The "placebo effect" is one of medicine's thornier problems. Placebos are pharmacologically inactive substances, and yet they often seem to help people recover from illnesses and injuries. Scientists of the body-and of the mind-struggle to explain why this should be so.

The placebo question is "a toxic waste site," said Lawrence Sullivan, a historian of religion at the Harvard Divinity School. "Nobody wants to own it. Even shamans and witch doctors would be offended by the idea that their healing powers depended on the placebo effect."

In December, scholars from a broad range of disciplines-ranging from medicine to anthropology to religion-gathered at the Harvard Faculty Club for a three- day conference titled "Placebo: Probing the Self-Healing Brain." The conference was the second organized by Harvard University's Mind/Brain/Behavior interdisciplinary initiative.

The value of that interdisciplinary approach became apparent even as the scholars argued over the definition of placebo. The scholars came from two distinct cultures, one more interested in mechanism, the other in meaning. Definitions and explanations that satisfied one group often left the other in doubt, and thus each side's conceptions and beliefs were challenged.

Placebos are best known for their use as inactive substitute treatments in randomized trials of drugs in clinical development. Placebos are meant to provide a benchmark for measuring the efficacy of those compounds, but instead often confound results by seeming to be effective themselves.

"Placebos do not help disease, only the way patients perceive disease," said Howard Spiro, a gastroenterologist at Yale Medical School.

Healing is Believing

The placebo effect seems to fall under the category of "faith heals." Placebos, said Anne Harrington, a science historian at Harvard College, "rally endogenous healing processes within patients." Furthermore, cultural beliefs inevitably affect how people respond to placebos.

"If you don't believe it, it doesn't work," said David Morris, author of "The Culture of Pain."

In the case of pain, there is some understanding of the mechanism that may be at work to explain the placebo effect. Specific pathways in the nervous system modulate pain when they are stimulated by drugs known as opioids, which mimic the body's own pain-inhibiting compounds (called enkephalins). Once a patient has experienced the pain- blocking effects of opioids, a placebo alone may serve to activate the body's enkephalins-but only if the patient is led to believe that the placebo is the real thing.

While that model of "conditioning" may explain how placebos relieve pain, it doesn't explain why they are also effective in cases of many other disorders, especially those that may be stress related, such as depression and insomnia.

In a somewhat similar vein, how can the "doctor" effect be explained? A patient's faith in his or her doctor almost certainly plays a role in healing, said Howard Brody, professor of family practice at Michigan State University.

"Some doctors by their manner alone reassure and comfort in a way that affects the course of illness," he said. "But one must always ask: 'Would the patient get well anyway? Did the doctor do something to make the patient get well? Or did the patient expect the doctor to do something that would make a difference?'"

A better understanding of the placebo effect may come from studies of alternative medicine, such as acupuncture and chiropractic medicine, now being funded by the National Institutes of Health, said John Spencer, program analyst in the Department of Alternative Medicine at the NIH.

Harvard Medical School anthropologist Arthur Kleinman noted that it is important to understand why narratives of healing that seem like superstition to western minds play so large a role in other cultures around the world.

"Why is the placebo regarded as pejorative?" he asked. "Is it threatening to medicine?"

--John de Cuevas

Copyright 1995, President and Fellows of Harvard College. Multiple distribution or commercial reproduction by permission only.