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Biomedicine

Wishful Medicine

The placebo effect is real, but what is it?

Placebos, not pills The Anatomy of Hope:
How People Prevail in the Face of Illness
By Jerome Groopman
Random House, 2004, $14.95 The Role of Complementary and Alternative Medicine:
Accommodating Pluralism
Edited by Daniel Callahan
Georgetown University Press, 2002, $29.95 The western medical establishment and drug industry have an uneasy relationship with the placebo effect. Both acknowledge that patients often benefit from their own expectations. But neither seems willing to support efforts to study the underlying physiology of the effect.

After reading Jerome Groopman’s The Anatomy of Hope and Daniel Callahan’s The Role of Complementary and Alternative Medicine, and much of the body of peer-reviewed research on the biological basis of the placebo mechanism, one begins to understand why placebo-enhanced healing gives doctors pause. There is growing evidence of its existence but little conclusive data as to how and why it works. And there is even less research on how to best manipulate the effect for the welfare of patients.

Groopman is a Harvard Medical School physician and a New Yorker writer whose articles offer a rare glimpse of the difference between the way medicine is taught and the manner in which it is practiced. For almost 20 years, Groopman suffered chronic and debilitating back pain. As we come to learn in Groopman’s memoir, the placebo effect, set into motion by the encouragement of a straight-talking yet exceedingly empathetic doctor at a small physical-therapy clinic near Boston, played a pivotal role in his recovery. Anatomy of Hope describes Groopman’s road to recovery and the lessons he learned from it that now inform his work as both a teacher and a clinician. The book is a testament to the power of the human spirit – and to the health and economic value of the placebo effect – from a highly credentialed member of the medical establishment.

Callahan approaches the issue of healing from a different vantage. He is not a physician but a philosopher. Callahan is cofounder of the Hastings Center in Garrison, NY, which is devoted to the study of bioethics. He is very much outside of the medical establishment but has featured prominently in every major biomedical debate in the United States in the last 35 years. This book is a collection of essays and reviews on the subject of alternative medicine and the placebo effect. Callahan says in his introduction that he compiled the book in an attempt to understand why a “large and prestigious group of clinicians and biomedical researchers seems so utterly hostile to [alternative medicine] while a large portion of the public (and the educated public at that) seems so attracted to it.”

These two authors each have their own reasons for being intrigued by the power of the placebo effect. But a common theme can be found in both books – namely that the placebo effect is not a figment of a patient’s imagination. And there are now technology and studies to prove it.

Feeling Is Believing
Latin for “I shall please,” the placebo takes many forms, the most common of which are the sugar pill, the saline injection, and distilled water. There are even placebo surgeries wherein patients are anesthetized, cut open, and stitched up to look as if they have had surgical interventions, even though they haven’t. The belief and expectation that a treatment will heal produces in many patients genuine feelings of relief. In some patients, there is even physical evidence of a benefit.

Doctors and researchers first discovered in 1931 that the placebo effect was a useful prop for better understanding the safety and efficacy of medicines in development. It was well known that some patients would say that they felt better at the very suggestion that they were being given a remedy. Researchers trying to measure the effects of a drug called sanocrysin on patients with tuberculosis wanted to control for this anomaly. Their solution was to give patients a glass of distilled water and tell them they were drinking sanocrysin. Ever since, placebo-controlled, double-blind studies have been embraced by the medical profession as a standard way of evaluating drugs in clinical trials.

But what has long puzzled researchers is whether the sense of healing that some patients feel when given a sugar pill is a function of human biology or psychology. It turns out that it’s both. New research indicates that in cases of maladies like chronic pain, asthma, and depression, a person’s expectation of healing sets off a chain reaction of neurochemical changes in the body that can alleviate physical symptoms.

As Groopman writes of Ted Kaptchuk’s placebo work at Harvard Medical School, “a change in mind-set can alter neurochemistry, both in a laboratory setting and in the clinic. When we are patients, suffering from pain and debility, we look to our doctors and nurses for the words and gestures that reinforce our belief in medicine’s power and solidify our expectation that we may benefit from an intervention. Recent research shows just how catalytic those neurochemical changes can be.”

