BSE is one of several similar diseases collectively called transmissible spongiform encephalopathies, or TSE, which affect a wide range of species, including humans.
We met with Caughey at his office last week and put these questions to him.
Q: What is known about the transmissibility of BSE to humans?
Caughey: BSE is linked to the human form of the disease, variant Creutzfelt-Jakob Disease (vCJD), by much circumstantial evidence, including the similar timing of the two outbreaks in cattle and people, and the fact that both outbreaks were largely confined to Great Britain. There are also striking similarities in the characteristics of both strains. And, the only consistent risk factor for exposure seems to be potential dietary exposure to BSE in beef. Although it’s almost impossible to prove the point directly, BSE is by far the most reasonable source of variant CJD.
Q: Does science have adequate techniques for detecting transmissibility?
Caughey: The best method is to inoculate animals, but we can’t do that with humans. To try to gauge the transmissibility of BSE to humans we can only do surrogate test tube assays or inoculations of BSE into laboratory mice that express human prion protein (the protein that becomes corrupted and pathological in CJD patients). Other labs have shown that such mice can become sick if given massive doses of BSE. Using a test tube assay developed here at RML, we also showed that the pathological BSE prion proteins can corrupt normal human prion proteins, but rather inefficiently. At this point, the indications are that BSE can infect humans, but much less effectively than BSE can infect cattle.
Q: The sporadic, or apparently spontaneous, form of Creutzfelt-Jakob Disease occurs in approximately one in a million people worldwide annually. Unlike variant CJD, which seems to be caused by eating infected beef, its cause is unknown. Does BSE occur spontaneously in cattle as well?
Caughey: It might, but there’s no evidence of it. If the infected cow from Washington is tied to the infected cow from the Alberta herd, one would wonder if there was a common source of infection.
Q: What’s the difference between sporadic CJD and vCJD?
Caughey: They differ in the average age of the patients, the set of clinical signs, and the pattern of damage in the brain. Variant CJD tends to occur in much younger people than sporadic CJD and there is more of an emphasis on motor control problems rather than dementia.
Q: Why is scrapie, the sheep form of TSE, not transmissible to humans, while BSE is?
Caughey: That’s an important, but unanswered, question. It’s clear that the subtle differences in the prion proteins of the respective species can strongly influence transmissibility. And those differences might be enough to allow BSE to occasionally sneak into humans where sheep scrapie does not.
Q: What other species are susceptible to TSE?
Caughey:Mink, cats, rodents, many other mammals. BSE affected some large cats and exotic African ungulates such as nyala, gemsbok and kudu in zoos. Kudu seem to be exquisitely susceptible to BSE. In the wild, TSE is endemic in deer and elk, and is called chronic wasting disease. Dogs aren’t susceptible to TSE, nor are pigs in natural settings, but pigs have been affected by massive laboratory injections of BSE directly into the brain. Chickens don’t get TSEs. One problem is that we have shown that even species that are not affected by certain TSE strains can sometimes propagate the infection.
One theory about the spread of TSE is that it originated in animal feed rendered from diseased kudu in southern Africa. The feed was then sold in Great Britain, and fed to cattle. The prevailing theory, however, is that BSE originated from scrapie-infected sheep, rendered into feed and then fed to cattle.
Q: The theory that TSE is caused by a corrupt host protein, called a prion, resulted in the awarding of a Nobel Prize to the discoverer, Dr. Stanley Prusiner. That theory was hotly debated within the scientific community at the time. Is it still under debate?
Caughey: Yes, the prion theory is still very much under debate. The theory is that prions are corrupted forms of normal proteins that propagate themselves as infectious agents by corrupting their normal counterparts. Corrupted prion protein is a necessary component of the infectious agent but it may not be the only component. We have shown that the corruption reaction between the corrupted and normal proteins can occur in the test tube, but no one has been able to show that new infectivity for animals is made solely by corrupting prion protein. That doesn’t mean the prion theory is necessarily incorrect, because our test tube conditions could be wrong. However, we could also be missing some essential ingredient. The debate about the essential nature of the disease-causing agent is heating up again.
Q: Is TSE contagious between known susceptible species to all other species?
Caughey: No. Often it is extremely difficult, if not impossible, to transmit TSEs between species, even when they are closely related.
Q: What is the incubation period for BSE in cattle?
Caughey: It depends on the dose and the route of infection. Usually it takes three to five years, so there is plenty of time when the infection could go undetected by clinical signs while being transmissible to others.
Q: Is there anything missing in the public discussion about BSE that you think should be addressed?
Caughey: I’m most concerned about people understanding the track record for BSE. About 750,000 infected cows in Great Britain were slaughtered for human consumption. Of the presumed millions of people who ate that meat over the last 20 years, a very small proportion, about 143, have died of vCJD. Thus the attack rate of BSE in humans is very low. Other food-borne infections, such as Salmonella, kill 5,000 Americans every year, and more than 300,000 people are hospitalized. That’s not to say vCJD should be considered trivial, because it’s not. But it poses a relatively low risk to human health, even in the UK, the BSE capital of the world.