Kuru, Creutzfeld-Jakob disease, Gerstmann-Sträussler syndrome, scrapie, and bovine spongiform encephalopathy are caused by so-called unconventional viruses which are really replicating proteins which induce by auto nucleation and autopatterning a configurational change in the precursor protein to produce an infectious amyloid form. Crystallography and NMR may eventually determine how amyloid precursor protein is converted to this infectious form by configurational changes in all tertiary and quaternary structure of the normal precursor. Most sporadic cases of CJD arise by de novo spontaneous conversion of the normal precursor to the infectious form, a rare event occurring at the frequency of one per million persons per year (the annual incidence of CJD throughout the world). In the familial forms of CJD and GSS, where the occurrence is an autosomal dominant trait, each family has one of five different mutations causing a single amino acid change or one of five insertions of 5, 6, 7, 8 or 9 octapeptide repeats. Each mutation causes a million-fold increased probability of the spontaneous configurational change to an infectious polypeptide, and appears as an autosomal dominant trait. Thus, the behavior of the transmissible brain amyloidosis parallels completely that of the transthyretin amyloidoses causing familial amyloidotic polyneuropathy, in which there are 19 different point mutations, each one of which increases enormously the likelihood of configurational change of transthyretin prealbumin to amyloid.