The year was 1810, and English novelist and diarist Frances Burney began to feel a small pain in her breast. Her doctors told her that “the evil was too far advanced for any remedy,” she revealed in a letter to her sister.1 The only recourse was to surgically remove the tumor. “You must expect to suffer,” they warned. She drafted her will as a precaution, while others equipped her home in Paris with the necessary bandages, compresses, and other preparations; the sight of which made her sick. “I walked backwards and forwards till I quieted all emotion, and became, by degrees, nearly stupid—torpid,” she wrote. The doctors set up an operating table in her salon. “I now began to tremble violently, more with distaste and horror of the preparations even than of the pain.” For a moment she peered at the door, then the windows, with thoughts of escaping. When reason took over, she climbed onto the mattress, and one surgeon placed a cambric handkerchief over her face. Through the transparent fabric she witnessed seven doctors and a nurse surround her. “I saw the glitter of polished Steel—I closed my Eyes.” From the moment the implement pierced her flesh, she described screaming unremittingly. “I then felt the Knife rackling against the breast bone—scraping it!—This performed, while I yet remained in utterly speechless torture.” Every time they withdrew the instrument, she hoped the ordeal would be over, but then the cutting would begin again.
In the era before anesthesia, torturous operations like these were not only difficult for the patients, but doctors struggled emotionally with them too.2 Burney’s surgeon had tears in his eyes when he informed her about the need for surgery, and his complexion turned ash-pale moments before the operation, she wrote. The lack of pain relief also meant ambitious or time-consuming operations were off the table. “You could lance a boil, you could pull a tooth, and do these minor procedures, mostly because they were quick, and so the pain that the patient experienced was brief,” said Talmage Egan, an anesthesiologist at the University of Utah. “If you were really quick, the most ambitious thing that could be done was the amputation of a limb, which required a bunch of people to hold you down,” he added. Some would try to show mercy by rushing procedures, including one surgeon who sawed off a leg in under 30 seconds.3 “A fast surgeon was considered a good surgeon,” said Ken Solt, an anesthetist at Massachusetts General Hospital.
Thomas Rowlandson's depiction of an amputation in 1875 captured the macabre suffering of the patient.
The Elisha Whittelsey Collection, The Elisha Whittelsey Fund, 1959 (Public Domain)
Physicians tried multiple tactics to knock out patients. Stephanie Snow, a historian of medicine at the University of Manchester, said, “If you bleed a patient in advance of an operation till they essentially faint, that was one way of reducing sensation.” She added that “surgeons pioneered using clamps to try and deaden sensation, but patients felt they were as bad as the pain of surgery itself.” Some Arabic medical texts dating back to 1000 CE showed that patients inhaled a “soporific” sponge of herbal mixtures, including opium or mandrake, though there is scant evidence that it was effective; however, “it was very easy to overdose from using those sorts of heavy opiates,” Snow said.4
Three decades after Burney’s operation, doctors mastered the art of rendering patients into an unconscious, pain-free, and amnesic state, doing away with the torturous butchery.
Scottish surgeon Robert Liston, also known as “the fastest knife in the West End,” is infamous for performing a surgery with a 300 percent death rate: While rushing an amputation, he accidentally slashed his assistant's fingers and a spectator's coat tails. The patient and assistant later died of gangrene, and the spectator died of shock on the spot.26
Painted by Ernest Board circa 1912, Wellcome Collection (CC BY 4.0)
“Anesthesia just absolutely radically changed surgery and medicine forever,” said Melissa Coleman, a pediatric anesthesiologist at the University of Minnesota and president of the Wood Library-Museum of Anesthesiology. It all began when one dentist spotted the pain-relieving properties of a pair of recreational drugs that people had taken for decades.5
The Feud Over the First Anesthetic
When naturalists discovered different gases during the Enlightenment, they found that some could cause a state of euphoria, such as nitrous oxide (laughing gas) or diethyl ether (often just called ether), and these drew crowds to “laughing gas parties” and “ether frolics.”6 People took these gases as part of traveling shows, which a dentist from Connecticut named Horace Wells attended. Having performed countless agonizing tooth extractions, Wells marveled at the site of a young man on stage who inhaled laughing gas yet showed no sign of pain upon battering his shin against a bench.7
Wells wondered if nitrous oxide could relieve pain during a tooth extraction and decided to be the subject of his own experiment. He inhaled the gas, and then a colleague removed one of Wells’s teeth, which indeed turned out to prove painless.7 He began using nitrous oxide in his practice until he felt confident enough to showcase its effects to other physicians in an operating theater. Unfortunately, his demonstration subject let out a cry during the tooth extraction, and his fellow physicians shouted insults at him and ruled the showcase a “humbug.”8
“It actually was successful,” Coleman said. “When they asked the patient afterwards, he didn't remember anything, and so it just had an appearance of failure,” she added. Wells’s mistake was choosing nitrous oxide because he deemed it safer than ether, Coleman said. Egan explained that nitrous oxide isn’t strong enough to produce a complete state of general anesthesia. One of Wells’s students, William Morton, wondered if ether would be a better substitute. A second public demonstration was underway, in which Morton showcased ether’s anesthetic effects while delivering the gas to a patient undergoing a neck-tumor removal at Massachusetts General Hospital. “Gentlemen, this is no humbug,” one of the surgeons proclaimed, turning to the stunned audience.9
“It's hard to fully appreciate just how momentous that occasion was,” Egan said. The date of the second demonstration, October 16, 1846, is now celebrated as “Ether Day,” and Egan said it marked a twin birth of anesthesia and modern surgery.
