Animal Sciences Research and Reviews

Special Circular 156

Facts and Speculation About Bovine Spongiform Encephalopathy (BSE)

H.W. Ockerman
Department of Animal Sciences

Bovine Spongiform Encephalopathy (BSE) recently has made international headlines. Because this is a new type of infectious agent, we need to keep abreast of its development. This unique and currently little understood disease, the speed of information transferred on the Internet, and the potential consequences of this disease make keeping abreast of the latest developments difficult (Table 1). Releasing anything in print is almost assured to be out of date before the ink dries. History we can record (Table 2); speculation has to be taken for what it is and in that light; and recommendations by experts must be considered their best judgment with the facts currently at hand.

This paper was written in May 1996 as a keynote speech for an International Meat Conference held in China. The BSE (Table 3) was first reported in British cattle in 1986. It is a disease of the central nervous system that results in abnormalities of stance, gait, and behavior. Scientists found a sponge-like degeneration of the nervous tissue and "scrapie-associated fibrils" in the brain of autopsied animals. This placed the disease in a category that has been known for more than one hundred years in animal and man and is called transmissible spongiform-encephalopathy (TSE), and thus, the name B(bovine)SE.

Scrapie (sheep and goat) is a prototype for this disease category. It has been known for about 200 years and can be found in most countries except Australia and New Zealand. In Great Britain, it is estimated that one-third of the sheep flock is infected with scrapie. The incubation period in sheep is usually considered to be approximately four years.

In 1995, 154,592 cattle had contacted BSE in Great Britain. A few other countries, such as Switzerland, France, Ireland, Portugal, Germany, Oman, Italy, Denmark, and Canada, have reported a small number of cases. No cases have been discovered in the U.S. Other related animal and human diseases can be found in Table 3.

It is speculated that BSE in England was caused by feeding cattle with meat and bone meal contaminated with scrapie pathogens. Since 1970, rendering plants in England have processed carcasses under conditions that do not guarantee that these pathogens will be completely eliminated. The BSE agent is relatively resistent to physio-chemical procedures that inactivate common microorganisms. It is speculated that the incubation period in cattle averages about five years. When the problem was realized, a ban (1988) was placed on feeding ruminants with rendered meal produced from ruminants. In 1996, at least one case of BSE had occurred in 34% of all British herds (54% in dairy herds and 15% in beef herds). In 1992 to 1993, the epidemic reached its peak, and since that time, a decrease has occurred, probably due to the feeding ban. Unfortunately, there is no test available for diagnosis of BSE in live animals, and because this pathogen is new, its characteristics are not fully understood.

Table 1. Chronological development.

Known more than 100 years - transmissible spongiform encephalopathies (TSE). 200 years ago - scrapie was described. 1985 - No live bovine animals imported from England into the U.S. after this date. 1985 - No fresh beef imported from England to the U.S. after this date. 1986 - Identification of BSE in England was announced. 1988 - The British banned the use of animal-derived food supplements. 1989 - No importation into the U.S. of live animals or beef by-products from countries with BSE after this date. 1995-96 - Ten human cases of Creutzfeldt-Jakob Disease (CJD) in England were found in younger than expected people. 1996 - Two farmers who had "mad cows" in their herds recently died of CJD. 1996 - The World Health Organization (WHO) met in Geneva No part of an animal with signs of TSE should enter the human or animal food chain. Slaughter and safe disposal of TSE-affected animals recommended. Review rendering procedures to ensure inactivation of TSE. Continuous surveillance and compulsory notification of BSE recommended. Without surveillance data, a country must be considered as unknown. Banned the use of ruminant tissue in ruminant feed. 1996 - USDA has monitored for BSE for 10 years and currently has not identified any case in the U.S. 1996 - Currently in the U.S., 12 to 15% of ruminant-derived meat and bone meal is used in ruminant rations. 1996 - U.S. livestock organizations established a voluntary ban on ruminant-derived protein being used in ruminant (cattle, sheep, and goats) feed. 1996 - The number of cases of CJD has remained stable (1/1,000,000 since 1979), and the age distribution has not changed in the U.S.

Table 2. Places to obtain additional information.

