G.A.S. Spells Stress
As with so many wondrous discoveries of science and medicine, it was by chance that Hungarian-born Hans Selye (1907-1982) stumbled upon the idea of the General Adaptation Syndrome (G.A.S.), which he first wrote about in the British journal Nature in the summer of 1936. The G.A.S., alternately known as the stress syndrome, is what Selye came to call the process under which the body confronts “stress” (what he first called “noxious agents”). In the G.A.S., Selye explained, the body passes through three universal stages of coping. First there is an “alarm reaction,” in which the body prepares itself for “fight or flight.” No organism can sustain this condition of excitement, however, and a second stage of adaptation ensues (provided the organism survives the first stage). In the second stage, a resistance to the stress is built. Finally, if the duration of the stress is sufficiently long, the body eventually enters a stage of exhaustion, a sort of aging “due to wear and tear.”

“Stress,” in Selye’s lexicon, could be anything from prolonged food deprivation to the injection of a foreign substance into the body, to a good muscular workout; by “stress,” he did not mean only “nervous stress,” but “the nonspecific response of the body to any demand.”

Selye’s breakthrough ideas about stress helped to forge an entirely new medical field – the study of biological stress and its effects – which blossomed through the middle part of the twentieth century to include the work of thousands of researchers, and it is a science that continues to make advances today by connecting stress to illness and discovering new ways to help the body efficiently deal with life’s wear and tear.

Though his efforts were met with skepticism early on (he did suggest some fairly radical things, including the idea that stress had a causal relationship to a number of major illnesses – heart disease and cancer, among them), Selye’s impeccable methods and research gradually won out, and his ideas were eventually treated with respect by health and science professionals of every stripe.

In Selye’s own words, his discovery was just “enough to prevent the concept from ever slipping through our fingers again; [making] it amenable to a precise scientific analysis.”

Stressed-out Lab Rats
Selye had actually been searching for a new hormone when he stumbled upon all of this. In 1934, at the age of 28, he was an assistant at McGill University’s Biochemistry Department in Montreal. He was a promising young endocrinologist carrying out quite orthodox biochemical experimentation involving the injection of rats with ovarian extract. His hope was to uncover changes in the organism that could not be caused by any known sex hormone, and the initial results gave him cause for great optimism.

The rats developed a triad of symptoms from the extract injections, including enlargement of the adrenal cortex, atrophy of the thymus, spleen, and lymph nodes, and deep bleeding ulcers in the lining of the stomach and duodenum — all of which could be increased or decreased in severity by adjusting the amount of extract.

It seemed obvious to the young Selye that he was on the verge of pinpointing a new hormone, as none then known produced these sort of symptoms. “You may well imagine my happiness!” he writes. “At the age of 28, I already seemed to be on the track of a new hormone.”

His hopes began to diminish, however, when, first, placental extract and, later, pituitary extract brought about the same symptoms. But he was not yet defeated, for, he writes, “mine was supposed to be a new hormone and (who knew?) perhaps the pituitary could also manufacture this one.”

Next, however, he injected the extract of kidney, spleen and numerous other organs, all of which produced the same effect. He was baffled. In a last ditch effort to clarify these bizarre results, he injected a toxic liquid, Formalin, (used in the preparation of tissues for microscopic study) and when even it produced these symptoms, he knew he had failed in discovering a new hormone.

The Unique View Afforded to the Young and Ignorant

He was left, at this point, with two options. The first and most apparent was to give up on this line of research. There was plenty of reason to believe that this trail would lead to nothing of worth, and, he knew, many capable scientists had wasted their best years being led around by just such a red herring. “I became so depressed that for a few days I just sat in my laboratory,” he writes, “brooding about how this misadventure might have been avoided and wondering what was to be done now.”

The other, much more difficult, possibility was to devise some new way of examining his data. This, of course, is the option he chose.

Selye revisited a theory he first began to formulate years before at the German-speaking University of Prague, where, at the age of nineteen, he began medical school. It was here that Selye unwittingly developed ideas that would eventually lead to the discovery of the G.A.S.

Selye recalled years later that as the various patients were brought in and examined during his introduction to clinical medicine, they all “felt and looked ill, had a coated tongue, complained of more or less diffuse aches and pains in the joints, and of intestinal disturbances with loss of appetite.” They also generally “had fever, enlarged spleen or liver, inflamed tonsils, a skin rash” and a number of other general symptoms. It wouldn’t be until later that the telltale signs would appear of, say, liver disease, and treatment could be recommended.

“Since these were my first patients,” Selye writes, “I was still capable of looking at them without being biased by current medical thought. Had I known more I would never have asked myself questions, because everything was handled just the way it should be.”

