BIOREGULATORY MEDICINE

HISTORY - János Hugo Bruno "Hans" Selye, MD, Ph.D.

The relationship between psychoemotional stress and pathophysiology is now well established but was not always recognized, at least in western conventional medicine. The word ‘stress’ is used in physics to refer to the interaction between a force and the resistance to counter that force. Dr. Hans Selye first incorporated this term into the medical lexicon to describe the “nonspecific response of the body to any demand “. Dr. Selye, who is known as the ‘father of stress research’, disavowed the study of specific disease signs and symptoms, unlike others before him, and instead focused on universal patient reactions to illness. His concept of stress impacted scientific and lay communities alike, in fields as diverse as endocrinology, complementary medicine, animal breeding, and social psychology.

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January 26, 1907 - October 16, 1982

Early Life

Born János Hugo Bruno "Hans" Selye in Vienna, Austria-Hungary on January 26, 1907. Hans grew up in Komárom, Hungary on the border between Czechoslovakia and Hungary in a multicultural family. After the shifting of national boundaries after WWI his homeland became Czechoslovakia. Hans’s father was a doctor of Hungarian ethnicity, his mother was Austrian, and his two governesses were English and French. His father, Hugo Selye, was a surgeon colonel in the Austro-Hungarian Imperial Army who later started his own surgical clinic. His mother, who administrated the clinic, had a strong influence on the boy with her constant quest for excellence and intellectual sophistication. Hans had a warm endearing relationship with his father, and it seemed inevitable that he would one day work in his father’s surgical clinic. Carrying on the surgical work would mean continuing the medical tradition into the fifth generation of the family.

Young Hans received his early education from a Benedictine monastery and private tutoring. By the age of four, he spoke four languages and due to the cultural diversity, he was exposed to easily learned several more. Hans was very proud of his Hungarian heritage, as his father was Hungarian, and his teachers had impressed upon him a strong sense of nationalism. As a young child, he was confident to the point of being boastful, always wanting to be first in everything that he did. These were personality traits that he carried into adulthood, and which helped to sustain him in his pioneering and controversial endeavors.

College and Post-Doctoral Years

At the age of 17, Hans attended the medical school of Charles University in Prague, Czech Republic, and received a Doctorate in Medicine there in 1929. After receiving his Doctorate in Medicine, he pursued a Doctor of Philosophy in organic chemistry. Dr. Selye was first exposed to the idea of ‘biological stress’ during his second year at the University of Prague medical school. He had observed during ward rounds that patients often had numerous complaints in common, even though they were each suffering from different and distinct diseases. Until that point, students had been taught that signs and symptoms were related and specific to a particular illness, a principle passed down by the famous German pathologist Rudolf Virchow in the late 19th century. Recalling an example, Selye recounted how one of his teachers would make the correct diagnosis in each of five different patients, solely on the basis of their presenting history and physical findings. What was ignored, however, were the generic complaints that all those patients had in common, such as looking tired, having no appetite, losing weight, preferring to lie down rather than stand, and not being in the mood to go to work. He called it the “syndrome of just being sick”. However, this obvious yet powerful observation would lie dormant for about ten years before Selye would launch his investigation into this ubiquitous phenomenon.

After graduation, excellence and diligence in his studies and research earned him a Rockefeller Research Fellowship at Johns Hopkins University where he went on to do pioneering work in stress and endocrinology. However, he found university life at Johns Hopkins unbearable and became homesick.

He was planning his trip home to Prague when, following the advice of some Canadian students at Johns Hopkins, he asked to transfer to McGill University in Montreal, Canada. There, he completed his fellowship under the renowned endocrine scientist Professor James Bertram Collip. At 27, he became an Assistant Professor of Biochemistry at McGill University. Thus, rather than returning home and taking over the family’s surgical clinic, Dr. Selye instead chose a career in research.

