September 30, 1997

New Evidence Said to Dispel Doubt on Mad Cow Disease

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By SANDRA BLAKESLEE

cientists in Scotland say they have found the first "compelling evidence" that mad cow disease -- a mysterious brain ailment that has killed thousands of cattle in Britain -- has been transmitted to people who apparently contracted the disease somehow after eating beef or being exposed to cattle.

So far 14 people have died from the cow disease -- bovine spongiform encephalopathy, named for the spongelike holes that it eats into the brain -- and another seven are seriously ill and expected to die from it. The research fuels fears that still others may become ill with the disease.

The cow disease has not occurred in the United States and Americans are not believed to be at risk.

The researchers said their findings, which will be published in the Oct. 2 issue of the British journal Nature, remove all doubts that mad cow disease is in any way distinct from the disease that struck the people. It resembles an ailment called Creutzfeldt Jacob disease and has been called new variant Creutzfeldt Jacob disease or nvCJD.

The new experiments also strongly suggest that a virus-like particle or co-factor is involved in the disease, challenging a widely held theory that it is caused by aberrant proteins called prions.

The researchers, led by Moira Bruce of the Institute of Animal Health in Edinburgh, Scotland, said they injected mice with tissue samples from the brains of people who died of the mysterious disease and the mice developed the same pattern of brain damage they developed when injected with brain tissue from sick cows. These findings were regarded as proof that people and cows were afflicted by the same ailment.

Dr. Robert Rohwer, another CJD expert at the Veterans Administration Hospital in Baltimore, said, "This nails it. We are about as close as we can get to having proof that people get the disease from contact with bovine products."

Until now, some mad cow experts in Britain have been arguing that the new variant of CJD, which differs from CJD in that it strikes young people, had existed in the population but had simply been overlooked, said Dr. Christopher Bostock, director of the Institute of Animal Health in Edinburgh, a government-funded agency that is looking into how mad cow disease is transmitted to other species. But that possibility is now ruled out, he said.

Mad cow disease emerged in Britain in the mid-1980s when cows began to stagger, behave weirdly and die by the thousands. Autopsies revealed bovine spongiform encephalopathy . Researchers quickly deduced that cattle had gotten the disease from eating brains and nerve tissue of sheep infected with scrapie. The tissues had been mixed into cattle feed. Since then, more than 1.7 million animals were destroyed on orders of the British government.

On March 20, 1996, the British government announced that a new variant of CJD had occurred in 10 young people over the previous 14 months, and that it might be related to mad cows.

Conventional CJD affects older people, mostly over age 65, and usually begins with dementia and movement disorders, said Dr. Robert Will, director of the National CJD Surveillance Unit in Edinburgh. New variant CJD begins with depression and only later leads to problems in moving arms and legs, he said. The new disease also produces "large florid" protein deposits in victim's brains in a pattern that is distinct from conventional CJD.

To discover the source of this new human disease, Dr. Bruce and her colleagues at the Institute of Animal Health carried out a series of experiments in mice.

First, they took brain tissue from various sheep infected with scrapie and injected it into the brains and abdominal cavities of four strains of mice. The mice all developed holes in their brains but in distinct ways.

Incubation periods for the disease and the pattern of holes in brain tissue varied, leading to the discovery of 14 distinct strains of scrapie. That is, sheep have many different versions of the disease.

In the second experiment, the scientists infected mice with brain tissue taken from mad cows. This time, the incubation period and pattern of holes in the brain were identical in the various strains of mice. In other words, cows have only one version of the disease, which the researchers called the "BSE signature."

In the next set of experiments, brain tissue was taken from three domestic cats, a greater kudu, a nyala and a pig, all of which developed holes in their brains after eating contaminated meat or, in the case of the pig, being injected with infected cow-brain tissue. The various tissues were again injected into mice. Again, all the mice developed the BSE signature. The cow disease agent was unchanged as it passed among species.

These experiments have been described in earlier reports.

Finally, in experiments described in this week's Nature, the researchers took infected human brain tissue, ground it up and injected it into mice. Three samples were taken from patients who died from new variant CJD. Six samples were culled from the brains of people who died from conventional CJD.

The mice injected with new variant CJD tissue are all developing the "BSE signature," Bostock said. One strain has full-blown disease, whereas the others are just now getting sick. But there is no doubt, he said, that the mice have mad cow disease that was passed on to them through human brains.

The mice infected with conventional CJD brain tissue show no clinical signs of disease, Bostock said.

Copyright 1997 The New York Times Company