WHO1 - Telephone: (41 22) 791-2535 or (41 22) 791-2660 FAX: (41 22) 791-4858 or (41 22) 791-4198 E-mail: strootp@who.ch or yeymannd@who.ch Home page: htto://www.who.ch USDA - World Wide Web: http://www.usda.gov

1 WHO = World Health Organization.

What is known or proposed is that BSE (sometimes called "mad cow disease") is a degenerative disease affecting the brains of cattle. It is caused by a small, infectious, almost pure protein agent called a prion ( pronounced "pree-on"). Remarkably, a prion can be inherited as well as be communicable, has no nucleic acids (DNA or RNA), and it multiplies by converting normal protein molecules into pathogenic ones simply by inducing the benign molecules to change their shape. These factors separate it from virus and any other known type of infectious agent. This is almost reminiscent of the time when microbiologists discovered that bacteria were responsible for producing diseases. Because a prion is a protein, there must be a gene that specifies its sequence of amino acids. This gene has been located in the chromosome of all animals examined to date. These animals make PrP (prion protein) without getting sick. Therefore, PrP must be made in two forms, and the bad type resists breakdown by cellular enzymes (protease-resistant). Because this is gene controlled, the disease is inherited in some families. In others, the infectious agent seems to influence the PrP gene to manufacture the altered (bad) protein.

Table 3. Terminology or nomenclature.

Animals: TSE - Transmissible spongiform encephalopathy BSE - Bovine spongiform encephalopathy Scrapie Transmissible mink encephalopathy - farmed mink Chronic wasting disease - captive elk and mule deer

Man: Creutzfeldt-Jakob Disease (CJD) - in every country - 80% sporadically, 5% infection with CJD, 15% familial. Gerstmann-Straussler-Scheinker syndrome (GSS) Fatal familial insomnia (FFI) Kuru - New Guinea - infectious V-CJD - Variant Creutzfeldt-Jakob Disease - 10 cases in the UK occurred at younger age than classical CJD, and there were several clinical and pathological differences. There was no distant link, but there were circumstantial evidence results in a hypothesis of BSE in V-CJD.

Causative agents: Prions (pronounced pree-ons) - infectious particles (inherited 10% and communicable). They manipulate normal protein molecules into dangerous ones by causing them to change their shape. Protein that contains no nucleic acids. PrP - Prion protein. Cellular PrP - normal protein. Scrapie PrP - infectious (protease resistant).

Genes consist of two strands of subunits called nucleotides, which differ in the bases associated with them. Bases on one strand pair up with bases on the adjacent strand to produce the "rung" of the familiar DNA ladder. The base is also a code to transmit the sequence of amino acids that are connected to make a protein. If the bases are paired up incorrectly, then the wrong code is transmitted (e.g., leucine substituted in place of proline), and the wrong amino acid is placed in the protein chain. This causes the altered protein to unfold or change its usual configuration to that of the infectious agent. The normal protein is usually an alpha helice, but the infectious form is destabilized and is usually in the form of beta-sheet strands. It is speculated that these beta strands accumulate in the lysosomes, burst the liposomes, and that these cells cause the familiar holes in the brain.

Concerns increased recently when 10 cases of Variant-Creutzfeldt-Jakob Disease (V-CJD) occurred in the United Kingdom in people of younger ages and contained several clinical and pathological differences when compared to the classical CJD. It was concluded that there was no definite linkage between BSE and V-CJD. Circumstantial evidence suggests that exposure to BSE is a likely hypothesis. Also, two farmers who had "mad cows" in their herds died of CJD. On the other hand, no butchers, abattoir workers, or veterinarians in the United Kingdom have contracted V-CJD to date. Also, in spite of the BSE epidemic in cattle in England, there has been no significant increase in V-CJD in the English population over the past 10 years. In addition, England does not have a significant difference in disease level when compared with other European countries.

In summary, it appears that the BSE pathogen is a new group of Transmissible Spongy Encephalopathy that we currently do not totally understand. The probability of BSE being transmitted to humans is low but not zero. Forsafety's sake, intelligent precautions (Table 4) should be taken, and new and updated information should be sought (Table 2).

Table 4. Currently considered safe items.

1. Current research suggests that milk will not transmit these diseases. 2. Gelatin currently is considered safe for human consumption. 3. Tallow currently is considered safe if effective rendering procedures are in place. 4. Medical preparations differ in that they may be injected as well as taken orally. 5. Blood currently has not been shown as a potential source of infection.