International Commentary

Will Ockham's Razor Cut
Mad-Cow Disease Down to Size?

By Brian M. Carney, an editorial page writer for The Wall Street Journal Europe.

C ould mad-cow disease be caused not by prions, the misshapen proteins invented to account for mad-cow and diseases like it, but by a simple bacterium?

If proved true, this theory would undermine scientific research that has so far earned the supporters of the prion theory two Nobel Prizes for medicine. It would also call into question the rationale behind Europe's enormous purchase-for-destruction program for older cattle and the assumption that mad-cow disease can be passed to humans through the eating of infected meat or tissue.

The suggestion that the whole approach to mad-cow disease is wrongheaded may seem shocking. But Alan Ebringer, a professor of immunology at King's College, London, has been doing some very suggestive research into the possibility that mad-cow disease, and other diseases related to it, are the result of the body's own immune response to a bacteria called Acinetobacter.

The 14th-century medieval philosopher William of Ockham formulated a principle that has since become a pillar of modern science. It says simply that other things being equal, the simplest available explanation of a phenomenon is the one to be preferred. In the case of mad-cow disease, the appeal of Dr. Ebringer's hypothesis is that is that it does not require the positing of a previously unheralded disease-causing agent called a prion. It relies instead on disease-causing mechanisms already well-understood by science.

Acinetobacter possesses a molecular sequence that is almost identical to one found in brain tissue. According to Dr. Ebringer's theory, this similarity causes antibodies produced by the body against this bacterium to attack the brain as well.

This would make mad-cow disease -- and its human form, Creutzfeldt Jacob disease, or vCJD -- not some exotic protein-caused "prion" disease, but one of a known class of diseases called autoimmune diseases. In these diseases, such as rheumatic fever, the body's own immune system mistakes parts of the body for disease-causing agents and attacks them. It would also imply that mad-cow, CJD and other so-called transmissible spongiform encephalopathies, or TSEs, are potentially treatable using antibiotics.

But first, a word on the scientific consensus that Dr. Ebringer is arguing against.

Prior to the 1980s, the scientific community had pretty much settled on two main causes of infectious disease -- viruses and bacteria. But mad-cow disease, and the TSEs related to it, had no identifiable bacterial cause, and anyway, lab tests had shown that infectious material -- usually brain matter from sick animals -- remained infectious even after subjected to conditions of heat and cold and decontamination that would have rendered any known virus or bacteria inert.

So the search was on for another cause, and that search identified prions, microscopic abnormal proteins that were somehow capable of causing the host to produce more of the proteins, which then go on to destroy the victim's brain.

One of the chief arguments for the prion theory is that it is the only one that has so far satisfied the three criteria for a disease-causing agent laid out in the 1880s by German physician Robert Koch. As described by Richard Rhodes in his book on mad-cow disease, "Deadly Feasts," these are: 1.) The agent must be present in every case of the disease; 2.) Inoculations of pure cultures of the agent must produce disease in animals; 3.) Cultures of the agent purified from such diseased animals must produce the disease again and repeatedly.

Prions are taken to be the agent of TSEs because they are always found in diseased animals, prion-infected tissue appears to cause the disease, and brain-matter taken from animals infected in this way will in turn (almost always) cause the disease in other animals.

But the theory is not perfect, and leaves certain questions unanswered. The chief among those is how a protein not thought to contain any genetic material of its own can reproduce itself or cause itself to be reproduced, or even how exactly a protein causes disease. And this is where Dr. Ebringer and Ockham's razor come in. If a theory could satisfy Koch's postulates and not require the positing of a unique agent, it would seem to be preferable, other things being equal.

Dr. Ebringer's theory is admittedly not yet at that point. Specifically, he has published scientific research that seems to show that the bacteria Acinetobacter is present in the blood serum of cows that have mad-cow at much higher levels than in healthy cows. According to his work, some of which is published, his diagnostic test -- which, unlike the current prion tests, can be administered to live cattle -- can distinguish infected cows from healthy ones with a high degree of confidence.

But what of the evidence that infected brain matter causes the disease even after being heated, frozen and treated with disinfectants and acids? Here Dr. Ebringer's theory becomes complex where the prion theory is simple. The disease exhibited when infected brain matter is injected into the brains of healthy animals is similar to, but not identical with, the TSEs observed in the field. It is, rather, a laboratory-created condition known as experimental allergic encephalopathy, caused by the rather violent expedient of injecting material from one animal's brain into another's. In short, it only appears to be a TSE.

This is vital because, according the autoimmune theory, TSEs are not really transmissible at all, at least in the sense that a human could get one from eating beef or other infected material. Rather, they are triggered by a build up of Acinetobacter in the body sufficient to trigger an immune response that in turn attacks the brain. If this is correct, antibiotics that rid the body of this bacteria would remove the cause of the disease, and -- most dramatic of all -- potentially stop it in its tracks.

While Dr. Ebringer's experimental work so far implies that indeed Acinetobacter is present in the diseased animals, what he has not shown is that he can cause the disease in animals by inoculating, or injecting, them with Acinetobacter. Therefore he has not satisfied the third postulate either.

Dr. Ebringer says he is eager to do that work, but has yet to secure funding for it. Yet for some in the field, this is a circular problem. If he could satisfy Koch's postulates, Dr. Ebringer could win some converts, but until he does, many will not accept his contention that he has shown what causes the disease. And unless he can do that, funding will be hard to come by. He says he has sought funding for the transmission study in the past, and is applying again, so he may yet get a chance to prove he is right.

Until then, his hypothesis remains an intriguing but inconclusive one.

-- From The Wall Street Journal Europe