The discovery which is indicated by the somewhat unfamiliar word^[16] which heads this article is perhaps the greatest which has ever been made in connection with the science of medicine. At least, there is no other discovery of modern times which has so largely and directly contributed to the assuagement of human suffering. Nay, in this respect there is perhaps in the whole annals of the healing art no other which can rival it, if we except that famous one of Jenner’s which has arrested the ravages of small-pox. During the last thirty years, all the more formidable operations of the surgeon have been, in almost every case, performed with a happy unconsciousness on the part of the patient. In unconsciousness, induced by the same means, has relief also been found for severe suffering arising from other causes. The substances which are denoted by the word “anÆsthetics” differ from the drugs which the older surgeons sometimes administered before an operation, in order to lull the patient’s sense of pain. They differ in their nature and in the mode of their administration; by the certainty and completeness of their action; by the entirely transient effects they produce, which pass off without leaving a trace.

To the great chemist whose name has already been mentioned as the discoverer of the metals of the alkalies and alkaline earths we are indebted for the first of the remarkable class of bodies we are about to discuss. The first work that Davy published had for its title “Researches, Chemical and Philosophical, chiefly concerning Nitrous Oxide and its Respiration.” This was in the year 1800, when the philosopher had hardly completed his twenty-first year. The work caused no little sensation in the scientific world, and it was in consequence of the reputation he acquired by these researches that Davy was appointed to the chemical professorship at the Royal Institution. Davy was not the original discoverer of nitrous oxide, but he first entered upon a full investigation of its properties, and announced the singular effect produced by its inhalation. The kind of transient intoxication and propensity to laughter which it excites have obtained for this compound the familiar name of laughing gas. Davy had by experiment on his own person proved the anÆsthetic properties of this gas, for he had a tooth painlessly extracted when under its influence, and he says in the work above named that “as nitrous acid gas seems capable of destroying pain, it could probably be used with advantage in surgical operations where there is no effusion of blood.” Davy’s observations and suggestions were destined to lie barren for nearly half a century, but they nevertheless formed the basis of the great results which have since been attained.

Before proceeding farther, it will perhaps be well to make the unscientific reader acquainted with the chemistry of nitrous oxide. We may presume that he knows that atmospheric air is a mixture of the two invisible gases, nitrogen and oxygen (the small quantity of carbonic acid also present need not now be considered). When a known quantity of air is passed over red-hot copper turnings, contained in a tube, the whole of the oxygen is seized upon by the copper, and only the nitrogen issues from the tube, and may be collected. Some of the copper is thus converted into oxide, and the increase of the weight of the tube’s contents shows the weight of oxygen contained in the air, while the weight of nitrogen may be known from the volume collected. In this way the chemist analyses atmospheric air, and determines that 100 parts by weight of dry air contain about 79 of nitrogen and 21 of oxygen; or, by measure, about four times as much of the former as of the latter. Now, chemists are acquainted with no fewer than five different substances which contain nothing but nitrogen and oxygen. These substances are either gases, or can be changed into the gaseous form by heat, and they can all be analysed in the same manner as air. The results of such analyses show in 100 parts by weight of each substance the following proportions of its constituents:

In casting the eye over this table, no relation will probably be detected between the five cases. But if we write down, not the quantities of nitrogen and oxygen contained in 100 parts of each compound, but the quantity of oxygen which in each compound is united to some fixed quantity of nitrogen, we shall at once detect a remarkable law: thus, taking 28 as the fixed weight of nitrogen, for reasons which need not be here explained:

Chemists have a sort of shorthand method of expressing the composition of substances, which may be conveniently illustrated by the case before us. Let it be agreed that the letter N shall not only represent nitrogen, but always fourteen parts by weight—grains, ounces, &c., &c.,—of nitrogen; and that, similarly, O shall stand for sixteen parts by weight of oxygen. It is plain that the composition of the compound No. 2 may be represented by simply writing down “NO;” and that of No. 4, in which there is just double the proportion of oxygen, by “NOO.” But to avoid an unnecessary repetition of the same symbol, when it has to be taken more than once, a small figure is written after and a little below it. Thus, for OO, “O₂” is written. The proportional composition of each of the five compounds will now be obvious from the following symbols:

These symbols may be regarded as merely a compendious expression of the composition of each substance—as a shorthand statement of the facts of analysis. But to the majority of chemists the symbols have a deeper significance; for they are taken as representing the atoms of each element which enter into each smallest possible particle of a compound; they express a certain theory of the ultimate constitution of matter. Thus, if we suppose that there exist indivisible particles of nitrogen and of oxygen, and that each smallest particle, or molecule, of the compounds under consideration is constituted of a certain definite and invariable number of each kind of atoms; and, further, if we suppose that an atom of oxygen is heavier than one of nitrogen in the proportion of 16 to 14, or 8 to 7, we shall have a simple theoretical explanation of the relations in the proportions already pointed out. In fact, these would result from the simplest combinations of the two kinds of atoms; and we can picture each one of the smallest particles of the several bodies as thus constituted:

The black circles represent nitrogen atoms, and the open ones oxygen atoms; the symbols are placed below in order that their relation to the supposed atomic constitution may be obvious at a glance. While the symbol of a compound must always accord with its percentage composition, the latter does of itself determine the symbol or formula. A number of other circumstances, which cannot here be discussed, are taken into account as evidence of the constitution of the molecule.

This digression on chemical formulÆ will, it is hoped, enable the general reader, who may not previously have been acquainted with them, to perceive their significance, instead of passing them over as unintelligible cabalistic letters when they occur in the following pages. With this object, it may be added that the elements, hydrogen, carbon, and chlorine, are respectively represented by H, C, and Cl; and that the proportional quantities, which are also implied in the symbols, and are those by which H, C, and Cl combine with other bodies, are 1, 12, and 35·5 respectively. Another point which should be understood is that the properties and behaviour of a chemical compound are different, and usually extremely different, from those of any of its constituents. This is well illustrated in the subject we are considering. Atmospheric air is a mixture (not a compound) of nitrogen and oxygen gases, and all its properties are intermediate between those of its ingredients taken separately. Nitrous oxide, N₂O, has properties not possessed by either constituent separately. For example, it is very soluble in water, whereas oxygen is very slightly so, and nitrogen still less. The other compounds we have referred to differ widely from nitrous oxide and from each other in their properties.

Nitrous oxide is an invisible gas, having a slightly sweetish taste and smell. It is dissolved by water, which, at ordinary temperatures, takes up about three-fourths of its volume of the gas. By cold and great pressure the gas may be condensed into a colourless liquid. The gas is obtained in a pure state by gently heating the salt called ammonium nitrate, which is formed by neutralizing pure nitric acid with carbonate of ammonia. The action which occurs may be explained thus: the hydrogen of the ammonium unites with a portion of the oxygen of the nitric acid, forming water, whilst the remainder of the oxygen combines with the nitrogen. As chemical actions are regarded as either separations or unions of atoms, they can be expressed by what is called a chemical equation, the left-hand side of which shows the arrangement of the atoms before the action, and the right-hand side the arrangement after it, the sign of equality being read as “produce” or “produces.” But the validity of the equations, like that of the symbolic formulÆ, is quite independent of the existence of atoms; for the equation always rests on certain facts, namely, the relations between the quantities of the substances which enter into, and those which are produced by, a chemical action. Thus, in the present case the action may be symbolically expressed as follows:

The equation expresses the fact that every 80 parts by weight of ammonium nitrate, which are used in this reaction, split up into 36 of water and 44 of nitrous oxide.

