In recent months, many of us have become familiar with the sense of fear expressing itself in our bodies. We may feel restless or physically exhausted. At times, we may even have trouble catching our breath. The deep connection between mind and body that seems so salient now was also at the center of our episode about the placebo effect. This week, we return to this 2019 story that asks what placebos might teach us about the nature of healing.
The transcript below may be for an earlier version of this episode. Our transcripts are provided by various partners and may contain errors or deviate slightly from the audio.SHANKAR VEDANTAM, HOST: At the end of March, New York magazine published a story with the title "Is My Chest Tightness Anxiety Or The Coronavirus? The author was concerned because for days, she'd felt tightness in her chest. That can be a symptom of COVID-19. But it's also a symptom of anxiety. In the last couple of months, many of us have become familiar with the feeling of fear expressing itself in our bodies. We may feel restless, physically exhausted. At times, we may even have trouble catching our breath. This deep connection between mind and body made us think about an episode we did a while back about a dimension of medicine that few of us recognize. And we thought we'd bring it back today as a reminder of how our minds our tied to our physical suffering and the complex ways in which healing unfolds. Here's the episode.(SOUNDBITE OF ARCHIVED NPR BROADCAST)VEDANTAM: This is HIDDEN BRAIN. I'm Shankar Vedantam.(SOUNDBITE OF MUSIC)VEDANTAM: When you're 8 years old, it's not easy to say goodbye to your dad for a whole year. But that's what Andrew Marvin (ph) had to do. His dad was a commander in the Navy and was deployed to Bahrain. While his dad was away, something happened to Andrew.ANNE MARIE MARVIN: Every time my husband's name was brought up, he would develop a headache.VEDANTAM: This is Andrew's mom, Anne Marie Marvin (ph). She knew her son's pain was real. She didn't want him to suffer. As she tried to figure out how to help, she remembered an episode of the TV show "M*A*S*H." The series is set in a fictionalized Army hospital.(SOUNDBITE OF TV SHOW, "M*A*S*H")UNIDENTIFIED ACTOR #1: (As character) Come on, guys. Let's go back to the tent. Come on. Come on.VEDANTAM: The doctors had a problem on their hands - the hospital was full of wounded soldiers but was out of painkillers. A colonel suggested an unusual solution - treat the patients with a placebo.(SOUNDBITE OF TV SHOW, "M*A*S*H")HARRY MORGAN: (As Colonel Sherman T. Potter) Here's the formula - if we believe it, they believe it. Otherwise, they're only taking sugar pills.VEDANTAM: The doctors gave out the placebos while pretending they were real pills. Sure enough, it worked.(SOUNDBITE OF TV SHOW, "M*A*S*H")MORGAN: (As Colonel Sherman T. Potter) You're really beginning to feel it, aren't you, son?UNIDENTIFIED ACTOR #2: (As character) Yeah. The arm stopped throbbing.MORGAN: (As Colonel Sherman T. Potter) It's going to feel even better. Now get some sleep.VEDANTAM: The lesson Anne Marie took away from the scene was - make the placebo treatment look real.(SOUNDBITE OF MUSIC)MARVIN: So I went to the store, and I got a bottle of Motrin. And I got a bottle of chewable vitamin C tablets. And I switched the bottles.VEDANTAM: As Anne Marie gave Andrew the vitamins, she made sure the lie didn't look like a lie.MARVIN: I would emphasize that he had to really have a headache. I would treat it as I would a regular drug, that I wouldn't want to medicate unless absolutely necessary. On a couple of rare occasions, he said it didn't work and asked for a second pill. I would make him wait 20 minutes to see if it would work first, as I would a regular medication, before I let him take a second one. I emphasized that I couldn't do any more than that because of the dose. Every single time we used the placebo, the headache went away, usually within about a half an hour.(SOUNDBITE OF MUSIC)VEDANTAM: Anne Marie's small act of parental deception raises lots of questions - if you can make a child's headaches disappear with a vitamin, what else can you do with a placebo? What was happening in Andrew's mind and body as he took the pills? How much was the cure linked to the rituals that Anne Marie built into the treatment? Perhaps most difficult of all, can you get the same results without deception?(SOUNDBITE OF MUSIC)VEDANTAM: These are not questions doctors generally ask. For centuries, scientists have used placebos mainly to deflate the claims of con men and to test the efficacy of drugs and medical interventions. This week on HIDDEN BRAIN, what it means to be sick and what it means to heal and the powerful tool that modern medicine has overlooked.(SOUNDBITE OF MUSIC)VEDANTAM: 1996 was quite the year for men's basketball. It's the year that "Space Jam," starring Michael Jordan and Charles Barkley, made it to theaters.(SOUNDBITE OF SONG, "SPACE JAM")QUAD CITY DJ'S: (Singing) Welcome to the space jam. Here's your chance, do your dance at the space jam. All right.VEDANTAM: It was also the year of Dream Team III - that was the nickname given to the 1996 U.S. men's Olympic basketball team. They dominated the court in Atlanta.Is that the year we won the gold?J BRUCE MOSELEY: We win the gold every year.VEDANTAM: (Laughter).(SOUNDBITE OF ARCHIVED RECORDING)UNIDENTIFIED ANNOUNCER #1: And they are headed to the gold medal.VEDANTAM: This is Bruce Moseley. If you look closely at old videos of those games, you can see him sitting near the sidelines wearing a sport jacket and tie. He was one of the physicians for the team. You might recognize some of the players Bruce has treated.MOSELEY: Hakeem Olajuwon, Shaquille O'Neal, David Robinson, Charles Barkley, Karl Malone, John Stockton, Mitch Richmond.VEDANTAM: For years, Bruce worked as an orthopedic surgeon for the Houston NBA team, the Rockets. He performed lots of intricate surgeries. He loved seeing players glide across the court and soar in the air. He would think, that dunk? I helped make that happen. In a way, that's my knee.