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Old 03-11-2012, 10:43 AM #1
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Default Blurring the distinction between genetic and infectious disease

The Good News About the Virus in Your Genes

Might some forms of neurological illness, such as multiple sclerosis and schizophrenia, be caused at least partly by bacteria, viruses or other parasites? A largely Danish team has recently published evidence of a strong association between multiple sclerosis and a retrovirus, together with hints that a gene called TRIM5, which is used by cells to fight viruses, is especially active in people with MS.

Other illnesses have unexpectedly turned out to be caused by parasites. In the 1980s, Barry Marshall of the University of Western Australia ran into a brick wall of official disbelief for suggesting that a bacterium caused stomach ulcers. Only by deliberately infecting and then curing himself did he finally get the medical establishment's attention (and eventually the Nobel Prize).

The virus implicated in multiple sclerosis is called HERV-Fc1, a bizarre beast called an "endogenous" retrovirus. What this means is that its genes are part of the human genome. For millions of years, they have been integrated into our own DNA and passed on by normal heredity. It was one of the shocks of genomic science to find that the human genome contains more retroviral than "human" genes: some 5% to 8% of the entire genome.

Normally, the genes of endogenous retroviruses remain dormant, but—a bit like a computer virus that springs into action on a trigger—something wakes them up sometimes, and actual viruses are made from them, which then infect other cells in the body. The Danish scientists suggest that this is what happens in multiple sclerosis. Bjørn Nexø of Aarhus University writes that "retroviral infections often develop into running battles between the immune system and virus, with the virus mutating repeatedly to avoid the immune system, and the immune system repeatedly catching up. One can see the episodic nature of multiple sclerosis as such a running battle."

The possibility that you can inherit the genes of a virus blurs the distinction between a genetic and an infectious disease. The HERV-Fc1 genes lie on the X chromosome. Since women have twice as many X chromosomes as men, this might explain why some forms of MS are more common in women. Dr. Nexø concludes hopefully: "The finding that a disease is caused by an infectious agent is an encouraging one. These are the diseases which we know best how to treat."

“A usually dormant virus may wake up and cause MS; a protozoan parasite is tied to schizophrenia.”

Meanwhile, following some promising cases, a clinical trial is now under way to find out if a cheap antibiotic called minocycline might be used to treat schizophrenia. Minocycline works against bacteria but can also kill a protozoan parasite called toxoplasma, which has long been suspected of causing at least some cases of schizophrenia. Toxoplasma can reproduce sexually only in cats; to get from cat to cat, its egg cells leave via the cat feces and wait to be eaten by other mammals, especially rats. Inside a rat, it invades the brain, where it alters the rat's behavior, disabling or even reversing the rat's fear of cats. Cats eat foolhardy rats, facilitating the parasite's entry into a new cat.

Human beings can also catch toxoplasma from cats, and it's known to affect behavior: altering personalities, slowing reaction times and increasing the risk of car accidents. More than 20 studies have now found an association between schizophrenia and toxoplasma. Schizophrenia is more common among those who had pet cats in their childhood homes (but not in those who had pet dogs).

Indeed, some scientists think that schizophrenia only became common, around 1870, when keeping cats as indoor pets became fashionable. The parasite has genes for dopamine, a neurochemical found in excess in schizophrenics.

For other kinds of disease, the search for an infectious agent has not been so fruitful. The rise of autism in recent decades, though partly attributable to better diagnosis, remains mysterious. Many viruses have been accused of causing it, but so far none looks especially guilty.

A version of this article appeared Mar. 10, 2012, on page C4 in some U.S. editions of The Wall Street Journal, with the headline: The Good News About the Virus in Your Genes.

http://online.wsj.com/article/SB1000...WhatsNewsThird
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