Introduction and History

The placebo effect itself is elusive. Though we can hope for it, no one can predict it. Even its definition is ambiguous. The placebo pill—and centuries of various snake oils—has nothing to do with the placebo effect, or the difference between the expected effect of a treatment and the one we observe.

The history of placebos is filled with mix-ups and errors. So it is not surprising that the term itself is based on a translation mistake[1]: Jerome was responsible for translating the Bible into Latin (eventually called the Vulgate, meaning it was written in the everyday language of the time), which until then had been in Greek. The soon-to-be saint made a mistake in Psalm 116 (line 9), writing Placebo Domino, "I shall please the Lord," rather than Ambulabo coram Domino, "I shall walk before the Lord." We should really be talking about the ambulabo effect, not the placebo effect! But regardless of the term, the history of the placebo marched ahead all the same.

From the 13th century on, bereaved families would chant the verse to pass the time during the recitation of the Office of the Dead. At some point, people began to mock the chanters, branding them as "placebos" for this apparently bizarre behavior. As society became more secular, the lord lost his capital "L" and Placebo was defrocked, instead donning the dress of the courtier. Decidedly pejorative, the word was then used to refer to flatterers and sycophants; in short, all those who sought to please by any means possible.

In the 16th century, a curious method was used to confuse the possessed: the placebo relic. In order to avoid over-the-top exorcisms administered by overzealous clerics, when an individual showed questionable signs of diabolical possession, he or she would be given false relics. If, upon seeing the relics, the "possessed" acted as if they were authentic, the healer deduced that their seizures were the result of their morbid imagination, not the work of the Devil. The idea of controlling a dubious clinical manifestation by administering a treatment that is both inactive and deceiving probably arose from this practice. Until recently, some doctors used placebos to confuse hypochondriacs whose symptoms closely mimicked those of actual maladies and might be triggered, in a very real way, accidentally. We have since learned that this test is not reliable and that it is even dangerous because organic symptoms can react to placebo while the aforementioned functional symptoms may not respond to it. This could cause delays, or even errors, in diagnosis.

In 1752, James Lind (1716-1794), a Royal Navy doctor, published his A Treatise of the Scurvy after performing, though he didn't know it at the time, the first experiment to use placebo groups. He devoted the rest of his life to trying to convince the Admiralty—and the school of medicine—of the merits of his discovery. Inventor of what would one day be called the "controlled trial," Lind selected 12 sailors suffering from scurvy. He divided them into groups of two, assigning each group one of six different treatments for 15 days: The first group received cider, the second an elixir of vitriol (sulfuric acid), the third vinegar, the fourth seawater, the fifth lemons and oranges, and the last a mixture of garlic, mustard, and horseradish root. The lucky patients belonging to the fifth group healed within days. Cider also performed miracles but not as quickly, it seems. The other four groups were placebo groups, and the assigned treatment proved fatal. From a moral standpoint, one hopes that Lind did not know for certain that four of his six groups received an inactive product, as he did choose substances that at the time were thought to be therapeutic.

Another example involves Franz Anton Mesmer. In 1784, Louis XVI appointed a commission headed by Benjamin Franklin to evaluate the effectiveness of the physician's famous "baquet," a sort of covered tub that allowed Mesmer to perform magnetic passes for several patients at a time. The conclusion was that "all is not imagination, but [that] the imagination is in everything." Again, it is possible that Mesmer acted in good faith and believed that his tub was effective because in reality it is thanks to his own conviction that he generated spectacular cures for his prestigious patients.