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. 

The History of the Double-Blind Experiment
visitor takes a phone photograph of a large back lit image of the Large Hadron Collider (LHC) at the Science Museum's 'Collider' exhibition on November 12, 2013 in London, England. Peter Macdiarmid/Getty Images

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. 


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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Inventions with revolutionary potential made by a mysterious aerospace engineer for the U.S. Navy come to light.

U.S. Navy ships

Credit: Getty Images
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7 most notorious and excessive Roman Emperors

These Roman Emperors were infamous for their debauchery and cruelty.

Nero's Torches. A group of early Christian martyrs about to be burned alive during the reign of emperor Nero in 64 AD.

1876. Painted by Henryk Siemiradzki.
Politics & Current Affairs
  • Roman Emperors were known for their excesses and violent behavior.
  • From Caligula to Elagabalus, the emperors exercised total power in the service of their often-strange desires.
  • Most of these emperors met violent ends themselves.

We rightfully complain about many of our politicians and leaders today, but historically speaking, humanity has seen much worse. Arguably no set of rulers has been as debauched, ingenious in their cruelty, and prone to excess as the Roman Emperors.

While this list is certainly not exhaustive, here are seven Roman rulers who were perhaps the worst of the worst in what was one of the largest empires that ever existed, lasting for over a thousand years.

1. Caligula

Officially known as Gaius (Gaius Caesar Augustus Germanicus), Caligula was the third Roman Emperor, ruling from 37 to 41 AD. He acquired the nickname "Caligula" (meaning "little [soldier's] boot") from his father's soldiers during a campaign.

While recognized for some positive measures in the early days of his rule, he became famous throughout the ages as an absolutely insane emperor, who killed anyone when it pleased him, spent exorbitantly, was obsessed with perverse sex, and proclaimed himself to be a living god.

Caligula gives his horse Incitatus a drink during a banquet. Credit: An engraving by Persichini from a drawing by Pinelli, from "The History of the Roman Emperors" from Augustus to Constantine, by Jean Baptiste Louis Crevier. 1836.

Among his litany of misdeeds, according to the accounts of Caligula's contemporaries Philo of Alexandria and Seneca the Younger, he slept with whomever he wanted, brazenly taking other men's wives (even on their wedding nights) and publicly talking about it.

He also had an insatiable blood thirst, killing for mere amusement. Once, as reports historian Suetonius, when the bridge across the sea at Puteoli was being blessed, he had a number of spectators who were there to inspect it thrown off into the water. When some tried to cling to the ships' rudders, Caligula had them dislodged with hooks and oars so they would drown. On another occasion, he got so bored that he had his guards throw a whole section of the audience into the arena during the intermission so they would be eaten by wild beasts. He also allegedly executed two consuls who forgot his birthday.

Suetonius relayed further atrocities of the mad emperor's character, writing that Caligula "frequently had trials by torture held in his presence while he was eating or otherwise enjoying himself; and kept an expert headsman in readiness to decapitate the prisoners brought in from gaol." One particular form of torture associated with Caligula involved having people sawed in half.

He caused mass starvation and purposefully wasted money and resources, like making his troops stage fake battles just for theater. If that wasn't enough, he turned his palace into a brothel and was accused of incest with his sisters, Agrippina the Younger, Drusilla, and Livilla, whom he also prostituted to other men. Perhaps most famously, he was planning to appoint his favorite horse Incitatus a consul and went as far as making the horse into a priest.

In early 41 AD, Caligula was assassinated by a conspiracy of Praetorian Guard officers, senators, and other members of the court.

2. Nero

Fully named Nero Claudius Caesar, Nero ruled from 54 to 68 AD and was arguably an even worse madman than his uncle Caligula. He had his step-brother Britannicus killed, his wife Octavia executed, and his mother Agrippina stabbed and murdered. He personally kicked to death his lover Poppeaea while she was pregnant with his child — a horrific action the Roman historian Tacitus depicted as "a casual outburst of rage."

He spent exorbitantly and built a 100-foot-tall bronze statue of himself called the Colossus Neronis.

He is also remembered for being strangely obsessed with music. He sang and played the lyre, although it's not likely he really fiddled as Rome burned in what is a popular myth about this crazed tyrant. As misplaced retribution for the fire which burned down a sizable portion of Rome in the year 64, he executed scores of early Christians, some of them outfitted in animal skins and brutalized by dogs, with others burned at the stake.

He died by suicide.

Roman Emperor Nero in the burning ruins of Rome. July 64 AD.Credit: From an original painting by S.J. Ferris. (Photo by Kean Collection / Getty Images)

3. Commodus

Like some of his counterparts, Commodus (a.k.a. Lucius Aelius Aurelius Commodus) thought he was a god — in his case, a reincarnation of the Greek demigod Hercules. Ruling from 176 to 192 AD, he was also known for his debauched ways and strange stunts that seemed designed to affirm his divine status. Numerous statues around the empire showed him as Hercules, a warrior who fought both men and beasts. He fought hundreds of exotic animals in an arena like a gladiator, confusing and terrifying his subjects. Once, he killed 100 lions in a single day.

