who had not been. Similar results have been found in Turkey, by Kor Yereli of Celal Bayar University, in Manisa. And Dr Flegr has found other abnormalities in infected people. These included reduced reaction times and shorter attention spans—both of which might help to explain the accident statistics—and a reduction in “novelty-seeking”.
This latter is curious. The sort of behaviour shown by rodents is, if anything, an increase in novelty-seeking. But the point is that novelty-seeking is controlled by nerve cells that respond to dopamine. Humans are dead-end hosts as far as Toxoplasma is concerned, so the exact effect will not have been honed by natural selection and may therefore be different from the one in animals that are actually useful to the parasite.
All of these suggested effects are obviously bad for the individuals involved, but some researchers go further and propose that entire societies are being altered by Toxoplasma. In 2006 Kevin Lafferty of the University of California, Santa Barbara, published a paper noting a correlation between levels of neuroticism established by national surveys in various countries and the level of Toxoplasma infection recorded in pregnant women (a group who are tested routinely). The places he looked at ranged from phlegmatic Britain, with a neuroticism score of -0.8 and a Toxoplasma infection rate of 6.6%, to hot-blooded France, which scored 1.8 and had an infection rate of 45%. Cross-Channel prejudices, then, may have an unexpected origin.
To repeat, correlation is not causation, and a lot more work would need to be done to prove the point. But it is just possible that a parasite’s desire to get eaten by a cat is shaping the cultures of the world.
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