Killing Us Softly

by Dr Paul Offit

  Psychologists have also argued that the placebo effect is simply an exercise in conflict resolution. People who use acupuncture are confronted with two conflicting facts: (1) acupuncture is unconventional; (2) acupuncture is expensive, costing between $65 and $120 a session, requiring frequent sessions, and often necessitating out-of-pocket payments. The conflict is best resolved by believing that acupuncture works. In his book When Prophecy Fails, Leon Festinger called it the “theory of cognitive dissonance,” the best example of which is Aesop’s fable “The Fox and the Grapes.” A fox comes upon a bunch of grapes hanging from a tree and confronts two opposing thoughts: (1) he loves grapes; (2) he can’t reach the grapes. The fox resolves the conflict by convincing himself that the grapes are sour.

  Another explanation for the placebo effect is something called “regression to the mean,” a phenomenon best exemplified by the Sports Illustrated cover jinx. For many years, sports fans have argued that an appearance on the cover of Sports Illustrated is the kiss of death for a professional athlete. The story is always the same: an athlete has a great season, gets on the cover of the magazine, then has a mediocre or poor season. But this isn’t really a jinx. When an athlete has a great season, it shouldn’t be surprising that the next season wouldn’t be as great. That’s because athletes have up and down years. The same can be said for pain, which can wax and wane. People usually go to an acupuncturist when they’re experiencing the most pain. So it’s possible that they feel better after their worst suffering because pain, like an athlete’s career, can fluctuate.

  During his face-off with Mehmet Oz, Dr. Novella alluded to yet another explanation for the placebo effect: the therapist’s presentation. Many studies have shown that a therapist’s clothes, demeanor, attitude, and phrasing make a difference. Therapists who say, “You will be better soon” or “These pills will help” find that patients do better than those who say, “I don’t know what you have” or “I don’t know if pills will help.” And the more time a therapist spends with patients, the better they do. Ted Kaptchuk, an alternative healer from Cambridge, Massachusetts, recognizes the healing power of personality. “I am a damn good healer,” he says. “That is the difficult truth. If you needed help and you came to me, you would get better. Thousands of people have. Because, in the end, it isn’t really about the needles. It’s about the man.” “The doctor who fails to have a placebo effect on his patients,” wrote J. N. Blau, “should become a pathologist.”

  Probably the best example of a therapist’s influence can be found in The Wizard of Oz. Because the Wizard can’t give the Scarecrow a brain, he does the next best thing: he makes him feel smarter. “Back where I come from, we have universities,” says the Wizard. “Seats of great learning where men go on to become great thinkers. And when they come out, they think deep thoughts—and with no more brains than you have. But! They have one thing you haven’t got! A diploma!” After receiving the diploma, the Scarecrow is smarter, reciting the Pythagorean theorem. “Oh joy, rapture,” he says. “I’ve got a brain.”

  In a sense, everyone uses the placebo effect, no one more than parents. “I have a four-year-old son,” writes John Diamond in Snake Oil and Other Preoccupations, “who, as is the way with four-year-old sons, climbs on things and then falls off them, losing chunks of skin and blood on the way down to the ground. And whenever this happens—about four times a week on average—and he runs to me crying and pointing to the latest graze, I apply strictly alternative remedies. I don’t give him strong drugs to kill the pain or stanch the flow of blood but I clean the tiny wound, ask him what happened, sympathize with him about the fickleness of gravity and the harshness of brick, sit him on my lap with a glass of water, kiss him and rub the hurt better. And it works, every time.” Diamond tried to label his not-so-unique brand of healing. “So what do you think I should call the technique?” he writes. “Fatherotherapy? Dynamic parentesiology? Because dealing with minor problems by calm talking, sitting down quietly and rubbing it better seems to be just what much of alternative therapy is about.”

