Maddening cow disease might be a better name, so frustrating is the causative agent with its apparent ability to move among species. Not to mention the public- health dilemmas facing authorities in Great Britain, where a cattle disease called bovine spongiform encephalopathy (BSE), or mad cow disease, may have infected humans.
"Whatever the agent is that's presumably responsible for transmissible spongiform encephalopathies, it has the most remarkable properties and it desperately needs more study," said Brian A. Summers, B.V.Sc., Ph.D., a board-certified veterinary pathologist specializing in comparative neuropathology and associate professor of pathology at Cornell's College of Veterinary Medicine.
The agent -- which is responsible for deadly brain diseases in victims ranging from cats to cannibals, Angus to antelope and men to mink -- is remarkably difficult to kill, Summers said. It is highly resistant to all the usual means (heat, ultraviolet light, ionizing radiation, DNA-cleaving nucleases, cycles of freezing and thawing, ether or strong fixative solutions such as formalin) that reliably inactivate conventional infectious organisms.
"It may not be an organism, in the usual sense of the word, but rather a kind of rogue protein," Summers said, referring to the "prion hypothesis." First proposed by University of California neurologist Dr. Stanley B. Prusiner, the prion hypothesis has gained widespread, if not universal, acceptance as the basis for the maladies that turn the brain's grey matter into a sponge-like mass riddled with empty vacuoles.
"Prion" comes from the transposition of letters in "infectious protein," and since the idea was proposed, it was learned that there are "normal," non-infectious prions in all animals and genes responsible for their manufacture in the brain. But if prions contain any nucleic acid at all, it has remained elusive, Summers said. The agent can't be grown in tissue cultures. It does not induce an immune response in the hosts, so there is no possible blood test for carriers of the diseases.
"Sheep that have developed the spongiform disease, scrapie, will react in a characteristic way when you scratch their backs. But for most animals, including humans, your presumptive diagnosis must await the appearance of characteristic neurological signs," Summers said, noting that a definitive diagnosis of spongiform disease can only be reached with brain tissue from a biopsy or post-mortem examination.
The Cornell neuropathologist described a BSE case he witnessed in England while visiting the University of Cambridge. The animal had lost its coordination, was swaying from side to side as it walked, and it was stumbling, kicking and bellowing.
Those signs spelled death for more than 100,000 British cattle, slaughtered under government orders since BSE was discovered in England in 1986. British government restriction on the use of certain parts of cow carcasses was generally thought to ensure safety of British beef -- until the official announcement March 20 that at least 10 new cases of human spongiform encephalopathy in England could be related to beef-eating.
Summers describes the human form, Creutzfeldt-Jakob Disease (CJD), and several others in his well-received new book,Veterinary Neuropathology, published in 1995 with co- authors John F. Cummings, D.V.M, Ph.D., and Alexander de Lahunta, D.V.M., Ph.D., both professors of anatomy at the Cornell veterinary college.
Scrapie in sheep and goats is the "prototype" spongiform disease, Summers said, and has been known for some 300 years. So named because afflicted animals rub against stationary objects to relieve their apparent irritation, scrapie persists at low levels in most countries where sheep are raised. British cattle are believed to have contracted BSE from meatmeal feed supplements, which were at one time made from brains and other offal of sheep, including those that died of scrapie.
That same route, feed made from diseased animals, is believed responsible for transmissible mink encephalopathy in ranch- raised mink in the United States and Europe, Summers said. In the western United States, some mule deer, black-tailed deer and Rocky Mountain elk are infected with chronic wasting disease, he noted. Spongiform encephalopathies similar to BSE have been observed in several species of antelope as well as a puma in British wildlife parks -- and even in a few domestic cats in England. These novel cases of encephalopathy in a variety of animals in Great Britain are thought to substantiate the hypothesis that the outbreak was spread in animal food, Summers said.
Pathologists performing post-mortem histological tests look for the distinctive vacuole structures in tissue of the brain and other parts of the central nervous system, and for amyloid plaques deposited in some forms of spongiform disease. There is no screening test for people who may have been exposed to spongiform diseases, and no treatment or cure for the fatal disease.
The most famous example of human transmission is the Fore cannibals of Papua New Guinea, who contracted Kuru by eating the brains of their deceased relatives. But there are others in the medical literature, Summers said. CJD has been transmitted on electroencephalogram probes, even though the electrodes were cleaned in formalin before being inserted in other scalps. And pituitary gland extracts, which once are given to treat dwarfism (before genetically engineered human- growth hormones from bacteria became available), have carried the infectious agent, as have tissue transplants.
One baffling aspect of the spongiform diseases is the extended lengths of incubation, Summers said. For example, CJD symptoms usually take decades to appear. However, some of the latest victims of the human form in Britain are adolescents. When spongiform diseases are experimentally transferred to laboratory animals, such as mice and hamsters, disease can occur in a matter of months.
"To get to the bottom of this, we really need to understand the nature of the infectious agent, whether it is a prion or a very small virus or whatever it turns out to be," Summers said. He is not optimistic that full knowledge of such a fundamentally different agent -- and how it acts to produce these neurological disorders -- will come soon. "It may take another 20 or 30 years," he said, adding that "the matter is further complicated by the fact that some of the human conditions have a genetic basis."
However, any new information could help answer the public- health questions that vex British authorities and now worry meat-eaters around the world. "No one knows how sensitive humans are to these infectious agents from other species," Summer said, noting that there are "probably minute quantities of the agent in the muscles and skin of infected British cattle."
"We seem to have a natural barrier to certain levels of the agent. After all, we have been eating lamb since the Pilgrims arrived and we don't all get scrapie. Indeed, the human spongiform diseases are rare."