There is evidence from invitro and transgenic mouse studies that the conversion to PrPSc implicates PrPC‐PrPSc interactions.84, 159, 160, 161, 162, 163 The rate of PrPSc formation and disease progression appears to be directly proportional to the level of PrPC expression, indicated by PrP knockout mice not propagating scrapie infectivity and transgenic mice heterozygous for a disrupted PrP gene requiring prolonged incubation times upon prion inoculation.164, 165, 166 In agreement with the “protein‐only hypothesis,” these findings have raised two models explaining prion replication (Figure 3). The gene discussed is PRNP; the disease is scrapie.