  By the 1970s it had become clear that psychologists hadn’t appreciated the whole story. And that what alternative healers had been calling “the mind-body connection” had a physiological basis. That’s when the placebo effect became the placebo response. It wasn’t that people merely believed they had less pain; they did have less pain. Dismissive notions that pain relief was “all in their heads” were replaced by a better understanding of how pain works. And why the placebo response cannot and should not be ignored.

  In the 1990 movie Postcards from the Edge, two women (Evelyn and Suzanne) realize they’ve been sleeping with the same man. Suzanne is mortified; Evelyn isn’t.

  SUZANNE: When did you see Jack last?

  EVELYN: Umm, Saturday. Saturday night.

  SUZANNE: I was with him Saturday afternoon. That’s two girls in one day.

  EVELYN: And that’s just the ones we know about. Think what you could find out if you had one of those satellite things.

  SUZANNE: How can you laugh? It’s completely disgusting. Especially in this day and age.

  EVELYN: You look like someone who can take care of herself. Buy some condoms. Don’t feel bad. He probably really likes you. If you can just … enjoy yourself with him like he’s enjoying himself with you. That’s what I do. I’m in it for the endolphin rush.

  SUZANNE: Endorphin.

  EVELYN: Whatever.

  Evelyn had offered a clue to the physiological basis of the placebo response.

  The single most powerful pain-relieving drug is morphine. Isolated from the poppy plant (Papaver somniferum), it’s the analgesic to which all others are compared. In the early 1970s, Rabi Simantov and Solomon Snyder discovered the receptor in the brain that binds morphine. That wasn’t surprising. What was surprising was that they also found chemicals that acted just like morphine and bound to the morphine receptor. These chemicals weren’t derived from plants or synthesized by pharmaceutical companies; they were made by the human pituitary gland and hypothalamus. Simatov and Snyder called them endorphins, a contraction of endogenous (produced in the body) and morphine. Later it was shown that endorphins are released in response to pain, spicy foods, exercise, excitement, and orgasm (Evelyn’s “endolphin rush”).

  With endorphins in hand, scientists could better determine how remedies like acupuncture worked. In 1978, Jon Levine, Newton Gordon, and Howard Fields divided people who had dental surgery into two groups. Both groups received diazepam (Valium), nitrous oxide (“laughing gas”), and a local nerve block (mepivacaine). After these analgesia wore off, one group also received a placebo pill to “relieve the pain” and the other group received nothing. Many in the placebo group experienced pain relief. More important, the placebo response was eliminated by administration of naloxone, a chemical that blocks endorphins. In a paper titled “The Mechanism of Placebo Analgesia,” the authors concluded, “These data are consistent with the hypothesis that endorphin release mediates placebo analgesia for dental postoperative pain.” Other groups have reproduced these findings.

  The results were in. Placebo pain relief could be physiological, real. When people said they felt less pain after acupuncture, it wasn’t “all in their heads”; it was in their bodies, caused by the body’s own drug. (Researchers have also shown that pain relief from acupuncture can be blocked by naloxone.) Knowing this, alternative healers argued that if acupuncture can spare people from prolonged use of analgesics—some of which have significant side effects—what’s the harm? Wouldn’t it be better to induce endorphins naturally than to rely on drugs?

  Those who dismiss acupuncture make three counterarguments.

  First: acupuncture is a deception. If acupuncturists were honest about studies comparing real to sham acupuncture, they’d say to their patients, “Before we begin, let’s set aside all this two-thousand-year-old-ancient-wisdom business. The truth is the Chinese didn’t believe in dissection, knew nothing about the anatomy of the nervous syst
em, wrongly assumed it was based on rivers in China and the lunar month, and inserted needles under the skin randomly. Forget chi; forget yin and yang; forget meridians. Acupuncture will work just as well if I use retractable needles. The reason it works is that you think it works. And thinking alone might be enough to release endorphins.” Acupuncturists don’t say this for the obvious reason that it would probably eliminate the placebo response. Maybe it would eliminate it because the mental image of yin, yang, and chi are important to the therapeutic process. Or maybe patients respond better to the assurance of ancient wisdom than to the caveats of modern science. Whatever the reason, deception is likely an essential part of the therapy.

