By David N. Leff

MIAMI — Of all the cattle routinely slaughtered for human food, nobody knows how many are infected with the prions that cause bovine spongiform encephalopathy (BSE) — mad cow disease.

"That would be an important number to know," Swiss molecular biologist Charles Weissmann told this year's Miami Winter Biotechnology Symposia Tuesday, "because the risk to humans is related to the number of cattle that get slaughtered and used for human nourishment."

Weissmann, regarded as a founding father of modern biotechnology, received the 1998 Distinguished Service Award here at the symposia, which he acknowledged with an address titled "Molecular Biology of Prion Disease." He directs the University of Zurich's Institute of Molecular Biology, in Switzerland.

"Something nobody seems to know about," he observed, "is how many cattle going to slaughter contain infectious agents without showing clinical symptoms. This is something that's never been published. I know that it is being done in Switzerland," he added, "but the results are not known."

Lacking a test for the presence of infectious prions in bovine brains, Britain has killed off millions of cattle in an effort to contain the disease.

"Something of very great commercial interest," Weissmann told BioWorld Today in an interview, "is a diagnostic test for prion disease, especially for BSE. Because ultimately, you'd like to survey all animals coming in for slaughter to see if they have contamination with the agent or not."

One of his former students, Bruno Hirsch, has founded a company in Zurich, Prionics AG, which has developed a monoclonal antibody specific for PrP^SC, the infectious prion protein. (Prion stands for "proteinaceous infectious agent.) "That should form the basis," Weissmann said, "for a rapid assay of the presence of PrP^SC in cattle brains. So as the animals come for slaughter, you would test their brains to see whether they were positive or not." (Weissmann noted he has no affiliation with Prionics.)

What he does have is a U.S. patent, issued within the last month or two, covering his process for making knockout animals resistant to prion disease.

"In principal," Weissmann pointed out, "the technology for doing knockouts in cattle and sheep is now available, based upon what people have been doing generating cattle from nuclear injection. This presages the development of special, noninfected herds for the pharmaceutical industry.

"I think it's technically feasible," he observed, "because first of all the deletion of the PrP gene has not seemed to have any detrimental effect on the normal life of the knockout mouse. So it can be assumed that you can do the same thing for cattle, without affecting its properties in a negative way. But that has to be ascertained."

Creation of certified non-infective herds of cattle would give the pharmaceutical industry another major boost, Weissmann told his symposia audience. "Sera, collagen and other bovine products are important starting materials for many pharmaceutical formulations," he pointed out: "serum for making vaccines and tissue cultures; collagen for injecting women, to make them more beautiful; gelatin for many uses; and phospholipids of bovine origin are popular in Italy for the health food industry."

Weissmann's "main efforts right now are, first, to elucidate the pathway by which prion infection gets from the periphery — the intestine, where contaminated meat goes — to the brain, where disease occurs. That research is well under way. And second, generating infectivity in mice in vitro, using normal PrP, and trying to convert it to the infectious state." *