Before nitrous oxide was used to numb pain during tooth extractions, people would inhale copious volumes at laughing gas parties.
William Combe, Wellcome Collection (Public domain)
Wells did not take well to the backlash from his failed demonstration, nor to learning that his peers attributed the discovery of ether’s anesthetic properties to his former student. Retrospective analyses of his life suggest he suffered major depressive disorder as a result, during which he began abusing anesthetics like ether and chloroform (trichloromethane).10 Two years after Ether Day, on Wells’s birthday, police arrested him for throwing vitriol (sulfuric acid) on a woman while under the influence of chloroform. Other women came forward to report similar assaults during his hearing. Once he sobered up in his cell at The Tombs Prison in New York, he developed overwhelming regret. He committed suicide by slitting his leg veins with a razor, inhaling chloroform to withstand the pain.11
As for Morton, he didn’t profit as much as he hoped from Ether Day: He tried to pass off ether as his “invention” and patented it alongside other chemicals under the name “Letheon,” but his contemporaries overlooked his patent and used ether on its own.12
Though researchers often regard Ether Day as the first demonstration of anesthesia, doctors in other parts of the world had made similar, independent discoveries that predate the famous event. Japanese doctor Seishu Hanaoka had pioneered the use of a drinkable general anesthetic made from plants called Mafutsusan (Tsūsensan) in 1795.13 In 1805, a few years before Burney’s tortuous mastectomy in France, Hanaoka successfully used Mafutsusan to anesthetize a breast cancer patient during a similar tumor-removal operation, meaning Burney may not have needed to suffer if her surgeons had known of this concoction.14 Doctors no longer use this anesthetic because it took hours to sedate the patient and sometimes elicited side effects such as permanent blindness, but Japanese doctors often used it until the arrival of inhalation anesthetics after Ether Day.15
Japanese doctors used Mafutsusan to extinguish pain during breast cancer operations long before ether's popularity.
Wellcome Collection (CC BY 4.0)
The use of ether and other inhaled anesthetics didn’t immediately take off. “In the US it was a slow building of prominent physicians that endorsed it,” Coleman said. Anesthesia faced resistance from some doctors who regarded pain as a “vital force.”16 “Certainly, the idea that there was something either therapeutic or necessary about the pain remained for a long time,” she added.
Queen Victoria was central to popularizing anesthesia across the pond. Upon hearing news of Ether Day, British doctor John Snow began experimenting with ether and other gases, including chloroform. He used this drug to knock out Queen Victoria during the birth of her seventh child, Leopold.17 Shortly after, inhalation anesthetics became mainstream in surgeries. “If it's good enough for the queen, it's good enough for us,” Egan said.
War, Truth Serum, and Dart Poison
Ether still remained the choice anesthetic for some time. “The disadvantage with chloroform was that it precipitated arrhythmias of your heart if you were anxious,” said Jamie Sleigh, an anesthesiologist at the University of Auckland who holds patents for some anesthetics.
Then, the World Wars begot intravenous (IV) anesthetics. Ether flasks were too bulky to carry around field hospitals where soldiers needed treatment, Sleigh said. The first IV anesthetics developed in the 1920s and 1930s included barbiturates like sodium thiopental, which was sometimes called “truth serum,” though this property has been dismissed.18,19 Later, in the 1970s, a drug called propofol took over as the go-to choice.20 “Propofol makes people wake up feeling happy and less nauseous,” Sleigh said, adding that the body breaks it down much more quickly than sodium thiopental, so patients wake up quicker when the flow stops.