  Art Caplan, professor of bioethics at New York University’s Langone Medical Center, has addressed the ethics of placebo medicine. “It’s ethical to deceive the patient at low risk, at low cost, and at low burden,” he says. “Medicine can learn from chiropractors, can learn from acupuncturists. But they have a duty to report what they’re doing in the medical literature. They should report that the placebo effect is powerful, that certain things can induce it, and that medicine ought to study how it can best be elicited.”

  In fairness, all practitioners—mainstream or otherwise—employ some form of deception. They know that a positive attitude, reassuring demeanor, and air of competence are important. “We use the placebo effect all the time,” says Caplan. “I’ve got a bow tie. I wear a white coat. You come to a big building that looks pretty impressive. I expect someday to see billboards go up in cities that say we have a really big machine and it makes a lot of noise and we don’t know how it works, but you can only get it from us, so come on down.”

  Indeed, it would be more honest if mainstream doctors walked into a patient’s room and said, “Look, we will definitely know more about how to treat you a hundred years from now. Frankly, I suspect doctors in the future will look back on some of the things we’re doing today and laugh. Although our understanding of many diseases is excellent, for some we’re just treading water, and for others we’re completely lost.” No clinician (in his right mind) says this. From the days of shamans and witch doctors to the modern-day physician, everybody has their props, their deceptions.

  The second argument against acupuncture is that it’s expensive. But, at least according to the theory of cognitive dissonance, the more expensive, the better. This concept was first tested at a racetrack in the 1960s. Researchers asked bettors to rate their horse as they walked toward and away from the betting window. Bettors faced two conflicting facts: (1) any horse could win the race; (2) I bet a lot of money on only one horse. To resolve the conflict, bettors rated the horse they’d picked much higher after placing their bets. The study was titled “Post-Decision Dissonance at Post Time.” In another study, researchers from MIT tested the capacity of two sugar pills to relieve pain. One group was told that the pill cost 10 cents, the other that it cost $2.50. Participants experienced less pain with the more expensive pill. “Look, at the end of the day, if you say to me the only way this works is if we charge fifty bucks and pretend we are going through this ceremony, and that’s the only thing that gives pain relief—okay,” says Caplan. “But I don’t think we’re there yet. I don’t think we’ve fully explored how to elicit the placebo response in other ways.”

  The final argument against acupuncture is the hardest to refute. Acupuncture needles are not without risk, having punctured hearts, lungs, and livers and transmitted viruses like HIV, hepatitis B, and hepatitis C. Perhaps the most famous case involved the former president of South Korea, Roh Tae-woo, who had an acupuncture needle removed from his lung in May 2011. “I can’t figure out how the needle got into there,” said Dr. Sung Myung-whun, the operating surgeon. “It’s a mystery for me, too.” At least eighty-six people have died from acupuncture.

  If sham acupuncture works as well as real acupuncture, and if putting needles under the skin can puncture lungs and cause infections, why not use retractable needles? Acupuncturists might argue that the use of retractable needles would be a deception; but they’re already knee-deep in the deception that acupuncture points have anything to do with the nervous system. So what’s one more? The goal should be to induce endorphins in the safest way possible.

  The discovery of endorphins changed everything. Now there was a clear, rational, physiological mechanism by which therapies that weren’t anchored in the anatomy of the nervous system could work. But alternative practitioners don’t limit themselves to chronic pain. They offer relief from a variety of immunologic, neurologic, and metabolic diseases, again with therapies that are often unrelated to the physiological basis of those diseases. Like the identification of endorphins, another discovery in the 1970s shed light on why some of these therapies might work. The discovery was so surprising that, until it was reproduced in two other laboratories, no one believed it.

