(A) shows PrP solubilization in 22L scrapie infected p18 particles, and (B) shows the corresponding TCID/gm after treatment with the denaturants indicated. The light gray bar is the residual p18 particle PrP (taken as 100%) and the black bars show the PrP solubilized by buffer control, and after parallel chemical denaturants. As much as 65% of PrP remains insoluble (medium gray bars) with treatments that induce the greatest >4 log loss of titer, e.g., with 6M urea + β-ME and with the 3 chemical combination of ThU, Urea + β-ME. The 22L scrapie agent is clearly more sensitive than the FU-CJD agent to destruction by 4M urea, and the 22L agent titer is also undetectable after 6M urea + βME, unlike FU-CJD. All p-values <0.05 (including * compared with **).