A contemporary view of cells in the bloodstream--lymphocytes, red blood cells, macrophages and monocytes. The cells are seen through a scanning electron microscope. Courtesy of Bruce Wetzel and Harry Schaefer, National Cancer Institute.

But there was always the rare patient who had a serious illness for which no "organic" cause could be found or measured. These patients were said to have "functional neuroses," problems that in some vague way had to do with their nervous systems.

At the end of the 19th century, the French neurologist Jean-Martin Charcot set his large boxy accordion-sized camera to the study of hysterical patients. Charcot's photographs captured the "fits" of his patients and thereby demonstrated that hysteria was no different from the organic diseases: it too was associated with distinguishing symptoms. "The camera did not lie." Although Charcot's pictures showed what was happening, they did not come close to explaining why.
Enter Sigmund Freud and his colleague Josef Breuer. Their approach -- "less in looking and more in listening" -- was known as psychoanalysis. It involved intensive probing over many months, years, or even decades into past events in patients' lives that may have led to the patients' current problems. Their slant was that physical symptoms could have "emotional causes and biographical meanings."


Charcot's camera. Charcot used this camera to take pictures of his patients during hysterical "fits." From the Historical Collections. Courtesy of National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C.

A landmark book called Emotions and Bodily Changes was published in 1935. The author, Helen Flanders Dunbar, was both a doctor and a theologian, and her book and her ideas--that spiritual, emotional, and physical suffering were inextricably linked--inaugurated a new field, psychosomatic medicine. It applied the Freud-Breuer psychoanalytic approach to medical problems in general and not just to the puzzling neuroses.

Psychosomatic medicine was highly controversial from the start. Some doctors argued that, if seriously ill patients relied too heavily on curing their diseases with positive thoughts, they might jeopardize their chances of benefiting from established therapies that worked best if started early in the course of a disease. Others worried that patients might blame themselves if they could not get well. Still, many patients found that "the power of positive thinking" was strong and that they were helped by relaxation, meditation and similar self-help techniques.


These patent medicines were in use in the early 20th century for treating various illnesses. From the Elaine and Arthur Shapiro Collection, Courtesy of the History of Medicine Division, National Library of Medicine.

By 1950, psychosomatic illness and medicine were so deeply embedded in popular culture that they had found their way to Broadway. In the musical Guys and Dolls, which premiered that year, Adelaide sings, ". . . just from worrying whether the wedding is on or off, a person can develop a cough . . ."
Adelaide was suffering from what Hans Selye, a physician in Montreal, had labeled a "stress syndrome." And she was not alone. Stress seemed to be an increasing fact of life. Selye said that, under certain circumstances, it was right for people and other animals to respond with stress responses to dangerous and frightening stimuli. He identified three stages to the response. The first was the "alarm reaction" during which bodily defenses are mobilized to the stressful situation; the second was the "stage of resistance" in which the person adapts to the situation that is causing stress, and the third was the "stage of exhaustion" in which the stress response dies out (2). When a person sees a tiger, for example, there is initial shock but then flight. And when tiger and person no longer share the same turf, the stress response appropriately ends.

Selye speculated that, in western cultures, people are bombarded with constant noise, constant danger, relentless feelings of powerlessness and hopelessness, and unremitting pressures at home and at work--what cartoonist Scott Adams has been capturing in his popular character Dilbert. Simply stated, stress never ends, and the stress response remains stuck in the 'on' position for days, months, even years, tipping the balance away from health toward stress syndromes that can have both physical and emotional components.

Selye's insights and hypotheses came unintentionally from his laboratory experiments with rats. He had not been studying stress at all. He was not adept at handling the rats and often bungled an experiment by dropping an animal while he was trying to give it an injection. Over the course of the experimental period, many of Selye's rats developed ulcers, shrunken immune tissues, enlarged glands and other physical signs and symptoms that were in no way associated with the substances he was injecting. He concluded that the animals' physiologic problems must be "due to the strains of life in his laboratory."

If the pace of everyday life could cause stress responses in animals and people, then it came as no surprise that crises--wars and other traumatic situations-- could produce even more dramatic stress responses and stress-associated diseases. In fact, roughly 20% of the disabled soldiers from World War II were classified as "shell shocked" or suffered from "combat neuroses."

