The Right Chemistry: Dr. Hans Selye and the ‘Just Being Sick Syndrome’

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In 2000, Canada issued a set of four stamps honoring “medical innovators”. These included Sir Frederick Banting, who pioneered the use of insulin in diabetes, Dr. Maud Abbott, an expert in congenital heart disease and one of the first women to graduate from medical school in Canada, Dr. Armand Frappier, Quebec promoter of vaccination, and Dr. Hans Selye, the “father of stress research”. Selye’s stamp featured his portrait, a partial molecular structure of a steroid molecule, the letters A, B, and C, and the word “STRESS.”

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I bought the set mainly because I have a special respect for Selye. In the early 1960s, my parents dragged me to a public lecture she gave at McGill University, not because they were particularly interested in the subject, but because Selye, like us, had a Hungarian background. I don’t remember much of what she said to her. Talking about stress hormones was surely over my head at the time. But he made a point that stuck in my mind. “You could leave here today,” he began, “get back in your car a little late and find a parking ticket on the windshield.” “Then you have a choice. You can rant and rave about the unfairness of it all, or just accept that you should have looked at the moment more carefully. In any case”, he concluded, “the cost to your wallet will be the same, but not the cost to your health”. The message was that anger could trigger biochemical changes with adverse health effects.

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I have often looked back to that example as the spark that ignited my interest in the mind-body connection and my fascination with Selye’s career. That started when she got degrees in medicine and organic chemistry in Prague. It was during her days in medical school that she made an interesting observation. In addition to displaying symptoms of her particular illness, the patients also shared identical symptoms regardless of their specific condition. All had tongue coating, diffuse joint aches and pains, intestinal disorders, as well as loss of appetite and muscle strength. Selye wondered if there was a scientific explanation for “just being sick syndrome.”

Years later, as a young researcher in biochemistry at McGill, he would propose an explanation based on his studies with rats. Selye described this work in a landmark article, “A Syndrome Produced by Various Noxious Agents,” published in 1936 in the prestigious journal Nature. That document is widely regarded as the seminal work that would eventually lead to Selye’s name being forever associated with “stress.”

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At McGill, his research focused on hormones and involved injecting cattle ovary extracts into rats. He reported that the thymus gland, spleen, and liver shrank, while the cortex of the adrenal gland enlarged. Acute erosions appeared in the digestive tract of the animals, body temperature dropped and there was a loss of muscle tone. It was not a big surprise, but Selye was surprised to discover that injections of sublethal doses of other “noxious” agents such as atropine or formaldehyde produced exactly the same changes. The same goes for subjecting rats to excessive muscle exertion on the treadmill, or exposing them to cold, heat, or surgical injury. No matter what trauma the rats were subjected to, the response was the same. Selye realized that she had stumbled upon an experimental replica of the “just being sick syndrome” that she had observed in humans in medical school.

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While continuing this research, Selye discovered that continuous treatment with relatively small doses of toxins or other stressors causes animals to develop resistance to insult. Approximately 48 hours after the injury, the appearance and function of his organs returned to normal. But if the low-level insults continued for months, the animals lost their ability to adapt and the initial symptoms returned, often with a vengeance. Selye called this the “exhaustion stage”.

He went on to describe the “stress syndrome” as being characterized by three stages, thus explaining why the letters A, B, and C appear on the seal. The initial, or “alarm” stage is the “fight or flight” response, first described in 1915 by Harvard physiologist Walter Cannon. The second stage is adaptation to the stressor, and in the third stage, as a result of continuous stress, the energy of adaptation is depleted and health suffers.

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Finally, the biochemistry involved was resolved. In the first stage, the adrenal glands release adrenaline and cortisol, which speeds up the pulse and breathing so that more oxygen reaches the tissues. Blood sugar rises to fuel muscles and blood platelets aggregate when the body anticipates possible bleeding from injury. At first, cortisol maintains the stress reaction, but then slows it down so that the body returns to normal. However, if cortisol remains elevated, it suppresses the immune system, keeps blood sugar and blood pressure elevated, and causes what Selye called “wasting” on the body.

Selye proposed that people can control how they adapt to stress and thus can exert control over cortisol levels. He gave the example of a drunk, clearly incapable of harm, hurling insults at someone. That person has a choice. Walk away, ignoring the insults, or get angry and start some kind of confrontation. In the latter case, adrenaline and cortisol will kick in, and if there is any faulty biochemistry, the second stage of the reaction, the adaptation stage, will be skipped and the exhaustion stage with its dire consequences will quickly set in. The result can be a cortisol-triggered heart attack that Selye says was caused by choosing the wrong reaction. She summed it all up by saying that stress is very much in the eye of the beholder; It’s not so much what happens to you as how you respond. You have to decide if “fight or flight” or “just relax” is appropriate. In other words, don’t sweat the small stuff. As Kenny Rogers reminded us: “You’ve got to know when to hold ’em / Know when to fold ’em / Know when to walk away / And know when to run.”

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Joe Schwarcz is director of the Office of Science and Society at McGill University (mcgill.ca/oss). Hosts The Dr. Joe Show on CJAD Radio 800 AM every Sunday from 3-4 pm