(SOUNDBITE OF ARCHIVED RECORDING)UNIDENTIFIED ANNOUNCER #2: ...In game No. 5 in New York.(CHEERING)VEDANTAM: Bruce's exceptional surgical skill is what makes it so surprising that he, of all people, would lead a study that questions the primacy of surgical skill.(SOUNDBITE OF MUSIC)MOSELEY: Did I ever see myself doing this? The answer is absolutely not. And it wasn't my idea.VEDANTAM: Let's back up a second. In 1989, years before he was a physician for the Rockets, Bruce started working at the Baylor College of Medicine in Houston. He became interested in a knee surgery that's meant to help people with arthritis. It wasn't a common surgery where he received his medical training.MOSELEY: And then when I came here to Houston, it seemed like surgeons were doing it almost nonstop.VEDANTAM: He found it odd that surgeons in some parts of the country were doing the procedure far more often than others. Patients reported feeling better after the surgery, but no one knew why. Was it because surgeons scrape away bits of tissue from the joint? Was that alleviating the pain? Or could it simply be an effect of salt water? As part of the procedure, surgeons flush the knee with saline solution. Bruce wanted to run a trial to answer these questions. One set of patients would get the standard surgery; another would just get their joint flushed with saline. He went to a colleague to discuss his plan.MOSELEY: When I pitched it, she was the one that said, well, how do you know it's not all a placebo effect?(SOUNDBITE OF MUSIC)VEDANTAM: A placebo effect - the same phenomenon that helped 8-year-old Andrew Marvin and the soldiers in "M*A*S*H."MOSELEY: As a surgeon, I was like, this doesn't have anything to do with sugar pills and things like that. This is surgery, after all.VEDANTAM: But Bruce's colleague explained to him that the placebo effect comes in many shapes and sizes.MOSELEY: If it's a small pill, sometimes, there's not as big a placebo effect as a bigger pill. Or if they say it's a new and exciting pill, there's probably more of a placebo effect than a traditional pill. And many times, an injection can have more of a placebo effect than a pill. And many times, you know, some other intervention can have more of a placebo effect than an injection. And perhaps surgery may have the biggest placebo effect of all.(SOUNDBITE OF MUSIC)VEDANTAM: Surgeons like Bruce don't think about these questions very much because the idea of comparing actual treatment to placebo treatment isn't built into the practice of surgery.MOSELEY: If you're trying to bring a new medication to the market, you have to go through all kinds of randomized trials, including, you know, a placebo group, and prove that your product is superior to the placebo treatment group, while surgeries don't go through that same scrutiny. Surgeries are many times adopted because it's an improvement over a previous surgery, which is an improvement on a previous surgery, which was an improvement on one before that. And long story short, very few surgeries ever go through randomized trials. And almost no surgeries have a placebo control group.VEDANTAM: Bruce and his team decided their study would have not two but three groups. The first would get the real surgery. The second would have saline washed through the joint. The third would be a placebo group. Anyone who signed up was informed about the three possible kinds of treatment.MOSELEY: We told them going in, you're going to get randomized to one of three groups. And these are the three groups. And we actually had them sign a piece of paper that said, I understand that I may be randomized to a control group that is a placebo group. And placebo means pretend - and that if I'm in this group, I'll have a pretend surgery, not a real surgery. And they had to write it in their own handwriting to make sure that they, you know, fully understood everything we were saying.VEDANTAM: The researchers followed certain procedures to make sure all three types of surgeries felt real to everyone involved - real to the patients and their families and as real as possible to the physicians. Bruce would put on his scrubs and walk into the OR without knowing what type of surgery he was going to perform. He found out only when he opened an envelope.MOSELEY: The patient would be wheeled into the room. They'd be placed onto the table. And once they're on the table, we would open the randomization envelope, which would disclose which of the three groups they would be placed into.VEDANTAM: All the patients were given general anesthesia. All got incisions in their knees. Patients in the first two groups received surgery or got their knees flushed with saline.(SOUNDBITE OF MUSIC)MOSELEY: And then the third group, the placebo group - they would go to sleep. I'd make three little holes in the skin. And then I wouldn't put any instruments actually inside the knee joint itself.VEDANTAM: Instead, Bruce fired up a video.MOSELEY: I had a videotape of a real arthroscopy that I had done on a patient, and I would pop it in the VCR machine - we would tape all of these surgeries during this time - and I would actually pretend like I was doing with the leg what I would normally do if I was doing those different things during the real surgery. If I put something in the knee on the videotape, I would actually ask for that instrument and pretend like I was doing something. I'd move the leg around. I would splash water. We would ask and pass instruments like we were doing the real thing, even though we weren't doing any real surgery.VEDANTAM: Bruce took these additional measures because he wanted to account for situations where a patient wasn't 100% out from the anesthesia.MOSELEY: The other thing about