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MARCH 7, 2005
Mad Cow's Stubborn Mystery Scientists still know far too little about it -- and the feds are making rules in the dark Nearly a decade ago, clusters of young people in Britain started suffering mysterious symptoms. First they became depressed and withdrawn, prone to crying fits, anxiety attacks, and bouts of physical pain. Within months they lost the capacity to remember or speak, then they slipped into comas and died. Autopsies showed brains ravaged by a novel form of bovine spongiform encephalopathy (BSE), or mad cow disease, which they contracted by eating infected beef. Public health experts feared an epidemic, with some predicting that tens of thousands of people would eventually die. So far the predictions appear overly alarmist. Only 159 people worldwide are known to have died from eating BSE-infected meat -- including a Japanese man whose death from the disease was confirmed on Feb. 3. But each new case is a painful reminder of the unanswered questions that swirl around mad cow and similar scourges in sheep, deer, and elk. Despite a decade of intense investigation, scientists still disagree about how these diseases are transmitted, how long they can incubate without symptoms, if they can be cured, and what steps should be taken to lessen the toll. In recent months scientists have made some startling discoveries. Yet they are dismayed that mad cow is so slow to yield its secrets. Those many uncertainties are in the spotlight right now as the Agriculture Dept. prepares to resume trading of some live cows and packaged beef with Canada on Mar. 7. Restrictions have been in place since May, 2003, when a mad cow was discovered in Canada. Three more have been found since, including one animal that was imported to the U.S. and slaughtered in December, 2003. The USDA is torn between its mission to protect public health, its commitments to meatpackers and ranchers who want access to Canadian cattle, and its desire to facilitate U.S. exports. The problems won't be resolved until scientists get a firmer grip on the pathology of the disease. Scientists such as Dr. Stanley B. Prusiner, a neurologist at the University of California at San Francisco, are making progress. Prusiner won a Nobel prize in 1997 for his discovery that proteins in the brains of mad cow victims -- both animal and human -- exhibit characteristic malformations. These proteins, called prions, exist in a benign form in many bodily tissues. But when they become misfolded, they can turn both toxic and infectious, eating holes in the brain. SLIPPING THROUGH? Prusiner's theory isn't universally accepted. But his experiments continue to illuminate the prion theory. In July, Prusiner's team at UCSF reported that it had synthesized prions to resemble their disease-causing counterparts. The scientists injected the lab-made prions into mice, and more than a year later the rodents developed diseases that resembled mad cow. "This tells us that prion diseases can occur in many forms," says Dr. Giuseppe Legname, UCSF neurologist. If that's the case, he adds, some people who die of undiagnosed brain diseases may actually be infected with prions that are slipping by undetected. "That has quite frightening implications," Legname says. Scientists across the pond are also chasing elusive rogue prions. In December, British researchers reported that some humans appear to be protected from BSE by their genetic makeup. But they also found that even the mice that had the same genetic barrier eventually developed a form of prion disease -- one that had never been seen before. To determine if humans might be infected with yet-undiscovered strains of prion diseases, the researchers are urging health authorities around the world to perform more autopsies on people who die of mysterious brain disorders. Part of the goal is to see if other prion-based illnesses -- such as chronic wasting disease in deer and elk -- are jumping from animals to humans. In the U.S., for example, the Centers for Disease Control is funding scientists in Colorado and Wyoming who are checking death records against hunting licenses. They're trying to determine if any hunters got sick from eating game. So far they haven't found any evidence of a link. The only way to confirm and identify prion diseases today is to examine brain tissue after death. Only about 66% of suspected cases are autopsied each year. The number should be 75% or more, says Dr. Pierluigi Gambetti, director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University. He likens the current situation to a faulty airport security system in which there are multiple lines of passengers subjected to different levels of scrutiny. "How would you feel if one line of people went through unchecked?" he asks. "We may be missing that critical case that tells us chronic wasting disease is passing from animals to humans." With funding from the CDC, Gambetti is setting up autopsy centers in state health departments around the country that will subsidize the procedure for families who can't afford it. Scientists at the National Institutes of Health are grappling with the prion-disease problem lower down on the food chain. The NIH's Rocky Mountain Laboratories in Hamilton, Mont., has launched a number of studies designed to unravel the mysteries of cross-species transmission. In a series of experiments they injected a hamster form of corrupted prions into mice. The mice were not visibly affected, but when tiny bits of their brains were injected back into healthy hamsters and mice, some rodents got sick. Eventually specific strains developed that could kill mice, hamsters, or both. LAYING BLAME Given how much remains unknown, U.S. restrictions on Canadian cattle and beef seem prudent. But there are economic costs. Tyson Foods Inc. (TSN ) took a $61 million charge against its fourth-quarter earnings last year because it couldn't import live cows from Canada. Nor could it export beef to Japan and other countries that restricted imports of American beef in the wake of the 2003 incident. The National Cattlemen's Beef Assn. (NCBA) reckons the U.S. has lost $3 billion in export sales since those bans went into place. Who is to blame? Consumer groups say the beef industry got the U.S. into this predicament by consistently thwarting calls to test cattle more aggressively. And even some within the NCBA agree that further research is urgently needed. "We should follow the science," says Gary Weber, an executive director at the NCBA. Some good news has emerged from Britain. In a recent study, 12 patients with the human form of BSE had a drug normally used to treat urinary tract infections injected directly into their brains. This seems to have cut prion production and limited brain damage. Two years later, only one patient has died. "Five years ago, no one was even thinking about treatments," says Dr. Stephen Dealler, a medical microbiologist at Britain's Lancaster Royal Infirmary who studies prion diseases. "I am very hopeful." It's a tiny bit of headway in the global effort to understand -- and ultimately conquer -- one of the world's most puzzling scourges.  By Arlene Weintraub in New York, with Kerry Capell in London
BW MALL
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