The painful story
  The painful story behind modern anesthesia
  BY Dr. Howard Markel
  One of the truly great moments in the long history of medicine occurred on a tense fall morning in the surgical amphitheater of Boston’s Massachusetts General Hospital.
  It was there, on Oct. 16, 1846, that a dentist named William T. G. Morton administered an effective anesthetic to a surgical patient. Consenting to what became a most magnificent scientific revolution were John Warren, an apprehensive surgeon, and Glenn Abbott, an even more nervous young man about to undergo removal of a vascular tumor on the left side of his neck.
  Both Warren and Abbott sailed through the procedure painlessly, although some have noted that Abbott moved a bit near the end. Turning away from the operating table toward the gallery packed with legitimately dumbstruck medical students, Dr. Warren gleefully exclaimed, “Gentlemen, this is no humbug!”
Clinical Case
  William Thomas Green Morton.
  Morton named his “creation” Letheon, after the Lethe River of Greek mythology. Drinking its waters, the ancients contended, erased painful memories. Hardly such an exotic elixir, Morton’s stuff was actually sulfuric ether.
  Regardless of composition, Letheon inspired a legion of enterprising surgeons to devise and execute an armamentarium of lifesaving, invasive procedures that continue to benefit humankind to this very day.
  Yet while the discovery of anesthesia was a bona fide blessing for humankind, it hardly turned out to be that great for its “discoverer,” William T. G. Morton.
  Morton began his dental studies in Baltimore in 1840. Two years later he set up practice in Hartford, ultimately working with a dentist named Horace Wells. At this time, surgeons could offer patients little beyond opium and alcohol to endure the agonizing pain engendered by scalpels.
  From the late 18th century well into the 1840s, physicians and chemists experimented with agents such as nitrous oxide, ether, carbon dioxide, and other chemicals without success. In an era before the adoption of daily dental hygiene and fluoride treatments, excruciating tooth extractions were an all too common part of the human experience. Consequently, dentists joined physicians and surgeons in the Holy Grail-like search for safe and effective substances to conquer operative pain.
  Around this time, Morton and Wells conducted experiments using nitrous oxide, including a demonstration at Harvard Medical School in 1845 that failed to completely squelch the pain of a student submitting to a tooth-pulling, thus publicly humiliating the dentists. Although Morton and Wells amicably dissolved their partnership, Morton continued his search for anesthetic agents.
  A year earlier, in 1844, during studies at Harvard Medical School (which were cut short by financial difficulties), Morton attended the lectures of chemistry professor Charles Jackson. One session was on how the common organic solvent sulfuric ether could render a person unconscious and even insensate.
Clinical Case
  An illustration of the first use of ether as an anesthetic in 1846 by the dental surgeon W.T.G. Morton.
  Recalling these lessons during the summer of 1846, Morton purchased bottles of the stuff from his local chemist and began exposing himself and a menagerie of pets to ether fumes. Satisfied with its safety and reliability, he began using ether on his dental patients.
  Soon, mobs of tooth-aching, dollar-waving Bostonians made their way to his office. Morton relished his financial success but quickly perceived that Letheon was good for far more than pulling teeth.
  Morton’s remarkable demonstration at the Massachusetts General Hospital that long ago October morning transmogrified his status from profitable dentist to internationally acclaimed healer.
  But the half-life of his celebrity turned out to be molto presto, followed by an interminable period of infamy and hardship during which he was lambasted for insisting on applying for an exclusive patent on Letheon.
  In the United States of the mid-19th century, it was considered unseemly, if not outright greedy, for members of the medical profession to profit from discoveries that universally benefited humankind, particularly from a patent for what turned out to be the easily acquired sulfuric ether.
  As long as Morton stuck to dentistry, many physicians argued, he could do as he liked; but if he desired acceptance of Letheon by physicians and surgeons, he needed to comply with what they considered their higher-minded ideals and ethics.
  Morton aggressively rejected all such suggestions, much to his detriment. There was also the issue of credit. Horace Wells demanded his share. So did Crawford W. Long, a Georgia practitioner who claimed to have used nitrous oxide and ether as early as 1842 but who was too busy to publish his findings. Morton’s former professor, Charles Jackson, argued that he, too, deserved a piece of the action.
Clinical Case
  Ether inhaler, c. 1846, developed by William T.G. Morton.
  While many toyed with anesthetic agents, it was Morton who first developed a novel delivery instrument to enable ether inhalation during an operation.
