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Most of us are familiar with the placebo effect. Dr. Michael H. Berstein explains the “nocebo”…

The term “nocebo effect” derives from the Latin word nocere, which translates roughly as “to harm” (as in the Hippocratic injunction, primum non nocere—first, do no harm). Whereas the better-known placebo effect is typically positive (the alleviation of pain or malaise through treatments that otherwise have no inherent therapeutic value); the nocebo effect is negative, often manifesting as headache, skin irritation, or nausea.

No surprise, then, that the nocebo effect has been called “the placebo effect’s evil twin.” It can be more formally summarized as “the occurrence of a harmful event that stems from conscious or subconscious expectations.” Or, more simply: When you expect to feel sick, you are more likely to feel sick.

Of course, human expectations come up in all sorts of banal, everyday contexts, such as when you tell a friend that you’re stuck in traffic and so he or she should expect your arrival in twenty minutes. But expectation is also an important term of art that academics use (sometimes interchangeably with “expectancy”), having been popularized by Dr. Irving Kirsch, who now serves as Associate Director of the Program in Placebo Studies at Harvard Medical School.

Kirsch’s work built on that of Dr. Henry Beecher, who served with the American military during World War II. While deployed in North Africa and Italy, he gave saltwater to wounded soldiers, but told them they were receiving a powerful painkiller. Beecher did not engage in this deception by choice, but by necessity: As an anesthesiologist treating a flood of battlefield injuries, he faced the difficult task of rationing his supply of morphine.

The roots of our understanding of the nocebo effect are more obscure. But we do find an early precedent involving the work of eighteenth-century German physician Franz Mesmer, best known for his interest in the eponymous proto-hypnotic therapy known as “mesmerism.” In the salons of Paris and Vienna, he promoted the idea that illnesses could be alleviated by using magnets to govern the flow of fluid in patients’ bodies. (If this sounds like obvious quackery, which it is, bear in mind that Mesmer lacked any of our modern-day tools of science. He lived in an era when bloodletting with leeches was still seen as state-of-the-art medical treatment.)

Louis XVI (yes, the French king of guillotine fame) learned of Mesmer’s claims, and (properly) regarded them with skepticism. He established a commission to investigate, led by none other than Benjamin Franklin, who was then serving as the United States Minister to France. The American polymath and Francophile performed what we would now refer to as placebo-controlled studies so as to (as the commission put it) “separate the effects of the imagination from those attributed to magnetism.”…

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… The mind’s unfortunate ability to create suffering ex nihilo can sometimes affect large groups of people though a process of social contagion (or, in the more indelicate language of the past, hysterical contagion). One such example, known as “The June Bug,” occurred in a U.S. textile mill in 1962. Many employees began to feel dizzy and nauseous. Some vomited. Rumors of a mysterious bug that was biting employees began to circulate, and eventually 62 workers became ill. Yet a subsequent Centers for Disease Control and Prevention investigation determined that no bugs could be identified. Nor could investigators find any other physical cause of the illnesses. This type of phenomenon is now referred to as psychogenic illness—sickness caused by belief.

Over the course of history, there have been countless other examples of psychogenic illness, with symptoms ranging from hysterical laughter to seizures. Aldous Huxley, the famed author of Brave New World, described one such seventeenth-century example in his lesser-known historically-based novel, The Devils of Loudun. In the 1630s, as Huxley documents, an entire convent of Ursuline nuns in the western French community of Loudun became convinced that they’d been demonically possessed (complete with convulsions, and other symptoms recognizable to any connoisseur of the modern exorcism-themed horror-movie genre) due to the unholy machinations of a (genuinely licentious) local priest named Urbain Grandier.

Could such a mass outbreak occur today, in an era when few believe in demonic spirits? Consider that during 2016 and 2017, no fewer than 21 American diplomats serving in Cuba reported a range of bizarre neurological symptoms that later came to be collectively described as “Havana Syndrome.” News of the outbreak spread globally through American diplomatic networks, and eventually more than 200 U.S. diplomats became ill. One leading theory was that the Russian government was attacking American embassies and consulates with microwaves.

To be clear: We do not yet know for certain the cause of these ailments. And it is conceivable that speculation concerning Russian involvement may prove correct (even if the microwave theory is far-fetched). That said, the possibility of psychogenic effects is obvious, and I regard it as concerning that this theory seems to have been rejected out of hand by American officials.

In 2021, in fact, a senior State Department official who’d been mandated to oversee the task force investigating Havana Syndrome was pushed out of her role when she refused to take psychogenic illness off the menu of potential causes. A former C.I.A. officer who claimed he’d been affected by Havana Syndrome while serving in Moscow declared that failing to rule out “mass hysteria” as a cause was “grotesquely insulting to victims and automatically disqualifying to lead the task force.”

I suspect that if Ben Franklin were alive today, he might take a different view…

When we experience pain, depression, or illness based on nothing more than negative expectations: “The Placebo Effect’s Evil Twin,” from @mh_bernstein in @Quillette.

Adapted, with permission, from the forthcoming book, The Nocebo Effect: When Words Make You Sick, by Michael H. Bernstein, Ph.D., Charlotte Blease, Ph.D., Cosima Locher, Ph. D., and Walter A. Brown, M.D. Published by Mayo Clinic Press.

* J.M. Coetzee, Waiting for the Barbarians

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As we adjust our attitude, we might recall that it was on this date in 1867 that Joseph Lister published the first of his series of articles in The Lancet on “The Antiseptic Principle of the Practice of Surgery.”  Lister, having noticed that carbolic acid (phenol) was used to deodorize sewage, had experimented with using it to spray surgical instruments, surgical incisions, and dressings.  The result, he reported, was a substantially reduced incidence of gangrene.

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