that videotape was it made certain that we spent the proper amount of time under anesthesia. And for instance, we didn't want the placebo group, where we didn't really do anything, to be much shorter than the other types of surgeries so that if I went and talked to the nurses in the recovery room or the patient's family afterwards, they could look at their watch and say, oh, that was only 10 minutes, so it must have been a placebo. So we spent the same amount of time with the placebo group pretending to do surgery as if we had done the real surgery in the other groups.VEDANTAM: In all, 180 patients, mostly men, took part in the study. Bruce followed up with them a few times over the course of two years. The results were jaw-dropping.MOSELEY: (Laughter) Yes. I'd say jaw-dropping was probably one of the best ways to describe it.VEDANTAM: Patients in all three groups had similar functioning in their knees.MOSELEY: All three groups basically were the same. All three groups felt they were better off for having had the surgery, that they'd recommend it to family and friends. They'd do it again if they had it - to do all over again. And so the conclusion was that all the benefit of arthroscopic surgery to treat arthritic knees was from a placebo effect.(SOUNDBITE OF MUSIC)VEDANTAM: To Bruce, the implications were clear.MOSELEY: We shouldn't be doing arthroscopic surgery to treat arthritic knees. And the reason is because, number one, it's invasive. And you do go to sleep, and there is risk. And although the complication rate is very low - the chance of bad things happening is pretty low - it's not zero. And so God forbid that you ever put somebody to sleep and did a surgery on them entirely for a pretend surgery effect, and they, you know, had a heart attack or stroke or any number of other things. And you would really regret under those circumstances, you know, ever having done that.VEDANTAM: Then there's the money.MOSELEY: If you do arthroscopic knee surgery, which currently is the most commonly performed orthopedic surgery worldwide today, and you're doing it all for a placebo benefit, it's going to run into the millions, probably billions of dollars of cost.VEDANTAM: If patients are benefiting from the surgery because they're experiencing the placebo effect, Bruce says we should find other more effective treatments and put our money there. To be clear, he doesn't want to suggest that this surgery is ineffective across the board.MOSELEY: This is not an indictment of arthroscopic surgery. I use arthroscopic surgery all the time to treat all kinds of things, just not arthritis. And it's not an indictment of surgery to treat arthritis. We have really effective treatments for severe arthritis. It's called a knee replacement.VEDANTAM: Bruce's study was published in The New England Journal of Medicine in 2002. Plenty of people appreciated having an evaluation of this widely used procedure, but many of Bruce's fellow orthopedic surgeons were not pleased.MOSELEY: Oh, my gosh, the vitriol that came out at the different meetings where we presented. And then if you're a surgeon and you were routinely performing arthroscopic surgery for arthritic knees and your patients were routinely telling you that they were better, you would like to think it's due to your surgical skill. And what my study showed - or I should say our study showed - is that it wasn't due to their surgical skill. It was due to the placebo effect and the fact that patients were going to sleep and believing that they were having something done that would make their knees better.VEDANTAM: Orthopedic surgeons eventually came around. Because of Bruce's study and later trials by other researchers, the American Academy of Orthopadic Surgeons does not recommend knee arthroscopy in patients with arthritis. In the years since Bruce's study was published, other researchers have run placebo-controlled surgery studies. They've covered a range of pain-related and chronic conditions, from back pain to obesity. In 2015, Bruce looked at the results. Real surgery did help lots of patients, but Bruce also found that substantial numbers of patients got better with placebo surgeries. In the case of pain, improvements from placebo surgeries were almost the same as the improvements were from real surgeries. For Bruce, these results have led him to think about surgery in a new way.MOSELEY: Well, it certainly makes you stop and take pause whenever we're doing a surgery purely for pain relief because from what I know now, just the act of bringing somebody to an operating room, having them go to sleep in this fairly dramatic environment, doing some kind of procedure and having them wake up and go home and then go through a recovery - all of that fuels this very strong emotional and psychological belief on the part of the patient that they're pain is going to get better or their, you know, shoulder is going to get better - knee's going to get better - whatever. So it certainly makes you take notice of that.VEDANTAM: But if Bruce has come to feel less confident about the power of some surgeries to heal, he has come to feel more confident about using a power that he previously undervalued. He's realized that the treatment he offers patients isn't just about what he can do in the operating theater. It's about what comes before, what comes after.MOSELEY: Well, I think every time I come out of surgery and go talk to a family, there are aspects of every surgery where you could probably say, I wish I'd done this better or, this could have happened a little more efficiently. And most of it's subtlety, nuance. It probably doesn't have anything to do with the ultimate outcome. But I always emphasize the positives - when I go talk to the family, that is. I'd share with them all the things that I'm extremely happy about. And I think by emphasizing those things rather than any kind of negatives, the patient's family gets a good feeling about it. They share those feelings with the patient. We emphasize with the patient when they come back to see me in the office the same things. And so I think, you know, all of that you're going to harness the benefit of the placebo effect by fueling into their belief that the surgery or the procedure is going to help them be better.VEDANTAM: All of this, of course, raises tricky ethical and philosophical questions. Should doctors prioritize honesty with their patients above everything else? Or should they prioritize healing even if that occasionally involves deception?