  The device consisted of a glass flask with a wooden mouthpiece that could be opened and closed depending on the patient’s state of consciousness. This was critical because other experimenters, including Wells and Long, could not ensure rapid reversibility of the anesthetic state and often overdosed their patients.
  Morton’s genius resided not only in his observations of the power of ether but also in his development of a crude but scientific method of regulating its inhalation, thus creating the field of anesthesiology.
  Not everyone saw it that way. Vigorously combating the whispered and shouted campaigns against him, the dentist spent his remaining days trying to restore his sullied reputation. Morton died broke and embittered in 1868. It would be many decades more before Morton was rightfully returned to the pantheon of medical greats.
  Morton’s search to conquer pain was a remarkable contribution to medicine and human health even if it did not turn out to be the personal and financial success he so badly craved.
  Although Morton was a man of great accomplishment, he was all too human. Sadly, like many human beings, Morton aggressively hunted for fame, glory, professional success, and ego gratification at the expense of judiciously contemplating the consequences of his actions. It was a quest that cost him dearly even as it made life– and surgically correctible illnesses — far better for the rest of us.
  Ether and the Discovery of Anesthesia
  Ether and the Discovery of Anesthesia
  A modern painting depicting the 1846 demonstration of ether at Massachusetts General Hospital
There is an unusual, and mostly forgotten monument in a shaded area at the edge of the Boston Public Garden in downtown Boston. It was completed in 1868, and, like many other monuments built during the 19th century, it features classical statuary, granite columns, and biblical inscriptions. But unlike any other monument in the world, it memorializes a drug. The inscription on the front face of the monument reads: “To commemorate that the inhaling of ether causes insensibility to pain. First proved to the world at the Mass. General Hospital in Boston, October A.D. MDCCCXLV”.
The molecular structure of ether
  The inscription refers to the most famous public demonstration of ether as an anesthetic during surgery. On October 16th, 1846 a crowd of doctors and students gathered in the surgical amphitheater at Massachusetts General Hospital to watch as a dentist named William T.G. Morton instructed a patient to inhale the fumes from an ether-soaked sponge. After the patient was sufficiently sedated, a surgeon removed a tumor from his neck. When the patient awoke from his ether-induced stupor, the surgeon asked how he felt, to which he reportedly replied, “feels as if my neck’s been scratched.”
The ether monument in the Boston Public Garden
The patient felt no pain during the surgery, which seemed like a miracle at the time. Up until this point surgery was quick and brutal. Fully conscious patients bit the bullet – quite literally in some cases – while surgeons did their work. Ether obviously made surgery a more comfortable experience for patients, but it also allowed surgeons to take their time operating on anesthetized patients, which in turn allowed doctors to develop more and more complex and beneficial surgical techniques.
  The Ether Dome at Massachusetts General Hospital
  After the ether demonstration someone nicknamed the surgical amphitheater at Massachusetts General Hospital the Ether Dome, and it has been known by this name ever since. Today the Ether Dome is a national historic landmark, and is open to the public. Although surgeons haven’t operated there for well over a hundred years, the room is still used for meetings and lectures at the hospital. With the exception of a laptop and a projector, the Ether Dome looks more or less like it did 165 years ago. The entrance to the room is overshadowed by a marble statue of the Greek god Apollo, and two display cases filled with rusted 19th century surgical instruments stand at either end of the room. An Egyptian mummy, dissected in the room in the early 1800′s, stares outward from behind a glass case at the front of the room, while the back of the room is occupied by a steeply terraced bank of wooden seats.
  At the time of William Morton’s ether demonstration, people had known about ether for more than 300 years. But for most of those 300 years no one had thought to use it as an anesthetic. Instead, people used it to get high. Straitlaced Victorians held parties where guests cut loose by inhaling ether fumes and losing motor control, to the amusement of everyone involved. These “ether frolics,” as they were known at the time, were part of a larger trend of inhaling drugs at parties for comic effect – helium and laughing gas (nitrous oxide) parties were also popular among wealthy Victorians.
  But Morton was not the first doctor to discover ether’s anesthetic properties. That honor belongs to a physician from Georgia named Crawford Long who operated using ether nearly four years before Morton’s demonstration at Massachusetts General Hospital. Long, who was known to occasionally partake in ether – he even threw “ether frolics” in his medical office from time to time – was inspired to use ether during surgery by recreational ether inhalation at parties. He noticed that party guests, himself included, often stumbled into furniture or fell down and suffered cuts and bruises while under the influence of ether. This isn’t all that surprising considering that ether severely limits motor control at low doses and leads to unconsciousness at higher doses. What surprised Long at the time was that none of these bruised revelers remembered receiving any injuries or experiencing any pain.