Beyond the battlefield, IV anesthetics had staying power because they anesthetized patients in seconds. Inhalation anesthetics, by contrast, would take minutes to kick in, causing distress to patients in the meantime. “They would often get combative and disoriented, and they would fight with you,” Egan said. Today, doctors typically use a combination, starting with IV anesthetics to induce anesthesia, followed by gases to maintain the state, he added.
But the gases required innovations too. “The big problem with ether is that it was flammable,” Egan said. “This was actually a very big deal because you had oxygen being administered in operating rooms” through gas masks, and doctors would use an ignition source to heat up a metal rod that could pierce through flesh, so there were all of the ingredients for a fire, Egan said. Chemists began exploring the use of non-flammable chemicals instead, by adding flame-retardant halogens, like fluorine, to organic compounds. This led to the invention of halothane in 1951, the first non-flammable inhalation anesthetic.21 “That was found to have pretty severe liver and cardiac effects in some people,” Coleman said, so less toxic inhalation anesthetics were developed soon after.
Even though surgeries were no longer limited to rushed amputations, some operations remained impossible. Solt said, “If you cut into someone's abdomen, there's this reflex where the muscles are going to tense up, but you need them to relax.” That changed when an American adventurer named Richard Gill traveled to the Amazon jungle in search for curare, a plant-derived poison used in blowgun darts.22 Curare blocks signals passing from nerves to muscles. Wondering if this poison could serve as a muscle relaxant, Gill learned from Ecuadorian locals how to purify the substance and brought it back to the United States. There, the pharmaceutical company E.R. Squibb and Sons developed derivates suitable for surgery. Egan said these neuromuscular blockers are often used in surgeries where movement must be completely halted, such as during eye operations.
Until the introduction of muscle relaxants, another problem with anesthesia had slipped under the radar. Doctors administered inhalation anesthetics to patients through gas masks, but Coleman said they did not consider that the dose of the drugs would depend on the breathing rate and lung volume of each patient. This meant an individual who breathed more heavily received a higher dose than one who breathed lightly. This only became obvious once muscle relaxants induced apnea, a temporary breathing halt, waking patients and bringing the issue to light, Coleman explained.
Doctors solved this problem with intubation. As opposed to a gas mask, an endotracheal tube ensured a fixed dose of oxygen and drugs were delivered directly to the lungs throughout an operation. Masks had other faults, too. “It was hard to breathe by mask for three or four hours, and their stomach would get full of gas, and then they would vomit, and that vomit would go into their lungs,” Egan explained. The intubation tube ensured the gas traveled to the lungs rather than the stomach, and a balloon inflated in the windpipe prevented vomit from inundating the airways, Egan explained.
Doctors continue to give patients gases to maintain the anesthetic state during surgeries.
Wikimedia Commons, United States Navy (Public domain)
As anesthesia progressed, doctors would provide multiple drugs to patients to achieve anesthesia. For example, surgeons used opioids to provide pain relief once the patients were rendered unconscious with drugs like propofol.23 Sleigh explained that highly addictive opioids like fentanyl don’t produce euphoria or addiction when administered to unconscious, amnesic patients; their addictive properties are only a concern when used to manage pain in awake patients after their operations.
Once multiple drugs that could trigger anesthesia were developed, the practice became a lot safer and the number of accidental deaths plummeted, Solt said.24 Most anesthetics have a narrow therapeutic index, meaning the dose that achieves anesthesia is close to the lethal dose, making them risky. However, Solt noted that if you use a combination of drugs to achieve anesthesia, you can lower the dose of each drug, rendering the process safer. Rather than achieving unconsciousness, amnesia, and pain relief with a high dose of ether, doctors can use lower doses of propofol, anesthetic gases, and opioids, as well as muscle relaxants to ease tension.
Besides working with a bevy of drugs, anesthesiologists improve safety by using technical equipment to monitor vital signs and brain waves throughout an operation, tailoring the anesthetic doses for each patient based on their readings. Egan said that, like flight pilots, anesthesiologists simulate crash scenarios during training, so they know how to react if a patient responds poorly to drugs.
Anesthesiologists are now trying to find other drugs to add to the mix that can wake patients up from their anesthetized state, some of which Solt has patented. “The current practice is to wait for drugs to wear off, and what we're trying to do is change that paradigm and develop reversal agents so that you can wake up on demand,” Solt said. There are some situations in which it would be helpful to wake up a patient immediately, Solt explained, such as if they stop breathing and need to be awake for doctors to adjust the breathing tube, or if they need to perform a behavioral exam immediately after brain surgery.