In a fascinating documentary film made after World War II by Hollywood director John Huston, a soldier with paralyzed legs is helped onto a hospital bed by two attendants. The doctor in the film hypnotizes the soldier, taking "a shortcut to his unconscious mind" by injecting him with the drug sodium amytal. Doctor and patient discuss the soldier's inability to walk, the nature of his "neuropsychiatric problem," why and how the paralysis began two days earlier, and what sorts of stresses he has encountered at home since he returned from the battleground. The film ends with the hypnotized soldier moving his legs, getting up off the table, and then rapidly regaining his ability to walk as a result of the doctor's "suggestion" and verbal encouragement. Days later, the soldier is playing a vigorous game of baseball, hitting a home run, and sprinting around the bases.
Few psychiatric symptoms and illnesses are "solved" as easily as were the problems of the film's soldier. (Few strictly medical ones are either.) But, the movie graphically illustrates the point that health is "a state of the whole brain and body."

Humphrey's Remedies, produced at the beginning of the 20th century, included cures for a range of problems. Advertisement from the Elaine and Arthur Shapiro Collection, Courtesy of the History of Medicine Division, National Library of Medicine.

Today "a critical mass of solid sophisticated scientific research" documents the mind-body connection, notes exhibit co-director (3) Dr. Esther Sternberg and these data are being accepted by "researchers in the hard-core biological disciplines." Sternberg commented that at a recent meeting of brain-immune interactions (4) that included researchers in numerous fields--psychiatry, neurobiology, neurology, endocrinology, immunology, neuroimaging, rheumatology, psychology -- "scientists all along the spectrum were learning the language of other disciplines and finding ways to interact."

Among the most valuable new tools for studying emotions and disease are "imaging" devices, like PET and MRI scanners, which record brain activities as they are taking place. These cutting-edge technologies were, says exhibition manager Patricia Tuohy, the most challenging parts of the exhibit to develop and present. "Everyone can relate to feeling withdrawn, to feeling anxiety. But making science accessible to the public was the hardest part. We had a big chunk of science to deal with, but we still had to talk about 'me' and what happens to my body. This most sophisticated science is all brand new." Commented one guest at the opening of the exhibit: "Scientists have instincts; technology is letting them prove them."


The genes that are active in the hypothalamus of the brain can be seen by combining molecular biology techniques and computerized imaging microscopy. The stained areas indicate exactly where the genes are expressed. Courtesy of Miles A. Herkenham, National Institute of Mental Health, NIH.

New model systems--knockout and transgenic mice--have also boosted understanding and given insights into the roles of individual genes in various diseases. Says Sternberg: "Part of how stress affects disease severity depends on you and your genes. Genes affect susceptibility and resistance to inflammatory and infectious diseases. You have to look at it as a package. But with strong enough stresses, even the most tuned-down system will respond." She comments that it may be most accurate to say that "stress is not what happens to you but how you respond to it."

In the early 20th century, decorative containers like this one were put on display in drug stores and symbolized the growing power of pharmaceuticals. From the Elaine and Arthur Shapiro Collection. Courtesy of History of Medicine Division, National Library of Medicine, NIH.

Ancient physicians understood disease as an imbalance of four fluid "humors" in the body--phlegm, blood, black bile, and yellow bile; a person could become healthy only when the balance was restored. Scientists today also talk about achieving a balance. This time around, the balance is understood in molecular terms, involving circulating molecules called interleukins, neurotransmitters, and hormones that send signals to each other and make people sick or well.

Strong, painful emotions trigger these chemical messengers in ways that tip the balance toward disease. Good health represents a different molecular balance. Laughter may thus actually be, as the saying goes, "the best medicine."

References:

1. Emotions and Disease is currently on display at the National Library of Medicine on the campus of the National Institutes of Health in Bethesda, Maryland. The show will run through 1997 April. The exhibit was made possible by support from the Charles A. Dana Foundation, the John D. and Catherine T. MacArthur Foundation, the Fetzer Institute, and the National Institute of Mental Health. All of the images in this story are from the exhibit.
2. From American Journal of Nursing 1965, 65(3): page 98.
3. The exhibit was developed by Sternberg, a neuroendocrinimmunologist and Dr. Elizabeth Fee, a historian of medicine.
4. Third International Congress of the International Society for Neuroimmunomodulation, Bethesda, MD, November, 1996.