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During the eighteenth century, progress in anatomical investigation, and the acceptance of a localized, lesion-based, or solidistic approach to pathology, provided an intellectual framework for surgical innovations. From the patient's point of view, however, pain was a powerful reason for avoiding even the most desperately needed operation. Physiologists define pain as an ''unpleasant sensory and emotional experience associated with actual or potential tissue damage,'' which, nevertheless, is important to the maintenance and preservation of life. Pain provides an essential warning about trauma and injury, but it can also have strong negative effects on health. Usually, pain motivates behaviors that help prevent further injuries, but fear of pain kept patients from accepting the advice of surgeons and dentists.

Despite the fact that narcotics have been used for rituals and recreation for thousands of years, Oliver Wendell Holmes (1809-1894) reflected conventional medical wisdom when he said that nature offered only three natural anesthetics: sleep, fainting, and death. Experimentation with mind- and mood-altering substances is older than agriculture, but the potions prepared for ceremonial, religious, or social purposes were rarely used for the relief of surgical pain. Perhaps the powerful religious associations of intoxicants militated against their use as secular anesthetics. On the other hand, the magical agents used in ceremonies culminating in ecstasy and self-mutilation might have worked primarily through the power of suggestion. If the potion did not work, the person using the drugs was to blame for lack of faith. If someone died as a result of an overdose, it was the will of the gods.

Thus, it is unreasonable to assume that the preparations used to induce ceremonial intoxication would satisfy the essential criteria for surgical anesthetics: relief of pain must be inevitable, complete, and safe. Drugs that are appropriate for ceremonial purposes might cause unpredictable and dangerous effects in a person undergoing surgery. As statistics for deaths due to drug overdoses indicate, people are willing to take risks with recreational drugs that they would not find acceptable in medical procedures. In the religious context, death was in the hands of the gods; in the operating room, the responsibility belonged to the surgeon.

If anesthetics are ''tamed inebriants,'' then alcohol should have been the drug of choice for surgery. Alcoholic preparations have been used as the ''potion of the condemned'' and in preparation for ceremonial tribal rites, such as circumcision and scarification. Unfortunately, the large doses of alcohol needed to induce stupefaction are likely to cause nausea, vomiting, and death instead of sleep. Healers could also try to induce what might be called a state of psychological anesthesia by means of mesmerism, hypnotism, shamanistic rituals,

Mastectomy procedures depicted in a 1666 text by Johann Schultes (15951645).

prayers, and the symbolic transference of pain to an animal or inanimate item. Such methods might not be inevitable and complete, but a mixture of hope and faith is likely to be safer than complex, impure mixtures of drugs and alcohol.

Various forms of self-hypnosis were used in India, but these practices require high levels of training, concentration, and self-discipline. The best known European version of psychological anesthesia was developed by the Austrian physician Friedrich Anton Mesmer (1734-1815). Although Mesmer's methods were criticized by physicians and exposed as fraudulent by skeptical scientists, including American scientist and statesman Benjamin Franklin (1706-1790) and French chemist Antoine Laurent Lavoisier (1743-1794), sensitive patients were easily put into a somnambulistic state by Mesmer's ''animal magnetism.'' Not surprisingly, physicians and scientists were generally suspicious of mesmerism, because of its close association with quackery. James Braid (1795-1860) coined the term hypnotism to separate the scientific study of mesmerism or ''nervous sleep'' from spiritualism and quackery. According to Braid, hypnosis was a subjective condition that depended on the suggestibility of the patient. Nevertheless, in sensitive subjects, the hypnotist could induce a state of somnambulism deep enough to overcome the pain of surgical operations. To demonstrate the power of this technique, a notorious French ''midwifery-mesmerist'' mesmerized women in a lying-in hospital and a lion at the zoo.

By the time European physicians began to take hypnotism seriously, the triumph of inhalation anesthesia was virtually complete. Somewhat out of phase with the tides of history, John Elliotson (1791-1868), lecturer on medicine at the University of London, founded a hospital for studies of mesmerism. He reported that even amputations at the thigh could be carried out under hypnotism. James Esdaile (1808-1859), who became interested in mesmerism while working in India, claimed that the mortality rate for more than two hundred operations he had performed using mesmerism as an anesthetic was less than six percent. Unfortunately, when he returned to Scotland in 1851, he found that mesmerism did not work as well there as it had in India. Eventually, hypnotism proved to be more significant in the development of psychoanalysis than in surgical anesthesia. The Parisian neurologist Jean Martin Charcot (1825-1893) used hypnotism in his clinical studies of hysteria, but considered the hypnotic state pathological in itself. Recent studies of the neuroendocrinology of pain may help explain the mechanism of hypnotism. Surprisingly, although hypnotism has generally been denigrated as ''mere suggestion,'' it is more likely to ameliorate ''real'' pain than ''imaginary'' pain.

