Laughing Gas Ether And Surgical Anesthesia

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Despite the wealth of soporific agents available in nature's medical garden, the remarkable products of the eighteenth-century chemical revolution eventually eclipsed the ancient anodynes. Joseph Priestly (1733-1804), British theologian, educator, writer, and political theorist, is best known as the discoverer of oxygen, but as Sir Humphry Davy (1778-1829) said of this indefatigable chemist, ''no single person ever discovered so many new and curious substances.'' Most curious of all was the gas known as nitrous oxide, or laughing gas. As he was in the habit of testing the effect of new gases on himself, Priestley might have discovered the anesthetic properties of laughing gas if his research had not been interrupted by the political and religious conflicts that forced him to emigrate to America in 1794.

The ingenious discoveries of the first pneumatic chemists provided new opportunities for quacks and charlatans. Conscientious experimentalists could not compete with charlatans promising miraculous cures for asthma, catarrh, consumption, and cancer through the inhalation of oxygen, hydrogen, and other ''factitious airs.'' Some physicians, however, attempted to find legitimate medical uses for the new gases. Fascinated by pneumatic chemistry, Thomas Beddoes (1760-1808) persuaded his friends Thomas Wedgwood (1771-1805) and James Watt (1736-1819) to help him establish the Pneumatic Institute, a hospital in which the inhalation of factitious airs was used in the treatment of lung disease. Many scientists, including Humphry Davy, were intrigued by his work. While suffering from toothache in 1795, Davy began inhaling nitrous oxide. In addition to feeling giddy, relaxed, and cheerful, Davy noted that the pain caused by his wisdom teeth had almost disappeared. Soon after the exhilaration wore off, the pain returned, worse than ever. Nevertheless, Davy suggested that nitrous oxide might be useful during surgical operations. Davy's associate, Michael Faraday (1791-1867), discovered the soporific effect of ether vapor during experiments on various gases. In comparing the effects of ether and nitrous oxide, Faraday found that both chemicals produced similar responses. Most subjects found inhalation of ether or nitrous oxide very pleasant, but, occasionally, people who inhaled ether or nitrous oxide experienced frightening and bizarre effects, such as loss of sensations, prolonged lethargy, hallucinations, and fainting. Other eighteenth-century chemists recommended ether for fits, headaches, gout, rheumatism, asthma, deafness, whooping cough, and other disorders.

Even the valiant attempts of Henry Hill Hickman (1801-1830) to validate the safety and efficacy of inhalation anesthesia failed to arouse the interest of the medical profession. Unlike many pioneers of anesthesia, Hickman did not simply sniff at various chemicals. Dogs and mice placed in a sealed glass vessel were subjected to various test gases until they were in a state of ''suspended animation.'' In this state, animals were insensitive to pain, but were at risk of circulatory collapse during surgery. Unsuccessful in his attempts to call attention to surgical anesthesia, Hickman apparently succumbed to an overwhelming sense of failure and committed suicide.

The story of the development of surgical anesthesia in the 1840s involves a most unlikely cast of characters more suited to farce than historical drama. Moreover, the major events took place not in the prestigious medical colleges and hospitals of Europe, but at the periphery of the medical and scientific world. The chief characters were peripatetic professors, show-business chemists, and dentists, who at the time were regarded as closer to quacks than to doctors. Bitter priority disputes consumed and even destroyed the lives of several of the participants in the discovery of surgical anesthesia. The cast of characters includes Horace Wells (1815-1848) and William Thomas Green Morton (1819-1868), dentists who had shared a successful partnership before Wells recognized the anesthetic properties of nitrous oxide and Morton demonstrated the value of ether. Charles Thomas Jackson (1805-1880), chemist and physician, later claimed that he rather than Morton discovered ether anesthesia. While the priority battle between Morton and Jackson raged in New England, Georgia physician Crawford Williamson Long (1815-1878) announced that he had discovered ether anesthesia before Morton.

During the nineteenth century, medicine shows and philosophical lectures by self-appointed professors brought edification and entertainment to the citizens of cities and towns throughout America. ''Professors of chemistry'' enlivened lectures on the amazing properties of newly discovered gases by breathing fire with hydrogen and encouraging volunteers to make fools of themselves after inhaling nitrous oxide. Students of dentistry, medicine, and chemistry did not have to wait for the itinerant professors; they could enjoy ''laughing gas parties'' and ''ether frolics'' whenever they wished. Indeed, the ''champagne effect'' of these substances was so well known that when Jackson attempted to claim priority, Morton's defenders noted that one could hardly find a school or community in America where the boys and girls had not inhaled these drugs.

