Stress and the General Adaptation Syndrome

With the concept of the general adaptation syndrome we have attempted to integrate a number of seemingly quite unrelated observations into a single unified biologic system.I would draw attention briefly to the work of Claude Bernard, who showed how important it is to maintain the constancy of the "milieu interieur" ; Cannon's concept of " homoeostasis "; Frank Hartmann's " general tissue hor- mone" theory of the corticoids; Dustin's observations on the " caryoclastic poisons," the " post-operative disease," the curative action of fever, foreign proteins, and of other " non-specific therapeutic agents "; the " nephrotoxic sera " of Masugi; and to the " Goldblatt clamp" for the production of experimental renal hypertension.At first sight it would seem that all these observations have little in common and that there is no reason to attempt their integration into a unified system of physio- logical and pathological events.Yet most of my research work has been devoted to the construction of bridges between these and many additional facts, since they were thought to be interconnected in nature.Through the com- prehension of their unity we hoped to learn how to use them better for the understanding of life and the treatment of disease.The keynote of this unification was the tenet that all living organisms can respond to stress as such, and thiat in this respect the basic reaction pattern is always the same, irrespective of the agent used to produce stress.We called this response the general adaptation syndrome, and its derailments the diseases of adaptation.Anything that causes stress endangers life, unless it is met by adequate adaptive responses; conversely, anything that endangers life causes stress and adaptive responses.Adaptability and resistance to stress are fundamental pre- requisites for life, and every vital organ and function par- ticipates in them.In order to present a well-proportioned outline of the general adaptation syndrome it was necessary, therefore, to peruse every branch of physiology, biochemis- try, pathological anatomy, and clinical medicine in search of the "stress factor" in all aspects of normal and abnormal life.It will take many years, indeed many generations, before the details of the general adaptation syndrome are satis- *The first part of the Heberden Oration, given on June 2, 1950.