Regular review: Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease

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Abstract
Origin of bovine spongiform encephalopathy: recycled scrapie The first case of a cow with bovine spongiform encephalopathy was diagnosed in 1986, and because of the long incubation periods that are characteristic of the transmissible spongiform encephalopathies—scrapie, for example, has an incubation period of about three years—the moment of infection can be assumed to have occurred years earlier. Was this just a chance occurrence, or was there some kind of environmental event that led to the infection? The theory favoured by most scientists who have studied the disease is that it originated from an infection by scrapie in sheep. It began in the United Kingdom and not elsewhere because of a comparatively high incidence of scrapie in UK sheep and a comparatively large proportion of sheep in the mix of carcases rendered for animal feed for livestock.4 It began in the mid-1980s because of the elimination several years earlier of a step in tallow extraction from rendered carcases that allowed some tissue infected with scrapie to survive the process and to be recycled as cattle adapted scrapie or bovine spongiform encephalopathy.5 Experiments to test the point with brain tissue infected with scrapie or bovine spongiform encephalopathy showed that the inactivation produced by the tallow extraction step (organic solvents and steam) was not very impressive—on average only about 10 median lethal doses (1 log LD50) per millilitre.6 Nevertheless, if infectivity was present at a concentration of less than 1 log LD50/ml before tallow extraction, which seems highly probable, then the elimination of a step that had caused a one log reduction might well have been sufficient for infectivity to survive the process and contaminate the resulting meat and bone meal feed. The probability of an input of infectivity considerably lower than 1 LD50/g in the carcases coming to a rendering plant can be appreciated by some simple arithmetic. The weight ratio of carcases to processed meat and bone meal is around 5 to 1. Thus, an input of infectivity of 1 LD50/g would be concentrated into 0.2 g of meat and bone meal. A growing calf consumes about 2 kg of feed daily, of which meat and bone meal constitutes 4.5% by weight, or 90 g of meat and bone meal, containing 450 LD50. Because 1 LD50 is defined as the amount of infectivity with a 50% probability of killing an animal, and even taking into consideration the effects of the different species and route of infection in natural versus experimental bovine spongiform encephalopathy, it could be reasonably surmised that a daily intake of 450 mouse intracerebral LD50 would have very likely killed every calf in the United Kingdom years ago. Another feature of the scrapie hypothesis that requires explanation is that if bovine spongiform encephalopathy is caused by scrapie, and epidemiological evidence gathered over the past 50 years indicates that scrapie does not infect humans, why does bovine spongiform encephalopathy infect humans? The explanation is that when a strain of transmissible spongiform encephalopathy moves from one species to another it may acquire an altered host range—that is, scrapie in its passage through cattle could have acquired the ability to infect humans even though in its natural host it is not pathogenic. The phenomenon is unpredictable, but precedents are well known: passage of mouse adapted strains of scrapie through hamsters changes the susceptibility to disease on further passage through mice or rats; human strains of kuru or Creutzfeldt-Jakob disease do not transmit to ferrets or goats unless first passaged through primates or cats, and bovine spongiform encephalopathy does not transmit to hamsters until passaged through mice.7–9