Dentists were probably more highly motivated than any other practitioners to discover novel and powerful anesthetics. Until the excruciating pain of a rotting tooth exceeded the anticipated agony of extraction, the victim of toothache was unlikely to submit to the services of a dentist. Throughout history, dentists claimed to possess potions that would remove bad teeth and eliminate pain. Ancient tooth-dressings included everything from honey and opium to sour apples, powdered beetles, and even rattlesnake venom in vinegar. Kissing a donkey, biting off the head of a mouse, inserting a live louse in the bad tooth, and applications of powdered crow dung were among the most peculiar treatments for toothache.

In France, dentistry evolved as an area of specialization in surgery. Textbooks written by and for surgeons typically included descriptions of the teeth, diseases of the teeth and gums, tooth extraction, the construction of artificial teeth, materials for filling teeth, and other methods of treating disorders of the teeth and gums. Although the status of those who only pulled teeth was lower than that of barber-surgeons, even master surgeons performed dental procedures. Texts devoted to dentistry had been published in the sixteenth century, but Le chirurgien dentiste (1728), a comprehensive, two-volume treatise by surgeon-dentist Pierre Fauchard (1678-1761), is considered a landmark in the history of dentistry. Surgeons who treated the dental problems of eighteenth century French aristocrats enjoyed considerable prestige.

Chapin Aaron Harris (1806-1860), a founder of American dentistry, began the study of medicine, surgery, and dentistry as apprentice to his brother. In 1833, Harris passed an examination administered by the Maryland State Medical Board and was awarded the M.D. Although Harris began his career as a doctor, he decided to specialize in dentistry and spent many years as an itinerant practitioner before he received a license to practice dentistry from the Medical and Chirurgical Faculty of Maryland and settled in Baltimore. Harris published many articles and books about dentistry, including The Dental Art: A Practical Treatise on Dental Surgery, Principles and Practice of Dental Surgery, and Dictionary of Dental Science: Bibliography, Biography and Medical Terminology. Harris was a cofounder of the first dental school in the world, the Baltimore College of Dental Surgery (1840), and established the first national dental society, the American Society of Dental Surgeons.

As nineteenth-century American dentists introduced improved dental appliances and instruments, their professional and economic advancement was limited by the fears of prospective patients and the disdain of the medical profession. These obstacles were especially galling to men like Horace Wells and his business partner William Morton. Wells and Morton had developed improved sets of false teeth and dental solder, but potential customers were reluctant to accept their ''money-back-if-not-satisfied'' deal because it required extraction of all remaining teeth and roots. Thus, Wells and Morton were keenly interested in any agent that could reliably achieve painless dentistry.

On December 10, 1844, Wells attended a lecture by Dr. Gardner Quincy Colton, during which the remarkable properties of nitrous oxide were demonstrated. Wells was struck by the fact that, while under the influence of laughing gas, a volunteer remained in a state of euphoria even though he fell off the stage and injured his leg. Wells asked Colton to bring laughing gas to his office for an experiment. The next morning, Colton administered the gas to Wells and John M. Riggs, a dental student, extracted a tooth. When Wells regained consciousness, he was elated to realize that he had not experienced any pain during the operation. Within a month, Wells had used nitrous oxide on over a dozen patients. At Morton's request, Dr. John Collins Warren (1778-1856), Professor

Laughing Gas Surgical Operation
Surgical anesthesia at Massachusetts General Hospital, 1846.

of Anatomy at Harvard Medical School, allowed Wells to address a class in surgery. However, Warren's skeptical attitude toward painless dentistry was evident in his introductory remarks. ''There's a gentleman here,'' Warren warned his students, ''who pretends he has something which will destroy pain in surgical operations.'' When the medical student who ''volunteered'' to have a tooth extracted groaned during the operation, Wells and Morton were ridiculed and humiliated by the hostile audience. Ironically, the patient later admitted that he had felt no pain.

