It used to be called mind over matter. For centuries, eastern mystics have described -- and western skeptics have ridiculed -- this alleged healing process. It's what allows firewalkers to tread barefoot across red-hot embers without pain and may explain a witch doctor's curative power. In the United States, Christian Scientists merged the idea with prayer and the faith healing tradition of Christ.
More recently, author/publisher Norman Cousins claimed that positive emotions helped him beat a life-threatening disease and then, 16 years later, survive a severe heart attack. Researchers like Stephanie and Carl Simonton, the Texas-based cancer specialists, purport to help patients boost their immune systems using relaxation and mental imagery.
Mind over matter may help explain the placebo effect -- the mysterious process that sometimes enables a sugar pill to act like a powerful drug just because the user believes that the pill will cure. It's the principle behind hypnosis, biofeedback, guided imagery and a host of other new therapies.
These ideas once bobbed on the fringes of modern scientific research. But today, investigation of the mind-body connection is becoming an increasingly popular research topic at some of the nation's most prestigious institutions.
The field is known as psychoneuroimmunology, a tongue-twisting term coined in 1981 by University of Rochester psychologist Robert Ader to reflect the apparently important relationship between behavior and health. Others prefer the equally unwieldy neuroimmunodulation. Both words describe this new discipline, which is etching a complex picture of how the mind and body interact. A key finding is the discovery of two-way communication between the brain and the immune system -- the body's first line of defense against disease.
"The time might come when someone would go into a doctor's office at age 50 and have special tests done," predicts University of South Florida neuropharmacologist John Hadden. "The doctor might find that the person's immune system is not working well."
Treatment might include psychological techniques from relaxation therapy to a daily dose of belly laughs. Or, suggests Hadden, the doctor might put the patient on a special drug to stimulate the immune system. This test for immune function could become as routine as high blood pressure screening is today.
Exploration of the intricate link between mind and body is now "a respectable field," sums up Nobel laureate and molecular biologist Marshall Nirenberg. Both the National Institutes of Health and the Office of Naval Research have approved funding for research on psychoneuroimmunology -- a scientific stamp of approval.
Increased interest in this emerging field prompted NIH to sponsor the First International Conference on Neuroimmunomodulation in November. The four-day meeting drew more than 100 scientists from around the world, including three American Nobel laureates -- Nirenberg, Daniel Carleton Gajdusek and Julius Axelrod.
"The thing that intrigues me," says Axelrod, who shared the 1970 Nobel prize in medicine for his work on brain transmitters and now studies the stress hormones, "is that the nervous system and the immune system have a lot in common." A person under stress releases hormones that inhibit the immune system, he notes. So chronic stress can literally make people sick.
What attracts scientists is this: Since the immune system can be depressed, there may be ways it can be boosted. If it can be boosted, scientists may one day be able to control it altogether, and that could be an important step in conquering a host of illnesses from cancer to the common cold.
Research already shows numerous physical and chemical connections between the brain and the immune system. For example, studies link hostile behavior with an increased risk of heart disease, while depression, bereavement and chronic stress are associated with impaired immune function and greater rates of cancer and other illnesses.
It's all pointing to attitude -- the old mind over matter concept -- as a kind of thermostat of the brain-immune system connection.
Consider these diseases: Rheumatoid arthritis, heart disease, allergies, warts, diabetes and cancer. Studies indicate that each may be affected by mind-body interactions:
* A woman's emotional response to breast cancer may be an important predictor of her survival, suggests a National Cancer Institute study. Women who showed fatigue and listlessness tended to have more malignant lymph nodes. They also had significantly lower levels of "natural killer" cells -- specialized white blood cells that fight tumors.
* University of California psychologist Lydia Temoshok has coined a "Type C" personality to describe people who seem prone to developing the skin cancer malignant melanoma and perhaps other cancers as well. Type C traits -- which include an inability to express anger and other emotions -- are associated with an increased division of tumor cells and a depressed level of white blood cells.
* At Beth Israel Hospital in Boston, psychologist Joan Borysenko is studying diabetes patients with Type A personality traits -- such as aggressiveness, impatience and feeling driven. Both Type A personality and diabetes are associated with an increased risk of cardiovascular disease. But Borysenko is finding that when these patients are taught meditation and relaxation techniques, their blood levels of the stress hormones epinephrine and norepinephrine decrease. So does their need for insulin.
* Relaxation therapy significantly increased the activity of tumor-fighting "natural killer" cells, concludes an Ohio State University study of 45 healthy senior citizens. These and other measures suggest that immunity can be enhanced -- an important finding, since the immune response gradually declines with age.
* A psychologically healthy state seems to protect those at high risk of rheumatoid arthritis from developing the disease, reports a study by University of California psychiatrist George Solomon and Stanford University psychologist Rudolf Moos. In the 1960s the researchers examined people who had rheumatoid factor in their blood -- which predisposes them to the disease. Tests showed that people who were well-adjusted psychologically -- that is, were not anxious, depressed or alienated -- tended to stay disease-free. "Being in great psychological shape protected them," Solomon says.
