Stanley Prusiner Discovered an Infectious Agent With No DNA, and Was Mocked for a Decade

Stanley Prusiner was a young neurology resident at the University of California San Francisco when one of his patients died of a slow brain-rotting disease called Creutzfeldt-Jakob. He could find no virus, no bacterium, no fungus. The literature on scrapie, the analogous disease in sheep, was already pointing somewhere strange — the infectious agent passed through filters that should have caught any virus, and resisted radiation doses that should have shredded any nucleic acid. Tikvah Alper had argued in 1967 that whatever caused scrapie might contain no DNA or RNA at all.

Prusiner spent the late 1970s purifying the agent from infected hamster brains. By 1982 he was confident enough to publish. The Science paper of April 9, 1982, proposed that the infectious particle was a protein on its own — no nucleic acid attached — and coined the name 'prion,' from proteinaceous infectious particle. The reaction in microbiology was hostile. Infectious agents replicated. Proteins did not replicate. The proposal violated the central dogma.

Prusiner's group spent the 1980s and early 1990s working out the mechanism. The host cell normally produces a harmless protein called PrP^C. A misfolded version, PrP^Sc, when introduced, acts as a template: it causes the host's PrP^C to refold into the same disease form, which acts on more PrP^C, and so on. Replication, but with shape rather than sequence. Stuart Lindquist and others later showed yeast versions behaving the same way, which let labs study the process safely.

The 1997 Nobel Prize in Physiology or Medicine cited Prusiner alone. By then the bovine spongiform encephalopathy outbreak in the UK and its human variant, vCJD, had made prions famous. Prusiner's idea is now the standard model of a class of disease that could not, by every prior rule, exist.