The Origins & Evolution of Stress Research: From Distress to Eustress

Hans Selye (1907, Vienna ‐ 1982, Montreal) first published his seminal papers in 1936 ( Nature ) & 1937 ( Science ) that described the three stages of stress reaction (i.e., alarm reaction, resistance & exhaustion) in rats exposed to cold, immobilization or toxic agents. He identified the adrenals & the pituitary as the main endocrine glands involved in this nonspecific reaction. He also knew & documented that although the sudden release of epinephrine (adrenaline) from the adrenal medulla, as described earlier by Walter Canon, plays a critical role in the initial alarm reaction, but the long‐term effects of stress reaction are due to the enhanced synthesis & release of glucocorticoids from the adrenal cortex. Based on this mechanistic reasoning he described in his first publications what has later become known the “morphologic triad of stress”: adrenal hypertrophy, gastric erosions/ulcers & thymo‐lymphatic atrophy. Furthermore, what we call today ‘stress‐related diseases’ in man, he described these in the 1940s & 1950s as ‘diseases of adaption’ in rats. In the last stages of his productive life, Selye realized that virtually all the stressors (i.e., stress‐causing agents) he used in experimental animals were unpleasant, negative factors that caused ‘distress’. But around the early 1970s, mostly based on the work of Swedish psychosocial scientist Lennart Levi who distinguished “negative stress” from “positive stress”, Selye in his last scientific books (1974 & 1976) “ Stress without distress ” & “Stress in Health & Disease ”, he called distress the stress reaction caused by negative, unpleasant factors & eustress (from ‘euphoria’) the similar reaction triggered by positive, pleasant factors like joy over major rewards, receiving surprising good news. Namely, we learned during the last about 40 years that our pituitary gland cannot distinguish between positive & negative stimuli to release ACTH (only our brain cortex, amygdala & hippocampus may perceive the difference). Because of these stress‐related creative discoveries Hans Selye is known as ‘father of biologic stress’, but he also made numerous other major discoveries, e.g., he also introduced the first physiologically sound, structure‐activity classification of steroids that was also based on the chemical structure of steroids in 1943. He not only introduced the names of glucocorticoids & mineralocorticoids but discovered their anti‐ & pro‐inflammatory properties, respectively, of these steroids in animal models. Furthermore, he not only described the first stress‐induced gastric ulcers in rats (1936 & 1937), but he also recognized the first human ‘stress ulcers’ during the air‐raids in London during World War II ( Lancet , 1943). Thus, Hans Selye not only introduced the concept & bodily reaction what we call today “stress”, but he also creatively synthesized the contributions of Walter Canon & Lennart Levi in a mechanistic molecular & cellular pathway.