Emperor Commodus (Joaquin Phoenix) questions the loyalty of his sister Lucilla (Connie Nielsen) In Dreamworks Pictures' and Universal Pictures' Oscar-winning drama "Gladiator," directed by Ridley Scott.Credit: Photo By Getty Images

The burning desire to kill living creatures as a gladiator for the New Year's Day celebrations in 193 AD brought about his demise. After Commodus shot hundreds of animals with arrows and javelins every morning as part of the Plebeian Games leading up to New Year's, his fitness coach (aptly named Narcissus), choked the emperor to death in his bath.

4. Elagabalus

Officially named Marcus Aurelius Antoninus II, Elagabalus's nickname comes from his priesthood in the cult of the Syrian god Elagabal. Ruling as emperor from 218 to 222 AD, he was so devoted to the cult, which he tried to spread in Rome, that he had himself circumcised to prove his dedication. He further offended the religious sensitivities of his compatriots by essentially replacing the main Roman god Jupiter with Elagabal as the chief deity. In another nod to his convictions, he installed on Palatine Hill a cone-like fetish made of black stone as a symbol of the Syrian sun god Sol Invictus Elagabalus.

His sexual proclivities were also not well received at the time. He was likely transgender (wearing makeup and wigs), had five marriages, and was quite open about his male lovers. According to the Roman historian (and the emperor's contemporary) Cassius Dio, Elagabalus prostituted himself in brothels and taverns and was one of the first historical figures on record to be looking for sex reassignment surgery.

He was eventually murdered in 222 in an assassination plot engineered by his own grandmother Julia Maesa.

5. Vitellius

Emperor for just eight months, from April 19th to December 20th of the year 69 AD, Vitellius made some key administrative contributions to the empire but is ultimately remembered as a cruel glutton. He was described by Suetonius as overly fond of eating and drinking, to the point where he would eat at banquets four times a day while sending out the Roman navy to get him rare foods. He also had little social grace, inviting himself over to the houses of different noblemen to eat at their banquets, too.

Vitellius dragged through the streets of Rome.Credit: Georges Rochegrosse. 1883.

He was also quite vicious and reportedly either had his own mother starved to death or approved a poison with which she committed suicide.

Vitellius was ultimately murdered in brutal fashion by supporters of the rival emperor Vespasian, who dragged him through Rome's streets, then likely beheaded him and threw his body into the Tiber river. "Yet I was once your emperor," were supposedly his last words, wrote historian Cassius Dio.

6. Caracalla

Marcus Aurelius Antoninus I ruled Rome from 211 to 217 AD on his own (while previously co-ruling with his father Septimius Severus from 198). "Caracalla"' was his nickname, referencing a hooded coat from Gaul that he brought into Roman fashion.

He started off his rise to individual power by murdering his younger brother Geta, who was named co-heir by their father. Caracalla's bloodthirsty tyranny didn't stop there. He wiped out Geta's supporters and was known to execute any opponents to his or Roman rule. For instance, he slaughtered up to 20,000 citizens of Alexandria after a local theatrical satire dared to mock him.

Geta Dying in His Mother's Arms.Credit: Jacques Pajou (1766-1828)

One of the positive outcomes of his rule was the Edict of Caracalla, which gave Roman citizenship to all free men in the empire. He was also known for building gigantic baths.

Like others on this list, Caracalla met a brutal end, being assassinated by army officers, including the Praetorian prefect Opellius Macrinus, who installed himself as the next emperor.

7. Tiberius

As the second emperor, Tiberius (ruling from 42 BC to 16 AD) is known for a number of accomplishments, especially his military exploits. He was one of the Roman Empire's most successful generals, conquering Pannonia, Dalmatia, Raetia, and parts of Germania.

He was also remembered by his contemporaries as a rather sullen, perverse, and angry man. In the chapter on his life from The Lives of the Twelve Caesars by the historian Suetonius, Tiberius is said to have been disliked from an early age for his personality by even his family. Suetonius wrote that his mother Antonia often called him "an abortion of a man, that had been only begun, but never finished, by nature."

"Orgy of the Times of Tiberius on Capri".Painting by Henryk Siemiradzki. 1881.

Suetonius also paints a damning picture of Tiberius after he retreated from public life to the island of Capri. His years on the island would put Jeffrey Epstein to shame. A horrendous pedophile, Tiberius had a reputation for "depravities that one can hardly bear to tell or be told, let alone believe," Suetonius wrote, describing how "in Capri's woods and groves he arranged a number of nooks of venery where boys and girls got up as Pans and nymphs solicited outside bowers and grottoes: people openly called this 'the old goat's garden,' punning on the island's name."

There's much, much more — far too salacious and, frankly, disgusting to repeat here. For the intrepid or morbidly curious reader, here's a link for more information.

After he died, Tiberius was fittingly succeeded in emperorship by his grandnephew and adopted grandson Caligula.

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New studies stretch the boundaries of physics, achieving quantum entanglement in larger systems.

Entangled drumheads.

Credit: Aalto University.
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