The Young Dr. Hans Selye

Photo: Árpád Somogyi/MTA

Dr. Selye was the first scientist to identify ‘psychoemotional stress’ as underpinning the nonspecific signs and symptoms of illness. The stress concept re-entered Selye’s life during his fellowship at McGill when Professor Collip placed him in charge of identifying various female sex hormones that were yet undiscovered. For this project, he collected cow ovaries for processing and examination, injected various extracts into female rats, and measured their responses. His autopsies yielded a triad of significant findings: enlargement of the adrenal glands, atrophy of the lymphatic system including the thymus, and peptic ulcers of the stomach and duodenum. It was not due to a hypothetical new hormone, as every injected noxious agent produced the same findings. He continued his experiments by placing the rats in various stressful situations, such as on the cold roof of the medical building, or the familiar revolving treadmill that required continuous running for the animals to stay upright. The findings in each experiment were the same: adrenal hyperactivity, lymphatic atrophy, and peptic ulcers. Dr. Selye recognized that his discovery was an expression of Claude Bernard’s milieu intérieur and homeostasis at work and astutely linked the hypothalamic-pituitary-adrenal axis to the way the body coped with stress.

It was in one of the papers emanating from this research in 1935, coauthored with Thomas McKeown (1912–88), who had been in Montreal between 1932 and 1934 as a National Research Council–funded doctoral student, that Selye first used the word “stress” to describe the adverse circumstances to which laboratory animals were subjected during experiments.

In 1936 Dr. Selye sent a short, barely half-page essay to the scientific journal Nature called “A Syndrome produced by Diverse Nocuous Agents.”

Nature considered the report on the rat experiments worthy of publication, which at the time remained without a serious response, but with a slight phase delay, it started a veritable avalanche, first in scientific circles and then among laymen.

The article set out what appeared to be a characteristic triphasic pattern of nonspecific physiological responses to injury. This was termed the “general adaptation syndrome”. It comprised an initial alarm phase that was followed by a stage of resistance or adaptation, leading eventually to a stage of exhaustion and death. Historians have often perpetuated the conviction that Dr. Selye’s article constituted a turning point in the history of stress on illness and have occasionally acclaimed Dr. Selye as the “father of stress.”

Within traditional narratives of stress history, it was the general adaptation syndrome, or what Dr. Selye sometimes referred to rather ostentatiously as “Selye’s syndrome,” that provided a conceptual framework for Dr. Selye and his colleagues to develop a complex neurohormonal model of stress that implicated pituitary and adrenal function in the etiology of many chronic diseases, such as hypertension, peptic ulceration, renal disease, arthritis, asthma, and cancer.

Dr. Selye knew a lot about the mechanisms of stress. He appreciated the endocrine, immune, and metabolic changes involved. At that time, it was not established that the pituitary gland was regulated by the hypothalamus. This was discovered later and then he included this knowledge in his “hypothalamus-hypophysis-adrenal-thymus axis”.

During the 1930s, 1940s, and 1950s, Dr. Selye and his colleagues authored an expansive number of articles and monographs that clearly shaped and energized biological and psychological studies of stress. Not only did Dr. Selye’s reputation attract scholars from around the world to his research institutes, but Selye himself also became a much sought-after speaker on stress and health in many countries.

In recognition of his contributions to stress research, Selye was nominated for the Nobel Prize in Physiology or Medicine seventeen times between 1949 and 1953, particularly for his “work on endocrinology and the adaptation syndrome,” for his contributions to the “isolation of steroid hormones,” and for his formulation of “stress reactions.” Although he received a total of 17 nominations in his career, he never won the prize. The mind-body connection has been slow to be recognized in conventional western medicine.

Although influential, Dr. Selye’s theories of adaptation and stress were not universally accepted by his students or contemporaries. On the contrary, his experimental methods, his conceptual framework, and his entrepreneurial style were all strongly challenged, and many of his findings were eventually discarded. Nevertheless, during the middle decades of the twentieth century, Selye’s ideas of biological stress and its impact on health were adopted and adapted by researchers in a variety of fields, including military medicine, veterinary medicine, clinical allergy, sociobiology, population studies, cybernetics, and psychiatry.

Dr. Selye’s studies of adaptation, steroids, and stress also generated support within the Rockefeller Foundation. In January 1950 a monthly report to the trustees explored recent studies of the relationship between adrenal function and disease. According to John S. L. Browne (1904–84), a British scientist who had received a Rockefeller Award at McGill and who had been best man at Dr. Selye’s first wedding, the general adaptation syndrome constituted “the new pool of Bethesda,” an original “philosophical point of view which alters our concept of disease”:

Despite Dr. Selye’s apparent prominence in the history of stress research, there have been few critical evaluations of the intellectual and cultural determinants of Dr. Selye’s theories, few challenges to Dr. Selye’s self-composed narrative of creation and progress, and few attempts to explore the heterogeneity of scientific responses to his ideas.

