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The bovine spongiform encephalopathy (BSE) epidemic in the UK peaked in the winter of 1992–1993 at nearly 4000 new cases per month. At the time of a report by the Ministry for Agriculture, Food and Fisheries (MAFF) in December 1995, the incidence had fallen to around 850 cases per month and was expected to continue falling. Beginning in 1988, the British government took a series of measures to protect consumers and control the epidemic. In their present form, they are generally considered effective and adequate. Although questions remain, available evidence strongly suggests that any human exposure that might occur had already occurred before these measures were instituted. Surveillance and preventive procedures in the USA also protect both people and cattle.
The UK’s Spongiform Encephalopathy Advisory Committee, SEAC, issued a statement on BSE on March 24, 1996. SEAC has concluded that a precise quantitative risk assessment is impossible due to uncertainties over the magnitude of the species barrier between cattle and people, the infectivity of cattle tissues that are below currently detectable levels, the uneven distribution of infectivity within a tissue, the time course for the appearance of infectivity, and the existence of a threshold infective dose. Nevertheless, from available evidence, SEAC came to several conclusions: (i) if human infection with the BSE agent occurs, infants and children are unlikely to be more susceptible than adults; (ii) immunosuppressed patients and pregnant women are not at increased risk; and (iii) gelatin is safe for use in food, pharmaceuticals, and medical devices (although a review of the use of gelatin and tallow is pending). SEAC reiterated its previous advice to prohibit use of mammalian meat-and-bone meal wherever there is a chance of its being ingested by ruminants. This includes its incorporation into feed for all farmed animals, even fish and horses, and into fertilizers that might be used on land accessible to ruminants.
There is no evidence of transmission of the BSE agent from beef (muscle) to humans or to mice injected with muscle tissue from cattle with BSE. The BSE agent has been found only in brain tissue and spinal cords of cattle naturally affected with BSE. Traces of the agent were seen in the small intestine and retina of experimental calves fed large amounts of BSE-infected material; this led to bans on use of additional specified animal parts for food and feed. The issue of contamination with infected nervous tissue through carelessness at slaughterhouses and other failures appears to have been addressed by the further tightening of controls on "specified bovine offals" in the fall of 1995.
The possibility of transmission of the BSE agent in milk is of particular concern. In a paper presented to the International Dairy Federation in April 1995, Bradley reviewed the epidemiologic evidence related to milk. Sheep are the only species in which significant maternal transmission of a spongiform encephalopathy occurs, and this is attributable to infectivity in the placenta rather than the milk. No infectivity for mice has been detected in the mammary gland or milk of goats and sheep with natural scrapie, in the colostrum of sheep, or in mammary gland or milk of cows with clinical BSE. The conclusion from numerous studies is that cow and sheep’s milk can be safely consumed in any form by any species.
Janice Swanson of the Animal Welfare Information Center in Beltsville prepared a special reference brief (SRB 91-05) on BSE. It provides a very short summary of 103 general and review articles published in 1988–1990. Web sites where information on BSE is available include:
Prions are extremely difficult to inactivate. Normal cooking would probably only reduce infectivity, not eliminate it. Scrapie-infected hamster brains retained a small amount of infectivity after a 1-hour exposure to dry heat at 360°C, although not after autoclaving (2). It is interesting that formaldehyde-treated brains maintained their infectivity after autoclaving, again indicating the pivotal role of molecular conformation.
Changes in the production of meat-and-bone meal from scrapie-infected ovine carcasses are thought to have permitted survival of infective prions, thus precipitating the BSE epidemic when infected meal was fed to cattle. Taylor et al. evaluated the ability of 15 rendering processes to inactivate the BSE agent (3). Meat-and-bone meal and tallow were produced from experimentally contaminated tissues. Tallow samples were not infective, but 4 of the 15 processes yielded meat-and-bone meal with infectivity for mice. Minimum conditions for rendering by these methods in the European Union were subsequently revised.
Cutlip et al. do not believe that the scrapie prion produces BSE in cattle (6). They induced a spongiform encephalopathy in cattle by inoculating newborn calves intracerebrally with the scrapie agent, but neither the signs of illness nor the histologic appearance of the brain lesions were characteristic of those of BSE.
