title: Spontaneous generation of mammalian prions.
abstract: Prions are transmissible agents that cause lethal neurodegeneration in humans and other mammals. Prions bind avidly to metal surfaces such as steel wires and, when surface-bound, can initiate infection of brain or cultured cells with remarkable efficiency. While investigating the properties of metal-bound prions by using the scrapie cell assay to measure infectivity, we observed, at low frequency, positive assay results in control groups in which metal wires had been coated with uninfected mouse brain homogenate. This phenomenon proved to be reproducible in rigorous and exhaustive control experiments designed to exclude prion contamination. The infectivity generated in cell culture could be readily transferred to mice and had strain characteristics distinct from the mouse-adapted prion strains used in the laboratory. The apparent "spontaneous generation" of prions from normal brain tissue could result if the metal surface, possibly with bound cofactors, catalyzed de novo formation of prions from normal cellular prion protein. Alternatively, if prions were naturally present in the brain at levels not detectable by conventional methods, metal surfaces might concentrate them to the extent that they become quantifiable by the scrapie cell assay.
authors.affiliation: Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London WC1N 3BG, United Kingdom.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Edgeworth
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gros
authors.forename: Jack
authors.initials: J
authors.lastname: Alden
authors.forename: Susan
authors.initials: S
authors.lastname: Joiner
authors.forename: Jonathan D F
authors.initials: JD
authors.lastname: Wadsworth
authors.forename: Jackie
authors.initials: J
authors.lastname: Linehan
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: Graham S
authors.initials: GS
authors.lastname: Jackson
authors.forename: Charles
authors.initials: C
authors.lastname: Weissmann
authors.forename: John
authors.initials: J
authors.lastname: Collinge
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D051379:Mice; D011328:Prions / Q000096:biosynthesis*; D012608:Scrapie / Q000209:etiology
chemical_list: D011328:Prions