Murphy E A
Am J Med Genet. 1981;8(1):35-52. doi: 10.1002/ajmg.1320080106.
The notional principles of the genetics of disease are broadly discussed. Disease is an intrinsically vague term that represents the incongruity between the inner milieu of the organism and the environment. Its dynamics, then, cannot be reduced to naive statements about selection which may operate, and operate conflictingly, on several different levels or organization. Evolutionary selection results from the advantage of complexity, and the fundamental theorem of genetic dynamics - that mutational debts must eventually be paid in full-may be false or, at best approximate. The traditional models (mendelian, galtonian, and threshold) are set in a context that identifies certain features of disease that hitherto have been totally ignored. Neither invention nor traditional analysis has been adequate. Models should be made individually adequate for the study of diseases; the diseases should not be trimmed to fit the models.