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Absent prions blow hole in BSE theory
25 October 2007
NewScientist.com news service
Andy Coghlan

Abnormal prion proteins assumed to be the infectious agents that cause mad cow disease and variant Creutzfeldt-Jakob disease might not be to blame after all. Experiments in mice also imply that current tests to detect and intercept meat from animals infected with BSE might miss some cases if diseased animals don't have the abnormal proteins in their brains.

"The accepted theory is that the abnormal protein is infectious," says Rona Barron, head of the team at the Roslin Institute in Edinburgh, UK, which undertook the research in collaboration with the Scripps Research Institute in La Jolla, California.

Normally when animals die of a BSE-like disease, their brains are full of holes and clogged up with abnormal prion proteins - mis-folded versions of normal brain-cell proteins. But when Barron's team deliberately infected mice with human or hamster strains of BSE-like diseases, the mice died of the diseases but had little or no detectable trace of abnormal prion in their brains. "What we're questioning now is whether the large amount [of abnormal prions] you usually see is the infectious agent itself or something produced by the disease," says Barron.

The results were the same in a follow-up experiment in which Barron injected brain material from the dead mice into the brains of other mice. The mice died rapidly, proving that the injected brain material was highly infectious, but once again there was little or no trace of abnormal prion in their brains (The Journal of Biological Chemistry, DOI: 10.1074/jbc.M704329200).

"This work tells us that the prion is probably the pathological consequence of infection rather than the infectious agent itself," says Laura Manuelidis of Yale Medical School, who believes virus-like particles might be responsible for diseases like BSE.

Other researchers remain convinced that a protein alone is responsible and that the prion hypothesis still holds. "What the research shows is that the prion we detect is not necessarily the one that has most infectivity," says Chris Higgins, chairman of the UK government's Spongiform Encephalopathy Advisory Committee. "We simply don't know what the infective folded state is yet." Barron's team hunted for other forms of mis-folded prion proteins in the mice's brains without success.

Despite the outcome of the experiments, both Higgins and Barron say that abnormal prions are still a very good marker of disease and current tests should not be withdrawn. While they may miss some cases of BSE, they probably pick up the majority. Higgins says that thanks to the tests and the UK's culling strategy, BSE has now been virtually eliminated from the UK.

From issue 2627 of New Scientist magazine, 25 October 2007, page 10

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