ABSTRACT
Since the 1980s, great strides have been made in the understanding of pathophysiology at the molecular level. Reverse genetic methods have been used to identify the mechanisms by which genetic defects cause a cascade of biochemical events leading to the development of disease. The promise of the molecular genetics has overshadowed much of the importance of conventional physiology and has shifted the focus of many scientists from the whole organism to microparticles. However, it is important to realize that ultimate potential of the molecular approach depends on a thorough understanding of how the organism functions in its environment. The reverse genetic methodology of molecular biology utilizes conventional genetics to map, localize, and clone genes related to disease. This approach is limited by our ability to identify individuals who show the phenotype of a particular disease. Diseases with "variable penetrance" are difficult to study genetically because the phenotype may not always be present in individuals who carry the genotype. One important lesson to come from behavioral medicine research is that many disease phenotypes result from the interaction of environmental stress and genetic predisposition. Acting through neuroendocrine pathways, stress disturbs the function of vulnerable end organ systems in predisposed individuals. This disturbance, if chronic, can lead to a permanent breakdown in function.