In 1848, when he evaluated the anesthesia controversy, Henry J. Bigelow (1818-1890) argued that Wells had not satisfied the criteria for surgical anesthesia. Surgeons needed an anesthetic agent that was inevitable, complete, and safe. Behaviors elicited by nitrous oxide inhalation were unpredictable and suggestion played an important role in determining the effect of the gas. Those who inhaled for amusement almost always became exhilarated; those well prepared for surgery became drowsy and lost consciousness. During the priority battle that followed the acceptance of inhalation anesthesia, Morton complained that he was the only person involved in the discovery who had suffered a ''pecuniary loss.'' His colleague Horace Wells, however, paid a higher price for his part in the controversy; he lost his sanity and his life. Failing to find professional recognition, Wells resorted to sniffing ether and chloroform to cope with depression. Less than four years after his humiliating experience at Massachusetts General Hospital, Wells was arrested for allegedly accosting a young woman and throwing something, which might have been acid, ether, or chloroform, at her. Two days later, Wells was found dead in his cell, with an empty vial of chloroform, a penknife, a razor, and a suicide note. Thus, Wells would never know that nitrous oxide, mixed with oxygen, would become an important anesthetic agent in dentistry.

Only a short time after Wells's dismal performance reassured the Boston Brahmins that a mere dentist could not teach them the secret of painless surgery, Morton convinced the same elite physicians that inhalation anesthesia was ''no humbug.'' Like nitrous oxide, ether had been used for recreational purposes. Moreover, during its long history as a chemical oddity, several investigators came tantalizingly close to discovering its anesthetic properties. The honor of being first to synthesize ether has been attributed to several Renaissance alchemists, but the nature of these alchemical preparations is obscure. The starting materials (sulfuric acid and alcohol) would have been widely available, but careful temperature regulation is needed to enhance the production of ethyl ether as opposed to other possible reaction products. Certainly, early preparations of ether would have been impure, and, as Morton discovered, purity was critical when ether was used as an anesthetic agent. Even though ether had been used as a sedative in the treatment of tuberculosis, asthma, and whooping cough, its anesthetic potential was rarely exploited. Extrapolating from the pleasant experience of an ether frolic to dental and surgical operations was not a simple, self-evident step before practitioners deliberately set forth on a quest for inhalation anesthetics.

According to family tradition, Morton graduated from the Baltimore College of Dental Surgery in 1842. There is, however, no proof that Morton ever matriculated at any dental school. Although dentistry was hardly recognized as a profession at that time, practitioners were working to improve the training and status of dentists by establishing journals, professional societies, and schools, such as the Baltimore College of Dental Surgery (later the School of Dentistry, University of Maryland). Whatever their education and training may have been, both Wells and Morton were apparently skillful and inventive dentists who specialized in ''mechanical dentistry,'' or ''plate work.'' Because of the suffering of his patients, and their tendency to prefer death to dentistry, Morton was obsessed with finding a way to mitigate the pain of dental operations. Like surgeons, dentists could offer their patients only unreliable soporifics. Moreover, the nausea caused by alcohol and laudanum was especially dangerous during dental procedures because vomiting could lead to suffocation and death.

Despite the financial success of the Wells-Morton partnership, Morton became one of Jackson's private pupils in order to make the transition from dentistry to medicine. In a discussion of toothache, Jackson recommended using ether as ''toothache drops.'' Jackson later claimed that he had known about ether anesthesia since the early 1840s, but when Morton performed tooth extractions on Jackson's wife and aunt, Jackson merely encouraged the ladies to be brave. Therefore, during the priority battle over the discovery of anesthesia, Morton argued that his former mentor had never thought of going beyond the application of liquid ether ''in the same manner that laudanum and other narcotics have always been applied to sensitive teeth.' Always on the alert for pain-relieving agents, Morton consulted the medical literature and found that ether had been used as an antispasmodic, anodyne, and narcotic. Noting that when ether was applied to a rotten tooth, the gums became numb, Morton wondered whether ether could numb the whole body. Taking elaborate precautions to ensure secrecy, Morton tested the effects of ether inhalation on various animals. Disconcerted by the variability of his results, Morton sought Jackson's advice and learned that the ether sold by pharmacists was rarely pure enough for special uses.