No attempt seems to have been made to turn Davy’s suggestion to practical account; but in courses of chemical lectures at the hospitals and elsewhere the peculiar physiological properties of nitrous oxide have, since Davy’s announcement, always been demonstrated by some person inhaling the gas. In the medical schools the students often operated on a comrade who was under the influence of nitrous oxide to the extent of bestowing sundry pinches and cuffs, which fully proved the anÆsthetic qualities of the nitrous oxide. In 1818 Faraday pointed out the similarity between the effects of ether and of nitrous oxide, and from that time Professor Turner regularly included among the experiments of his course of chemistry the inhalation of the vapour of ether by one of the students. This was done by simply pouring a little ether into a bladder of air, and by means of a tube drawing the mixed air and vapour into the mouth. Until 1844 the effects of nitrous oxide and of ether vapour remained without application, although thus continually demonstrated in lectures. At the close of that year, Mr. Horace Wells, a dentist, of Hartford, Connecticut, U.S.A., witnessed the usual experiments with nitrous oxide at a public lecture. At his request the lecturer attended at Mr. Wells’s residence the following day, to administer to him the nitrous oxide, in order that he might try its efficacy in annulling pain, for he was himself to have a tooth extracted by a brother dentist. His exclamation on finding the operation painlessly over was, “A new era in tooth-pulling!” Mr. Wells continued his experiments on the use of nitrous oxide in dental operations, but he did not apparently obtain uniform results, for he pronounced its effects uncertain, and he gave it up. On the occasion when Mr. Wells’s tooth was extracted, Dr. W. T. G. Morton was present, and he soon afterwards found that under the influence of ether vapour, teeth might be painlessly extracted and surgical operations performed. Dr. Morton attempted to conceal the substance he used under the name of “letheon,” for which he obtained a patent. But the well-known and characteristic odour of ether declared the nature of the “letheon;” and Dr. Bigelow having in consequence tried ether, found it to produce all the effects of “letheon.” So the matter was no longer a secret. Dr. Morton was, therefore, the person who first applied ether vapour, and the extraction of a tooth was the occasion of its first application. This was in 1846. It was used for the first time in England on the 19th of December, 1846, also for the extraction of a tooth; and two days afterwards Mr. Liston, the eminent surgeon, performed the operation of amputating the thigh while his patient was under the influence of ether. The employment of ether in surgical operations quickly spread, and its administration in hospitals became general throughout Europe and America.

The chemical constitution of ether, and its relation to alcohol, may be indicated by the following formulÆ:

If we suppose one of the hydrogen atoms in the molecule of water to be removed and replaced by the group (C₂H₅), the result is alcohol. If, now, (C₂H₅) be substituted in the alcohol for the remaining atom of hydrogen, we get a particle of ether. Ether was discovered in 1540, and described as sweet oil of vitriol, but its real nature was first pointed out by Liebig. It is prepared by distilling a mixture of sulphuric acid and alcohol. It is a colourless transparent liquid, extremely volatile, and possessing a peculiar and powerful odour. It evaporates so rapidly that a drop allowed to fall from a bottle on a warm day may be converted into vapour before it reaches the ground. When its vapour is inhaled in sufficient proportion mixed with air, it soon produces a complete insensibility to pain. In the case of a full-grown man who inhales air containing 45 per cent. of the vapour, about 2 drams per minute of the liquid are consumed. The air is allowed to stream over the surface of the liquid in a proper apparatus, where it takes up the vapour, and the two pass through a flexible tube to a piece fitting over the mouth and nostrils of the patient. The effects produced are progressive, and may be thus described:

For about two minutes after the beginning of the inhalation, the patient retains his mental faculties, and has some power of controlling his movements, but in a confused and disordered manner. At the end of the third minute he is unconscious; there are no voluntary movements, but muscular contractions may agitate the frame. At the end of the fourth minute, the only perceptible movements are the motions of the chest in respiration. If the inhalation be discontinued at the end of the fourth minute, when 1 oz. of ether will have evaporated, similar stages are passed through in reverse order during recovery. The condition reached at the end of the fourth minute continues about two minutes; the intermediate state lasts three or four minutes; the condition of confused intellect and will about five minutes. This is succeeded by a feeling of intoxication and exhilaration, which continues for ten or fifteen minutes. It was probably this excitement of the system produced by ether which has caused it to be superseded—in Britain, at least—in about twelve months after its adoption, by chloroform.

