The legacy of Hans Selye and the origins of stress research: a retrospective 75 years after his landmark brief "letter" to the editor of nature.
Szabo S, Tache Y, Somogyi A.
VA Long Beach Healthcare System and Departments of Pathology and Pharmacology, University of California-Irvine, Long Beach, CA 90822, USA.
Hans Selye's single-author short letter to Nature (1936, 138(3479):32) inspired a huge and still growing wave of medical research. His experiments with rats led to recognition of the "general adaptation syndrome", later renamed by Selye "stress response": the triad of enlarged adrenal glands, lymph node and thymic atrophy, and gastric erosions/ulcers.
Because of the major role of glucocorticoids (named by Selye), he performed extensive structure-activity studies in the 1930s-1940s, resulting in the first rational classification of steroid hormones, e.g. corticoids, testoids/androgens, and folliculoids/estrogens. During those years, he recognized the respective anti- and pro-inflammatory actions of gluco- and mineralocorticoids in animal models, several years before demonstration of anti-rheumatic actions of cortisone and adrenocorticotrophic hormones in patients.
Selye did not receive a Nobel Prize, which was awarded in 1950 to the clinician Hench and the two chemists who isolated and synthesized some of the glucocorticoids. Nonetheless, Selye was internationally recognized as a world authority in endocrinology, steroid chemistry, experimental surgery, and pathology. He wrote over 1500 original and review articles, singly authored 32 books, and trained 40 PhD students, one of whom (Roger Guillemin) won a Nobel Prize for isolating the hypothalamic releasing factors/hormones. Here, we consider the main implications of his first article launching the biological stress concept and the key ideas and problems that occupied him. Selye said "Stress in health and disease is medically, sociologically, and philosophically the most meaningful subject for humanity that I can think of."