Far From the Madding Herd

Birmingham, U.K.--A provocative new theory about the origin of "mad cow disease" and its human counterpart stirred debate at the annual International Congress of Biochemistry and Molecular Biology here yesterday. Stanley Prusiner of the University of California, San Francisco (UCSF), suggested that the aberrant prion proteins thought to cause bovine spongiform encephalopathy (BSE), as the disease is formally known, may coexist in sheep along with the prions implicated in scrapie, an illness that does not appear to infect humans. If he's correct, it would mean that the proteins still lurk in sheep.

Ever since BSE first broke out in cattle in the United Kingdom in the mid-1980s, scientists have wondered where the disease came from. Studies on the origins of BSE--a fatal disease marked in the early stages by loss of balance--gained urgency with the 1996 emergence in humans of the BSE-like new variant Creutzfeldt-Jakob disease (nvCJD). Linked to the consumption of BSE-tainted beef, nvCJD has so far killed several dozen people in the United Kingdom, France, and Ireland. With the scale of the nvCJD threat to public health still unclear, scientists have been busy investigating the relationship between the strains of prions blamed for neurodegenerative illnesses, including the presumed connection between BSE and scrapie.

Scientists generally assume that BSE arose in cattle whose feed was enriched with a high-protein supplement: sheep parts, unfortunately infected with scrapie. While the diseases have similar symptoms, BSE prions do not trigger scrapie and vice versa. The leading theory is that a technique for heat rendering of sheep parts that became mandatory in the 1970s somehow altered the scrapie prions enough to allow them to jump the species barrier and cause BSE. (The BSE prions and nvCJD prions appear to be identical.)

Challenging that scenario are UCSF neurologist Michael Scott and Prusiner, who won a Nobel prize for the theory that prions cause disease. They speculate that sheep may be infected both with BSE and scrapie prions, but only the latter cause disease in sheep. The heat rendering process, they suggest, may in fact destroy or otherwise inactivate the scrapie prions, paving the way for the scarcer but more hardy BSE prions to infect the cattle. The idea is that scrapie prions might somehow interfere with the infectivity of BSE prions. "It's a sort of selection mechanism. You wipe out the labile scrapie prion" by heat rendering, Prusiner says. "Scrapie prions may even protect humans [from BSE]."

The duo admits they have little evidence to back up their proposal, but they point to studies in their lab on mice, which were altered to be susceptible to both BSE and scrapie prion infection. The different strains infected different brain areas. Moreover, mice infected with scrapie progressed more quickly to disease. Extrapolating from these findings, says Prusiner, "there seems to be a reservoir of different [prion] strains in sheep": a fast-acting one that causes scrapie and a slower one that causes BSE/nvCJD. Because the scrapie strain propagates faster, Prusiner says, it would vastly outnumber the BSE/nvCJD strain in infected sheep.

Experts contacted by ScienceNOW are skeptical. Prion specialist Moira Bruce of the Institute for Animal Health's Neuropathogenesis Unit in Edinburgh says that sheep experimentally infected with BSE become ill about as fast as sheep naturally infected with scrapie. "There is no direct evidence that BSE was in sheep" at the start of the BSE outbreak, she says, although such a scenario "cannot be ruled out." And even if BSE prion is present in sheep, Prusiner says, that's no reason to avoid eating lamb chops. "In some 25 years of intense studies, nobody has ever found any signs of transmission [from sheep to humans]," he says.

With reporting by Michael Balter.