The basis of strain vartation in scrapie and other transmissible spongrform encephalopathies is a crucial issue in the ongoing debate about the nature of the infectious agent. The clear evidence for the existence of multiple strains leads us to conclude that these agents carry some form of stram-specific information that determines the characteristics of the disease Any valid molecular model must, therefore, include an informational component that can be replicated in the infected host. Further, the behavior of strains when serially passaged in different host species or genotypes limits the range of possible models for the informational component of the agent In this chapter the methods used for agent strain discrimination are described. The strategies used for the isolation and passaging of dtfferent strains are presented and the implications of the results of these simple experiments are discussed.
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