On September 30, 1846, Morton saturated a handkerchief with ether, looked at his watch, and inhaled deeply. He regained consciousness about 8 minutes later with no ill effects other than mild exhilaration, followed by headache. That evening Morton tested the effect of ether while extracting a patient's firmly rooted bicuspid. After the painless operation, the patient gave Morton a written testimonial. Convinced of the validity of his discovery, Morton again approached Dr. Warren to ask for an opportunity to demonstrate his method of producing insensibility to pain. Thinking that inhaling ether through some special apparatus might produce more reliable results than the ''rag-and-gag'' method previously employed, Morton sought the assistance of a well-known scientific instrument-maker.

By October 16, 1846, the day of the hospital demonstration, Morton was in a state of terrible anxiety and his inhalation apparatus was still unfinished. The patient was already strapped to the table in preparation for his ordeal when Morton rushed in with his new inhaler and administered his secret ''Letheon gas.'' Amazed by the patient's complete quiet and tranquility during the extirpation of a large tumor from his mouth and tongue, Warren graciously announced: ''Gentlemen, this is no humbug.'' Witnesses later recalled this demonstration as ''the most sublime scene ever witnessed in the operating-room.'' The operation performed by Warren at Massachusetts General Hospital under ether anesthesia was seen as the beginning of a new age for the ancient art of surgery. It also marked the beginning of a vicious priority battle that found its way into petitions, patent applications, pamphlets, testimonials, and learned articles in professional journals and encyclopedias.

According to Morton, the first intimation of the trouble to come was a visit from Jackson on October 23, 1846. Jackson had heard that Morton intended to take out a patent for surgical anesthesia and expected to make a good deal of money. Dentists routinely patented their inventions, but physicians supposedly answered to a higher code of ethics. However, Jackson demanded fees for professional advice, his name on the patent, and 10 percent of the net profits. Shortly after presenting his demands to Morton, Jackson sent a sealed report to the Academy of Sciences of France in which he claimed that he had discovered ether anesthesia and had instructed a certain dentist to use ether when extracting teeth. Jackson's sealed report was his insurance policy; if ether proved to be dangerous, his report could be destroyed, but if it was successful, he intended to use it to claim priority. As soon as the success of ether anesthesia seemed assured, Jackson presented himself as its sole discoverer and denounced Morton as a ''stooge'' acting under his direction. When Jackson spoke to the Massachusetts Medical Society, most of his audience accepted the claims of the eminent physician, chemist, and geologist against his rival, the ''quack dentist.'' Not everyone was convinced that Jackson deserved credit for the discovery. Indeed, Jackson was asked whether he would have accepted the blame if Morton's patient had died. Jackson's critics saw this as an example of the old adage: success has many fathers, failure is a bastard.

On the grounds that the Massachusetts Medical Society's ethics code did not allow doctors to use secret remedies, when Morton offered his services for another operation, hospital surgeons refused to employ him until he revealed the identity of Letheon. They also assured him that the patient would die if her leg was not amputated, and would probably die of shock if the operation was conducted without anesthesia. It was not easy for Morton to envision the greater good of humanity while his dreams of fame and fortune evaporated even more quickly than ether itself. Opportunities to profit from his discovery continually eluded him. In 1868, shortly after consulting his lawyer about issues related to his 20-year conflict with Jackson, Morton died of a cerebral hemorrhage. An inscription on Morton's tomb, composed by Dr. Jacob Bigelow, honors him as the inventor of inhalation anesthesia. Jackson survived Morton by 12 years, but he did not enjoy a peaceful old age. According to a story probably too good to be true, after considerable drinking, Jackson wandered into the Mount Auburn Cemetery and was overcome by a frenzy while reading the inscription on Morton's tomb. Declared hopelessly insane, Jackson was confined to a mental asylum for the rest of his miserable life.

