THE NATURE OF TRANSMISSION IN PRION DISEASES

Replicating biological information is usually stored only within nucle ic acid. The existence of 'strains' of agent in prion disease (scrapie , BSE, CTD has been taken to indicate an independent genome within the transmissible agent. Other replicable information exists, however, bo th in biology and elsewhere, including, for example, the 'meme' (the n eural correlate of ideas which replicate in human brains by communicat ion) and the computer virus. From this broader viewpoint, we explore t he possibility that 'strain' differences in prion disease reflect biol ogical information stored within the prion protein rather than in nucl eic acid. Much of the disease variation in mice (used as evidence for strain differences) can be accounted for by the primary structures of the prion protein of the host (the experimentally infected mouse) and the donor mouse (from which infectious tissue is taken). Information d etermining residual disease variation (when these factors have been ex cluded) map reside in different conformational states of host prion pr otein, Prion protein can adopt different conformational and glycosylat ion states. The information which these states contain is only partial ly conserved on transmission between animals, permitting the appearanc e of both 'strain stability' and 'strain mutation'. Different sources of replicating, biological information including information in the 'a gent' (the abnormal form of prion protein) and in the host prion gene (PRNP) are in evolutionary competition, We argue that, in the prion di seases, replicating information is not carried in nucleic acid in eith er the host or the 'agent' but is carried within the conformational st ate of the abnormal form of prion protein.