Transgenic mice have provided the opportunity to evaluate the species hurdle between cattle and people. Collinge et al. showed that transgenic mice expressing both human PrPC (normal cellular PrP, protease-sensitive) and mouse PrPC generate both post-translationally modified human prions (PrPSc, protease-resistant) and "human" prions as well as mouse prions when challenged with CJD inocula (7). Incubation periods for BSE in such mice are not shortened by expression of human PrP, and only mouse PrPSc is produced in response to challenge with the BSE agent. These experiments are only preliminary, but their results are consistent with the hypothesis that bovine prions do not induce formation of human PrPSc. Hope discussed the implications of these findings and of possible results of ongoing experiments (8).
A possible exception to other evidence on transmission of CJD was reported by Tamai et al. (9). They described a case of CJD in a pregnant woman who delivered a healthy baby boy by cesarean section. He did not receive any of his mother’s milk. He remains healthy after 6 years, but samples of placenta, cord leukocytes, and colostrum taken at the time of birth and post mortem samples of the mother’s brain were infective.
The British Medical Journal solicited opinions from a range of specialists on how likely it is that the BSE agent can be transmitted from infected cows to people (10). Jeffrey Almond said that because the BSE phenotype is distinct and stable, even when passed through another species, strain-typing of necropsy material from the disputed cases of CJD should provisionally answer the question of whether BSE has been transmitted to people. Paul Brown said that the jury is still out. For the idea is that "sporadic" CJD is rare in people younger than 25 years, but a more uniform age distribution would be expected if the source of infection were ingestion of cattle products. As for the four farmers, all had contact with one or more infected cows in their herds. Against the idea is that sporadic CJD has occurred in adolescents and farmers at times and in places that virtually exclude the possibility of infection with the BSE agent. Brown sees no need for further governmental hearings, committee meetings, or debates about what more might be done because precautions already taken have been logical and thorough. What remains is possible present consequences of past events over which there is now no control. Statistician Sheila Gore said that across five European countries in 1993 and 1994 the incidence of CJD in dairy farmers was consistently higher than in farmers overall. All four British farmers were male, life-long, full-time workers, and the probability of observing four or more confirmed cases in this population is less than 1 in 10,000. Together with the cases in young people, she finds the unusual occurrence CJD "more than happenstance." Experiments to transmit the infection from brains of the farmers to mice are underway but will require at least two more years for completion. Hofman and Wientjens argued that the incidence of CJD in Britain is similar to that in other European countries, despite the BSE epidemic. They feel the evidence neither demonstrates nor strongly rejects a causal link between BSE and CJD. Veterinarians Ridley and Baker emphasize that the incubation period for human spongiform encephalopathy can be considerably less than 10 or 20 years; for kuru, it has been less than 4 years. They also stress that 15% of cases are considered entirely genetic in origin, various other causes (usually iatrogenic) have been identified for an additional subset of cases, and in the remaining cases no cause is ever identified. They see no evidence that feed producers and slaughterhouse workers are at increased risk of CJD, as they would be if exposure to infected animals had caused CJD in the farmers. G.W. Roberts asked three questions related to whether the BSE agent causes CJD. "Could it happen?" Perhaps. "Has it happened?" We don’t know. "How will we know if it happens?" More people will die of prion disease, even taking into account improved diagnosis and reporting. Kenneth Tyler summarized the importance of inoculum size, route of inoculation, and host factors in determining whether infection occurs. He suggested precautions for occupational groups that might be at increased risk of contracting CJD, although at present there is no strong evidence for a higher incidence in these groups.
Lacey and Dealler discussed evidence for the vertical transmission of prion disease (11). They consider the threat of BSE to the human population to be serious. However, Paul Brown (11) and Will and Wilesmith (11) refuted most of the "data" and arguments of Lacey and Dealler. In another paper, Dealler and Kent discussed the latest statistical evidence on BSE (12). Their interpretation of the data (which include some of the disputed data in reference 11) seems to be at odds with the interpretations of most others. It is very critical of the MAFF and the alleged politics of the epidemic. Nevertheless, the paper contains some useful ideas, information, and analysis.
Groschup and Haas reviewed and discussed the health risk BSE poses to man (13). They summarized evidence for the magnitude of the species barrier, the stability of the BSE agent after animal passage, the importance of the route of infection, and the paucity of information on infectious dose. They concluded that the explosive nature of the BSE epidemic in the UK makes it impossible to rule out the possibility of transmission to humans because the BSE agent is new, and its characteristics are not fully known. They regard the probability of the BSE agent’s transmission to humans as low but not zero. Exposure is declining as the epidemic subsides.
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