  And then, in 1839, word got back to Long about a boy slave from nearby Athens, Georgia who lost consciousness when he was given ether. The boy was apparently watching a group of teenagers who were using ether when they invited him to try some. He refused, but a few of the teenagers held him down and forcibly covered his nose and mouth with an ether-soaked rag. When they released him, the boy was unconscious and unresponsive. Worried that he was dead, someone ran to get a doctor. When the doctor arrived an hour later the boy was still unconscious but the doctor was able to revive him, and upon waking he seemed none the worse for wear.
  These observations led Long to believe that ether could prevent pain during surgery. So, in 1842, he administered ether to a patient and then painlessly removed a tumor from his neck. Over the next few years, Long continued to operate with ether, and shared his discovery of ether’s anesthetic properties with other local physicians. But Long’s discovery was never widely publicized. So when William Morton demonstrated ether in Boston four years later, he touted it as a revolutionary new treatment, unaware that Crawford Long and his colleagues in Georgia had already used ether during surgery a number of times. It seems to have been a bizarre coincidence that ether was first used by both Long and Morton to anesthetize a patient before removal of a neck tumor.
  Unlike Long, who, for whatever reason, chose not to immediately publish his ether discovery, it seems that Morton intended to capitalize on ether’s medical applications from the get-go – he was aware that ether could revolutionize medicine and he wanted to cash in. So he filed for a patent. Morton received his patent, but ether was already so widely known at the time that doctors around the world simply began using ether without paying Morton any royalties. Morton petitioned Congress for $100,000 (something between $2-3 million in today’s dollars) in compensation related to widespread royalty-free use of ether. Unfortunately for Morton, several others, including Crawford Long, came forward claiming that they were the original discoverers of ether’s anesthetic properties, and Morton never received any compensation. He spent the rest of his life trying to prove that he was the first to use ether as an anesthetic, and he died young and poor in 1868.
  Today, Crawford Long is recognized as the first physician to use ether as an anesthetic during surgery. But it was William Morton’s ether demonstration at Massachusetts General Hospital, and his desire for fame and fortune, that first alerted the world to the miracle of anesthesia. At the time anesthetic ether was recognized as a medical revolution. So much so that an anonymous citizen of Boston raised funds to construct a monument to commemorate humankind’s triumph over pain.
  Reference :
  Lewis JH (1931). Contribution of an Unknown Negro to Anesthesia. Journal of the National Medical Association, 23 (1), 23-4 PMID: 20892436
  Paracelsus (1493–1541)—First to use ether on animals
  Darwin Etherizes Venus Flytraps
 In his 1875 text Insectivorous Plants, naturalist Charles Darwin noted that the “plant, commonly called Venus’ fly-trap, from the rapidity and force of its movements, is one of the most wonderful in
  iControl-RP the world.” While investigating anesthetics’ effects on the botanical carnivore’s leaf-closing, he tried chloroform and then ether vapors. Using a 2-oz. vessel, the naturalist determined that the flytrap’s leaf required 24 hr to recover sensibility from 20 min exposure to “15 minims” of ether, but only 52 min to recover from 3 min exposure to “10 drops” in a larger bottle. Darwin conceded that he did not know whether “the larger doses of . . . ether, which caused the leaves to close slowly, acted on the sensitive filaments or on the leaf itself. . . .”
  Valerius Cordus
  German physician and botanist Valerius Cordus (1515–1544), synthesizes diethyl ether by distilling ethanol and sulphuric acid into what he called "sweet oil of vitriol."
  iControl-RP Cordus' Synthesis of Ether
In 1540 Valerius Cordus (1515–1544; German botanist, pharmacist, and physician) synthesized ether (“sweet oil of vitriol”) in his alchemist’s still from ethanol (“triply-distilled” wine) and sulfuric acid (“sour oil of vitriol”). His “sweet” mixture floated on water (the volatile diethyl ether portion,which would be vaporized three centuries later as an anesthetic) yet felt greasy to touch (the aromatic diethyl sulfate portion). Hailed later as the
  Father of Descriptive Botany and of the Legally Sanctioned Pharmacopoeia, Cordus died, possibly from malaria, soon after the 29-year-old’s leg was kicked savagely by a horse. The world’s first record of the synthesis of ether, De Artificiosis Extractionibus, was published 17 years later in a posthumous compilation. In July of 2009, the Wood Library-Museum acquired this “new” tome from 1561 (see above—note its pigskin-quarterbound, antiphonal-vellum-over-pasteboard covers).