Dr. Selye provided an important methodological platform for scientists and clinicians interested in understanding the relationship between stressful modern lives and disease.

General adaptation syndrome stages:

1. Alarm reaction stage

The alarm reaction stage refers to the initial symptoms the body experiences when under stress. You may be familiar with the “fight-or-flight” response, which is a physiological response to stress. This natural reaction prepares you to either flee or protect yourself in dangerous situations. Your heart rate increases, your adrenal gland releases cortisol (a stress hormone), and you receive a boost of adrenaline, which increases energy. This fight-or-flight response occurs in the alarm reaction stage.

2. Resistance stage

After the initial shock of a stressful event and having a fight-or-flight response, the body begins to repair itself. It releases a lower amount of cortisol, and your heart rate and blood pressure begin to normalize. Although your body enters this recovery phase, it remains on high alert for a while. If you overcome stress and the situation is no longer an issue, your body continues to repair itself until your hormone levels, heart rate, and blood pressure reach a pre-stress state.

Some stressful situations continue for extended periods of time. If you don’t resolve the stress and your body remains on high alert, it eventually adapts and learns how to live with a higher stress level. In this stage, the body goes through changes that you’re unaware of in an attempt to cope with stress.

Your body continues to secrete the stress hormone and your blood pressure remains elevated. You may think you’re managing stress well, but your body’s physical response tells a different story. If the resistance stage continues for too long of a period without pauses to offset the effects of stress, this can lead to the exhaustion stage.

Signs of the resistance stage include:

irritability
frustration
poor concentration

3. Exhaustion stage

This stage is the result of prolonged or chronic stress. Struggling with stress for long periods can drain your physical, emotional, and mental resources to the point where your body no longer has the strength to fight stress. You may give up or feel your situation is hopeless. Signs of exhaustion include:

fatigue
burnout
depression
anxiety
decreased stress tolerance.

The physical effects of this stage also weaken your immune system and put you at risk for stress-related illnesses.

“It’s not stress that kills us, it’s the reaction to it.”- Dr. Hans Selye

Dr. Selye knew a lot about the mechanisms of stress. He appreciated the endocrine, immune, and metabolic changes involved. At that time, it was not established that the pituitary gland was regulated by the hypothalamus. This was discovered later and then he included this knowledge in his “hypothalamus-hypophysis-adrenal-thymus axis”.

During the 1930s, 1940s, and 1950s, Dr. Selye and his colleagues authored an expansive number of articles and monographs that clearly shaped and energized biological and psychological studies of stress. Not only did Dr. Selye’s reputation attract scholars from around the world to his research institutes, but Selye himself also became a much sought-after speaker on stress and health in many countries.

In recognition of his contributions to stress research, Selye was nominated for the Nobel Prize in Physiology or Medicine seventeen times between 1949 and 1953, particularly for his “work on endocrinology and the adaptation syndrome,” for his contributions to the “isolation of steroid hormones,” and for his formulation of “stress reactions.” Although he received a total of 17 nominations in his career, he never won the prize. The mind-body connection has been slow to be recognized in conventional western medicine.

Although influential, Dr. Selye’s theories of adaptation and stress were not universally accepted by his students or contemporaries. On the contrary, his experimental methods, his conceptual framework, and his entrepreneurial style were all strongly challenged, and many of his findings were eventually discarded. Nevertheless, during the middle decades of the twentieth century, Selye’s ideas of biological stress and its impact on health were adopted and adapted by researchers in a variety of fields, including military medicine, veterinary medicine, clinical allergy, sociobiology, population studies, cybernetics, and psychiatry.

