The History of the Double-Blind Experiment

In a time when many agencies and researchers are threatened, let's remember how the scientific method originated. 

As scientists, researchers, doctors, and science fans are taking the spotlight with initiatives like the March for Science on April 22, it’s a good time to reflect on the scientific method—in this case, the double-blind experiment—originated. Forward thinkers in France and England developed the method over a matter of decades; it has since been the crowning achievement in how we approach and understand medicine.


The image to mind is a mad scientist chasing lighting with a kite. Benjamin Franklin might have had a bit of craziness in him, but for an inventor in the eighteenth century to succeed a little suspension of disbelief was necessary. In 1784, while serving as an American ambassador to France, the Académie des Sciences asked Franklin to co-chair a commission on animal magnetism. The claim that invisible forces exerted by animals provide therapeutic relief in humans was first made by German physician Franz Mesmer; the term mesmerism is alternately used to describe this supposed phenomenon. Mesmer’s ideas influenced medical practices for nearly a century in Europe and the United States. Even today this form of vitalism is still regarded as potent spirit medicine in New Age circles.

Franklin teamed up with French chemist Antoine Lavoisier to investigate this claim. Without realizing it the team would define the future of medical science by creating the first blind trial. Mesmerists were given flasks filled with vital fluids to find out if the essence of certain objects, such as trees, would improve their health. The answer was a resounding no. The team then investigated the healing potential of mesmerism and inadvertently discovered a peculiar aspect of human psychology and physiology: the placebo effect. As biographer Richard Holmes writes regarding their increased health, “It was simply because the patients believed they would be cured.”

During this time Humphry Davy was only six years old, but fifteen years later the Cornish chemist would help revolutionize the blind experimental method. Just entering the second decade of his life, the small and volatile scientist was already critical of Lavoisier’s theories on chemistry. A voracious reader, he taught himself much of what he knew about chemistry, which was a lot: he was the man who first isolated potassium, sodium, calcium, barium, and magnesium, among others. He discovered chlorine and iodine. He invented an early miner’s lamp and a prototype of an incandescent light bulb. Notoriously vain, he spent as much time writing poetry as playing with gases in his laboratory. While he had a nearly mystical affinity for earthly elements, he was also an early proponent that if properly understood, neurochemical reactions could very well describe the innumerable functions of the human brain.

Science was flourishing in the last decades of the eighteenth century. Davy was an early proponent of gases and spent years exploring potent combinations, a few of which nearly killed him. (The Bunsen burner experiment in which every young student holds iron gauze to observe how the flame does not pass through? Thanks Humphry.) In 1799 Davy began inhaling compounds, such as carbon dioxide, carbon monoxide, and hydrogen to note the bodily effects. He powered through the intense migraines and stomach cramps that followed in the name of science. Then he hit upon a peculiar gas that brought him great pleasure: nitrous oxide. (Ironically, I would unknowingly repeat Davy’s experiments a number of times in college, though I was not as meticulous in my note keeping.)

Whereas carbon monoxide nearly killed him, he eventually consumed up to eighty quarts of nitrous over a seventy-five minute period. Yes, eighty. And I thought a full balloon was intense. This superman of the gaseous world became the life of the party. For a over a year he consumed it regularly, subsequently measuring respiration rates of test subjects in series of blind, controlled studies. While he eventually abandoned nitrous as a therapeutic tool to pursue his newfound passion of voltaic batteries, his experiments led to two important discoveries.

First, it helped spur the invention of modern anaesthesia, which revolutionized surgeries worldwide. Humans had been trying for millennia to sedate patients with a variety of sedatives—alcohol, opium, mandrake, ether—to varying degrees of success. Davy’s enthusiasm for nitrous inspired others to pursue this line of enquiry; it remains in use today. No longer were amputations and cancer extractions done consciously. Today ‘going under’ is routine in many surgeries and procedures. We probably don’t realize what a luxury it is in the history of medicine.