(SOUNDBITE OF MUSIC)VEDANTAM: In 1778, an Austrian physician named Anton Mesmer arrived in Paris. He set up a salon to treat patients. He wanted to heal people, but his treatments involved much more flair and drama than you'd find in most doctor's offices. For one thing, he wore a distinctive outfit.EMILY OGDEN: Mesmer would wear a special purple robe that seemed to be designed to associate him with the signs of the zodiac and astrological power.VEDANTAM: This is Emily Ogden. She's the author of a book about Anton Mesmer and his followers. She's also a professor of English at the University of Virginia. Anton Mesmer's purple robe was a hint of the theatrics that were to come. He'd gather patients in a room decorated with celestial symbols with glass harmonica music filling the air.(SOUNDBITE OF MUSIC)VEDANTAM: In the middle of the room, there was a device that he called the baquet. Think of a hot tub except shorter with a lid on top. Inside the baquet, there was water and broken glass.OGDEN: And then rods would protrude out of it.VEDANTAM: A group of patients who suffered from a range of physical and psychological maladies sat around the baquet.OGDEN: And he would have each one of them touch one of these metal rods, and he gathered around them a rope which would connect all of the patients to each other.VEDANTAM: Anton Mesmer and his assistants performed a choreographed set of gestures with the patients.OGDEN: They would touch their diaphragms and their stomachs. They would wave iron wands over them.VEDANTAM: The iron rods were supposed to remove the obstructions in the body that cause disease.(SOUNDBITE OF MUSIC)VEDANTAM: What happened to these patients after these gestures is part of what made Anton Mesmer famous and infamous.OGDEN: Some of them would become drowsy. Others would become agitated. Some would start to cough and especially cough up fluid, which was not unexpected in the context of signs of illness in humoral medicine at the time. And then some of them would undergo some really dramatic effects, like convulsions. And what seemed to happen, according at least to some of the observers, is that patients would convulse and then that convulsion would spread throughout the room. So it turned into a kind of a pandemonium of symptoms, of convulsions but then also, Mesmer claimed, of cures.(SOUNDBITE OF MUSIC)VEDANTAM: Some patients, in fact, did get better. Anton Mesmer had a theory to explain what was going on.OGDEN: He thought that there was a fluid called animal magnetism that permeated the cosmos but that was particularly active in human nerves. And he thought that through gestures and the use of special instruments, you could control the fluid and that by controlling it, you could cure a wide range of diseases, especially diseases that were thought of at the time as nervous diseases.VEDANTAM: The physician had influential followers, like the French aristocrat Marquis de Lafayette. Lafayette toured the United States to spread word about animal magnetism's miraculous powers. If you're thinking this is bonkers - this Mesmer guy is a fraud - well, you and Ben Franklin have something in common. Yes, that Ben Franklin. He was appointed by the king of France to lead a commission to investigate Mesmer. The commission ran experiments to see if patients were getting better because of animal magnetism or something else. These tests were groundbreaking. They were the first known experiments that involved what we now call a placebo control.OGDEN: Which means that they made people believe that they were magnetizing them when they were not magnetizing them. And also, conversely, they magnetized patients without their knowledge.VEDANTAM: The results of the experiments did exactly what Anton Mesmer's critics had hoped. They made him look like a fraud.OGDEN: They had one woman who was known to be magnetically susceptible, and they brought her to a room. They blindfolded her. And they had one of the members of the commission pretend to magnetize her. But in fact, he was doing nothing at all. And she, without any magnetization after a certain period of time, went into an elaborate magnetic crisis.VEDANTAM: They did the reverse, too. In one test, an investigator stood behind a panel and waved iron rods at a patient who couldn't see what was happening.OGDEN: She showed no effects whatsoever, although he magnetized her vigorously for some time. And so what the commissioners believed they had shown here was that the effects that Mesmer was eliciting had to do with patient belief and with the bond between the patient and the mesmerizer and not with the animal magnetic fluid.