The Mighty Placebo
A placebo has been defined as “a substance or procedure… that has no active ingredient or process for the condition being treated”.
The case of the likeable Mr Wright
Mr Wright had advanced cancer of the lymph nodes. None of the normal treatments had been exhausted and Wright appeared to have little time left. His neck, armpits, chest, abdomen, and groin were filled with tumours the size of oranges, and his spleen and liver were so enlarged that two quarts of milky fluid had to be drained out of his chest daily.
There was a new drug, heralded as a new wonder drug, being trialled called Krebiozen. Mr Wright heard about the trial and he begged his doctor, Dr Bruno Klopfer to let him try it.
At first the doctor refused because the drug was being tried on people with a life expectancy of at least three months. Finally the doctor gave in and gave Mr Wright an injection of Krebiozen on Friday, but in his heart of hearts he did not expect Wright to last the weekend.
To his surprise, on the following Monday he found Mr Wright out of bed and walking around. Dr Klopfer reported that his tumours had ‘melted like snowballs on a hot stove’ and were half their original size.
Ten days after Wright’s first treatment, he left the hospital and was, as far as his doctors could tell, cancer free. When he entered the hospital he had needed an oxygen mask to breathe, but when he left, he was well enough to fly his own plane at 12,000 feet with no discomfort.
Mr Wright remained well for about two months, but then the newspapers began to publish articles stating that Krebiozen had not lived up to it’s expectancy and had no effect on cancer.
Mr Wright, who was very logical and scientific in his thinking, relapsed and became very depressed, and was readmitted to the hospital.
Fascinated by the earlier results Dr Klopfer decided to experiment. He told Mr Wright that the initial batch was faulty and that a new refined batch had been received and could treat Mr Wright with this.
He then proceeded to give Mr Wright a course of injections of the new drug. However the physician used only plain water and went through an elaborate procedure before injecting Wright with the placebo.
Once again the results were dramatic as tumour masses melted, chest fluid vanished, and Mr Wright was quickly back on his feet and feeling great.
He remained symptom-free for another two months, but then the AMA announced that a nationwide study of Krebiozen had found the drug worthless for the treatment of cancer. This time Wright’s faith was completely shattered. His cancer blossomed anew
The Origins of the Placebo
The roots of the placebo problem can be traced to a lie told by an Army nurse during World War II as Allied forces stormed the beaches of southern Italy. The nurse was assisting an anaesthetist named Henry Beecher, who was tending to US troops under heavy German bombardment. When the morphine supply ran low, the nurse assured a wounded soldier that he was getting a shot of potent painkiller, though her syringe contained only salt water. Amazingly, the bogus injection relieved the soldier’s agony and prevented the onset of shock.
Returning to his post at Harvard after the war, Beecher became one of the nation’s leading medical reformers. Inspired by the nurse’s healing act of deception, he launched a crusade to promote a method of testing new medicines to find out whether they were truly effective. At the time, the process for vetting drugs was sloppy at best: Pharmaceutical companies would simply dose volunteers with an experimental agent until the side effects swamped the presumed benefits. Beecher proposed that if test subjects could be compared to a group that received a placebo, health officials would finally have an impartial way to determine whether a medicine was actually responsible for making a patient better.
In a 1955 paper titled “The Powerful Placebo,” published in The Journal of the American Medical Association, Beecher described how the placebo effect had undermined the results of more than a dozen trials by causing improvement that was mistakenly attributed to the drugs being tested. He demonstrated that trial volunteers who got real medication were also subject to placebo effects; the act of taking a pill was itself somehow therapeutic, boosting the curative power of the medicine. Only by subtracting the improvement in a placebo control group could the actual value of the drug be calculated.
Arthroscopic Surgery For Osteoarthritis Of The Knee
In a controlled trial of arthroscopic surgery for osteoarthritis of the knee, New England Journal of Medicine in 2002 comparing placebo surgery with 2 different surgical interventions concluded that “In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.”
An interesting statistic has shown that virtually all newly introduced surgical techniques show a decrease in success over time. Is this also a placebo response?
In 1961 Henry K. Beecher found that surgeons he categorized as enthusiasts relieved their patients’ chest pain and heart problems more than skeptic surgeons. In 1961 Walter Kennedy introduced the word nocebo. Beginning in the 1960s, the placebo effect became widely recognized and placebo controlled trials became the norm in the approval of new medications. Later, researchers became interested in understanding the placebo effect, rather than just controlling for its effects, and in 2011, a Program in Placebo Studies was established at the Harvard Medical School.
Studies on Anti-Depressant drug treatments.
These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients.
The findings also show that the effect for these latter patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective.
In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to
 (Brono Klopfer, Psychological Variables in Human Cancer, Journal of Prospective Techniques 31, 1957, pp. 331-40.)
 N Engl J Med 2002; 347:81-88July 11, 2002