Britain Announces Human Cases of Mad Cow Disease

During the mid-1990’s, unusual forms of Creutzfeldt-Jakob disease, a type of spongiform encephalopathy, began to appear among young persons in England. The outbreak of what was later termed “mad cow disease” was traced to beef contaminated with a bovine form of the disease-causing agent.

Summary of Event

The first recognition of what is now known to be a prion disease was in the eighteenth century, when British farmers observed a degenerative disease among sheep in which the animals would scrape their wool off, rubbing themselves raw on fence posts. The disease, dubbed “scrapie” by the English, was demonstrated in the 1930’s to be transmissible among the animals. Creutzfeldt-Jakob disease[Creutzfeldt Jakob disease] Bovine spongiform encephalopathy Diseases;bovine spongiform encephalopathy [kw]Britain Announces Human Cases of Mad Cow Disease (Mar. 20, 1996) [kw]Human Cases of Mad Cow Disease, Britain Announces (Mar. 20, 1996) [kw]Cases of Mad Cow Disease, Britain Announces Human (Mar. 20, 1996) [kw]Mad Cow Disease, Britain Announces Human Cases of (Mar. 20, 1996) [kw]Disease, Britain Announces Human Cases of Mad Cow (Mar. 20, 1996) Creutzfeldt-Jakob disease[Creutzfeldt Jakob disease] Bovine spongiform encephalopathy Diseases;bovine spongiform encephalopathy [g]Europe;Mar. 20, 1996: Britain Announces Human Cases of Mad Cow Disease[09450] [g]United Kingdom;Mar. 20, 1996: Britain Announces Human Cases of Mad Cow Disease[09450] [g]England;Mar. 20, 1996: Britain Announces Human Cases of Mad Cow Disease[09450] [c]Biology;Mar. 20, 1996: Britain Announces Human Cases of Mad Cow Disease[09450] [c]Health and medicine;Mar. 20, 1996: Britain Announces Human Cases of Mad Cow Disease[09450] [c]Science and technology;Mar. 20, 1996: Britain Announces Human Cases of Mad Cow Disease[09450] Gajdusek, D. Carleton Prusiner, Stanley B.

Initially thought to be a “slow virus disease” of animals, scrapie Scrapie was not at first associated with human forms of disease. In the 1950’s, D. Carleton Gajdusek, a visiting investigator working at the Walter and Eliza Hall Institute of Medical Research in Australia, began an investigation of a neurological disorder/dementia known as kuru among the Fore tribe on the island of New Guinea (the Fore word kuru means “shaking”). Gajdusek determined that the disease, found primarily among the women and children of the tribe, was passed by the Fore practice of cannibalism. Transmission of the disease to nonhuman primates by inoculation of brain tissue from victims demonstrated the infectious nature of the etiological agent. In subsequent years, a number of similar human dementias, most notably Creutzfeldt-Jakob disease (CJD), were found to be associated with a similar agent.

Microscopic analysis of brain tissue obtained from both humans and other animals stricken by similar illnesses demonstrated a “spongy” appearance resulting from extreme vacuolation (the formation of small spaces in the tissue containing air or fluid). The diseases were termed transmissible spongiform encephalopathies Transmissible spongiform encephalopathies (TSEs). Certain forms of these diseases were shown to be inherited, but most commonly they appeared sporadically among persons in their sixties or older.

In the 1970’s, Stanley B. Prusiner at the University of California, San Francisco, began a series of studies on the agent associated with scrapie in animals. At the same time, a similar agent associated with CJD in humans was likewise undergoing study. Prusiner’s data increasingly suggested that the infectious agents lacked any evidence for genetic material composed of nucleic acid. In 1982, Prusiner termed the agent a “prion” (PrP), or “proteinaceous infectious substance.” Prions Prusiner’s hypothesis that the agent lacked nucleic acid went against the core of geneticists’ belief, that only deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) would allow transmission and replication of an infectious agent.

Although Prusiner’s suggestion did not achieve universal acceptance, the overwhelming consensus has been that he was correct. Indeed, for their work in prion research, Gajdusek and Prusiner both received the Nobel Prize in Physiology or Medicine, Nobel Prize in Physiology or Medicine;Stanley B. Prusiner[Prusiner] Nobel Prize in Physiology or Medicine;D. Carleton Gajdusek[Gajdusek] Gajdusek in 1976 and Prusiner in 1997.

