Abstract
Traditional concepts of sickle cell disease as a monogenically inherited disorder that is understood completely on the basis of polymerization based pathophysiology are more simple that what clinical observations allow. Detailed explications of the determinants of polymerization can be counted, but these do not account for all aspects of sickle cell disease. Neither can all perturbations that count in the course of sickle cell disease be counted as determinants of polymerization. The polymerization based theory that has been extrapolated to describe clinical disease often is not identical to clinical reality. Although contemporary understandings of sickle cell pathophysiology have been described as crazy by those bound to traditional polymerization based understandings, increasingly iconoclastic, seemingly crazy notions are regularly providing important new understandings of sickle cell disease. One of the major challenges to contemporary investigators is to describe new scientific insights in a way that can be understood by others, particularly those reluctant to afford polymerization independent discoveries validity among the interdependent processes that account for sickle cell disease.