Dr. Selye’s studies of adaptation, steroids, and stress also generated support within the Rockefeller Foundation. In January 1950 a monthly report to the trustees explored recent studies of the relationship between adrenal function and disease. According to John S. L. Browne (1904–84), a British scientist who had received a Rockefeller Award at McGill and who had been best man at Dr. Selye’s first wedding, the general adaptation syndrome constituted “the new pool of Bethesda,” an original “philosophical point of view which alters our concept of disease”:

Despite Dr. Selye’s apparent prominence in the history of stress research, there have been few critical evaluations of the intellectual and cultural determinants of Dr. Selye’s theories, few challenges to Dr. Selye’s self-composed narrative of creation and progress, and few attempts to explore the heterogeneity of scientific responses to his ideas.

Dr. Selye provided an important methodological platform for scientists and clinicians interested in understanding the relationship between stressful modern lives and disease.

Hans Selye, 1956. Photograph by Chris Lund. National Film Board of Canada, Library and Archives

“Adopting the right attitude can convert a negative stress into a positive one.” – Dr. Hans Selye

Later Life and Scholastic Contributions

Dr. Selye transformed his home, a brick house built across the McGill University campus, into the International Institute of Stress, where he planned some of his experiments. Notwithstanding his prodigious contributions, Dr. Selye’s personal life was one of tumult. He was married three times and had one daughter from his first marriage and four children from his second. He purportedly stayed in his second marriage for 28 years because he wanted to provide a good home for his children until they were independent. His third and final marriage was to Louise, his laboratory assistant of 19 years and someone whom he felt had always understood his goals. In his memoirs, Selye compared himself to a racehorse with Louise riding on his back, racing together toward the finishing line. Dr. Selye's mother was killed by gunfire during Hungary's Anti-Communist revolt of 1956.

A few of his most renowned books: The Stress of Life published in 1956 appeared in Hungarian as Az Életünk és a stressz in 1964 and became a bestseller; Hormones and Resistance in 1971, Stress in Health and Disease in 1976, Stress Without Distress was published in 1974.

Dr. Selye’s relentless work ethic was evident in his publications, which numbered more than 1,600 scientific articles and about 40 books. An innovative and creative scientist with a rich and invigorating personality, he considered himself a practitioner of experimental, not clinical, medicine. He even delved into the association between stress and cancer, using his own personal experience after a histiocytic reticulosarcoma formed under his skin, for which he had to undergo surgery and radioactive cobalt therapy.

As a professor and director of the Institute of Experimental Medicine and Surgery at the University of Montreal, he at one point directed 40 laboratory assistants and worked with 15,000 laboratory animals. He often returned to visit Hungary, giving lectures as well as interviews on Hungarian television programs. He conducted a lecture in 1973 at the Hungarian Scientific Academy in Hungarian and observers noted that he had no accent, despite spending many years abroad. In 1975, he founded the International Institute of Stress and created the Hans Selye Foundation, and the Canadian Institute of Stress. Selye János University, the only Hungarian-language university in Slovakia, was named after him.

1976

Dr. Selye’s relentless work ethic was evident in his publications, which numbered more than 1,600 scientific articles and about 40 books. An innovative and creative scientist with a rich and invigorating personality, he considered himself a practitioner of experimental, not clinical, medicine. He even delved into the association between stress and cancer, using his own personal experience after a histiocytic reticulosarcoma formed under his skin, for which he had to undergo surgery and radioactive cobalt therapy.

As a professor and director of the Institute of Experimental Medicine and Surgery at the University of Montreal, he at one point directed 40 laboratory assistants and worked with 15,000 laboratory animals. He often returned to visit Hungary, giving lectures as well as interviews on Hungarian television programs. He conducted a lecture in 1973 at the Hungarian Scientific Academy in Hungarian and observers noted that he had no accent, despite spending many years abroad. In 1975, he founded the International Institute of Stress and created the Hans Selye Foundation, and the Canadian Institute of Stress. Selye János University, the only Hungarian-language university in Slovakia, was named after him.

Photo: Archives Université de Montréal, P03591FP07607 Les travaux d’Hans Selye ont fait de Montréal une importante capitale de la recherche sur le stress dans le monde.

Dr. Selye died on October 16, 1982, in Montreal, Quebec, Canada at the age of 75.

As Dr. Selye wrote in his biography, The Stress of My Life (one of 39 books he authored to promote the concept of stress), "Stress will have been my cathedral and I shall polish and perfect it. ... I know my child will outlive me."

References

Cartoon drawing of 4 books lined on a shelf