* A man with cancer spread throughout his body was able to increase the number of white blood cells in his blood stream by visualizing his immune system. This guided imagery technique also increased levels of the hormone alpha thymosin 1, which boosts the immune system. When the man stopped using guided imagery, levels of the hormone and white blood cells again dropped. Although the man died, the positive findings have prompted George Washington University immunologist Nicholas Hall to try a larger, controlled trial of 10 cancer patients.
* At the American Psychiatric Association's annual meeting last spring, Rush-St. Luke's Medical School psychiatrist Bennett Braun reported an unusual type of allergy in a man with multiple personality disorder. The man is violently allergic to citrus fruit except when he exhibits one personality -- then he can eat the fruit with impunity.
* Hypnosis cured warts in an early 1970s study by doctors at Massachusetts General Hospital. Dr. Owen Surman reports in the journal Advances that hypnosis is still one of several therapies used at the hospital to treat both common and plantar warts -- warts on the soles of the feet. One disabled Boston policeman found that it was the only treatment that brought relief from his recurrent -- and very painful -- plantar warts. Other studies at the hospital are testing the use of hypnosis in treating genital herpes.
Studies like these are drawing increased attention to the links between attitude and health. "Psychoneuroimmunology is not yet mainline immunology, but it will be," predicts University of Rochester immunologist Nicholas Cohen.
Until recently, immunologists lacked both the interest and the tools needed to study this complicated field. They were trained to believe that the immune system operates independently of the brain in a kind of headless vacuum.
At the core of the immune system are white blood cells, which are produced in the bone marrow. Some white blood cells are called lymphocytes -- which come in two forms, T-cells and B-cells.
Immature T-cells pass from the bone marrow to the thymus gland, an organ beneath the breastbone that stores and activates them on need by the body. T-cells conduct a kind of hand-to-hand combat with invaders, while other white blood cells, known as macrophages, devour the invaders.
B-cells fight invaders by producing substances called antibodies, which target specific intruders -- for instance bacteria, viruses or allergens such as rag-weed -- for destruction. B-cells also are produced in the bone marrow and are believed to pass through the tonsils, parts of the intestine and the appendix for activation. New genetic engineering techniques allow investigators to document the intricate connections between the mind and the white blood cells. These ingenious studies are uncovering subtle changes in the body never before revealed.
Animal studies suggest that conditioning -- the Pavlovian techniques that once had dogs salivating at bells -- can be used to enhance the immune response. Studies in mice by Karen Bulloch at State University of New York at Stony Brook show connections between nerve endings and developing white blood cells in the thymus gland, an indication that the brain can stimulate cells directly.
University of Texas researchers Eric Smith and J. Edwin Blalock will report in the journal Nature that white blood cells produce a hormone -- called ACTH -- once thought to be manufactured only by the pituitary gland in response to brain signals. Blood levels of ACTH rise in response to any kind of stress. Now Smith's findings show that ACTH is also produced by lymphocytes and may signal the brain about bacteria or other invaders in the body.
Other white blood cells -- the macrophages -- carry special receptors for chemical messages from the brain. Receptors are a kind of keyhole on the cell membrane surface. The brain sends messages in the form of neurotransmitters such as adrenalin. When the messages reach the cell, they fit like a key into the receptor and begin a cascade of changes. Sometimes the brain's signal enhances cell action; other times it stops it.
National Institute of Mental Health biochemist Candace Pert and her colleague Michael Ruff report that macrophages also carry receptors for the tranquilizers Valium and Librium and for opioids -- the drug family that includes heroin, morphine and endorphins. These findings could explain why heroin addicts have an already damaged immune system that makes them more susceptible to immune deficient diseases, such as AIDS. It might also shed light on how exercise -- which raises levels of endorphins -- produces beneficial effects on the body.
The many interconnections lead Nobel-winner Axelrod to speculate that perhaps some white blood cells thought to be part of the immune system may also serve as a kind of "free-floating nerve cell," capable of two-way communication with the brain.
Among the most hotly pursued areas of research in the field is the link between cancer and emotions. One clue to their relationship comes from research conducted at Ohio State University College of Medicine. Psychologist Janice Kiecolt-Glaser and immunologist Ron Glaser found significant differences in DNA repair in white blood cells of recently hospitalized psychiatric patients and people without mental illness. Blood was drawn from participants and then exposed to X-rays. Investigators measured how fast certain white blood cells repaired their DNA. People in the high distress group "had significantly poorer DNA repair than normal subjects." These findings, the researchers report, provide some evidence of how emotional distress may be "directly associated with an increased risk for cancer and infectious disease."
Do these and other findings mean that a future prescription for good health will include doses of relaxation therapy, guided imagery and hypnosis -- particularly for people at high risk of developing illnesses?
In some ways, it's already happening. Biofeedback is an accepted treatment for migraine headaches. Relaxation therapy is prescribed for reducing high blood pressure. Hypnosis is effective in removing some otherwise intractable warts. University of California psychiatrist Solomon says he advises patients with rheumatoid factor -- but no symptoms of arthritis -- "to seek psychotherapy" as a preventive measure if they experience any major, stressful life events.
"The biochemistry of emotion is more than just a speculation," says author Norman Cousins. "Just as panic can do damage . . . so the positive emotions can act as blockers against that damaging process."