Seeking to Illuminate the Mysterious Placebo Effect

for The New York Times

The phrase “mind-body connection” has many connotations. For some, it’s shorthand for New Age quackery. For others, it’s a source of hope and a way to reconcile their spiritual life with modern science.

For Tor D. Wager, it’s just another day at the office.

Dr. Wager (pronounced WAY-gur) is a professor of psychology at theUniversity of Colorado. His specialty is neuroscience and brain imaging, but his passion is the placebo effect — a phenomenon that has undergone a resurgence in recent years and is now being studied by researchers in many corners of science.

Much of this attention is a result of the kind of brain imaging Dr. Wager does, and he is a leading figure in the new generation of placebo researchers.

Which may make his background seem unlikely. Dr. Wager, 35, was raised in Christian Science, a religion mostly known for its aversion to medical treatment. His family was not strict about it, however; he recalls an incident from his Colorado childhood that could have served as a harbinger for his career.

As a baby, he says, he came down with a rash, and after much prayer his mother took him to a doctor, fearing scarlet fever. “The doctor said, ‘Here’s a cream, rub it on there,’ and it went away,” Dr. Wager said.

So did his mother’s distress. Her pulse probably slowed, he says now, and her breathing relaxed — just the effect a placebo may have on a terrified patient.

Increasingly, placebo effects are being viewed as real and tangible, if mysterious. In various surveys, 45 percent to 85 percent of American and European practitioners say they have used placebos in clinical practice, and 96 percent of academic physicians in the United States say they think placebos have therapeutic effects.

Even so, many scientists mistrust them.

“When I started grad school I felt like it was kind of taboo to study the placebo,” Dr. Wager said. The research at the time was spotty at best, “and then there were whole sections of society that were ready to jump on that and say, ‘Oh, look how powerful the mind is!’ ”

But placebo research has gained respectability in recent years, thanks largely to the work of Dr. Fabrizio Benedetti, an Italian neuroscientist widely seen as the patriarch of the field. Dr. Benedetti argues that there is not a single placebo effect, but many.

One common effect involves the assumption that a particular pill is responsible for easing pain or discomfort that is actually subsiding naturally. Another is classic Pavlovian conditioning, in which a patient is so accustomed to feeling better after a shot that it works no matter what is in it. Another is the relief a patient like Dr. Wager’s mother feels when a doctor offers a concrete solution.

As a graduate student at the University of Michigan, Dr. Wager used imaging to watch emotions in the brain. It was fascinating work, he says, but emotions are hard to define with precision and he wanted to do something that could help patients.

So he decided to look at placebos in a clinical setting. In 2001 he joined forces with Dr.Robert M. Rose, a University of Texas scientist who had done pioneering studies of stress in Vietnam War veterans, and a group of respected researchers called the Network on Mind-Body Interactions.

Within a few years, Dr. Wager’s name was at the top of a groundbreaking study in the journal Science that used functional magnetic resonance imaging — a specialized scan that measures changes in blood flow — to link specific brain activation to people experiencing a placebo effect (in this case rubbing unmedicated cream on a burn). Since then, he has written roughly a dozen scientific papers on placebo effects, including a 2007 study linking pain-related effects to parts of the brain that process opium or heroin (which may help explain why many placebos are temporary). “Tor is a person who has to convince himself of something,” Dr. Rose said. “He doesn’t buy it because someone else does it. He is a skeptic. But once he buys it, boy, is he dogged.”

When Dr. Wager isn’t writing about placebos, he is defending the tools he uses to study them. Many critics are skeptical of functional M.R.I., and Dr. Wager says that at first he was, too.

To deal with that skepticism, he said, one can either “a) say, ‘Ah, this is all sort of bogus, let’s do something else,’ or b) try to work and develop things that make it a lot more believable.”

At the recent conference of the Organization for Human Brain Mapping, Dr. Wager gave a presentation about placebos to a full house of scientists. But his laboratory at the University of Colorado also shared arcane new statistics for reading brain scans. Such attention to detail, he said, is the only way to convince skeptics.

Until recently, the government and the drug industry have been hesitant to finance studies of placebo effects.

“Companies who are developing new treatments like to think that actually their new treatment works well enough to do better than just the power of positive thinking,” said Dr. Helen S. Mayberg, a neurologist at Emory University known for her work with functional M.R.I. in patients with depression. (She quickly added that placebo effects were very different from positive thinking.)

Drug trials sometimes start with everyone getting a placebo; those who recover are then weeded out. While perhaps strengthening the results, this does not help researchers understand why people in the first group got better.

That persistent question — why some people are more responsive to placebos than others — has long frustrated scientists. “There’s decades of research that has more or less failed,” Dr. Wager said. “New methods are going to let us get a lot more out of it.”

Solving the mystery would potentially unlock whole new areas for therapy. Dr. Wager recently attended a meeting sponsored by the National Institutes of Health about enlisting multiple institutions in an effort to understand placebos. Several drug companies were present; some have begun their own research into the mystery.

Dr. Wager (who receives financing from the N.I.H., the National Science Foundation and the Michael J. Fox Foundation) says drug companies were cautious about bringing too much attention to placebos, but recognized a potential for better therapies.

But for him it is a deeper question, tied to his childhood religion and the way he sees the world.

“What is the placebo effect?” he asked. “It’s not some weird magical thing that just kind of happened out of the blue.

“I think it’s connected to systems that generate emotional responses,” he continued. “It’s a window into ways in which psychological factors can affect brain and body factors that are related to health.”