  Ether, a man-made liquid , was first described by Valerius Cordus in the 16th Century. Ever since, it has been known that inhaling the vapors of ether could cause, first, euphoria, and then drowsiness. It was applied topically, and taken orally, for numerous conditions, as well as being inhaled for respiratory ailments. In the 19th Century, it was the first substance to be publicly shown to alleviate the dreaded pain of surgery.
iControl-RP In 1842, Dr. Crawford W. Long (1815-1878) used ether for surgical anesthesia in his private practice in Jefferson, Georgia. In 1846, dentist William T. G. Morton (1819-1868) used ether to give the first successful public demonstration of surgical anesthesia, at Massachusetts General Hospital. The technique was quickly adopted worldwide, but the ether made at that time was of variable quality, and gave unpredictable results. Dr. Edward Robinson Squibb (1819-1900) published a description of his process for the production of chemically pure ether in 1856. He did not patent this process, but founded a pharmaceutical company
two years later. E. R. Squibb & Sons became the leading manufacturer of anesthetic ether for nearly a century.
  Ether’s flammability, its lengthy period of induction, and post-anesthetic nausea, were disadvantages that caused many to begin hunting for a better alternative. One of the first of these was chloroform, which quickly surpassed ether in popularity. But chloroform’s side effects eventually returned ether to prominence, and it was not completely replaced by newer agents until the 1970s.
  "First Operation Under Ether" painting by Robert C. Hinckley. Courtesy of the Boston Medical Library in the Francis A. Countway Library of Medicine
  On October 16, William T. G. Morton (1819-1868)-First in the world to publicly and successfully demonstrate the use of ether anesthesia for surgery. This occurred at what came to be called "The Ether Dome," at Massachusetts General Hospital on patient Edward Gilbert Abbott. Surgeon John Collins Warren noted, "Gentlemen, this is no humbug." Dr. Oliver Wendell Holmes, Sr. (1809-1894)-suggests the terms "anaesthetic" and "anaesthesia" in a letter to William T. G. Morton. News of Morton's ether demonstration was carried by the paddle steamship Acadia from Boston to Dr. Francis Boott and then on to Dr. James Robinson (1813-1862), who extracted a tooth on December 19, 1846, under ether anesthesia. In 1847 Robinson authored one of the first textbooks on anesthesia: A Treatise on the Inhalation of the Vapour of Ether for the Prevention of Pain in Surgical Operations.* On December 21, Scottish surgeons in Dumfries, Scotland (Dr. William Scott) and in London (Dr. Robert Liston) amputate limbs of etherized patients- the first such surgical anesthetics in the British Isles. Liston commented, "This Yankee dodge beats mesmerism hollow." Dr. Liston describes the surgery in a letter to Dr.Francis Boott, which is published in The Lancet. The WLM owns this letter.
Replica of Morton InhalerEdward Gilbert Abbott
  W. T. G. Morton’s “Letheon” Advertisement
  After successfully demonstrating in 1846 the use of diethyl ether for surgical anesthesia, William T. G. Morton (1819–1868) adulterated his anesthetic agent with oil of orange, branded the mixture “Letheon,” and dreamed of collecting royalties from future etherizers. In this advertisement, Morton notes that the “subscriber is prepared to furnish a person fully competent to administer his compound to patients who are to have surgical operations performed, and when it is desired by the Operator that the patient should be rendered insensible to pain. Personal or written application may be made to W. T. G. Morton, Dentist . . ..”
  The Morton House by Vandam
  History tells us that the etherizer who first publicly demonstrated surgical anesthesia was William Thomas Green Morton (1819–1868). However, the muse Clio seems confused as to whether Morton was born at the site above on August 9 or 19. A retired Editor of ANESTHESIOLOGY, watercolorist and anesthesiologist Leroy D. Vandam (1914–2004), after visiting Morton’s birthplace, had observed that the “original Morton house was a large, square old-fashioned wooden house on a farm that was deeded to William Thomas Green Morton’s mother, Rebecca, by her father, John Stevens.” Because the original Morton house had burned, its successor was the edifice (above) that Professor Vandam captured with watercolors.