(SOUNDBITE OF MUSIC)VEDANTAM: The members of the commission believed they had humiliated Anton Mesmer. A future president of the United States made a prediction after the report came out. John Adams said it would annihilate the enthusiasm for mesmerism. The debunking of Anton Mesmer, however, itself fell victim to a falsehood. Investigators did show that mesmeric techniques were no better than a placebo. Critics concluded that mesmerism was worthless. But in fact, this was not true. Some of the investigators themselves noted that while Mesmer's theory of animal magnetism was nonsense, many of his techniques worked.OGDEN: They certainly did think that Mesmer's gestures, that Mesmer's pressure on the stomach, that the excitement of the public treatment salon - they thought that all of those things had their effect. It was just that their effect didn't happen immediately through the communication of animal magnetism but in effect directly by the drama acting on the imagination of the patient.VEDANTAM: When people said mesmerism was worthless, they were saying that only some kinds of cures were real cures. Cures created by drama didn't count.OGDEN: It seems like there's been a kind of an agreement in some of these conversations that in order for a cure to be real, it has to have a physical event associated with it, not a psychological event.VEDANTAM: What Mesmer had really shown was that patients often get better not because of the doctor's skill and not because of the doctor's cure but because of the very presence of the doctor. Ironically, most physicians have shied away from this starring role. Only some, like Benjamin Rush, a respected doctor and one of the signers of the Declaration of Independence, understood the powerful tool that Anton Mesmer had inadvertently revealed.OGDEN: He said at the time that he deplored Mesmer's silly pretensions to cure by animal magnetism but that he encouraged his medical students to avail themselves of the ability that the imagination had to cure.VEDANTAM: The dilemmas posed by this debate live on in our own time. Even today, centuries after Anton Mesmer produced convulsions in patients, most people in medicine do not believe their job is to harness their patients' imaginations. Ted Kaptchuk is an exception. He believes the drama embedded in the doctor-patient relationship is deeply connected to healing. It's a focus of his research.TED KAPTCHUK: I'm a professor of medicine at Harvard Medical School, and I'm director of the Program in Placebo Studies at the Beth Israel Deaconess Medical Center.VEDANTAM: In the 1970s, when he arrived in Cambridge, Mass., he was about as far from the world of elite Western medicine as you could imagine. Ted is not a physician. He's an herbalist. He'd studied Chinese medicine in Macao, Taiwan and China. He set up shop on a street in Cambridge with an unflattering reputation.KAPTCHUK: I rented an apartment on quack row. I didn't know it was quack row, but there were lots of all kinds of healers on the street. There were all kinds of energy healers. There were past life - you know, all the new age kind of stuff was on that block.VEDANTAM: Ted's office decor was not what you might call Boston Brahmin.KAPTCHUK: You know, herbalist, so I had at least 200, 300 herbs in jars all over the waiting room and along the walls. I had really wonderful pictures of China. And some of the herbs were animal parts and, you know, lizards and geckos and seahorses.VEDANTAM: Ted got positive feedback from patients all the time, but there were moments that made Ted ask, why exactly were patients feeling better?KAPTCHUK: I see people walk into my office, sit down with me for 15, 20 minutes, half hour. And, sometimes, I'd only write a prescription for herbs. And as they walked out, I saw them walking out with less pain, more bounce in their gait. And their faces were different when they left. And I said, Ted, you just changed that person. That was not the herbs.(SOUNDBITE OF MUSIC)VEDANTAM: Ted looked to traditional Chinese medical texts to help him make sense of these kinds of interactions.KAPTCHUK: And I realized there were statements like the medicine should start working before the patient takes the herbs. I started realizing that something else was going on that was more than my herbs and acupuncture.VEDANTAM: Ted asked himself what was going through the minds of his patients when they walked through his clinic door. They had hope. They'd made the effort to come see him, but many had seen several doctors before him and had been disappointed.KAPTCHUK: So they come with those kinds of feelings, and they go into a ritual that - you know, I ask them how they are. I start talking. They expect me to ask some questions. I usually ask questions they didn't expect to make sure they knew they were getting something different. I listen. I would lean over when I thought the patient wanted me to be a little closer. I'd pull back when I saw the patient didn't want me to be closer. I would actually think and say, let me think for a minute - if I thought the patient needed to see me be attentive. I'd sometimes ask people to explain things better. I got to know something about them personally that was important, so I could bring it up the next time. All those maneuvers in the context...VEDANTAM: That sounds like acting.KAPTCHUK: Hey, it's a drama.(SOUNDBITE OF MUSIC)KAPTCHUK: Healing is a ritual and drama that everyone in the world knows, at least their cultural forms of it. That drama activates neurons and activates a neurological process that's involved what we call now in biomedicine at this point the placebo effect. You got it right on the head.(SOUNDBITE OF MUSIC)VEDANTAM: Ted was doing what Anton Mesmer was doing. He was using drama to unleash healing. This is where Ted's work on quack row and at Harvard Medical School connect. In 1990, Harvard recruited Ted to do research on alternative medicine. The idea was his experience practicing traditional Chinese medicine would give other researchers useful perspective. At first, Ted didn't feel at home amongst the M.D. and Ph.D.s.KAPTCHUK: I felt like a reptile in a mammalian environment. I was, like, pre-scientific.VEDANTAM: Gradually, Ted became more comfortable with the techniques and norms of contemporary science. Harvard gave him research training and assigned him to some projects.KAPTCHUK: They told me that your job, Ted, is to help us decide or discover or uncover whether any of these alternate treatments are more than a placebo effect. And I would ask my mentors - I said, so what is this placebo effect? And they said, it's