While Wells, Morton, and Jackson were disputing the discovery of inhalation anesthesia, Crawford Long emerged from his obscure existence in rural Georgia with testimonials documenting his own priority claim. Like Wells, Long came to an appreciation of the medical potential of a drug from casual observations of its recreational uses. When a traveling chemist sparked local interest in laughing gas, Long had suggested that ether would be just as exhilarating. According to Long, sniffing ether became a popular form of entertainment at local social events. After these ether frolics, participants sometimes discovered bruises and other injuries acquired while "under the influence.'' Long concluded that ether might be used to induce insensitivity to pain during surgery, but he apparently had more opportunities to stage ether frolics than surgical operations. In March of 1842, Long persuaded James M. Venable to have a tumor on his neck surgically removed. Knowing that Venable was afraid of the knife, but fond of ether, Long suggested that he sniff ether prior to the operation. It was not until 1849 that Long published an account of his discovery in the Southern Medical and Surgical Journal. Technically, Long established his priority, but as Sir William Osier said: ''In science the credit goes to the man who convinces the world, not to the man to whom the idea first occurs.''

Despite warnings from the Philadelphia Medical Examiner that the physicians of Boston would soon constitute one fraternity with the quacks, ether anesthesia quickly spread from Massachusetts to Paris and London. Although anesthesia was certainly an important factor in the surgical revolution, more subtle and complex factors were also involved. Indeed, given the increased use of the knife that accompanied the decline of humoralism and the rise of morbid anatomy during the period from about 1700 to the 1830s, the rapid acceptance of anesthesia might have been the result of the increasing role of surgery rather than the reverse. Potentially useful anesthetic agents had obviously been available before the 1840s. In any case, with the rapid dissemination of surgical anesthesia advances in the art were inevitable; so too were iatrogenic accidents and deaths. Anesthesia so transformed the art of surgery that Henry J. Bigelow urged reform of the curriculum at Harvard Medical School to inculcate humanity and sensitivity back into medical students. Within two years of Morton's first public demonstration of inhalation anesthesia, ether, nitrous oxide, chloroform, and other anesthetic agents were widely used in dentistry, obstetrics, and surgery. Physicians also prescribed these powerful anesthetic agents for convulsions, asthma, whooping cough, menstrual cramps, vaginismus, neuralgia, insomnia, and insanity.

Inspired by his successful use of ether, James Young Simpson (1811-1879), Professor of Midwifery at Edinburgh and one of Scotland's leading surgeons and obstetricians, initiated a search for an anesthetic without ether's disadvantages. Using himself and his friends as guinea pigs, Simpson began a systematic, but dangerous search for a volatile anesthetic agent with a better aroma and more rapid action than ether. Having asked for advice from chemists and sniffed his way through samples of acetone, benzene, benzoin, and a variety of organic solvents, Simpson tested chloroform. This dense, colorless liquid produced a sense of euphoria as well as loss of consciousness. Within a week, Simpson's patients were enjoying the benefits of chloroform analgesia. Chloroform easier to administer than ether, but it also seemed to be more dangerous. Indeed, it was fortunate that the principle of surgical anesthesia had been established with ether, because the relatively high mortality rate with chloroform might have inhibited development of this branch of the healing art. Emphasizing the more unpleasant aspects of using ether, Simpson noted that it irritates the respiratory tract and is highly inflammable, which would be very dangerous to anyone operating by candlelight. In 1868, chemists found that chloral hydrate, which was used in the synthesis of chloroform, also acted as a soporific agent. Instead of releasing chloroform, however, chloral hydrate formed trichloroethanol in the liver. Chemists synthesized more useful analogues of chloral hydrate in the 1870s and 1880s.

The safety of anesthesia was not the only point of contention, as demonstrated by the ferocity of the attack on the use of anesthetics in obstetrics. Clergymen, doctors, and assorted amateur moralists argued that pain had a God-given, and therefore holy role to play in the lives of men, and especially in the lives of women. Midwives had been put to death for the blasphemous, sinful, unnatural crime of attempting to alleviate the pains of childbirth. Clergymen denounced Simpson and commanded women to endure the pains of childbirth with patience and fortitude. Did the Bible not say that Eve was condemned to bring forth children in sorrow? Obstetricians warned women that labor contractions were identical to labor pains. Therefore, without pain there would be no contractions and normal delivery could not occur. Suffering was inherent in female physiology and labor pains enhanced woman's capacity for tenderness, femininity, and maternal feelings.

