Beefeaters no more - research on mad cow disease and Creutzfeldt-Jakob disease

Can humans catch a fatal disease by eating infected beef? No one knows for sure, but a few suspicious deaths have shaken the British.

Shepherd's pie, a mashed-potato-and-beef conglomeration foisted upon generations of British children, has been struck off the menu in over a thousand schools throughout the United Kingdom. Gone also are hamburgers, beef stew, beef sausages, and even Yorkshire pudding, that drippings-soaked symbol of British culinary aplomb. Why? Fear of bovine spongiform encephalopathy (BSE), also known as mad cow disease, is sweeping Britain. The disease, thought to be caused by rogue proteins called prions, eats away at cow brains, eventually killing the cows. This nation of beef eaters is worried that mad cow disease may spread to humans.

BSE first broke out in Britain in the early 1980s. These days infections are cropping up in 300 cows a week. Infected cattle are supposed to be destroyed before they reach market, but because BSE's incubation period is 8 to 12 years, some infected cattle probably show up in slaughterhouses. Public concern has peaked in recent months amid worries that contaminated meat is being sold and eaten.

The outcry, fueled by Britain's tabloid press, started with the deaths last year of two teenagers from Creutzfeldt-Jakob disease (CJD) - BSE's human equivalent, which is also thought to be caused by prions. An extremely rare, incurable disease - only one person in a million gets CJD - it has an incubation period of up to 30 years, usually appearing in people 45 and over and hardly ever in those under 30. Moreover, within the past three years four British farmers, all of whom apparently had contact with BSE-infected cows, have died of CJD. All this might have been dismissed as freakish had not the incidence of CJD in Britain doubled in the last decade, with 55 cases reported in 1994, the last year for which data are available.

Britain's prime minister, John Major, evidently thinks beef is safe; he told Parliament last December that "there is currently no scientific evidence that BSE can be transmitted to humans or that eating beef causes CJD in humans." But he was contradicted by a former government medical adviser, Sir Bernard Tomlinson, who said he would not eat beef burgers or meat pies "under any circumstances."

The cow epidemic has been traced to a protein supplement in cattle feed that included the remains of sheep infected with scrapie, a disease similar to BSE, (While scrapie afflicts sheep in the United States, there is no direct evidence that BSE has infected American cattle.) At the height of the British epidemic three years ago, the disease infected about 1,000 cattle a week. It also showed up in zoo cats - cheetahs, ocelots, and pumas - that had apparently been fed fresh beef.

Whatever causes BSE cannot be killed by boiling or radiation, as viruses can, and it passes through filters that would catch a virus. No virus has ever been found in infected cow brains. But a characteristic protein has - and many researchers believe that this protein alone, dubbed a prion, is the infectious agent. Prions are thought to damage the brain by somehow converting a normal, harmless version of the same protein, found on all types of cells and known as PrP, into new prions. According to one theory, prions clump together and block molecular traffic, killing the cells and leaving spaces where once there were nerves. Even worse, it's suspected that the new prions are themselves infectious.

But can cow prions infect humans? That is, can a prion from a BSE-infected cow brain alter the normal human Prp protein, converting it into an agent of Creutzfeldt-Jakob? The answer is far from clear. The most direct evidence comes from John Collinge, a neurologist at London's Imperial College School of Medicine at St. Mary's, who has run a series of rather complex experiments to try to answer the question. Since he couldn't experiment on humans, Collinge studied mice genetically engineered to carry only the human gene for PrP and not the mouse one. Unlike normal mice, these can be infected with human CJD: when Collinge injected them with cells from the brain of a patient who had died of the disease, the mice soon developed its characteristic symptoms - hunched posture, a wobbly walk, and a tendency to fall. They died within 200 days. Autopsies revealed the sponginess in the brain typical of CJD.

That told Collinge that his engineered mice are a good way of testing whether prions from BSE-infected cows can also alter human PrP. When he injected cow, prions into the brains of normal mice, the rodents developed a mouse version of BSE within 450 days. When he injected the prions into mice with a mixture of human and mouse genes, those mice, too, got BSE - but it seemed it was their normal mouse proteins rather than their human ones that were being converted into prions. (Collinge used antibodies to zero in on which proteins were being hijacked.)

Finally, Collinge did the acid test: he injected cow prions into the brains of mice that carried only human PrP genes. That experiment is still going on. The mice are now more than 400 days old and still healthy - indicating, perhaps, that BSE prions cannot convert human protein. But normal mice in previous experiments have developed symptoms of BSE as much as 700 days after inoculation, so it's still possible that the mice with human genes will get the disease. Collinge will have to wait at least another year before giving them the all clear.