the effect of an inert substance. And I said, that's an oxymoron. And I said, you know what? I'm going to make a pivot. I'm going to study the placebo effect, not alternate medicine.VEDANTAM: It's hard to overstate just how unusual that was. In the 1990s, placebos were not a subject of study. They were a tool that pharmaceutical companies and medical researchers used to figure out whether a drug or treatment was effective.KAPTCHUK: If people get better, we want to know if it's because the drug we gave them - or is it spontaneous remission? Or is it because of the doctor-patient interaction? Is it because of the ritual of taking pills? Biomedicine is really - is very interested in whether a drug has a specific target that works independent of all those other factors. That's where the placebo control comes in. It's a way of making medicine more like science and more scientific. And it is.VEDANTAM: The problem is this can lead to the same kind of logic we heard from the people who debunked Anton Mesmer. If a drug improves patients' pain by 70%, and a placebo improves it by 70%, researchers don't stop and say, wait. Sugar pills are alleviating 70% of the pain. They say, this drug doesn't work. In other words, cures don't count as cures when they are caused by placebos.KAPTCHUK: It totally dismisses what happens in the placebo arm of a randomized controlled trial. It says, well, this drug is no good. It's no better than placebo. Or this drug is really good. It's better than placebo.VEDANTAM: Rather than dismiss the placebo effect as merely what happens in the control arm of a trial, Ted decided he would study the placebo in its own right. In 2008, he published a study on treatments for irritable bowel syndrome, or IBS. Two hundred sixty-two patients were randomly assigned to one of three groups. All the patients were screened by a doctor. The first group was told to keep doing what they had been previously doing. The idea was to see if patients got better merely through the passage of time. Think of this as the time heals arm of the study. The second group was assigned to a pretend treatment involving acupuncture needles. The last group got the pretend treatment plus a bonus. They also had a warm, empathetic conversation with the acupuncturist who was trained to ask them a number of questions.KAPTCHUK: Why they thought they had the illness, what made it better. We asked them, how does it affect their work? How does it affect their lives? And we did things like touch, attentive listening. We asked them to repeat words to explain to us what was meant.VEDANTAM: Ted also gave the acupuncturists acting advice.KAPTCHUK: Ask the patient if you can be still for 20 seconds and think about them and then ask them an important question that they would want to hear.VEDANTAM: What Ted and his colleagues did with the study was to break down the placebo effect into three components, each arm built on the other. One - time heals. Two - time heals plus a pretend treatment. Three - time heals plus a pretend treatment plus warm interactions with a health care provider.KAPTCHUK: And we got really a very straight line. We had a small placebo effect with no treatment because time heals. We had a moderate placebo effect with just a fake treatment. And then we did the full monty - it went up to 60% improvement of adequate relief. That's incredible amount of placebo effect.VEDANTAM: Ted had shown that the placebo effect could be valuable in its own right as a treatment. His study demonstrated that the placebo effect was made up of different factors, each of which could be deliberately employed to unleash healing. But Ted also recognized that placebos demanded something that made doctors uncomfortable - deception.KAPTCHUK: Everyone believed that deception or concealment is necessary for people to respond to placebo because the idea was, well, you fake people. You trick them. Placebo's kind of this trickery. And I sat with myself for a long time, read the literature. And I said, you know what? No one's tested that ever in history. What's going on here?(SOUNDBITE OF MUSIC)VEDANTAM: When we come back, is deception necessary for the placebo effect to work? Can honesty and the placebo effect mix?LINDA BONANNO: I find this just as astonishing as anybody else, and I'm the patient here.(SOUNDBITE OF MUSIC)VEDANTAM: There's something about sitting in a chair at a hair salon that makes people talk. It feels safe to discuss personal things. When clients have a cape draped around their necks and wisps of hair are falling to the floor, they gab.BONANNO: Oh, yeah. They tell you all their problems, their troubles and the good stuff, the bad stuff, yeah (laughter).VEDANTAM: This is Linda Bonanno (ph). She's been a hairdresser in northern Massachusetts for decades. Linda realized that people often walk out of her salon with a feeling of ease. She thinks it's because she's a good listener.How would you be able to tell when someone felt better after they had talked with you? Would you look for signs to sort of know that they were happy?BONANNO: Oh, you could see. You could see they'd have a smile on their face. Their personality changes. Their attitude changes, tone of their voice.VEDANTAM: Linda has also seen what such interactions look like from the opposite perspective - as someone who confides in others. That's because for many years, she's had to seek out medical care for a debilitating condition.BONANNO: I'd end up with severe diarrhea, intestinal pains, running to the bathroom all the time. Sometimes, the pains would come, like, every half an hour. I couldn't even move. It was worse than labor pains. You're better off having a baby than what I went through. It was very, very severe.