Strangely enough, the numerous means of attaining insensibility, then more or less known to the common people, and especially to criminals and executioners, do not appear to have found favor for use during operations. Whether this was due to unpleasant after-effects, or from what reason, we are not informed. Only one or two surgical writers beside Guy de Chauliac (1498) refer in their works to agents for relief of pain, and then almost always to their unpleasant effects, the danger of producing asphyxiation, and the like. Ambrose Paré wrote that preparations of mandrágora were formerly used to avert pain. In 1579, an English surgeon, Bulleyn, affirmed that it was possible to put the patient into an anaesthetic state during the operation of lithotomy, but spoke of it as a "terrible dream." One Meisner spoke of a secret remedy used by Weiss, about the end of the XVII Century, upon Augustus II., king of Poland, who produced therewith such perfect insensibility to pain that an amputation of the royal foot was made without suffering, even without royal consent. The advice which the Friar gave Juliet regarding the distilled liquor which she was to drink, and which should presently throw her into a cold and drowsy humor, although a poetic generality, is Shakespeare's recognition of a popular belief. Middleton, a tragic writer of Shakespeare's day, in his tragedy known as "Women beware Women," refers in the following terms to anesthesia in surgery:
"I'll imitate the pities of old surgeons
To this lost limb, who, ere they show their art,
Cast one asleep; then cut the diseased part."
Of course, of all the narcotics in use by educated men, opium has been, since its discovery and introduction, the most popular and generally used. Surgeons of the last century were accustomed to administer large doses of it shortly before an operation, which, if serious, was rarely performed until the opiate effect was manifested. Still, in view of its many unpleasant after-effects, its use was restricted, so far as possible, to extreme cases.
Baron Larrey, noticing the benumbing effect of cold upon wounded soldiers, suggested its introduction for anesthetic purposes, and Arnott, of London, systematized the practice, by recommending a freezing mixture of ice and salt to be laid directly upon the part to be cut. Other surgeons were accustomed to put their patients into a condition of either alcoholic intoxication or alcoholic stupor. Long-continued compression of a part was also practised by some, by which a limb could, as we say, be made to "go to sleep." A few others recommended to produce faintness by excessive bleeding. It was in 1776 that the arch-fraud Mesmer entered Paris and began to initiate people into the mysteries of what he called animal magnetism, which was soon named mesmerism, after him. Thoroughly degenerate and disreputable as he was, he nevertheless taught people some new truths, which many of them learned to their sorrow, while in the hospitals of France and England severe operations were performed upon patients thrown into a mesmeric trance, and without suffering upon their part. That a scientific study of the mesmeric phenomena has occupied the attention of eminent men in recent years, and that hypnotism is now recognized as an agent often capable of producing insensibility to pain is simply true, as these facts have been turned to the real benefit of man by scientific students rather than by quacks and charlatans.
In 1799, Sir Humphrey Davey, being at that time an assistant in the private hospital of Dr. Beddoes, which was established for treatment of disease by inhalation of gases, and which he called The Pneumatic Institute, began experimenting with nitrous oxide gas, and noticed its exhilarating and intoxicating effects; also the relief from pain which it afforded in headache and toothache. As the results of his reports, a knowledge of its properties was diffused all over the world, and it was utilized both for amusement and exhibition purposes. Davey even wrote as follows of this gas:
As nitrous oxide, in its extensive operation, appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place.
It is not at all unlikely that Colton and Wells, to be soon referred to, derived encouragement, if not incentive, from these statements of Davey. Nevertheless, Velpeau, perhaps the greatest French surgeon of his day, wrote in 1839, that "to escape pain in surgical operations is a chimera which we are not permitted to look for in our day."
Sulphuric ether, as a chemical compound, was known from the XIII Century, for reference was made to it by Raymond Lully. It was first spoken of by the name of ether by Godfrey, in the Transactions of the London Royal Society, in 1730, while Isaac Newton spoke of it as the ethereal spirits of wine. During all of the previous century it was known as a drug, and allusion to its inhalation was made in 1795 in a pamphlet, probably by Pearson. Beddoes, in 1796, stated that "it gives almost immediate relief, both to the oppression and pain in the chest, in cases of pectoral catarrh." In 1815, Nysten spoke of inhalation of ether as being common treatment for mitigating pain in colic, and in 1816 he described an inhaler for its use. As early as 1812 it was often inhaled for experiment or amusement, and so-called "ether frolics" were common in various parts of the country. This was true, particularly for our purpose, of the students of Cambridge, and of the common people in Georgia in the vicinity of Long's home. It probably is for this reason that a host of claimants for the honor of the discovery appeared so soon as the true anesthetic properties of the drug were demonstrated.