Hidden Models

Our understanding of genetic inheritance has gone through a number of models or “paradigms,” each of which has conditioned a method of testing and certified associated findings. Nevertheless, as models have changed, we cease to appreciate or even understand former findings. Consider the following shifts in the notion of inheritance: 1) the notion of gene as trait (e.g., “feeblemindedness”) to gene as coding region of DNA; 2) the central dogma of molecular biology that “DNA makes RNA makes protein”(106) and that “information cannot be transferred back from protein to either protein or nucleic acid”(107) to the epigenetics revolution that rediscovered a role for macro- and micro-environments to influence genetic inheritance; 3) the Mendelian notion of “one gene/one phenotype” to pleiotropy (one gene/many effects), heterogeneity (one effect/many genes), and epistasis (one effect/multiple genes combined non-additively). Each of these shifts involved the replacement of one model with another, altering the design specifications for a test required to demonstrate a meaningful “genetic influence.” For example, tests that identified single genetic influences associated with what later became viewed as a complex phenotype must be reinterpreted or discarded: the phenotype (e.g., schizophrenia) is now understood to be the outcome of many interacting genetic and environmental components. It is not necessarily that prior studies were misguided; rather, their significance diminishes as the model on which the test was predicated comes to be seen as incomplete. Notably, these underlying models are not always explicitly stated in research, but widely assumed. This makes them an ideal target for metaknowledge investigation.