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U.S. Agriculture department researchers stand guard against mad cow disease;
brain-wasting disease may jump species more easily than was thought

April 1, 2001 St. Louis Post-Dispatch by Tina Hesman
On the outskirts of this city in the Corn Belt, scientists from the U.S. Department of Agriculture are standing guard, trying to keep mad cow disease out of the United States.

Researchers at the National Animal Disease Center and the National Veterinary Services Laboratories are learning that the species barrier -- a natural immunity that prevents diseases from crossing from one type of animal into another -- may not be as high or unbreachable as once thought.

What the scientists discover about natural defenses against brain-wasting diseases, such as mad cow disease, could help government regulators improve surveillance systems designed to discover and eradicate potential problems before they become epidemics. Researchers here are closely watching diseases in sheep and deer for evidence that they could make the jump.

The agriculture department's animal health institute is housed in a modest collection of low, dark-brick buildings nestled into the gentle Iowa hills just off Interstate 35. The institute came to national attention when the government trucked two flocks of sheep from Vermont into the facility late last month.

The sheep had been diagnosed last year with a prion disease -- a type of brain-wasting disease caused by misshapen proteins that includes mad cow disease in cattle and scrapie in sheep. Authorities were concerned that the sheep could be carrying mad cow disease. The sheep may have been exposed to feed tainted with the mad cow disease agent, before the animals were brought from Europe during a brief window of time when the agriculture department relaxed its ban on sheep imports.

Owners of the two flocks argued that government tests for the much-feared mad cow disease were flawed, and that they should be allowed to keep their sheep. The government says that the shepherds knew from the beginning that the sheep would be monitored for any sign of a brain-wasting disease -- regardless of whether the disease was mad cow or scrapie.

"There was an implied risk even from the get-go," said Linda A. Detwiler, the senior staff veterinarian for the agriculture department's Animal and Plant Health Inspection Service.

Government scientists decided not to risk having any new prion disease enter the United States, Detwiler said. The USDA seized the sheep from the Vermont farms and brought them to Iowa where the animals were euthanized and tested. By early last week, all of the sheep were dead and their carcasses consigned to "the digester" -- a hot lye bath built specially to deal with animals infected with prion diseases.

Scientists won't have the results of tests to determine if the sheep were infected with scrapie or mad cow disease for a couple of years, Detwiler said. But if they were, the Vermont sheep would be the first domestic livestock other than cattle to come down with mad cow disease outside of a laboratory, she said.

If mad cow disease -- formally known as Bovine Spongiform Encephalopathy or BSE -- managed to bound across the species barrier into sheep, it could potentially spread more easily and quickly than in cattle. That is because the misformed protein that leads to the disease is found only in nerve tissue in cattle, while sheep carry it in other organs as well, Detwiler said.

So while the prion can only infect cows when they eat nerve tissue from other sick cows, the agent could be passed from sheep to sheep through the placenta or other means -- just as scrapie is.

"A wake-up call"

It would not be the first time mad cow disease has slipped over the species barrier.

A few years after mad cow disease was diagnosed in cattle in Britain in 1986, British tabbies and zoo cats started coming down with a prion d isease that showed the same characteristics as the cow disease. A Siamese cat named Max was the first non-cow victim to die from mad cow disease.

"That should have been a wake-up call for the British people," said Amir Hamir, a veterinary medical officer at the National Animal Disease Center.

But scientists and government officials denied that the cattle disease posed any risk for humans. When the research showed that a new variant of Creutzfeldt-Jakob disease is associated with eating infected beef and has the same traits as the cattle disease, scientists had a hard time digesting the news.

The people who were most familiar with prion diseases were probably the most surprised, said Janice M. Miller, a veterinary pathologist at the National Animal Disease Center.

"Up until the time BSE appeared in England, we were pretty secure in the species barrier," Miller said.

When it became clear that cats and people could all get the cattle form of prion disease, scientists began to wonder if the species barrier for other prion diseases might also be vulnerable.

Although no case of mad cow disease has been found in the United States, the livestock industry was nervous that two other prion diseases -- scrapie in sheep and chronic wasting disease in deer and elk -- could somehow infect the cattle herd.

Experimenting with scrapie

Scrapie has been known for more than 300 years but has never made the leap across the species barrier to attack humans. [New data published 3/20/01 in the Proceedings of the National Academy of Science (vol 98, p 4142) suggest that some strains of scrapie may indeed infect humans and cause the classic form of CJD--BSE coordinator] But there was speculation that the sheep disease could have crossed into cattle and caused mad cow disease. From there it would have been just a hop and a skip to jump into humans and cause new variant Creutzfeldt-Jakob disease. In effect, scrapie could have tunneled under the species barrier.

To find out, Miller and Randall C. Cutlip injected scrapie-infected material directly into the brains of cattle. The cows got sick from a degenerative brain disease 14 to 18 months after the injections.

But when the scientists examined the cows' brains they got a surprise -- the pattern of holes and other abnormalities caused by scrapie weren't like the lesions made by mad cow disease. That means that the diseases are not the same, and scrapie may not have been the original source of mad cow disease.

The results from the scrapie injections made the scientists realize that veterinarians looking for signs of mad cow disease in American cattle might not recognize other prion diseases that had crossed the species barrier. The researchers decided to do another injection experiment to see if the chronic wasting disease that infects deer could get into cattle, and what it would look like if it did.

Miller and Cutlip and their colleagues took material from the brains of mule deer that had chronic wasting disease and injected it into the brains of 13 cattle. The researchers fully expected the deer disease to affect the cows the same way scrapie did.

"I thought it would really knock those cattle for a loop, but it didn't," Miller said.

The scientists had to wait nearly two years before any of the cows showed signs of having a prion disease. At first the effect was so subtle that only the caretaker who watched over the cows every day could detect any change in behavior. Two of the cows began to lose weight and one of them walked in aimless circles in its pen.

The researchers euthanized the cows and looked at their brains. Again the pattern of holes in the brain cells was different than in mad cow disease.

A third cow from the group went lame in one leg five months later and then suddenly collapsed. When the scientists looked at its brain they couldn't find any holes in the nerve cells, but they found clusters of the prion protein. The misfolded protein probably clutters up the brain cells and makes it impossible for them to function, Hamir said.

The other 10 cows in the experiment are still alive and healthy, and the scientists will watch the cattle for several more years to see if they will contract chronic wasting disease.

Even though the deer disease managed to infect the cattle, the results of the study are actually good news, Miller said. It's clear that chronic wasting disease really has to scramble to get over the species barrier, and when it does, it does not cause mad cow disease, she said.

Other scientists are investigating whether the deer disease can infect cattle by more natural means. For now, though, Hamir said there is little cause for concern that American cattle could get a prion disease from deer or sheep.

Recent test-tube studies in Montana have suggested that humans are probably at less risk than cattle for deer-transmitted prion disease.

Many mysteries about the origins of mad cow disease remain, and the Iowa scientists say they may never be solved.

"I expect to go to my grave not knowing," Miller said. "Mother Nature has some secrets she just doesn't give up."


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