The Boscombe Valley mystery: A lesson in the perils of dogmatism in science

Abstract

The central dogma enunciated by Francis Crick and the postulate that sequence defines protein structure and function put forth by Christian Anfinsen (also referred to as the Thermodynamics Hypothesis) are some of the most fundamental tenets of molecular biology that have had very profound influences and implications. They were formulated based on observations (evidence) that was obvious to the preceptors. However, as is well known, exception is the rule in biology and several works in the literature cite examples that appear to challenge these dogmas suggesting that being dogmatic can be perilous. In this perspective, using the Boscombe Valley Mystery from Sir Arthur Conan Doyle's fabled Sherlock Holmes stories as a paradigm, I ponder the necessity to revise the two dogmas in light of new evidence, especially concerning prions and intrinsically disordered proteins, much like the call for revising the Modern Synthesis to enunciate the Extended Evolutionary Synthesis.