February 17, 2004 The Oregonian by  JOE ROJAS-BURKE

The discovery of two new strains of brain-destroying proteins, called prions, in slaughterhouse cattle has shaken one of the firmest conclusions about the nature of mad cow disease.

Since the emergence of the cattle disease in 1986, researchers had concluded that all of the nearly 200,000 cases worldwide came from a single strain of prion.

The new findings, made in Italy and France, raise the disturbing possibility that previously undetected strains pose a threat to people at least as severe as mad cow disease, or bovine spongiform encephalopathy (BSE).

"This is just one more piece of information that makes the risk to people less predictable," said Dr. Richard Johnson of the Johns Hopkins University School of Medicine, a special consultant on prion disease to the U.S. National Institutes of Health.

BSE, according to the current scientific explanation, swept through British herds in feed containing meat and bone meal from infected cattle. The incidence in cattle plummeted after that practice was banned, but puzzling cases still occur. To date, the cattle-borne disease has killed about 150 people, most of them in England, presumably through eating contaminated meat.

"The new agents could be more or less virulent in humans, and we have no way to predict that," Johnson said.

Because the new agents behave different from typical BSE, experts worry that standard cattle-testing methods might miss some infections. Although BSE has not proven capable of spreading from animal to animal, the same might not be true of the recently discovered strains. The findings are spurring renewed calls for broader and more detailed study of cattle in the United States, where the first and so far only case of BSE was detected two months ago at a Washington state slaughterhouse.

"These findings clearly indicate that we have to use the best possible surveillance, as broadly as possible, until we understand precisely how these atypical cases occur," said prion expert Jiri Safar, an associate professor at the University of California at San Francisco.

The U.S. Department of Agriculture plans to test 40,000 cattle this year for BSE. Italy tests significantly more than that each month -- about 51,000 cattle.

The new strains may have already caused unrecognized cases of human illness, according to a study published Monday in the Proceedings of the National Academy of Sciences. Such human cases, the authors point out, could mistakenly be attributed to the sporadic, or randomly occurring form of the fatal, brain-destroying illness Creutzfeldt-Jakob disease.

"This remains a possibility," said researcher Salvatore Monaco, of the Policlinico G.B. Rossi in Verona, Italy.

Sporadic Creutzfeldt-Jakob occurs at the rate of about one case per million people per year, a rate that has remained stable in the United States and worldwide while cases of the variant Creutzfeldt-Jakob linked to beef climbed rapidly starting in 1995 in England. Swiss authorities, however, recently reported an unexplained doubling of the annual incidence of sporadic Creutzfeldt-Jakob in that country.

Monaco and colleagues compared the new strain to sporadic Creutzfeldt-Jakob and reported similarities in the molecular "fingerprints" of the prion proteins, and in the pattern of brain damage they inflict.

Johnson, the Johns Hopkins professor, said it is possible that some cases diagnosed as sporadic Creutzfeldt-Jakob could have come from cattle infected with the previously unknown prion strains. But he said it is unlikely given the apparently random occurrence of sporadic Creutzfeldt-Jakob and its stable rate of incidence.

Dr. Pierluigi Gambetti, director of the National Prion Disease Surveillance Center at Case Western Reserve University in Cleveland, said the brain distribution pattern of the strain discovered in Italy is different enough from the known forms of sporadic Creutzfeldt-Jakob for experts to make a distinction. He considers the link to sporadic Creutzfeldt-Jakob unlikely but very difficult to rule out until more studies are completed.

But Gambetti warned of another risk: that the new strains could be invisible to the standard tests performed on slaughterhouse cattle in the United States and Europe, which focus on specific tissues of the brain stem. The newly found Italian strain concentrates in other parts of the brain and is scarcely detectable in the brain stem.

"My personal opinion is that more testing should be done in this country," Gambetti said. "Otherwise, we will never know how many cases we have."

The new strain discovered in France also concentrates in different parts of the brain, said co-discoverer Thierry Baron of the Agence Francaise de Securite Sanitaire des Aliments in Lyon, France. Baron and his colleagues have identified a total of six atypical cases since their report of three cases in the January issue of the journal EMBO Reports.

Nobody knows the origins of the new strains, but they could represent the first documented cases in cattle of the spontaneous or random conversion of a normal brain protein into the infectious prion form. That is the hypothesis used to explain sporadic cases of Creutzfeldt-Jakob in people. If that is the case, Baron said, then mad cow disease could arise in countries that never fed cattle meat and bone meal from other cattle, "and it would still occur in the future even if the contamination source of meat and bone meal is fully controlled."

Safar offered two other explanations: the original British strain of BSE could be mutating; or cattle could have acquired the strains from contact with other animals, such as sheep known to harbor a prion disease called scrapie.

No matter the origin, the consequences are equally impossible to predict, and more definitive experiments in genetically manipulated mice are likely to take a year to complete.

"Everything is up for grabs," Johnson said, who also stressed the need for broader testing of cattle herds. "Weird things happen in this field."