A HUNDRED YEARS OF CHLOROFORM* By DOUGLAS GUTHRIE I HAVE been asked to address you at this centenary meeting on " The Discovery of Chloroform Anaesthesia," and no doubt the University has acted wisely in apportioning the duty to one who is neither an anaesthetist nor an obstetrician, but simply a worker in the neutral field of history. It is good to praise famous men and to recall great achievements, and surely the discovery of chloroform anaesthesia by Professor James Young Simpson was one of the most important advances, as well as one of the most dramatic episodes, in the long history of medicine, which we do well to celebrate upon this, its hundredth anniversary. As we do so, we may find it hard to realise that the discovery was so long delayed, and that only so recently as the middle of last century was surgery completely revolutionised by the introduction of anaesthesia and antisepsis. The quest for some means of relieving pain had been pursued down the ages since prehistoric times. Nepenthe, used by Helen of Troy, was followed by mandragora, a drug which retained its popularity for many centuries. Other pain-relieving agents?opium, " and henbane, and various drowsy syrups," as well as physical means, such as freezing or pressure, were employed with very varying degrees of success. Animal magnetism, or mesmerism, was the anaesthetic method which held the popular imagination and also the attention of surgeons in this country about the middle of last century, when there arrived from America news of the spectacular use of ether by inhalation. The first public demonstration of the value of ether anaesthesia in surgery was given by William T. G. Morton at Boston, on 16th October 1846. There were other claimants to the priority of the discovery? Crawford Long, Horace Wells, and Charles Jackson. There is no need to revive this complex controversy, so widely publicised a year ago. Suffice it to say that our present festival in no way detracts from the merit due to the American pioneers of ether anaesthesia. Robert Liston, at University College Hospital, London, is usually regarded as the first to employ ether anaesthesia in major surgery in Britain in December 1846; while James Young Simpson was the first to introduce it into obstetric practice, in January 1847. On hearing of the American discovery, Professor Simpson had written " to his brother, It is a glorious thought ; I can think of naught else." Here was the solution to a problem which had intrigued him since * Address delivered in the Upper Library Hall, University of Edinburgh, on 4th November 1947, at a reception to celebrate the centenary of the discovery of chloroform ansesthesia by Sir James Young Simpson. A HUNDRED YEARS OF CHLOROFORM 247 his student days, and now he readily grasped the opportunity of testing its efficiency. As he continued to use ether, it became apparent to Simpson, and to many others, that this was not yet the ideal anaesthetic. It was uncertain in action, irritating to the air passages, and required special apparatus for its administration. Simpson resolved that he would find some anaesthetic which would be free from such disadvantages. He inhaled all manner of gases and vapours, and it is said that on one occasion at least, before his discovery, he rendered himself unconscious, greatly to the alarm of his family. In his search for a new anaesthetic he enlisted the services of his assistants, Keith and Matthews Duncan. On many an evening, when each day's work was over, the trio sat around his dining-room table at 52 Queen Street, engaged in a strange but heroic experiment upon themselves. Early each morning, Simpson's next door neighbour, Professor Miller, " would call to ascertain the results, or, as he himself remarked, to find out whether everyone was still alive." The little team of investigators had been at work for several months, and a variety of substances had already been tested. Shortly before the night in question, David Waldie of Liverpool had mentioned to Professor Simpson that it might be worth while to try the effect of perchloride of formyle, or chloroform. Waldie, a medical man who had become a chemist, deserves credit for his suggestion, although he made no experiments on his own account. A small quantity of chloroform had been prepared for Simpson by the professor of chemistry, William Gregory, but it had been laid aside as it appeared heavy and unpromising. On the night of the discovery, after several substances had been tested without result, this little phial was searched for, and found under a heap of waste paper. Simpson himself was the first to inhale it, and his companions followed his example on observing that it seemed effective. Naturally he was also the first to regain his senses, and the thought prominent " in his returning consciousness