February 14, 2000

n December 22, 1984, Peter Stent noticed that there was something wrong at his farm in England. Cow 133 had seemingly gone mad; the cow was shaking its head violently and staggering around the pasture. By February of the next year, the cow had died. Postmortem studies revealed that it died of "a novel progressive spongiform encephalopathy," which causes large spongy holes to develop in the brain, eventually resulting in loss of coordination, behavior changes, hallucinations, and death. It was the first documented case of bovine spongiform encephalopathy (BSE), now commonly known as mad cow disease.

The Human Condition   By Jonathan Freedhoff, M.D.

A variation on an old theme

On May 21, 1995, 19-year-old Stephen Churchill died unexpectedly at a hospital in England; his doctors couldn't explain the cause of death.

Churchill's symptoms had begun months earlier. They started with jerky movements and lead to hallucinations and then paralysis. Death was the final result. On the surface, Churchill's symptoms appeared to be indicative of a disease called Creutzfeldt-Jacob disease (CJD), also a spongiform encephalopathy, but CJD had never been seen in someone so young. Churchill's autopsy confirmed that he had indeed died of a kind of spongiform encephalopathy -- one that closely resembled CJD. A few months later, in August 1995, another case surfaced, and this time the victim was only 16 years old. By 1996 the disease had been given a name -- new variant CJD (nvCJD). To date, it has proven to be universally fatal; nvCJD has claimed 87 lives across Europe.

Spongiform encephalopathies

Spongiform encephalopathies are not new. They have been known to affect animals and humans alike. Scrapie, a spongiform encephalopathy found in sheep, was first described in 1750, and similar diseases have been found in cats, goats, mink, deer, and elk. In humans, there are at least seven different spongiform encephalopathies. These diseases are unique in that they have extremely long incubation periods -- anywhere from one to 30 years. Before the emergence of nvCJD, perhaps the most famous of these diseases in humans was kuru, which afflicted cannibals living in Papua New Guinea. Kuru was contracted as a result of ritualistic ingestion of the brains of dead relatives.

Kuru disappeared once these practices were stopped, clearly demonstrating that spongiform encephalopathies were transmissible. But what was the infectious agent? It was not until 1982 that one was found, and , but it wasn't one of the four most common infectious agents -- a bacterium, a virus, a parasite, or a fungus.

In March 1986, after the diagnosis of "mad cow" disease in English cattle, the first laws banning the use of animal by-products in feed were passed in Europe. Similar laws have since been passed around the world, including here in the United States.

New variant CJD is transmitted through a prion -- a common protein that all humans create. What is remarkable is that for unknown reasons, exposure to this protein results in the deposit and replication of large spongy plaques in the brain. The condition is incurable and fatal.

Before nvCJD, all of the cases of spongiform encephalopathy in humans had been linked either to genetic abnormalities in the prion gene or to a clear exposure to cells from an affected person's spinal fluid, growth hormone, corneas, or the matter surrounding the brain. In the case of kuru, contact with the brain of an affected individual caused infection. Until recently, one simply could not catch spongiform encephalopathy from an animal. But now, terrifyingly, it seems that has changed: mad cow disease, or BSE, has managed to jump the species barrier.

The link between BSE and nvCJD

Because the brains of cows with BSE look so similar to those of humans with nvCJD, scientists proposed that there might be a link. That link has yet to be confirmed, but research shows that the prion responsible for BSE is identical to the prion responsible for nvCJD. In a recent study, two different groups of mice -- one inoculated with the BSE prion, the other with the nvCJD prion -- developed identical neurological diseases. This proved two things: first, that the BSE/nvCJD prion could jump across the barriers between species; and second, that the BSE prion is indeed the same as the nvCJD prion.

On March 20, 1996, with the assumption of a link, experts began to propose that humans were catching nvCJD from eating beef infected with BSE. Just seven days later the European Commission imposed an international ban on British beef. By then, unfortunately, more than 150,000 cows had already died of the disease. It was obvious that authorities had to consider the possibility of a BSE epidemic that stretched across international borders.

In an attempt to halt the transmission of BSE between cows -- and, ultimately, to humans -- every cow in Britain older than 30 months was slaughtered in April 1996. Millions of cows were killed, resulting in billions of dollars in lost revenue and a crippling of the British beef industry. Since then, however, BSE has surfaced all across Europe -- in France, Spain, Italy, Germany, Switzerland, Holland, Belgium, Denmark, Luxembourg, Ireland, Liechtenstein, and Portugal. The disease has also been diagnosed in cattle in Canada and Oman.

The spread of BSE

It seems clear that BSE spread because cows ate feed contaminated with the remains of BSE-infected cattle. It had been a common practice in Europe, and also in the United States, to use slaughterhouse remnants -- blood, meat, and bone meal -- in cattle feed. In March 1986, after the diagnosis of BSE in British cattle, the first laws banning the use of animal by-products in feed were passed in Europe. Similar laws have since been passed in many countries, including the United States. As a consequence of these measures, the incidence of BSE has dropped dramatically, falling from a peak of over 100,000 new BSE cases in 1992 to only 1,277 in 2000.

More questions than answers

So far there have been 87 cases of nvCJD in Europe, and there is very little known about them. Did those patients contract their illness from eating BSE-infected meat? Are those cases representative of a few genetically susceptible people, or are they in fact the tip of the iceberg of a disease that may incubate for decades after a person eats the wrong cheeseburger? And is nvCJD transmissible between people through blood, organ donations, or other bodily fluids? This concern is compounded by the fact that other than a brain biopsy, which can be done only after an individual dies, scientists have no test for the disease.

With all of these questions still unanswered, the American Red Cross recently banned blood donations from people who have lived anywhere in western Europe since 1980. For now, the BSE scare in Europe is causing many people to turn away from beef products, at least until a solution is found. Many restaurants in France, for instance, have simply taken the beef entrees off their menus to appease nervous customers. European governments continue to ban British beef and test their own herds for the disease. Meanwhile, research to find a way to stop the spread of both BSE and nvCJD continues. We can only hope this scientific detective work turns up more solutions than it does patients.

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