`Mad cow' protein stirs mystery, debate

While some researchers study cellular structures, others search for virus


WASHINGTON - It sounds like a Michael Crichton horror story. One out of the thousands of tiny proteins that are the molecular building blocks of every living cell twists out of its normal shape and becomes a silent killer.

The rogue protein turns its neighbors into copies of itself. Each new recruit repeats the process. The number of rogue proteins grows faster and faster.

Clumps of these misshapen proteins - known as prions - cause havoc in the human or animal nervous system. Victims lose control of their minds and limbs. In a few months, they are dead; their brains riddled with spongelike holes. That is the scientific understanding of what happens in "mad cow" disease, formally known as Bovine Spongiform Encephalopathy and its rare but incurable human counterpart, Creutzfeldt-Jakob disease.

About 100 people, mostly in Great Britain, are known to have died from Creutzfeldt-Jakob. Two elderly Americans died of the disease in a Denver hospital last year. As a precaution, U.S. officials are quarantining sheep in Vermont and cows in Texas that were imported from areas of Europe that are infected with mad cow disease.

These prion diseases are not the same as the foot-and-mouth epidemic now ravaging livestock in Europe. Foot-and-mouth is caused by a virus, not a protein, and is not harmful to humans.

Creutzfeldt-Jakob disease, mad cow disease and a related sheep ailment called scrapie are especially scary because they can jump among species - from sheep to cows, from cows to people - and because there is no known cure. Unlike bacteria or viruses, prions can't be destroyed by radiation, chemicals or sterilization.

Identified in 1982 by Stanley Prusiner, a biologist at the University of California at San Francisco, prions (pronounced pree-ons) are a previously unknown mechanism for transmitting disease.

According to Prusiner's theory, a chance mutation occasionally switches a protein from its normal spiral shape to a flatter configuration. This triggers a lethal chain reaction of prions.

In some cases, the disease is passed on by infection, say from eating prion-infected meat or using infected surgical instruments. In 10 percent to 15 percent of the cases, the affliction is inherited by a child from a parent.

"For a protein to function properly, it must be folded into just the right shape," said Susan Lindquist, a prion researcher at the Howard Hughes Medical Institute in Chicago. "Sometimes, however, proteins take on the wrong shape. In humans the consequences can be deadly."

Although Prusiner won a Nobel Prize in 1997 for his work with prions, his theory remains controversial. Some scientists insist that proteins alone cannot transmit disease and a virus must be implicated. So far, no such virus has been found.

To better understand these bizarre proteins, researchers are creating artificial prions in baker's yeast, a simple fungus whose complete genetic code has recently been deciphered. Using yeast models, some have convinced themselves that a twisted protein alone is able to transmit disease without help from a virus or bacterium.

But skeptics such as Laura Manuelidis, a neuropathologist at Yale Medical School in New Haven, Conn., want more confirmation, noting there is a great difference between yeast and a human being.

Scrapie, the sheep version of prion disease, has been known for centuries. It gets its name from the way infected sheep rub against a fence to ease their itching. Cases have been detected in the United States since the 1940s.

In Vermont last month, Agriculture Department agents seized 234 sheep that had been imported from Belgium and the Netherlands in 1996. In Texas, 21 cows imported from Germany in 1997 are being held in quarantine on a ranch and may be destroyed.

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