As the placebo effect arises out of the patient’s confidence in the treatment, Haygarth wondered about the factors that would increase that confidence and thereby maximize the power of the placebo. He concluded that, among other things, the doctor’s reputation, the cost of the treatment and its novelty could all boost the placebo effect. Many physicians throughout history have been quick to hype their reputations, link high cost with medical potency and emphasize the novelty of their cures, so perhaps they were already aware of the placebo effect. In fact, prior to Haygarth’s experiments, it seems certain that doctors had been secretly exploiting it for centuries. Nevertheless, Haygarth deserves credit for being the first to write about the placebo effect and bringing it out into the open.
Interest in the placebo effect grew over the course of the nineteenth century, but it was only in the 1940s that an American anaesthetist named Henry Beecher established a rigorous programme of research into its potential. Beecher’s own interest in the placebo effect was aroused towards the end of the Second World War, when a lack of morphine at a military field hospital forced him to try an extraordinary experiment. Rather than treating a wounded soldier without morphine, he injected saline into the patient and suggested to the soldier that he was receiving a powerful painkiller. To Beecher’s surprise, the patient relaxed immediately and showed no signs of pain, distress or shock. Moreover, when morphine supplies ran low again, the sly doctor discovered that he could repeatedly play this trick on patients. Extraordinarily, it seemed that the placebo effect could subdue even the most severe pains. After the war, Beecher established a major programme of research at Harvard Medical School, which subsequently inspired hundreds of other scientists around the world to explore the miraculous power of placebos.
As the twentieth century progressed, research into placebo responses threw up some rather shocking results. In particular, it soon became clear that some well-established treatments benefited patients largely because of the placebo effect. For example, in 1986 a study was conducted with patients who had undergone tooth extraction, and who then had their jaw massaged by an applicator generating ultrasound. These sound waves, whose frequency is too high to be heard, could apparently reduce post-operative swelling and pain. Unknown to the patients or the therapists, the researchers tampered with the apparatus so that there was no ultrasound during half of the sessions. Because nobody can hear ultrasound, those patients not receiving ultrasound did not suspect that anything was wrong. Astonishingly, patients described similar amounts of pain relief regardless of whether the ultrasound was on or off. It seemed that the effect of the ultrasound treatment was wholly or largely due to the placebo effect and had little to do with whether the equipment was working. Thinking back to Haygarth’s criteria for a good placebo, we can see that the ultrasound equipment fits the bill — dentists had promoted it as effective, it looked expensive and it was novel.
An even more startling example relates to an operation known as internal mammary ligation, which was used to relieve the pain of angina. The pain is caused by a lack of oxygen, which itself is caused by insufficient blood running through the narrowed coronary arteries. The surgery in question was supposed to tackle the problem by blocking the internal mammary artery in order to force more blood into the coronary arteries. Thousands of patients underwent the operation and afterwards stated that they suffered less pain and could endure higher levels of exercise. However, some cardiologists became sceptical, because autopsies on patients who eventually died revealed no signs of any extra blood flow through the remaining coronary arteries. If there was no significant improvement in blood flow, then what was causing the patients to improve? Could the relief of symptoms be due simply to the placebo effect? To find out, a cardiologist named Leonard Cobb conducted a trial in the late 1950s that today seems shocking.
Patients with angina were divided into two groups, one of which underwent the usual internal mammary ligation, while the other group received sham surgery; this means that an incision was made in the skin and the arteries were exposed, but no further surgery was conducted. It is important to point out that patients had no idea whether they had undergone the real or sham surgery, as the superficial scar was the same for both. Afterwards, roughly three-quarters of the patients in both groups reported significantly lower levels of pain, accompanied by higher exercise tolerance. Incredibly, because both real and sham operations were equally successful, then the surgery itself must have been ineffective and any benefit to the patient must have been induced by a powerful placebo effect. Indeed, the placebo effect was so great that it allowed patients in both groups to reduce their intake of medication.
Although this suggests that the placebo effect is a force for good, it is important to remember that it can have negative consequences. For example, imagine a patient who feels better because of a placebo response to an otherwise ineffective treatment — the underlying problem would still persist, and further treatment might still be necessary, but the temporarily improved patient is less likely to seek that treatment. In the case of mammary ligation, the underlying problem of narrowed arteries and lack of oxygen supply still existed in patients, so they were probably lulled into a false sense of security.
So far, it would be easy to think that the placebo effect is restricted to reducing the experience of pain, perhaps by increasing the patient’s pain threshold through placebo-induced will power. Such a view would underestimate the power and scope of the placebo effect, which works for a wide range of conditions, including insomnia, nausea and depression. In fact, scientists have observed real physiological changes in the body, suggesting that the placebo effect goes far beyond the patient’s mind by also impacting directly on physiology.
Because the placebo effect can be so dramatic, scientists have been keen to understand exactly how it influences a patient’s health. One theory is that it might be related to unconscious conditioning, otherwise known as the Pavlovian response, named after Ivan Pavlov. In the 1890s Pavlov noticed that dogs not only salivated at the sight of food, but also at the sight of the person who usually fed them. He considered that salivating at the sight of food was a natural or unconditioned response, but that salivating at the sight of the feeder was an unnatural or conditioned response, which existed only because the dog had come to associate the sight of the person who fed it with the provision of food. Pavlov wondered if he could create other conditioned responses, such as ringing a bell prior to the provision of food. Sure enough, after a while the conditioned dogs would salivate at the sound of the bell alone. The importance of this work is best reflected by the fact that Pavlov went on to win the Nobel Prize for Medicine in 1904.
Whilst such conditioned salivation might seem very different from the placebo effect on health, work by other Russian scientists then went on to show that even an animal’s immune response could be conditioned. Researchers worked with guinea pigs, which were known to develop a rash when injected with a certain mildly toxic substance. To see if the rash could be initiated through conditioning, they began lightly scratching the guinea pigs prior to giving an injection. Sure enough, they later discovered that merely scratching the skin and not giving the injection could stimulate the same redness and swelling. This was extraordinary — the guinea pig responded to scratching as if it were being injected with the toxin, simply because it had been conditioned to associate strongly the scratching with the consequences of the injection.