It is now not possible to be sure which of the hypotheses as to the origin of the novel agent is correct. Current knowledge suggests that the original agent was not the unmodified scrapie agent or agents. It is a common misconception that reduction in temperature or a failure to prescribe minimum holding times in the rendering of carcass waste led to failure of inactivation of the scrapie agent and transmission across the species barrier to cattle. Changes in the rendering process in the late 1970s and early 1980s, namely the switch from batch to continuous processing and the abandonment of solvent extraction of tallow, might have led to reduction in inactivation of the agent in MBM, but it is now known that the processes used previously were also incapable of completely inactivating TSE agents. No commercial rendering procedure has been designed capable of completely inactivating BSE in MBM before or since.
All evidence points to the specific association of an abnormal form of the prion protein and TSEs.
Contact between normally shaped and abnormally shaped proteins induces the normal to convert to the abnormal. This leads to a build up of the abnormal form of the protein, which accumulates in and eventually causes the death of nerve cells. Nerve cells are particularly susceptible to PrP Sc because they cannot re-generate. The presence of PrP Sc can be demonstrated in the brain and spinal cord of all humans and animals affected with TSEs. These observations virtually eliminate other hypotheses as to the direct cause of TSEs, such as autoimmune disease of the CNS, because those hypotheses do not incriminate the prion protein.