The Discovery of Chloroform as an Anæsthetic
The next epoch-making event in the history of anæsthesia was the discovery of the anæsthetic properties of chloroform. The substance itself had been known for over a quarter of a century. Thomson, in his “System of Chemistry,” 1820, describes a liquid which is formed by the union of chlorine and olefiant gas, called “Dutch liquid,” or chloric ether. Early in the year 1831, Samuel Guthrie of Brimfield, Massachusetts, who was then residing in Sackett’s Harbour, New York State, in consequence of a statement that he had read that the alcoholic solution of this chloric ether was useful in medicine as a diffusible stimulant, devised an easy method of preparing it. This being done, he wrote an article which he entitled “A Spirituous Solution of Chloric Ether,” and forwarded it to the editor of the “American Journal of Science and Art,” in which it was published in October of the same year. In this article he fully describes his method of preparation. A few months later, in January, 1832, Soubeiran published a paper in a French journal, stating that he had discovered this method in 1831, and to the distilled fluid he produced he had given the name of “bichloric ether,” the formula being CHCl. Still a third claimant to the discovery came forward in the person of Liebig, who published his account in November, 1831, six months after Guthrie’s manuscript was in the publisher’s hands, and one month after its publication. The formula which Liebig deducted from his analysis was C4Cl5, and he called his product “chloride of carbon.” Although there may be some doubt as to which of these claimants was actually the first to manufacture the liquid, it is clear that Guthrie was the first to publish the account of the discovery. He was born in 1782, was a surgeon in the United States Army in 1812, and died in 1848.
From an account given by D. B. Smith, of Philadelphia, in the “Journal of the College of Pharmacy”[2] in 1832, there can be little doubt that the liquid first made by Guthrie was a fairly pure chloroform. He describes it in the following words: “The action of this ether on the living system is interesting, and may hereafter render it an object of importance in commerce. Its flavour is delicious, and its intoxicating properties equal to or surpassing those of alcohol.” In 1834, Dumas examined the liquid as prepared by Soubeiran, and declared that he had not obtained it pure, and further, that Liebig had made an error in its composition. On further research, Dumas gave the liquid the name of “chloroform,” and first worked out the real formula, C2HCl3 (or, using the present system of atomic weights, CHCl3).
[2] Now the “American Journal of Pharmacy”
Previous use of chloroform in medical practice
Although its narcotising properties were known to some extent, no one who used it at that time seems to have conceived the idea of fully testing its properties. In 1831, Ives, of Newhaven, treated a case of difficult respiration by actual inhalation of the vapour, and published the facts in “Silliman’s Journal” in January, 1832. Four years later, Dr. Formby, of Liverpool, prescribed it in hysteria; and Tuson, of London, employed it in the treatment of cancer and neuralgia in 1844.
Simpson’s investigations
The fact that one or two deaths had been attributed to the use of ether about this time, caused many workers to make a search for other agents with similar properties. Foremost among these investigators was Dr. James Young Simpson, Professor of Midwifery in the University of Edinburgh, who personally experimented with several chemical liquids in the hope of finding something less disagreeable and persistent in smell than ether.
David Waldie
Waldie suggests the use of chloroform
About this time, Jacob Bell, a chemist, and a founder of the Pharmaceutical Society, published a suggestion that chloric ether should be used for inhalation instead of sulphuric ether; but his suggestion was apparently never put into practice. In October, 1847, Waldie, a chemist of Liverpool, was visiting Edinburgh, and in conversation with Professor Simpson, suggested to the latter the use of chloroform. He recommended the Professor to try it as an anæsthetic, and promised to make and send him some on his return to his home in Liverpool.
Sir James Young Simpson
It appears to have been in that city that the drug was first introduced and probably first used in England as a medicinal agent. Waldie states that about the year 1838 a prescription was brought to the Apothecaries’ Hall, Liverpool (where he held the position of manager), of which one of the ingredients was chloric ether. The preparation was at that timen apparently not known in this country, for Dr. Brett, the chemist of the Company, specially prepared some from the formula he found in the United States Dispensatory. Its properties pleased some of the medical men, particularly Dr. Formby, by whom it was introduced into local practice. Waldie, finding that the preparation was not uniform in strength, improved the process by separating and purifying the chloroform, and dissolving it in pure spirit, by which a product of sweet flavour was obtained.