Saddened by the controversy, Simpson met his critics on theological as well as scientific grounds. Using the Bible to substantiate his work, Simpson asserted that the curse in Genesis had been revoked by a passage in Deuteronomy that promised: ''The Lord will bless the fruit of the womb and the land.'' Moreover, the word translated as ''sorrow'' in the case of Eve's punishment was really the word for ''labor,'' which referred to both farming and childbirth. Furthermore, God established the principle of anesthesia when he caused a deep sleep to fall upon Adam before operating on his rib. When John Snow (1813-1858) administered chloroform to Queen Victoria in 1853 during the birth of her eighth child, the issue of whether a proper lady would accept anesthesia was settled. When one of her daughters gave birth, Queen Victoria said: ''What a blessing she had chloroform.'' Unlike his American counterparts, Simpson died rich in honors and respect. He was knighted, appointed Physician in Scotland to the Queen, awarded an honorary doctorate by Oxford University, received the Freedom of the City of Edinburgh, and, after his untimely death at age 59, academic and commercial activities in Scotland were suspended to accommodate one of the largest funerals ever to honor a Scottish doctor.

The priority battle in America became part of a broader controversy about which agent, ether or chloroform, was better, as well as arguments about the relative value of Simpson's work and that of the Americans who had discovered inhalation anesthesia. When the Edinburgh Daily Review called the introduction of chloroform for anesthesia ''the greatest of all discoveries in modern times,'' Bigelow complained that Simpson was ignoring his American predecessors and claiming too much credit for surgical anesthesia. In response, Simpson informed Bigelow that he saw the use of chloroform and ether as anesthetic agents not as great discoveries in themselves, but as steps in a long history that included Sir Humphry Davy, as well as the Greek, Roman, and medieval surgeons who had used various soporific vapors. For Simpson and his British colleagues, the discovery of chloroform was the climax of a sweeping historical narrative. Infuriated, Bigelow insisted that it was wrong to call chloroform the ''greatest discovery'' in any account of surgical anesthesia. Ether had been used successfully and safely for many years before chloroform anesthesia caused ''hundreds of cases of disaster and death.'' According to Bigelow, Simpson's self-aggrandizing historical account was nothing but ''antiquarian dust'' that was used ''to obscure the truth.'' Bigelow wanted the world, especially the British, to acknowledge the difference between ''the modern discovery of anesthesia and the less important use of chloroform.'' Even after Simpson and Bigelow were dead, the controversy continued. Jacob Bigelow's son, Dr. Henry J. Bigelow, wanted to make it perfectly clear that Americans had discovered the first surgical anesthetic agent that was ''inevitable, complete, and safe.'' That agent was ether, not chloroform.

The changing nature of surgical practice must have been rather painful to those who had established their reputation through speed and strength and now saw surgeons developing a deliberate and subtle touch. Practitioners who had struggled to attain the professional detachment (or callousness) needed to operate in the pre-anesthetic era had taken great pride in their achievements. Like the librarian who objects to people taking books from neatly ordered shelves, the master surgeon might resent the trick that obviated the need for his painstakingly acquired skills. Some doctors believed that inhalation of anesthetic agents would poison the blood, promote hemorrhages, cause convulsions, nausea, intoxication, prolonged stupor, cerebral excitement, asphyxia, bronchitis, pneumonia, inflammation of the brain, paralysis, insanity, depression, local or systemic infection, miscarriage, or damage to the fetus. Anesthetics might damage nerves and muscles or interfere with wound healing. Many sectarians, such as hydropaths, homeopaths, and naturopaths, opposed the use of all powerful, chemical agents, including anesthetics. Some temperance advocates denounced Demon Anesthesia as well as Demon Rum.

While some practitioners denounced anesthesia as a dangerous and blasphemous novelty and others adopted it without reservations, most doctors cautiously accepted it as a mixed blessing that had to be used selectively. The risks and benefits of anesthesia had to be evaluated by a new ''utilitarian calculus'' that took into consideration a host of variables, such as age, sex, race, ethnicity, the seriousness of the operation, and so forth. The rapid spread of anesthetic techniques was unprecedented in medical history, but not all patients received the blessings of painless surgery, even for major limb amputations. Some surgeons justified anesthesia by arguing that pain itself was dangerous, because it caused shock, depleted precious stores of vital energy, and damaged the body. Moreover, anesthesia encouraged patients to accept operations and allowed surgeons to refine their skills. Advocates of universal anesthetization accused doctors who insisted on the selective use of anesthetics of exaggerating potential risks in order to maintain exclusive control over anesthesia. The American Medical Association's Committee on Medical Science warned that chloroform and ether should only be used by physicians; with respect to anesthesia, even dentists should defer to physicians. To put this concern in context, note that doctors also warned patients that bathing could prove fatal unless prescribed by a physician instead of a hydropath.