(SOUNDBITE OF MUSIC)VEDANTAM: The pain and diarrhea interfered with every part of Linda's life. She had to skip meals before social events. She got used to leaving gatherings early. She couldn't get work done.BONANNO: I used to run machinery. I worked for a medical company. And I remember one time, I was keeling over in pain. I went, oh, how am I going to run this machine? And I figured I'd better go home. My boss wouldn't let me leave early I had to wait until 7 o'clock. And I'm thinking, how am I going to run this machine? So thank God my buddies there. They know what I go through. They said, Linda, sit down. Don't worry about it. We'll take care of it for you until 7 o'clock comes, and then you can leave. But the thing is the episode makes me drag at least two days. I can't go to work. I can't do anything.VEDANTAM: A doctor told her she was lactose intolerant. She cut out dairy, but it didn't help. She continued to organize her life around the inevitability of pain. Linda had been suffering for a decade when an opportunity appeared on TV.BONANNO: It was like a commercial. The advertising came on, and my eyes perked. I went, oh, what's this?VEDANTAM: A nearby hospital was conducting a study on patients with intestinal problems. Linda wasn't sure she'd be a good fit, but she figured, hey, you never know. She made an appointment and took some tests. It turned out she was a good fit. She was diagnosed with irritable bowel syndrome, or IBS. A physician gave Linda capsules to take twice a day. But then he told Linda something that dashed her hopes - the capsules she was about to take - they were a placebo.BONANNO: Oh, I was disappointed. I knew it was a sugar pill. Because I graduated from Hesser College (ph) as a medical assistant. So I knew a placebo was a sugar pill. And I thought, he made me come all the way down here to take a sugar pill? (Laughter) I thought to myself, why is he doing this?VEDANTAM: Why tell Linda she was getting a placebo? Wouldn't that undermine the effect of the sugar pill? Well, that's what the study was supposed to test - could a placebo help patients if they knew it was a placebo?(SOUNDBITE OF MUSIC)VEDANTAM: The study had 80 patients and was being run by Ted Kaptchuk. It was an open-label placebo trial - instead of deception, patients would receive what Ted has called radical honesty. The study was based on an insight - the placebo effect wasn't just about the pills. It was about an edifice of drama, rituals and the trust between patients like Linda and their doctors. Even though Linda was disappointed to get a placebo, she followed her doctor's orders.BONANNO: I just took them and went about my day. I said, this is not going to work if it's a sugar pill. And it wasn't until the fourth day I realized I wasn't sick anymore. I said, this can't be.VEDANTAM: Starting on that fourth day, the pain that Linda had suffered through for a decade vanished.(SOUNDBITE OF MUSIC)BONANNO: For three weeks, I felt fantastic. I had no IBS. I wasn't sick. I was taking those pills every day. And I couldn't believe it.VEDANTAM: Many other patients in the study got similar relief. Volunteers who received the open-label placebo reported twice the improvement in their quality of life as those who received no treatment. Now, this was a small study, but Ted has looked at the effects of using open-label placebos for other medical conditions. He's found similar, sometimes even better, results for low back pain and cancer-related fatigue. Placebos administered with radical honesty have the potential to help people.KAPTCHUK: We turned the apple cart over on placebo studies. We said that everything we were saying about placebo before was actually not true, and there's probably more that's not true.(SOUNDBITE OF MUSIC)VEDANTAM: After being on the placebo for three weeks, Linda went back to her doctor. She told him how great she felt. She wanted to keep taking the pills, but the doctor said no. The study protocol only permitted patients to get placebos during the study.BONANNO: He said, no, no, no, I can't let you keep them. I said, what? I said, what am I supposed to do now? He says, well, you'll be fine. And I thought, well, all right. And I'm thinking I'm not going to be fine. I know I'm not going to.VEDANTAM: Linda tried to be optimistic. The first few days, she didn't feel pain, so she thought the pills might have gotten rid of her IBS. But on the fourth day, the pain came back. Linda returned to her old ways of coping - taking anti-diarrhea drugs, restricting her diet, staying away from social activities. It went on for years. Finally, Linda reached out to Ted Kaptchuk. He agreed to take her on as a patient, and he offered to put her on a placebo once again.BONANNO: And then I thought, well, that would be great.VEDANTAM: But then her mind quickly jumped to concern.BONANNO: OK, it worked last time. If I take it again this time, is it going to work? I thought maybe it's not going to do anything second time around, and then I would have been even more disappointed.VEDANTAM: Despite her concerns, she decided to try the placebo again.BONANNO: Because when you're really sick with IBS, you will do and try anything, anything to get rid of the pain and get back to normal. I did whatever these doctors told me to do. And thank God I did because when I went back with Dr. Kaptchuk and he put me back on the placebos, it didn't even take a week, and everything was gone again. And I'm - I still - when I think about it, I'm stunned.