Groopman writes that “belief and expectation – the key elements of hope – can block pain by releasing the brain’s endorphins and enkephalins, mimicking the effects of morphine” and can affect “fundamental physiological processes like respiration, circulation, and motor function.” As Groopman notes, hope can trigger a placebo effect whose biology “can be imagined as a domino effect, a chain reaction in which each link makes improvement more likely.”

Research supporting the biological basis of the placebo effect has been appearing with greater frequency in peer-reviewed journals like Science, Nature, and the New England Journal of Medicine and in nearly all of the leading specialty journals in the depression and pain treatment field.

One of the definitive analyses of the placebo effect’s role in treating depression remains a 1998 meta-analysis – a study that reviews previous studies in search of themes and conclusions – by Irving Kirsch and Guy Sapirstein called “Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication,” which appeared in Prevention and Treatment. Deciphering the data on the subject, Kirsch and Sapirstein discovered, suggests that the placebo effect might account for up to a third of the clinical benefit of modern antidepressants.

The analysis raises an obvious question: might more clinical benefit be achieved if the placebo effect could be harnessed and directed? And given the physical, emotional, and economic cost of depression, why isn’t the government funding more research on the placebo effect’s potential role in treating it?

Pain is the object of most placebo-effect studies, many of which use brain imaging to compare and correlate the biological activity produced by opiates like morphine with treatments that stimulate the placebo effect. One such study appeared in the Feb. 20, 2004, issue of Science, describing work done by the University of Michigan’s Tor Wager (now at Columbia University) and colleagues from Princeton University, Harvard University, the University of Wisconsin, and the Veterans Affairs Medical Center at the University of Michigan. The team of researchers discovered in two functional magnetic-resonance imaging experiments that placebo analgesia is related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex.

The researchers also observed increased brain activity in the prefrontal cortex when pain – or pain relief – was anticipated, which would seem to offer some evidence that placebos alter the experience of pain. In July 2002, the New England Journal of Medicine published a study that found that patients who underwent a placebo surgical procedure instead of a type of arthroscopic surgery did just as well as patients who actually received the surgery.

The importance of these and other recent findings is twofold. First, they show that more researchers and scientific publications are taking seriously the placebo effect. Second, it is clear that researchers are now seeking to go well beyond correlation studies, instrumental as they are for defining the broad reach of the placebo effect. The new goal of placebo-effect researchers is to establish and identify a direct cause-and-effect link between the placebo effect and physical healing in a wide variety of diseases.

Suspended Disbelief
Many experts point out that recent brain-imaging studies purporting to prove the existence of a placebo response are suggestive but far from conclusive. Howard Brody, whose chapter on the placebo effect appears in Callahan’s book, warns against reading too much into brightly colored brain scans that seem to show how certain regions of the brain “light up” when the placebo effect is induced. Brody, who is a family physician and researcher at Michigan State University, says, “I support the idea that PET [positron emission tomography] scanning data are helpful because they suggest which brain centers are involved in placebo effects and thereby suggest possible neural mechanisms that can be explored in future studies.” But, Brody adds, “I don’t agree with the notion that the placebo effect can now be proven to be real [just] because we can see it on a PET scan.”

To pinpoint the mechanisms responsible for the physiological changes associated with placebos, defenders of the effect will have to work more closely with their skeptical peers. Proponents have made much scientific progress and picked up some key endorsements. But they need to work harder to identify the type of research that will fully explain the phenomenon. In turn, the medical community needs to be more open to the potential benefits offered by placebos.

The most obvious common ground between the two camps is the economic imperatives they both face. If enthusiasts of the placebo effect want more notice and respect, they must prove the financial advantages of promoting the effect as a way to boost and supplement mainstream treatments. They must show that higher expectations will mean faster healing and better quality of care and will save money. That’s a message that will surely carry weight in the economically stressed health-care industry. As Groopman’s book illustrates, the practice of medicine ultimately comes down to what happens at the bedsides of patients. And there, Groopman reminds us, it’s worth keeping in mind the value of hope as a powerful and very real medicine.

Stephan Herrera is a contributing writer for Technology Review who often writes about the business and politics of health care.

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