BEWARE OF MADCOW

A year after the British cattle scare, some scientists fear a broader outbreak of the mysterious disease. Peter Hall did not notice when the proteins in his brain started to change. He noticed other things: a vague depression, general anxiety, sudden mood swings. But blaming any of that on brain chemicals wouldn't have occurred to him.

The proteins in Hall's brain were changing, however. Ordinarily made up of tiny strands of intertwined amino acids the complex molecules had begun to assume a very different shape, collapsing into sticky sheets. Before long, these gummy structures began to clump sloppily together, creating pits and divots where there had once been vital brain tissue. Within months Hall was delusional and bedridden. Not long after, he was dead.

Hall, who was 21, was one of nine Britons felled in 1996 by a brain disorder linked to exposure to bovine spongiform encephalopathy (BSE), better known as mad-cow disease. The appearance of this degenerative disease widely suspected to be contracted by eating contaminated beef organs-set off a panic as Europe slammed its doors to British beef, and travelers anxiously cast their minds back to London vacations, trying to recall whether they had ordered the fish or the sausage.

The scare died down after the British government destroyed tens of thousands of cattle, removed infected feed from the food chain and promised to step up slaughterhouse inspections. Mad-cow disease has stopped turning up in the new generation of cattle, and the crisis is generally considered to have passed.

That conclusion may be premature. While public health officials believe the risks are remote, concern is building in both Europe and the U.S. that the madcow problem may be larger than it seems. This week the science journal Nature published a paper on the possibility that last year's outbreak might be only the tip of an epidemiological iceberg, and that tens of thousands of Europeans are unknowingly infected and could die from the disease. Moreover, a number of researchers in the U.S. aren't convinced that some of the same conditions that led to the mad-cow breakout in Britain might not exist in the U.S, leading to the same spread of the BSE pathogen. Making things even harder, scientists still can't agree on what that pathogen is-a first step in figuring out how to treat the disease if it does surface. The only thing that stands between us and an epidemic, says Robert Rohwer, director of molecular virology at the Veterans Administration Medical Center in Baltimore, is unmitigated luck.

Britain's problems began in 1986, when a BSE epidemic struck herds across the country, ultimately leading to the death of up to 1,000 cows a week. To protect the food supply, the government ordered the slaughter of affected cattle and banned the sale of cow brains, intestines and other offal, thought to be the organs likeliest to harbor the disease. And in 1988 it halted the practice of feeding cattle the remains of diseased sheep, which is where the infection is believed to have started. But by that time the damage was done.

The cheapest way to get protein into cattle is to feed them scraps of animals left over from slaughter, says Richard Rhodes, author of the soon-to-be-released book Deadly Feast (Simon & Schuster), which traces the history of BSE and similar diseases. When British cows started to get sick, this practice wasn't banned. Instead industry was merely required to avoid using parts from animals known to be infected. This was hardly foolproof, and it was inevitable that some diseased flesh would be eaten by cows and enter the food chain.

When Britons started falling ill last year, some scientists concluded that that was just what happened. If cattle feed was indeed the indirect avenue of the recent infections, it could spell big trouble, since most Britons ate from a contaminated meat supply for at least 10 years. just how many got bad beef is what the Nature paper tried to determine.

Using a complex epidemiological model, the study concluded that the outlook for the beef-eating population is unclear: at the very least, an additional 75 Europeans will come down with the disease; at the very worst, a chilling 35,000 could fall ill. The researchers caution that too little is known to make confident projections, and in Britain the paper has had little impact. Beef consumption is about where it was a year ago, and although the government last week banned the transplantation of animal organs into humans, saying the risks needed to be studied, no new panic has broken out.

Ironically, the Nature paper generated concern in the U.S. where not one case of mad-cow disease has been diagnosed. I hope we're not on the same course as the British, says Rohwer, but we could be. What concerns Rohwer and others is that the U.S. agricultural industry, like its British counterpart, recycles animal scraps, turning them into both cattle feed and garden fertilizer. Should even one domestic cow develop the disease spontaneously-something that is known to occur in nature-the pathogen could quickly spread through U.S. herds.

In order to prevent that, U.S. Food and Drug Commissioner David Kessler is proposing a new measure-set to take effect later this year-that forbids using cattle parts in animal feed but still permits them in fertilizer. The government concedes that switching to protein substitutes like soy would cost U.S. feed producers up to more $48 million a year, and the industry insists that the final figure would be much higher. Whatever the price, however, Kessler believes it's worth it. The risk of BSE is small but real, he says. If a case did occur in this country, we want to wall it off and not have the amplification that occurred in Britain.

Of course, no regulatory measure will take the place of finding a way to treat or prevent BSE infection. But the disease may at last be starting to give up its secrets. A number of researchers are convinced that mad cow is caused not by a common bacterium or virus but by a vanishingly small crumb of protein known as a prion.

First postulated in 1982 by neurologist Stanley Prusiner of the University of California, San Francisco, prions are thought to be strikingly similar in their amino-acid sequence to proteins found naturally on the surface of certain brain cells but strikingly different in shape. Some types of normal brain proteins form open coils that allow them to be destroyed by protective enzymes when they become damaged. Studying diseased animal brains, however, Prusiner concluded that prion proteins form sticky sheets that are impervious to this defense system. When the two proteins come into contact, the sticky ones seem to induce the coiled ones to assume the new shape, forming the protein clots seen in the brains of mad-cow victims. Prusiner believes diseases like BSE start when a single prion is introduced into the body-either by ingestion or chance mutation-and begins converting brain proteins.

Not all researchers are sold on the prion theory; many believe that a more traditional pathogen like a virus will yet be isolated. Last week this camp got a boost when the journal Science published a study in which a group of lab mice injected with BSE-infected tissue all came down with the disease, yet fewer than half were shown to harbor Prusiner's infectious prions. Opponents of the prion theory say this proves the proteins don't cause disease. Proponents insist that the methods used to detect the molecules were simply not sensitive enough.

Whoever is right, it's in no one's interest for the debate to go on too long. There are more 44 million head of cattle in the U.S., and 7 million are killed for food each year. If just one of those slaughtered cows turns out to be a mad cow, the illness that's now an ocean away could establish its first beachhead on American shores.

PRIONS IN ACTION

Abnormal proteins, known as prions, may trigger mad-cow disease simply by coming into contact with healthy proteins in the brain. A healthy brain protein is made up of strands of amino acids twirled into helices. Prions are thought to be made of the same amino acids flattened into sheets. When a prion touches a protein, the protein flattens out too. A chain reaction of such transformations ravages brain tissue.