February 18, 2002 Providence Journal-Bulletin (Providence, RI) by Stanley M. AronsonIN 1920, a previously undocumented form of subacute neurodegenerative disease was de-scribed in an article by H. Creutzfeldt, a German neurologist. The next year, another German neurologist, A. Jakob, published four additional cases of this disease, which he called spastic pseudosclerosis. These and subsequent cases shared the following clinical characteristics: The brain disease typically began beyond the age of 50 and was fatal in six months to a year. Its clinical course was progressive and included advancing dementia, involuntary twitching movements, imbalance, disturbed speech culminating in mutism, and blindness. Other organ systems were not implicated. Men and women were equally vulnerable.
Little further knowledge was added in the next decade except to appreciate its rarity (about one case in a million people a year) and that while most cases were isolated (sporadic), a few appeared to cluster in families (familial). The inciting cause and mechanism of progression of this ailment, now called Creutzfeldt Jakob disease (CJD), remained unknown. And were it not for some seemingly unrelated events surfacing in the next eight decades, awareness of this disease would have been confined to a few academic neurologists and the families of its victims. In 1934, a vaccination program was undertaken in Scotland to lessen the economic impact of a viral brain disease of sheep called louping ill. Unbeknownst to the veterinarians, the vaccine batch was contaminated with yet another disease of sheep called scrapie. Some 18,000 vaccinated lambs subsequently developed scrapie, a slow, degenerative brain disease causing staggering, loss of weight, tremors, compulsive scratching and death within months.
In 1957, Australian civil servants, assigned to the inhospitable highlands of New Guinea, described a bizarre disease, locally called kuru, in the indigenous Fore people. Its symptoms included tremors, unsteady gait, dementia, los of weight and death, usually in six months of its onset. Medical anthropologists noted that ritual consumption of tissue derived from deceased family members was practiced by this ethnic group, a reverential form of cannibalism. The local authorities have since banned cannibalism and the disease has gradually disappeared.
Pathological studies of the brains from kuru victims, however, showed distinctive mic-roscopic changes that were essentially indistinguishable from the spongiform changes seen in both CJD and scrapie.
By the 1960s, evidence accumulated to indicate that CJD and kuru were indeed infectious, but only after a very prolonged incubation. By 1968, both CJD and kuru had been transmitted to experimental animals. Furthermore, there were rare instances of human-tissue transplantation, such as corneal grafts, which had inadvertently transmitted CJD to the graft recipient. Three forms of CJD were then recognized: the sporadic form, the familial form and, now, the accidentally acquired (iatrogenic) form.
When CJD was first recognized as a distinctive form of organic dementia, little thought was given to its possible infectivity since it demonstrated none of the clinical or pathological features typical of infection. Accordingly, no precautions were taken by those in intimate contact with the brain tissues of CJD patients. Incomplete data now suggest an elevated frequency of CJD among neurosurgeons, pathologists and perhaps even morticians. Surgical instruments that had touched CJD brain tissue, despite rigorous sterilization, have been known to transmit CJD to other patients.
Mink farmers in the Midwest noted a devastating wasting disease amongst their caged animals that pathologists stated was microscopically indistinguishable from scrapie, kuru and CJD. This mink encephalopathy was also transmissible to experimental animals. Epidemiologists then surmised that the infective agent of the disease was probably introduced into the mink farms through the processed sheep carcasses used to feed mink.
In 1985, a fatal disease of cows was documented in Britain ultimately affecting close to 200,000 animals. The affected animals showed weight loss, diminished milk production and a staggering gait. Local papers called it "mad cow disease." Because of its resemblance to scrapie, mink encephalopathy, kuru and CJD, pathologists called it bovine spongiform encephalopathy (BSE). English dairy farmers traditionally supplemented the diet of their cows with a commercial bone meal derived from processed animal products, including sheep carcasses. In 1988, the United Kingdom finally banned the use of ruminant tissue in animal feed. The government also prophylactically slaughtered large numbers of infected and potentially infected cows in an effort to prevent the further spread of BSE.
But there then arose a new, but not unanticipated, component to the dismal tale of CJD. English neurologists began to encounter cases of CJD in larger numbers than before. These newer CJD victims were younger (averaging 27), with dramatic behavioral change, involuntary movements, progressive paralysis, loss of speech and death in about one year. The disease was considered a variant of CJD (vCJD) and was presumed to represent a spread of BSE to humans via consumption of infected meat products. A surveillance unit was then established to monitor the British Isles. In 1995, the first year in which confirmed vCJD was encountered, there were three cases. By 1997, there were an additional 20 cases. And by the summer of 2001, there have been 95 pathologically confirmed cases of human vCJD. These cases were in addition to the sporadic, familial and acquired cases of CJD.
Given the lengthy incubation interval of these diseases, some bio-statisticians have speculated that the number of Britons, already infected, who will develop the disease in future years may exceed 85,000.
Public-health officials were now confronting a class of fatal brain disease in humans, cattle, sheep, mink (and even a wasting disease in wild elk) with certain common features: prolonged in-cubation period, pathological changes marked by a sponginess of the brain and transmissibility of the causative agent, called a prion, to experimental animals. This family of diseases has then been called the transmissible spongiform encephalo-pathies (TSE).
U.S. dairy herds, as of late 2001, show no signs of BSE. Feed derived from processed offal has long been banned, and no cattle or cattle products from the United Kingdom may be imported.
Last July, the authorities in the Japanese prefecture of Chita announced that a dairy cow had de-veloped verified BSE, and the source of the infection was presumed to be commercial animal feed. It was the first documented case of Mad Cow Disease in Asia.
This is the stuff from which horror movies and epidemiological nightmares are built.
Stanley M. Aronson, M.D., a weekly contributor, is dean of medicine emeritus, Brown University.