The Canadian Rutherford Lecture: An Evolutionary View of Disease in Man

It is said that genes propose and experiences dispose. Biological adaptation (to fit with the experiences of life) implies functional and structural homeostasis. Disadaptation (the undoing of fitness, that is, morbidity, disease) occurs when experience overwhelms homeostasis or phenotypic variation undermines it. Human disease has social and cultural contexts, but it is also measurable in the biological dimensions of viability, development, reproduction, and longevity. Heritability is a description of `cause' and, for some classes of disease, heritability is high in modern society relative to the past. Mendelian variation in man is immense; 90% of that occurring in single-copy DNA and associated with disease (selective mutation) is expressed in pre-reproductive life in the universal environment. Neutral (non-selective) mutations also occur in both coding and non-coding DNA regions; when the latter are tightly linked with selective mutations they can be used as markers of risk for disease. Accordingly, molecular genetics and other methods for defining genotype provide ways to anticipate risks to health and to prevent disease.