The Path from Pain to Peaceful Surgeries
Starting off with crude, recreational gases, anesthesia evolved into a highly sophisticated specialty. Sleigh has witnessed this change throughout his lifetime. The first time he gave an anesthetic was as a medical student in Lesotho in the 1980s, and he used a single drug infused on a cloth. “The last anesthetic I gave was a couple of years ago, where the monitoring equipment basically filled this huge theater.”
Surgeons have come a long way from Burney’s wide-awake breast-cancer operation, which lasted a grueling 20 minutes, during which she fainted twice.1 Her strength was annihilated by the end. “I was obliged to be carried, and could not even sustain my hands and arms, which hung as if I had been lifeless; while my face, as the Nurse has told me, was utterly colourless,” Burney wrote. Snow said, “Her description of the pain is beyond anything imaginable, and it was six months before she was able to even recollect or write about it.”
Every year, over 100,000 women in the United States undergo a mastectomy, but none of them suffer the agony that Burney endured. Her operation was viewed as a dangerous last resort, whereas today’s surgeons readily perform mastectomies even in early stages of breast cancer to boost survival odds.25 What was once a torturesome, rushed ordeal, where a team of surgeons held down a howling patient, has morphed into a calm, painless procedure, thanks in no small part to a traveling showman, a dentist, and his student. This is no humbug.
Conflicts of Interest: Stephanie Snow is distantly related to John Snow through her husband.
- Burney F. Letter to Esther Burney. March 22, 1812.
- Brown M. Surgery and emotion: The era before anaesthesia. The Palgrave Handbook of the History of Surgery. Palgrave Macmillan UK. 2018:327-348.
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- Takrouri MS. Historical essay: An Arabic surgeon, Ibn al Quff′s (1232-1286) account on surgical pain relief. Anesth Essays Res. 2010;4(1):4-8.
- West JB. Humphry Davy, nitrous oxide, the Pneumatic Institution, and the Royal Institution. Am J Physiol Lung Cell Mol. 2014;307(9):L661-L667.
- Marston AD. The centenary of the first anæthetic use of ether. Proc R Soc Med. 1942;35(4):279-286.
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- Finder SG. Lessons from history: Horace Wells and the moral features of clinical contexts. Anesth Prog. 1995;42(1):1-6.
- Hardy R. Ether Day: The strange tale of America’s greatest medical discovery and the haunted men who made it. Am J Psychiatry. 2001;158(12):2103-2104.
- Martin RF, Desai SP. An examination of Horace Wells’ life as a manifestation of major depressive and seasonal affective disorders. J Anesth Hist. 2016;2(1):22-27.
- So A, et al. The New York Herald’s very first report on Dr. Horace Well’s arrest and suicide—an original article found in New York City Public Library. J Anesth Hist. 2019;5(3):109-112.
- Haridas RP, et al. Morton’s Letheon: When was the name Letheon chosen? J Anesth Hist. 2021;7(1):1-10.
- Matsuki A. Seishu Hanaoka did not describe his anesthetic as Tsusensan--a misunderstanding of the terms Mafutsusan and Tsusensan. Masui. 2015;64(10):1101-1105.
- Matsuki A. Annals of anesthetic history: Seishu Hanaoka, a Japanese pioneer in anesthesia. Anesth. 1970;32(5):446-450.
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- Ramsay MAE. John Snow, MD: Anaesthetist to the Queen of England and pioneer epidemiologist. Proc Bayl Univ Med Cent. 2006;19(1):24-28.
- Cascella M. Rise and decline of the barbiturate methitural for intravenous anesthesia: A systematic search and narrative synthesis. J Anesth Hist. 2021;7(1):11-16.
- Kala AK. Of ethically compromising positions and blatant lies about ′truth serum′. Indian J Psychiatry. 2007;49(1):6-9.
- White PF. A history of intravenous anesthesia. In: The wondrous story of anesthesia. Springer New York; 2014:629-639.
- Jones R. A history of inhaled anesthetics. In: The wondrous story of anesthesia. Springer New York; 2014:609-627.
- Elsherbini N, Backman SB. The connection between Dr. Harold Griffith and Richard Gill: New insights into the history of curare use in anesthesia from previously unknown correspondence. Can J Anaesth. 2024;71(12):1664-1671.
- Bovill JG, et al. Opioid analgesics in anesthesia: With special reference to their use in cardiovascular anesthesia. Anesth. 1984;61(6):731-755.
- Roberts GJ, et al. Deaths associated with GA for dentistry 1948 – 2016: The evolution of a policy for general anaesthesia (GA) for dental treatment. Heliyon. 2020;6(1):e02671.
- Kummerow KL, et al. Nationwide trends in mastectomy for early-stage breast cancer. JAMA Surg. 2015;150(1):9-16.
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