Many nineteenth century critics of anesthesia sincerely believed that pain was God's punishment for human failures and wickedness. William Henry Atkinson, M.D., the first president of the American Dental Association, contended that anesthesia was a Satanic plot to deprive men of the capacity to reason and endure the pain that God intended them to experience. Certainly doctors were influenced by religious dogma, but professional norms also conditioned them to be suspicious of an innovation that challenged centuries of medical experience in which insensitivity to pain (as in coma, shock, or brain damage) was a harbinger of death. Pain, life, and healing had always been inextricably linked.

Opponents of the new surgery pounced upon reports of deaths after anesthesia, ignoring the fact that it was not uncommon for patients to die after operations performed without anesthesia. Some critics feared that anesthetics gave doctors excessive power over patients. Anesthetic agents could be used to subdue and tranquilize uncooperative patients into unnecessary, experimental operations. It was even possible that the relief of pain was an illusion; the patient might actually suffer pain but be rendered incapable of expressing or recalling the experience. Although many of these fears were obviously exaggerated, further experience proved that anesthetics, like any potent drug, could cause serious side effects: fatal cardiac arrhythmias, circulatory failures during surgery, postsurgical pneumonia, vomiting that could cause suffocation or tissue damage, and more subtle effects on the liver, brain, fetus, or newborn infants. As a modern medical specialty, anesthesiology includes the administration of surgical anesthesia, acute and chronic pain relief, postoperative care, the management of intensive care, respiratory intensive care, chronic pain management, resuscitation, and emergency medicine. Some departments of anesthesia have become departments of anesthesia and perioperative medicine. Nevertheless, even under optimum, fully modern conditions, the dangers of anesthesia should never be underestimated. In many cases, general anesthesia may be the most dangerous part of an operation.

With proper management, inhalation anesthesia was generally safe, complete, and inevitable. Complete insensibility, however, is not suitable for all operations. Although some of the drugs and instruments involved in the development of local, regional, and spinal anesthesia predate Morton's demonstration, the development of special techniques for their use began in earnest after the acceptance of inhalation anesthesia. In 1803, Friedrich Wilhelm Sertürner (1783-1841) isolated crystals of a powerful analgesic agent from crude opium. Sertürner named this chemical morphine, for Morpheus, the Greek god of dreams. Morphine paste could be introduced locally with the point of a lancet, or a solution of morphine could be instilled into a wound. In the 1850s, Charles Gabriel Pravaz (1791-1853) and Alexander Wood (1817-1884) independently invented the modern type of hollow metal needle. (The device known as a hypodermic syringe in the United States and England is called a Pravaz syringe on the Continent.) Injections of morphine were generally used for the relief of localized pain, but some surgeons administered morphine in preparation for surgery under general anesthesia in the belief that it prevented shock, delirium, nausea, and lessened the amount of inhalant needed. Heroin, a derivative of morphine first synthesized in 1874, was widely marketed in the 1890s as a pain reliever that was allegedly safer than morphine. After the chemical structure of morphine was elucidated in 1923, many other derivatives of morphine were tested, but very few had any particular advantages.

The ancient Incas had successfully exploited the anesthetic qualities of the coca leaf as well as its mood-altering properties, and their Peruvian descendants continued to use coca leaves to drive away pain, hunger, nausea, fatigue, and sorrow. While Europeans quickly took up the native American custom of smoking tobacco, they ignored coca leaves until nineteenth-century chemists isolated interesting alkaloids, including cocaine. After reading a report on the physiological effects of cocaine, Sigmund Freud (1856-1939) decided that the drug might serve as a tonic in the treatment of mental and physical diseases. Using himself as guinea pig, Freud discovered that cocaine banished his depression and increased his energy. Freud urged Carl Koller (1857-1944), a physician who specialized in eye disorders, to try cocaine for the relief of eye diseases such as trachoma and iritis. When a solution of cocaine was instilled into the eye of a frog, Koller could touch the cornea without eliciting any reaction. Following successful tests on rabbits and humans, Koller announced his discovery at the 1884 Ophthalmologic Congress in Heidelberg. Freud credited his colleague Carl Koller with discovering the local anesthetic properties of cocaine, but some scholars think that Freud should be considered one of the founders of psychopharmacology for his own studies of cocaine. By the end of the nineteenth century, many popular ointments, snuffs, suppositories, cigarettes, cigars, patent medicines, and beverages contained cocaine. The best known is Coca-Cola, a patent medicine introduced in 1886 as a therapeutic agent and general tonic. In addition to coca leaf extract, Coca-Cola contained an extract of the kola nut, which is high in caffeine. By 1906 when the Pure Food and Drug Law was passed in the United States, the makers of Coca-Cola were using decocainized coca leaves, but the caffeine remained.

