The prion hypothesis proposes that a cellular protein, PrP^C, is converted to an aberrant, infectious protein, PrP^Sc, by encountering exogenously introduced PrP^Sc.  This protein, PrP^Sc, must have two different, but vital, capabilities to fulfil its duty in the context of the prion hypothesis:  First, it must be able to convert PrP^C into more PrP^Sc, i.e., a form of replication.  Second, the PrP^Sc must imprint subtle differences in the structure of the newly formed PrP^Sc to account for the many agent strains found among the transmissible spongiform encephalopathies (TSEs).  Recent findings regarding the relationship between structural integrity of PrP^Sc and the infectivity evidenced by biological assays raise serious questions concerning the capacity of one molecule (PrP^Sc) to both induce conversion of PrP^C and serve as the informational molecule for specific strains.  This presentation details some of the recent anomalous findings that need to be explained in the context of the prion hypothesis and provides data that argue for an alternative hypothesis.  Finally, information is presented concerning interaction between various types of nucleic acids and PrP molecules.