  In 1975, Robert Ader and Nicholas Cohen, from the University of Rochester School of Medicine, published a paper titled “Behaviorally Conditioned Immunosuppression.” The experimental design was simple. Ader and Cohen injected one group of rats with sheep red blood cells; as expected, the rats made antibodies against the cells. A second group was given saccharine-flavored water at the same time they were injected with the cells; like the first group, they developed an immune response. A third group of rats was inoculated several times with the cells suspended in saccharine-flavored water containing cyclophosphamide—an immunosuppressive drug—which, not surprisingly, inhibited the immune response. Then Ader and Cohen gave this third group the red blood cells in saccharine-flavored water without cyclophosphamide. And they found something remarkable: saccharine-flavored water alone suppressed the immune response. By pairing an immunosuppressive drug with a distinct taste, the third group of rats had learned to suppress their own immune systems. Amazing.

  In a way, the Ader-Cohen experiment shouldn’t have been that surprising. In 1896, J. N. MacKenzie studied several people who suffered itching, sneezing, and watery eyes when exposed to pollen on flowers—an allergic response mediated by histamine. In a paper published in the American Journal of the Medical Sciences, MacKenzie reported that artificial flowers elicited the same symptoms, even though they were pollen-free. People had learned to make an allergic response—learned to release their own histamine.

  In 1957, John Imboden, Arthur Canter and Leighton Cluff, scientists at Johns Hopkins School of Medicine, performed another landmark experiment. They administered a series of psychological tests to military personnel working at Fort Detrick, in Frederick, Maryland. A few months after the tests were completed, an influenza pandemic swept across the camp. Imboden and his colleagues found that recruits who were depressed had symptoms of influenza that lasted longer and were more severe than those who weren’t. Mood determined illness. The results of this study lent credence to the adage that people get sick when they want to get sick. “The mind,” wrote Milton in Paradise Lost, “can make a heaven of hell and a hell of heaven.”

  The next question was, could these findings be put to practical use? Could researchers teach people to suppress or enhance their own immune response? Robert Ader was one of the first to step forward. Working with a teenager with the autoimmune disease lupus, Ader paired cyclophosphamide with a distinct taste (cod liver oil) and smell (rose perfume). Like the rats, the boy learned to suppress his immune response, requiring less frequent dosing of the drug needed to control his disease. Others replicated Ader’s findings. Marzio Sabbioni found that healthy men could learn to release their own cortisol, a natural steroid produced by the adrenal gland. And it worked both ways: not only could people learn to suppress their immune responses; they could also learn to enhance them.

  If people can learn to stimulate or suppress their own immune responses, it’s not a leap to believe that placebos can impact a variety of diseases. Even though most alternative medicines don’t work better than placebos, some placebos work. So why not use them?

  For example, Wolf Storl’s claim
that the weed teasel cures Chronic Lyme disease might be of some value. Even though Chronic Lyme disease doesn’t exist, chronic pain and fatigue do. For some, it’s possible that the mental image of bacteria being killed by teasel causes them to experience less pain and fatigue. The same can be said for the image of balancing yin and yang to release chi. If these mental constructs work to relieve pain, where’s the harm? Teasel’s cheap and is better than taking long-term pain medications (or, worse, long-term antibiotics). Similarly, Bryan Rosner’s promotion of Rife machines is harmless. Although claims that it kills Lyme bacteria are fanciful, at least it doesn’t kill anything else. (The electric current produced by the machine probably doesn’t penetrate the skin.) Assuming that the problems aren’t amenable to conventional therapies, one could make the same argument for treating chronic symptoms with magnets, crystals, saunas, aromatherapy, emu oil, or prayer.

  Furthermore, many alternative healers recommend chondroitin sulfate and glucosamine for chronic joint pain. Although these remedies don’t work better than placebo pills, they’re harmless. And if that means avoiding pain medicines that occasionally cause serious side effects, why not give them a try? Even though chondroitin sulfate and glucosamine don’t work better than placebos, that doesn’t mean that they don’t work as placebos.