UNTIL 1982, brain diseases such as scrapie and Creutzfeldt-Jakob disease (CJD) were biological enigmas. In that year, Stanley Prusiner suggested a simple explanation for their cause: a misshapen prion protein that could convert any normal prion it met into its own aberrant form. The abnormal protein resists degradation by enzymes, so it accumulates in the brain, causing damage and death.
Controversy followed. The idea of an infectious agent that could replicate without genetic material was too much for some biologists. Prusiner’s explanation is still the best we have, and it earned him a Nobel prize in 1997, but though it offers a skeleton for the story of infection, putting flesh on the bones is proving frustrating.
How do abnormal prions – if not in food – spread between unrelated individuals, for example? It seems they can move from the brain along facial nerves to the tongue (see “Double rethink on prion diseases”). Does this mean the disease spreads among sheep, cows and deer by the shedding of tongue cells packed with harmful prions? Animals could pick them up by visiting salt licks or grooming others that have already been licked by an infected creature. It’s a plausible theory, but as yet nobody has found prions or infected tongue cells in saliva.
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We are also stumped by what happens when abnormal prions enter a new host. It had been assumed that when eaten they would turn up in zones of the small intestine called Peyer’s patches, where foreign antigens are presented to the immune system. Yet this did not happen when infected material was introduced into the guts of sheep. The abnormal prions disappeared into the body and did not turn up in Peyer’s patches until weeks later, by which time they were being produced by cells from the Peyer’s patches themselves. This disappearing trick has reignited speculation that something else in the infected material helps to transmit disease (Â鶹´«Ă˝, 15 April, p 18).
Perhaps the most urgent question is how many people will eventually develop variant CJD as a result of eating beef from cattle with another prion disease, BSE. In the UK, all cases of vCJD so far have been in people with two copies of a variant of the prion gene, called M. Now abnormal prions have been found in tissue taken from people with two copies of another variant, called V (see “vCJD risk revised”). This matters, because about one-tenth of the UK population has the VV genotype. The sting in the tail is that the tissue came from an anonymous study, so there is no record of whether the people it came from went on to develop vCJD.
Tantalising is the word. Our best research efforts seem to take us so far but no further. Prion diseases may not be the enigma they once were, but plenty of puzzles remain.