There seems little doubt that Waldie was the first to suggest the use of chloroform, as an anæsthetic, to Professor Simpson, who at once resolved to try it by experimenting on himself and his assistants. He made the first experiment in his own house on November 4th, 1847, and in a letter written to Waldie thus describes the event: “I am sure you will be delighted to see part of the good results of our hasty conversation. I had the chloroform for several days in theOn the eve of the great discovery. house before trying it, as, after seeing it such a heavy, unvolatile-like liquid, I despaired of it, and went on dreaming about others. The first night we took it, Dr. Duncan, Dr. Keith and I all tried it simultaneously, and were all ‘under the table’ in a minute or two.” Professor Miller, who was a neighbour of Simpson’s, used to come every morning to see if the experimenters had survived! He describes how, “after a weary day’s labour, Simpson and his assistants sat down and inhaled various drugs out of tumblers, as was their custom. Chloroform was searched for and found beneath a heap of waste paper, and with each tumbler newly charged the inhalers resumed their occupation. . . . A moment more, then all was quiet; then a crash. On awakening, Simpson’s first perception was mental. ‘This is far stronger and better than ether,’ said he to himself. His second was to note that he was prostrate on the floor, and that among the friends about him there was both confusion and alarm. Of his assistants, Dr. Duncan he saw snoring heavily, and Dr. Keith kicking violently at the table above him. They made several more trials of it on that eventful evening, and were so satisfied with the results that the festivities did not terminate until a late hour.”
On November 10th, 1847, Simpson communicated his discovery to the Medico-Chirurgical Society of Edinburgh, in a paper entitled, “Notice of a new anæsthetic agent as a substitute for sulphuric ether.” A day or two afterwards an arrangement was made with Simpson to administer the new anæsthetic to a patient who was about to be operated upon, but, owing to some cause, he was unable to be present. The operation went on without him, and the patient died on the first incision of the knife. Simpson’s absence was providential indeed, for it saved the reputation of chloroform at the outset. On November 15th, chloroform was used for the first time in a surgical operation in the Edinburgh Royal Infirmary.Simpson achieves success Three patients were operated on successfully under its influence. One, who was a soldier, was so delighted with the effect that, on awaking after the operation, he is said to have seized the sponge with which administration had been made, and, thrusting it into his mouth, again resumed inhalation more vigorously than before.
To Simpson, there is no doubt, belongs the merit of having made anæsthesia triumph over all the opposition, which was at first, actively, offered to its use. For this he well deserved the rewards which fell upon him in the evening of his life.
Among those who aided in the establishment of the use of anæsthetics, mention must be made of the work of John Snow, who by his researches placed the practice on a scientific basis.
The advent of chloroform gave an impetus to other investigators in the field of anæsthesia, and during the last fifty years many other bodies have been introduced and tried with more or less success for the same purpose. Methyl chloride, which was discovered by Dumas and Peligot, was introduced by Deboe in 1887, who used it extensively in local affections. In 1867, Sir B. W. Richardson introduced methyl bichloride or methylene [methylene dichloride]. He formed a very high estimate of its properties as a good general anæsthetic, and said he preferred it for many reasons to chloroform, as he found that the anæsthetic sleep was produced more quickly and was more prolonged.
Sir T. Spencer Wells also advocated its use, and stated, in 1872, that it had fewer drawbacks than any then known anæsthetic. Tetra-chloride of methyn [carbon tetrachloride], which much resembles chloroform, was discovered by Regnault in 1839, and its anæsthetic properties were first made known by Sansom and Harley in 1864. Simpson was of the opinion that it had a more depressing effect upon the heart than chloroform, and was more dangerous generally as an anæsthetic.
Nunneley, of Leeds, also contributed work of value in this department of research, and introduced ethyl bromide and chloride of carbon. He dispelled the idea, long prevalent, that anæsthetics could be found only in a limited class of chemical compounds.
Among other substances which have been introduced during the last twenty-five years, but which, owing to one defect or another, have since been practically abandoned, mention should be made of butylic hydride [butane], ethylene, amylene, ethyl nitrate, aldehyde (introduced by Poggiale), carbon bisulphide, ethidene dichloride [ethylene dichloride] (discovered by Regnault and first used as an anæsthetic by Snow), and ethyl bromide, first prepared by Serullus in 1827.