ABSTRACT
The protein hypothesis of the structure of transmissible spongiform encephalopathy agents (or prions1) radically altered the scientific view of infectious pathogens. Thomas Kuhn, in his classic analysis of science history and philosophy The Structure of Scientific Revolutions (1), has described this type of change as a paradigm shift and the entire process as a scientific revolution. In this chapter, I examine the transition from a conventional microbiological paradigm (the virus hypothesis) to a new paradigm (the protein hypothesis) within Kuhn’s framework and show that the transition to the prion paradigm follows the pattern of previous scientific revolutions. Anomalous observations accumulated and precipitated a crisis in the field, from which radical new hypotheses appeared. A period of extraordinary science ensued wherein five major hypotheses for the structure of these unusual agents (the virus, membrane, virino, protein, and genetic hypotheses) competed to explain the key inconsistencies. Over time, the membrane and genetic hypotheses lost ground and the virus, virino, and prion hypotheses came to predominate. Now, after more than three decades, the revolution appears to be drawing to a close and it seems likely that the prion hypothesis will be the new paradigm that succeeds in displacing the previously accepted virus hypothesis. This transition, however, does not depend on formal proof of the prion hypothesis or on disproof of the virus or virino hypotheses; rather, the paradigm shift has occured because a majority of scientists believe that the prion hypothesis provides the best model for explaining key observations. In viewing the virus to prion paradigm shift from Kuhn’s perspective, we gain an important insight into the nature of scientific discovery.