Davy’s nitrous explorations also helped make the blind experiment mainstream. It is now the basis of any credible scientific study. The simple yet elegant double-blind experiment is the gold standard of modern medicine. Whereas the single-blind trial that Franklin and Lavoisier spearheaded, and Davy utilized often, means the subjects do not know if they’re getting an actual drug or a placebo, in a double-blind trial the researchers themselves don’t know either. Researchers leading single-blind trials may either consciously or unconsciously influence the reactions, and therefore results, by leading subjects in certain directions. This could occur through facial expressions or incriminating words, or, if the researcher has a vested interest in the results, which is common in an age when pharmaceutical companies foot the bill for experiments on potential drugs, they might purposefully lead the subject toward their objective. The first double-blind study was conducted in 1907 on the effects of caffeine—yet another substance I’ve long experimented with on myself.

By the time Davy’s results on his ten months of nitrous experiments were published in book form he’d already emotionally and mentally moved on. Researches Chemical and Philosophical chiefly Concerning Nitrous Oxide or Dephlogisticated Nitrous Air, and its Respiration was published in 1800 by the same man that committed to page the words of Wordsworth and Coleridge. It included personal accounts of inhalation sessions, which created the largest public stir. Davy also gassed up cats, rabbits, and dogs, which in hindsight was not the best idea as some died as a result. This did have the beneficial result that Davy began to contemplate the nature of pain, which influenced his later work.

Davy’s nitrous fascination lasted a year-and-a-half. While discouraged that he did not find the results he desired—nitrous as a potent therapeutic medicine—his empirical approach to his work steeled his resolve. Most importantly he did not finagle results to fit his preconceived notion of what this and other gases accomplish. He was an exemplar of good science by letting the data write the narrative—and he kept reams of data, scrupulous and meticulous when keeping track in his notebooks. He loathed those who let theories guide their research, which he knew was a sure way of skewing evidence. Arrogant as he could be socially and personally, his great muse, science, had to be honored on its own terms, not on his. Such a mindset requires extreme discipline and a willingness to admit fault. In the two centuries since, humans continue to worship false gods that they call facts—or, more troublingly, eschew facts completely.

For science to work we need to move out of the way of ourselves and observe the data. Right now too many emotionally stunted and corporate-backed obstacles stand in the way of that. Given how long this journey has taken in the history our species, running backwards is destructive. Remembering those who persevered—Davy was called plenty of names in his day—is a catalyst to those that continue to march forward. 

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Derek's next book, Whole Motion: Training Your Brain and Body For Optimal Health, will be published on 7/4/17 by Carrel/Skyhorse Publishing. He is based in Los Angeles. Stay in touch on Facebook and Twitter.

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17th August 1973: An American tattoo artist working on a client's shoulder. (Photo by F. Roy Kemp/BIPs/Getty Images)
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In the slightly macabre experiment to find out where tattoo ink travels to in the body, French and German researchers recently used synchrotron X-ray fluorescence in four "inked" human cadavers — as well as one without. The results of their 2017 study? Some of the tattoo ink apparently settled in lymph nodes.


Image from the study.

As the authors explain in the study — they hail from Ludwig Maximilian University of Munich, the European Synchrotron Radiation Facility, and the German Federal Institute for Risk Assessment — it would have been unethical to test this on live animals since those creatures would not be able to give permission to be tattooed.

Because of the prevalence of tattoos these days, the researchers wanted to find out if the ink could be harmful in some way.

"The increasing prevalence of tattoos provoked safety concerns with respect to particle distribution and effects inside the human body," they write.

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Image by authors of the study.

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The study's authors will keep working on this in the meantime.

“In future experiments we will also look into the pigment and heavy metal burden of other, more distant internal organs and tissues in order to track any possible bio-distribution of tattoo ink ingredients throughout the body. The outcome of these investigations not only will be helpful in the assessment of the health risks associated with tattooing but also in the judgment of other exposures such as, e.g., the entrance of TiO2 nanoparticles present in cosmetics at the site of damaged skin."

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