Prusiner SB 1982, Novel proteinaceous infectious particles cause scrapie (Science 216:136-144, PMID 6801762, doi 10.1126/science.6801762)

This is a single-author paper by Stanley Prusiner in Science, issue of 9 April 1982, that proposed the word prion for a small infectious particle made of protein that resists the treatments normally used to destroy nucleic acids. The scrapie agent, which causes a slow degenerative brain disease in sheep and goats, had long been assumed to be a virus; the paper argued from the abstract's six lines of evidence, including sensitivity to proteases, that a protein is needed for infectivity, and that the agent differs from viruses, plasmids and viroids. It was contested for years, in part because nobody had yet shown that the proposed agent could convert normal protein, and it is cited as the starting point of the protein-only prion hypothesis, which the 1997 Nobel Prize in Physiology or Medicine later recognised in Prusiner's name. Earlier work in 1966 and 1967 on radiation resistance (Alper) and self-replicating protein models (Griffith) is described in secondary accounts as precursors. Citation verified against PubMed and Europe PMC; only the abstract and secondary accounts were read, not the full article. Information only, not medical advice.

Key facts

  • The citation is correct: Prusiner SB, Science, volume 216, issue 4542, pages 136-144, 9 April 1982, PMID 6801762, doi 10.1126/science.6801762, and PubMed lists Prusiner as the only author.
  • The abstract reports six lines of evidence, including protease sensitivity, that the scrapie agent contains a protein required for infectivity, while it resists five procedures aimed at nucleic acids and is inactivated by alkali.
  • The abstract reports that the agent's apparent size varies, attributed to hydrophobicity, with its smallest form perhaps 50,000 or less.
  • The abstract proposes the term prion because the properties differ from viruses, plasmids and viroids, and suggests the agent's structure may bear on other degenerative diseases.
  • A review of Prusiner's book says he began scrapie work in 1978 and that Science held the accepted paper for months, apparently from concern about the reaction.
  • The same review lists three contested claims in the paper: infectivity survived treatments that destroy nucleic acids, a protein alone could be the agent, and the name prion.
  • Reaction was hostile for years: the review describes shouting matches at talks and many researchers still favouring a virus, and a magazine account says critics pointed out that conversion of healthy protein by the diseased form had not been shown, with some proposing slow viruses instead.
  • Secondary accounts trace the protein-only idea back to Alper and colleagues' 1966-1967 finding that the agent resists radiation and to Griffith's 1967 self-replicating protein models; one 2014 Nature commentary cautions that the Alper paper does not use the word protein.
  • Prusiner was the sole laureate of the 1997 Nobel Prize in Physiology or Medicine, for the discovery of "Prions - a new biological principle of infection", and gave his Nobel lecture on 8 December 1997.
  • Europe PMC listed 3409 citations to the paper when read on 1 November 2026.

Timeline

  1. 1967Alper and colleagues (radiation resistance of the scrapie agent) and Griffith (self-replicating protein proposals) publish in Nature; described in secondary accounts only.
  2. 1978Prusiner begins scrapie research, when scrapie, CJD and kuru were attributed to unidentified viruses.
  3. 1982Paper published in Science, issue of 9 April, proposing the term prion.
  4. 1984Prusiner suggests other neurodegenerative diseases might work through a similar mechanism; largely ignored at the time.
  5. 1986BSE emerges in Britain, raising the profile of prion research.
  6. 1997Nobel Prize in Physiology or Medicine announced for Prusiner, 6 October per a magazine account; Nobel lecture 8 December.
  7. 2010A Science study read as meeting Koch postulates for prions published on 26 February, per a magazine account.

People

Last checked 1 November 2026

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