Where did mad cow disease come from?

While working on a story on mad cow disease (bovine spongiform encephalopathy, or BSE), I came across an article about where the disease originally came from. (Brown P. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease. BMJ 2001; 322: 841-844.) This article is oft-quoted, and I haven’t seen anything new on the thinking in the intervening nine years.

What bothered me about the article is that, with caveats, it rehashed the theory that BSE came from a similar sheep disease called scrapie — a theory I thought had been discredited. Is this an academic argument? Does it matter where BSE or any disease, really, comes from? I think it does. How can public health authorities cope with the threat to people and to civilization from serious pandemic diseases if we don’t understand how they arise?

Scrapie was a brain-wasting disease that had affected sheep for at least 50 years… or that’s the length of the recorded experience. (No one asks where scrapie came from.) But it did not explode in the sheep population the way BSE did in cattle, and it never infected a person, although sheep are widely eaten (marinated in a rosemary-red wine sauce before grilling is my favourite way).

When British cattle started coming down with BSE, one of the logical places to look for a source of infection was feed. Certainly, it appeared that ingesting infected products was the source of the human outbreak. Rendered animals were used in ruminant feed at the time, so it was plausible that scrapie could have infected cattle. And contaminated batches of feed would account for the sudden explosion of cases.

Except that, as a leading expert in the UK pointed out at the time, scrapie and BSE “looked” very different. Animals with BSE had very specific behaviours, such as walking backward, not seen in sheep with scrapie. There was some discussion at the time (I have been unable to find it again) about differences in the incubation period.  In 1996, Kevin Taylor, deputy chief veterinary officer at the British Ministry of Agriculture, Fisheries and Food said that none of the 20 strains in scrapie resembles BSE. As for the source of infection in feed, that could have been infected cattle rather than sheep. Also, as the 2001 BMJ article acknowledges, scrapie did not infect other animals or humans, whereas BSE clearly has the ability to “jump species.”

A short digression about this: many of our human diseases come from animals. These diseases can move from one species to at least one other (us); many can infect several species. Jumping species makes a disease more likely to be successful. Think of West Nile virus (birds and humans, using mosquitos as a vector), malaria (various species, using mosquitos again), and influenza (pigs or birds and humans).

Not only can BSE infect people, it infected several exotic animals in English zoos, such as kudus, a kind of antelope in the cow family. Presumably, they were being fed cattle feed. So, whereas scrapie had never infected another animal, this new entity was infecting several other species. The explanation given for this is that passage through cattle somehow changed the disease so that it could infect other species. This is speculative and, I think, the least likely explanation.

For one thing, there are other animal spongiform encephalopathies such as elk wasting disease now affecting cervids (deer family animals) in western Canada and the US in epidemic proportions. Where did it come from? How does it spread? Why is affecting only animals in the deer family? Clearly, these diseases crop up from time to time, without any evidence that they are linked to each other.

Another thing: BSE and other spongiform encephalopathies are caused by prions — proteinaceous infective particles. Basically, misfolded proteins set off a chain reaction, altering proteins throughout the nervous system. It’s like a computer program that does exactly one thing — folds proteins. While viruses and bacteria mutate, there is no evidence of mutation in prions. In fact, studies show BSE has the same DNA fingerprint over time, evidence against mutation. So why would scrapie mutate when it was contracted by cattle?

If BSE did not come from scrapie, where did it start? How do these prion-based diseases get a toehold in a species? Did a spontaneous mutation in one animal become infective? Is there a small reservoir of disease in a few animals that escapes notice until some mechanism like an animal rendering process at a feed plant disseminates the infection to hundreds of animals? We need to understand how prion diseases arise before we can jump to any conclusions. And before we can figure out how to prevent these terrible, lethal diseases from infecting people again.