was that something far stronger and better than ether" had been discovered. Then he noticed that Matthews Duncan was snoring in his chair with open mouth and staring eyes, while Keith, having reached only the stage of excitement, had slipped under the table and was kicking it vigorously. Each of them on recovery echoed Simpson's satisfaction with the effect of the new agent. The witnesses of this strange scene, who must surely have been much alarmed, included Mrs Simpson, her sister Miss Grindlay, and her niece Miss Petrie. When further trials were made, Miss Petrie insisted upon inhaling the drug, and thus became the first woman subjected to its influence. Some few days later in the Royal Infirmary of Edinburgh, Professor Simpson administered chloroform to three patients, two of whom underwent operation by Professor James Miller, the third by Mr John 248 DOUGLAS GUTHRIE Duncan. The first of them was a highland boy, whose name is unrecorded and who could speak only Gaelic. A large fragment of diseased bone was removed from his arm. He continued to sleep soundly after the operation and felt no pain. Simpson lost no time in making known his discovery. Within a week, on ioth November 1847, he presented to the Medico-Chirurgical " Society of Edinburgh his Account of a New Anaesthetic Agent." Chloroform rapidly became the anaesthetic of choice, and soon superseded ether in this country and on the continent. Nevertheless Simpson continued his researches, hoping to improve the method. Every member of his household was now eager to share in the work. At one time Professor Simpson resolved to try the effect of drinking a mixture of chloroform and champagne. Hearing of this, his butler, named Clarke, administered a dose of the potent cocktail to the cook, who promptly fell insensible on the kitchen floor. " Clarke rushed upstairs to his master, calling Come down, sir, come down for God's sake, I've poisoned the cook." Fortunately the victim rapidly recovered. It seems advisable that one should include in this brief survey some account of the life-story of the discoverer, of whose accomplishment this University may well be proud. Born at Bathgate in 1811, the youngest of a family of eight children, James Simpson climbed the ladder of fame from a lowly rung. From his earliest years he had an insatiable appetite for learning, and even at the village school he " was known as the wise wean." Poor though they were, his father and mother resolved that Jamie would proceed to the University, and this he did at the age of fourteen. " Thus, I entered Edinburgh University," he told the audience " on receiving the Freedom of the City many years later, very young, very solitary, very poor, and almost friendless." His estimate of the relative values of nourishment and knowledge is shown by an entry in his diary of expenses as a student : Finnan haddies, 2d. ; Book on Osteology, 21s. During his student days he was so repelled and shocked by the dreadful scenes of suffering in the operating theatre that on one occasion he actually resolved to abandon medicine and to devote himself to the study of law. Leaving the Infirmary he proceeded to Parliament House with this object in view. Fortunately, his better judgment prevailed. He accepted the existing conditions as a challenge rather than as a deterrent, and it seems probable that from that very day he gave much thought to the clamant need for the prevention and relief of pain in surgery. After graduating M.D. in 1832, he became assistant to John Thomson, the professor of pathology, and it was Thomson who advised him to specialise in midwifery. In 1840 the Town Council of Edinburgh, by a majority of one vote, appointed him professor of midwifery in succession to Professor Hamilton. He brought great repute to the chair and he contributed very materially to the progress A HUNDRED YEARS OF CHLOROFORM 249 of midwifery and gynaecology. Nevertheless he did not allow his specialty to monopolise all his energies. A versatility such as his could not accept the limitations of specialist practice. His advocacy of the control of haemorrhage by needles in place of ligatures, acupressure, as he called it, brought him into conflict with some of his surgical colleagues. Simpson regarded this discovery as equal to the discovery of chloroform anaesthesia, although acupressure has now become a mere historical curiosity. Another campaign of Simpson's was directed against the evil of large hospitals, the so-called hospitalism. In place of the great solid structures, so conducive to septic infection, he advised the building of small temporary hospitals. His conclusions were not always correct: indeed, he was one of the strongest opponents of Lister's methods. Nevertheless his arguments were always supported by evidence carefully collected.