Does the infective agent of scrapie replicate without nucleic acid? An assessment

The dogma of a unique status for the scrapie agent falling outside the virological spectrum is critically examined in the light of the circumstances which gave rise to it, and it is concluded that such an extreme view cannot be justified. The dogma arose in the first place by a combination of inadequate methodology and the lack of comparable data from other systems. It has been sustained partly by the same factors, and partly by a general failure to understand the impact on all relevant investigations of the exceptionally tenacious binding of infective agent to host-cell (membrane) components. This has not only greatly distorted the experimental findings, but as a consequence has resulted in extensive data misinterpretation. It is concluded that there is no hard evidence for the absence of a nucleic acid core in the scrapie agent so long as it is accepted that this is very small--i.e., of the order of 30 KDa (kilodaltons)--and is embedded within a cell membrane component matrix which protects it by forming a sequestered microenvironment: further that this is by far the simplest hypothesis.