William S. Halsted (1852-1922), one of New York's leading surgeons, realized that Koller had barely begun to exploit the possible range of cocaine anesthesia. Impressed with the drug's effects, Halsted performed a series of tests on himself, his medical students, and experimental animals. Because cocaine constricts blood vessels, it seemed to be the ideal local anesthetic for surgery in highly vascularized areas. Halsted developed a technique that he called conduction anesthesia or nerve block anesthesia—a means of specifically anesthetizing various parts of the body by injecting cocaine solutions into the appropriate nerves.

When using cocaine, Halsted enjoyed feelings of increased energy and creativity, as well as freedom from pain and fatigue, but when he stopped taking cocaine he experienced vertigo, cramps, anxiety, insomnia, and hallucinations. When his addiction to cocaine interfered with his ability to operate, Halsted was sent to an asylum for the mentally ill. He was quite a different person when he emerged a year later, cured of the cocaine habit, but addicted to morphine. Encouraged and supported by his colleagues William Osler (1849-1919) and William Henry Welch (1850-1934), Halsted continued his distinguished career as the first professor of surgery at Johns Hopkins. A century later, descriptions of the symptoms of cocaine abuse included intense anxiety, depression, acute psychosis, paranoid delusions, auditory or visual hallucinations, and seizures followed by respiratory or cardiac arrest.

The history of anesthesia is closely related to studies of the meaning and mechanism of pain. While scientific understanding of the mechanism of pain is far from complete, the problem can now be reformulated in terms of neuroendocrinology and the discovery of the opiate receptors and the endorphins, the body's own endogenous morphine-like substances, in the 1970s. Given the fact that opium and morphine are not natural constituents of the nervous system, scientists reasoned that there must be opiate receptors that play a role in the control of pain via some endogenous narcotic. Avram Goldstein (1919—), one of the pioneers of this field, said that when thinking about the effects of morphine he asked himself ''why would God have made opiate receptors unless he had also made an endogenous morphine-like substance?" Just as enzymes and substrates fit together like locks and keys, so too might natural opiates interact with the receptors on nerve cells that apparently interacted with morphine and morphine-like drugs. In 1973, Solomon Snyder (1938 ) and Candace Pert (1946-) identified the opiate receptors in the brain. Within the year, scientists at several other laboratories confirmed their discovery. By 1975, scientists had discovered the endogenous opiates, neurotransmitter peptides called endorphins or enkephalins that mimic the action of morphine. Several families of endorphins were found in the brain, pituitary gland, and other tissues. Through studies of the endorphin system, neurobiologists and pharmacologists expect to find ways to control the production of endorphins, develop safe endorphin-like drugs, and modulate acute and chronic pain.

Although patients and lay people tend to believe that the relief of suffering is one of the primary goals of medicine, pain and suffering have received relatively little attention in medical education and training. Subjective pain, and the cultural contexts in which patients experience pain are not necessarily considered aspects of the ''functional impairments'' and disabilities that fall into the domain of medicine. Pain was traditionally regarded as a symptom, rather than a diagnosis, and thus, of little interest in and of itself. Control of surgical pain presumably raised expectations that all forms of pain could be controlled by appropriate analgesics. However, success in the development of surgical anesthesia was not readily extended to the broader problem of acute and chronic pain. Since the 1960s, patients and patient advocates have become increasingly vocal about the problem of pain, particularly chronic pain, which was not a major concern of surgeons. Chronic pain, in particular, has been called one of the most intractable of modern epidemics. In response, many hospitals and medical centers have established multidisciplinary pain clinics.

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