(SOUNDBITE OF MUSIC)BONANNO: I don't understand it. I don't - I'm at a point - to tell you the truth (laughter), I don't even care anymore. I just want it to disappear, and that's it.VEDANTAM: Even if Linda didn't fully understand what happened, she has some guesses about what relieved her pain. One vital factor - her deep faith in Ted Kaptchuk.BONANNO: He has a lot of patients. He's extremely intelligent. Something about his personality - very calming. When you talk to him, you feel like you had a complete body massage.VEDANTAM: Contrast this with her impersonal interaction with a doctor who diagnosed her with lactose intolerance.BONANNO: He was the kind of doctor just like a patient at the deli, you know (laughter)?VEDANTAM: Of course, there are still many things we don't know. We don't fully understand why Linda got better on the placebo and why she got worse when she stopped. We don't know how generalizable her experience is to others. Would we get less impressive results if placebos became a common treatment rather than a novel one? What if patients obtain placebos from a pharmacy rather than from a kind doctor in a clinic? There's another problem - for some, the idea that placebos may be helpful is frustrating, even infuriating.In 2018, researchers from Northwestern University published a study showing that sugar pills can be effective in treating some patients who suffer from chronic pain. Some of the very patients who might benefit from that insight, people in chronic pain, took to Facebook to describe how demeaned they felt. One woman wrote, this is one of the worst insults to those with true chronic pain. This kind of pain is not all in their heads. They have real, documented reasons to have moderate to severe pain, and offering a placebo is unethical and a grave insult. Ted understands where such criticism is coming from; people think that if a placebo works, that means a patient was faking or that her suffering wasn't real or that the pain was purely psychological. Ted says nothing could be further from the truth.KAPTCHUK: The placebo effect is not a mind-body New Age mind cure. Those things happen not because you think but because you do. You perform. And you enact. The placebo effect is embodied in what patients and doctors do. It's way below and much stronger than thinking you're going to get better, and you get better.VEDANTAM: Patients aren't the only ones who are skeptical of the placebo effect. Some researchers are, as well.ASBJORN HROBJARTSSON: My name is Asbjorn Hrobjartsson. I'm a professor at the University of Southern Denmark.VEDANTAM: Asbjorn has analyzed hundreds of placebo-controlled studies. In general, he does not find a very strong placebo effect in most of the studies he reviewed.HROBJARTSSON: There is no indication, based on the trials we looked at, that there is a very large effect of placebo on very many patients across very many conditions.VEDANTAM: That said, Asbjorn did find variations in the studies. And in some cases, he did find a large effect. The placebo effect was larger in conditions where patients reported their own outcomes, things like pain and nausea, and smaller in cases where doctors made measurements, things like hypertension. Asbjorn also found what Bruce Moseley discovered in Houston - if a pill produces a small placebo effect, treatments that look and sound dramatic induce bigger effects.HROBJARTSSON: We clearly see that the more theatrical or dramatic placebo, those with kind of - with needling or with machines that make a sound, they tend to have larger effects.VEDANTAM: Most of the studies Asbjorn looked at were testing the efficacy of various drugs. They just had a placebo arm. They were not designed to elicit the placebo effect in the way Ted Kaptchuk has done. They didn't focus on all the rituals around treatment. Asbjorn agrees that studies like those - what are sometimes called active placebo studies - could produce very different results. That's because they're designed to look beyond the effect of pills to activate things like the doctor-patient relationship.(SOUNDBITE OF MUSIC)VEDANTAM: About a year into her second round of placebo treatment, Linda ended up in the hospital for back surgery. She couldn't get to Ted's office to pick up placebo pills. She was worried her IBS would return. But it didn't.BONANNO: Now I don't even take placebos. You know what it's like to be back to normal, to have a normal life like everybody else and never have to think once what condition you're in or if you're going to get sick or what's going to happen? It doesn't even enter my mind.(SOUNDBITE OF MUSIC)VEDANTAM: When we go to a doctor, we need two different things. The first is explicit and obvious - we want someone skilled and knowledgeable who can diagnose us correctly, who knows which pills or procedures are likely to help. But we also have implicit needs. We want someone who can attend to our suffering, not just to our illness. We need someone to trust in moments of fear and vulnerability. We want more than answers. We want reassurance.For overworked doctors and overburdened medical systems, our explicit needs can feel more urgent than our implicit needs. Surgeries and medications can seem more rigorous than the techniques to address our implicit needs - acting and storytelling and rituals. On top of that, these elements of performance may feel unseemly, like the behavior of snake oil salesmen. But when both kinds of needs are met, doctors and patients are more likely to get the outcome they both want - healing.(SOUNDBITE OF MUSIC)VEDANTAM: This week's episode was produced by Rhaina Cohen. It was edited by Tara Boyle and Jenny Schmidt. Special thanks this week to Parth Shah and Angela Hsieh, Patrice Howard, Davis Land and Ted Mebane. Our team includes Thomas Lu, Laura Kwerel, Cat Schuknecht and Lushik Wahba. Our unsung heroes are Barbra Bonsu and Rebecca Mevora (ph). They work at the Wellness Center at NPR's headquarters. While most of us are working from home these days, it's good to know that when we return to the office, we'll have Wellness Center staff to rely on for everything from flu shots to checkups. We're lucky to have them close by and, just as important, to have health care practitioners with a great bedside manner. For more HIDDEN BRAIN, you can follow us on Facebook and Twitter. If liked this episode, please remember to share it with a friend or with your doctor. I'm Shankar Vedantam, and this is NPR.(SOUNDBITE OF MUSIC) Transcript provided by NPR, Copyright NPR.