The main question that stuck in Selye’s mind was a simple one really: how was it that doctors over the long history of medicine had spent so much time and energy on the discovery and treatment of individual diseases and had given so little thought to “the syndrome of just being sick”? Though captivated by this idea, being young and inexperienced – and working under the deadlines and demands of medical school – Selye hadn’t the time, energy or expertise to pursue it. He briefly mentioned the idea to his advisor who promptly chuckled at the young mans naivete, and thus the idea fell dormant for the better part of the next decade.

On “the Syndrome of Just Being Sick” and Bloodletting
The memory of the nonspecific illness did not altogether abandon Selye, though, and years later, when he was casting around for a rubric under which he could examine his failed hormone experiments, he was reminded of the symptoms of the patients in the Prague hospital. Those patients, he understood, shared something in common with his sick rats. His intention was to find out what that connection was, and he in fact decided very quickly to devote his life to the discovery of the root of this nonspecific illness.

“If there was such a thing as a single nonspecific reaction of the body to damage of any kind,” he writes of his jubilant epiphany, “this might be worth study for its own sake. Indeed, working out the mechanism of this kind of stereotyped syndrome of response to injury as such might be much more important to medicine than the discovery of yet another sex hormone.”

In piecing together the puzzle, Selye was aided by two other bits of medical knowledge. Certain treatments, he knew, were useful to patients suffering from just about anything. Doctors prescribed to most patients things like rest, eating easily digestible food, and protection against great variations in temperature. Also, he recalled that there existed a number of nonspecific treatments in the history of medicine – and, in fact, in contemporary medicine, too – that, though odd (some would say barbaric), had met with undeniable (if sporadic) success: practices like the injection of foreign substances into the body, fever therapy, shock therapy, and bloodletting.

It didnt take long for Selye to formulate an idea that made all of this seemingly disparate information coalesce. There was some mechanism in the body, he rightly surmised, whose response to external agents – “noxious agents” was the best term he could then muster – was somehow general. The quality of just being sick he had seen in the Prague patients, the shared symptoms in his experimental rats, the universal usage of certain treatments, as well as the successful practice of stressful remedies like shock therapy, when taken together, suggested that specific illnesses, if not wholly caused by a single influence, were certainly bound by similar forces; there was a link in the body’s reaction to illness that gave the appearance of some internal mechanism combating the stressing agents.

The Hypothalamus-Pituitary-Adrenal System
Selye’s genius, then, was in suspecting and, through research, identifying this complicated internal stress-processing mechanism, which came to be known as the hypothalamus-pituitary-adrenal system.

This system, in short, governs the amount and kind of response the body produces to combat a stressing agent. Simplified, the hypothalamus (the bridge between the brain and endocrine system) sends a message to the pituitary gland (a hormone-producing gland embedded in bones at the base of the skull) to release ACTH (adrenocorticotrophic hormone) into the blood stream. This signal prompts the adrenal cortex (located above the kidneys) to create corticoids, another hormone, from available raw material. These corticoids are then dispersed to the places in the body they are needed, where they are put to use in the various stages of defense against a stressing agent.

This was the fruition of Selye’s goals: the identification of stress based upon “demonstrable biological laws.” Sometimes a discovery is in part remarkable for the fact that nobody has made it before; this was just such a discovery. It “could have been discovered during the Middle Ages,” writes Selye. “[Its] recognition did not depend upon the development of any complicated pieces of apparatus, but merely upon an unbiased state of mind, a fresh point of view.”

The Legacy
With the knowledge of the G.A.S. and hypothalamus-pituitary-adrenal system, it was all of a sudden possible to begin gauging the role of stress in our lives – which is precisely what Selye and a multitude of researchers have been doing for the last half century.

Selye himself went on to publish 33 books and over 1,600 scientific articles, almost all of them on the subject of stress. Among his many scientific texts, he also wrote a handful of popular books intended to educate about stress, the most popular of which was The Stress of Life, an in-depth explanation of the stress syndrome and its origins.

Selye served as professor and director at the Institute of Experimental Medicine and Surgery at the University of Montreal from 1945 until retiring in the mid-1970s. But he also evolved into a sort of philosophical leader whose views on health helped to change the way the body and mind were viewed in the decades after World War II.

Selye moved easily into the role of well-being representative, and was just as likely to be asked to speak to a religious group as to a medical group. He often spoke of the value of love, and of the essential importance in our own well-being of helping others. He was not, at any point in his career, anyone’s vision of a “normal” scientist. But he was indeed an innovator, and his influence stretches behind him still, nearly twenty years after his death, as his students and colleagues continue to toil in the wake of his ideas.