Surgeons experimented with many methods of distracting the patient from the pain of an imminent operation. A direct, but crude way of inducing a state of insensitivity was to knock the patient unconscious with a blow to the jaw. This technique is not very specific or complete, but the surgeon might be able to extract a bullet before his patient recovered from the shock. Distraction could also be achieved by rubbing the patient with counterirritants such as stinging nettles. Pressure applied to nerves or arteries could induce insensitivity to pain, but it could also result in asphyxia and death. Even phlebotomy could act as a painkiller when it was carried out aggressively enough to induce fainting. Such bleedings were used in preparation for childbirth, reducing dislocations, and setting fractures. Such methods were too unpredictable to fit the criteria for surgical anesthesia.

Mythology and folklore are rich in allusions to wondrous potions such as the potion used by Helen of Troy to quench pain and strife. Unfortunately, the ingredients in the perfect painkillers of mythology were secret and mysterious. More accessible recipes for sleep potions typically contained so many dangerous ingredients that it was safer to inhale them than to ingest them. With inhalation, the amount of the active ingredients need not be calculated too precisely, because the inhalant could be withdrawn as soon as the patient was sufficiently affected. In contrast, an overdose of drugs swallowed or injected could not be recalled.

The medieval prototype of the ''sleep apple'' that appears in the story of Snow White usually contained opium, mandrake, henbane, hemlock, wine, and musk. Usually, the user was expected to inhale the fumes of the apple rather than eating it. The ''soporific sponges'' recommended by medieval surgeons contained similar mixtures. By the sixteenth century, surgeons were describing old favorites like mandrake as poisonous drugs that lulled the senses and made men cowards. In Shakespeare's Antony and Cleopatra, Cleopatra safely used mandrake to sleep away the hours before Antony's return. Shakespeare alludes to various soporific agents, such as poppy, mandragora, and ''drowsy syrups,'' but these agents were unreliable at best. In the real world, surgeons found that drugged patients who slept like the dead during surgery often failed to awaken afterwards. Opium retained its favored status long after mandrake was discarded. Eminent physicians like Thomas Sydenham (1624-1689) and John Hunter (1728-1793) saw opium as a powerful drug and proof of God's mercy. As Hunter told a colleague seeking advice about treating a patient with a painful malignant cancer, the only choice was ''Opium, Opium, Opium!" In large doses, opium generally causes drowsiness and depression, but excitation, vomiting, headaches, and constipation are not uncommon side-effects. Opium and other opiates do not prevent breathing, but they do reduce the sensitivity of the respiratory center to carbon dioxide. Because the automatic drive to breathe is reduced, a person who falls asleep after taking such drugs may die. Opiates may also cause constipation, severe sedation, nausea and vomiting, repression of the cough reflex, or bronchospasm. Despite such problems, opium was used in cough medicines, sleeping potions, and soothing elixirs for crying babies. Some critics recognized the dangers of drug dependence, but opium remained widely available into the twentieth century. Soporifics and narcotics were also prepared from marijuana, hellebore, belladonna, henbane, jimsonweed, and enough miscellaneous greens to make a very exotic salad. Henbane, which was known as the poor man's opium, was recommended for insomnia, toothache, and pain.

Poisonous substances are present throughout the tissues of the ubiquitous jimsonweed, but the powerful alkaloids atropine and scopolamine are concentrated in the seeds. Reports of atropine-like poisoning in people who have eaten the seeds and washed them down with alcohol are not uncommon. Long used as a hypnotic and sedative, scopolamine became popular with twentieth-century obstetricians, who claimed that the so-called twilight sleep induced by a combination of scopolamine and morphine allowed scientific management of painless childbirth. Critics argued that twilight sleep was more effective as an amnesiac than an anesthetic. When this method was used, women experienced labor pains, but later forgot them and thought that the birth had been painless. Even though she knew that women had to be restrained when given scopolamine-morphine anesthesia, Dr. Bertha Van Hoosen (1863-1952) praised twilight sleep as ''the greatest boon the Twentieth Century could give to women.'' Van Hoosen devised a special crib to confine women undergoing this allegedly painless form of childbirth in order to prevent injury as they thrashed about and screamed. In 1915, Van Hoosen founded and became first president of the American Medical Women's Association. By the 1920s, skepticism about twilight sleep and the availability of other drugs ended the era of scopolamine-morphine anesthesia. Scopolamine has even been marketed for relief of seasickness, despite the fact that it can produce dangerous hallucinations.

Hemlock was the active ingredient in the infamous death potion given to the Greek philosopher Socrates (470-399 b.c.e ), who was condemned for corrupting the minds of the youth of Athens. Although clearly a dangerous drug, hemlock was sometimes used in anesthetic concoctions. The drug depresses the motor centers before the sensory centers are affected; this may be good for the surgeon, but bad for the patient. Surgeons were eager to find drugs that would produce muscle relaxation as well as analgesia. Curare, an arrow poison used by South American Indians, was brought to the attention of European scientists by naturalist and explorer Alexander von Humboldt (17691859), who came close to killing himself in the course of this research. Curare does not relieve pain, but it is useful in surgery because it prevents movement and provides profound muscle relaxation. Since the state of paralysis induced by curare can be fatal without artificial respiration, it would not have been useful in nineteenth century surgery. Many decades later, surgeons would redefine the ''classical triad'' of anesthesia as: unconsciousness (or amnesia), analgesia, and muscle relaxation (where appropriate).

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