2. Mad-cow history

GLOSSARY:
Bovine spongiform encephalopathy (BSE): Mad cow disease.

Chronic wasting disease: A TSE in deer and elk.

Creutzfeldt-Jakob disease (CJD): Fatal, human TSE, strikes one person in a million.

Prion: A protein that, when misshapen, can cause other prions to fold wrongly. Causes all TSEs.

Scrapie: A TSE in sheep. Known since the 1700s; does not infect people.

Transmissible spongiform encephalopathy: TSE. Infectious brain diseases caused by prions.

Variant CJD (vCJD): The "human" version of mad cow. Similar to CJD; strikes younger people.

Variant CJD, caused by eating mad-cow meat, affects younger people. Sporadic CJD (cause unknown) affects older people. The appearance of CJD in young people in 1996 triggered concern during the British mad-cow epidemic. Diagram: U.S. Food and Drug Administration

'You can rest assured that this has been looked at,' says another prion researcher.

When mad cow disease broke on the British isles in the mid-1980s, the government responded to the specter of cows that showed (as the USDA now describes the symptoms) "changes in temperament (e.g., nervousness or aggression), abnormal posture, incoordination and difficulty in rising..." with reassurances. Not to worry, mad cow did not threaten people. After all, it was just another version of scrapie, an old sheep disease that people never caught.

Sick sheep cowers in cage. The first TSE was scrapie, found in sheep in Great Britain during the 1700s. This ewe had seizures and difficulty moving her rear feet, both signs of brain damage, but not intense itching, the classic scrapie symptom. Itchy sheep incessantly scraped themselves against trees and fences, earning the name "scrapie." USDA

But not even a cabinet minister's public devouring of British beef could prevent mad cow from infecting humans. Since 1995, about 140 Britons have been diagnosed with variant Creutzfeldt Jakob disease -- a human TSE that's blamed on eating meat from mad cows. Death comes in six months.

To put the matter in perspective, millions of Britons ate beef during that period. Nevertheless, in the United States, which we have been repeatedly assured has the world's safest food supply, that risk is difficult to swallow.

Abnormal history
Scrapie, the first TSE, began killing sheep in Europe and Great Britain in the 1700s. In the 1920s, doctors Creutzfeldt and Jakob began exploring a rare, fatal human brain disease that ripped holes in the brain. In the 1960s, another version of this disease showed up in a New Guinea tribe that ritually ate deceased relatives.

Until the 1980s, the TSEs remained an obscure problem, but a baffling one. Although they were infectious, the cause of the disease could slip through a filter that would trap bacteria. That pointed the finger at a virus -- but the agent survived treatments that kill all viruses.

Compounding the problem is the long incubation period. In cows, for example, BSE is unheard of in animals younger than 30 months, which explains the emphasis in this country on testing only older animals.

TSEs hit the headlines in the 1980s and 1990s, when British cows began going mad. In 1995 and 1996, a group of unusual cases of CJD tipped off doctors to the emergence of what's now called variant CJD. Immediately, suspicion focused on eating meat from mad cows as the cause, and that suspicion is now the accepted wisdom in terms of cause. By the end of 2003, 137 cases of variant CJD had appeared in the United Kingdom. The rate of new vCJD infections is declining, from a high of 28 in 2000 to 16 in 2003 (as of Dec. 1).

Victims of sporadic CJD are usually older than vCJD victims.

Why was British beef so infectious? Partly, it was the huge size of the problem, with the number of mad cows eventually eaten numbering at least in the thousands. But it's also what was eaten. Most scientists think British beef contained parts of brain or spinal cord, where diseased prions are concentrated.

And thus a key consumer-protection strategy has been to exclude these tissues from meat. Muscles contain no prion -- or so goes the accepted wisdom.

A muscular disease?
But Stanley Prusiner, the Nobel-winning neurologist and biochemist at San Francisco State University who identified prions as causing TSEs, casts some doubt on the "nervous-system only" theory. In a 2002 study (see "Prions in Skeletal Muscle" in the bibliography), Prusiner and colleagues found prions in the muscles of mice they had infected with TSE prions. In a press release, Prusiner said, "Whether prions accumulate in the skeletal muscle of other animals remains to be established. But our findings indicate the need to carry out a comprehensive and systematic investigation of the distribution of prions in the skeletal muscle of animals who develop prion diseases."

Perhaps because it's been, until recently, extraordinarily difficult to test for small concentrations of prions, the medical literature includes few studies of the matter. A report published this month found no abnormal prions in the muscle of 20 cattle, sheep, elk, and raccoons that had been experimentally infected with TSEs (see "Failure to Detect ..." in the bibliography).

Prion discoverer: "Whether prions accumulate in the skeletal muscle of other animals remains to be established."

However, another study reported this month (see "Creutzfeldt-Jakob Disease and Inclusion ..." in the bibliography) found "abundant disease-associated prion protein" in the muscle of a patient with sporadic CJD. And a study published last fall (see "Extraneural Pathologic Prion..." in the bibliography) found abnormal prions in the muscle of 8 of 32 CJD patients.

That study, said Nature, "resurrects the idea that BSE-infected cows might harbour trace levels of prions in their muscle meat. He [researcher Adriano Aguzzi] plans to use his sensitive test on cow tissue to see if he can pick up prions." However, Nature concluded, "All other evidence so far suggests that cow muscle is not infectious. 'You can rest assured that this has been looked at,' says Neil Cashman," a prion researcher at the University of Toronto.

Since, in searching back to 1998, no other studies listed in PubMed (when searching for "prion muscle") appears to specifically address the presence of abnormal prions in muscle. As the authors of the above-mentioned negative study of 20 animals concluded, in a sentiment that may apply to the whole issue, "Further testing of muscle tissues is needed to confirm the findings of the present study."

Mad-cow Nobel
In the 1980s, it was Prusiner who finally developed the prion hypothesis to explain mad cow and other TSE diseases. Scientists had recognized for years that the cause of TSEs broke the rules Although the diseases are infectious, the causative agent, unlike that for any other known infectious disease, contains neither DNA nor RNA.

Cows meander in large feedlot. You'd think mad cow could cause an epidemic in a crowded feedlot, but the disease spreads through infected feed, not directly from one cow to another. And steers are typically slaughtered long before they reach 30 months of age, when BSE become detectable. Photo: USDA

As Prusiner and many of his former skeptics see it, prions are normal proteins that somehow fold into a decay-resistant, infectious shape that somehow causes chain-reaction misfolding among other normal prions. Eventually, the growing mass of misshapen prions somehow kills nervous tissue, cutting holes in the brain and causing fibrous plaques that resemble those seen in Alzheimer's disease.

In cattle, humans, mink, deer, elk and sheep, the TSEs go thru a long period of incubation and then cause neurological decline and rapid death. Today, despite some quite tentative advances in treatment, the only way to deal with TSEs is to prevent them, which, in turn, calls for some cumbersome and expensive changes in the way beef is raised and slaughtered.

Will new American beef regulations make us safer?

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