Prusiner and Charles Weissman Weissman, Charles later collaborated on cloning the cell gene that encodes the prion. The normal function of the cell prion, dubbed PrPc, is unknown. The agent itself is made entirely of protein, a chain of some 231 amino acids prepared from a larger precursor. Mutations in the amino acid sequence alter the shape of the protein, which is key to its ability to cause disease. When the mutated agent enters a cell, it twists or transforms the shape of the normal PrP ^c , resulting in degeneration and death of the infected cells and, eventually, the organism. The particular site of the mutation determines the form of disease the TSE will exhibit.

The presence of a prion disease in cattle, termed bovine spongiform encephalopathy (BSE), was observed in Europe in the 1980’s. This development was probably the result of changes in the ways feed for animals was produced. It had long been common practice to use ground-up animal carcasses in cattle bonemeal, but prior to the mid-1980’s, the bonemeal had been subjected to solvent extraction followed by heating at 70 degrees Centigrade for eight hours, a practice that destroyed the scrapie (PrP ^sc ) agent. Changes in the process allowed the scrapie agent to survive and resulted in infection of the cattle that ate the bonemeal. The actual source of the BSE outbreak was never determined. Whether it originated from a spontaneous case of BSE, an admittedly rare phenomenon, or from the ingestion of material from scrapie-infected sheep is unknown.

A cow afflicted with bovine spongiform encephalopathy, or “mad cow disease,” which causes progressive degeneration of the nervous system.

(USDA/APHIS/Art Davis)

BSE, which became known as “mad cow disease” in the popular press, was first recognized in Great Britain in 1986. Approximately one hundred animals were known to be involved at that time. The extent of the disease within the cattle industry was unknown, but the evidence even then was that the disease was more widespread in cattle than was initially apparent. As a result, the use of protein obtained from sheep or other animals in cattle feed was banned. The outbreak of BSE was a serious blow to the British cattle industry, as consumption of beef dropped steeply in what had always been a beef-eating population.

The first evidence that BSE might pass from cattle to humans appeared in 1994 and 1995 with an increase and change in the demographics of CJD. CJD typically appears in older persons; it rarely develops in persons under age sixty-five. In 1994 and 1995, however, a variant of CJD was observed in ten younger persons, nine of whom were under age thirty-five. The brains of those who subsequently died from the variant CJD demonstrated large protein deposits typical of TSEs but not commonly found in classical CJD. On March 20, 1996, the British government released a report that conceded that the variant form of CJD was likely the result of the victims’ having eaten contaminated meat.

Confirmation of the link between the variant CJD in humans and BSE in cattle was provided in October of 1996. John Collinge Collinge, John of the Prion Disease Group at Saint Mary’s Medical School in London reported the results of a “fingerprint” analysis comparing the proteins of BSE and variant CJD in which the proteins were shown to be effectively identical. The infectious nature of the human agent was also shown the following year, when scientists used infected human brain tissues to transmit the disease to mice. The lesions that developed in the brains of the infected mice were identical to those in the human brains, confirming the likely source of the variant disease.

Although the number of new cases of variant CJD continued to increase in subsequent years, the rate of increase leveled off. By 2006, approximately 150 cases of variant CJD had been diagnosed in Great Britain. Not surprisingly, the average age of the victims had increased, with some cases developing in persons in their mid-fifties.

Significance

Recognition that the BSE agent could pass from cattle to humans resulted in a ban on the use of bonemeal from diseased animals in animal feed. Further, diseased cattle could no longer enter the human food chain. Strict enforcement of these rules was successful in preventing transmission of CJD from cattle to humans in the United States. Vigilance, of course, remains necessary, and occasionally meat from a “mad cow” has managed to enter the food chain. There has been no evidence for any human disease associated with these animals, however.

Long-term effects of the BSE outbreak in Great Britain may remain unknown for some time. The total number of persons exposed to the agent was probably in the hundreds of thousands. Given that the incubation period for the CJD agent can be measured in decades, by the early twenty-first century it was not known whether the approximately 150 persons diagnosed with variant CJD by that time would represent the likely total or merely the tip of a disease iceberg.

The ability of the agent to be transmitted through ingestion also raised concerns about similar diseases in other animals. For example, a prion-associated illness known as chronic wasting disease has been observed in deer and elk in the western United States. Although there has been no evidence that the agent has been passed to humans who have eaten animals with this disease that have been killed by hunters, there is still concern that transmission is possible. Creutzfeldt-Jakob disease[Creutzfeldt Jakob disease] Bovine spongiform encephalopathy Diseases;bovine spongiform encephalopathy

Britain Announces Human Cases of Mad Cow Disease Summary