Chloroform appears to have been independently discovered in 1831, by Soubeiran, and by an American chemist, Guthrie. It is usually procured by distilling a mixture of bleaching powder, spirits of wine, and water. Chloroform is a colourless volatile liquid, of an odour much more agreeable than that of ether. Its composition is represented by CHCl₃. The merit of having first applied the singular properties of this substance to the alleviation of human suffering belongs to the late Sir J. Y. Simpson, of Edinburgh. Its use as an anÆsthetic was apparently suggested to this eminent professor by Mr. Waldie, of Liverpool. It was first applied at Edinburgh on the 15th November, 1847; and when its efficacy had been proved, it was soon extensively used, and in Europe, at least, almost entirely superseded ether, as being more rapid and certain in its action, not producing injurious excitement, and being pleasanter to inhale. A notion prevailed that chloroform was not only more powerful in its operation than ether, but also more safe. In January, 1848, its administration, however, proved fatal to a patient; and since then a certain number of casualties of this kind have occurred with chloroform, ether, and other anÆsthetics.

The patient is often made to inhale the vapour of chloroform by merely holding before his mouth and nostrils a sponge or handkerchief, on which a small quantity of the liquid has been poured. Dr. Snow contrived an apparatus for administering the vapour with more regularity. A metal box adapted to the shape of the face is made to cover the mouth and nostrils. This piece has two valves, one of which admits the air and vapour from an elastic tube connected with the apparatus containing the chloroform, and prevents its return; the other valve is a flap opening outwards, which allows the expired air to escape. There is also an adjustment for admitting directly into the mouthpiece more or less atmospheric air.

The sensations first experienced when chloroform is inhaled are said to be agreeable. Many persons have described the feeling as resembling rapid travelling in a railway carriage; there is a singing in the ears, and when the power of vision ceases, and the person is no longer conscious of light, the sensation is that of entering a tunnel. After this there is a lessened sensibility to pain; and in the next stage the unconsciousness to outward impressions is deeper, but the mental faculties, though impaired, are not wholly suspended, for the patient may speak, and usually dreams something which he afterwards remembers. When the person is still more under the influence of the chloroform, no voluntary motions take place, although there may be some inarticulate muttering. Dr. Snow describes several conditions which may be observed in patients undergoing operations under the influence of chloroform. First, the patient may preserve the most perfect quietude without a sign of consciousness or sensation; this is the most usual condition. Second, he may moan, or cry, or flinch under the operation, without, however, having the least memory of any pain when he recovers. Third, the patient may talk, laugh, or sing during the operation; but what he says is altogether devoid of reference to what is done. Fourth, he may be conscious of what is taking place, and may look on while some minor operation is proceeding, without feeling it, or without feeling it painfully. This is often the condition of the patient as the effect is passing off, while some smaller operation is still proceeding. Fifth, the patient may complain he is being hurt; but afterwards, when the effect of the chloroform has passed off, he will assert that he felt no pain whatever. When the chloroform has been inhaled for but a short time, the patient becomes conscious in about five minutes after its discontinuance; but with a longer inhalation the period of unconsciousness may last for perhaps ten minutes. The return of consciousness takes place with tranquillity: not unfrequently the patient’s first speech, even after a serious operation, often being an assertion that the chloroform has not taken effect.

In the strongest degree of ether and chloroform effects, all the muscles of the body are relaxed; the limbs hang down, or rest in any position in which they are placed; the eyelids droop over the eyes, or remain as they are placed by the finger; the breathing is deep, regular, and automatic; there is often snoring, and this is, indeed, characteristic of the deepest degree of unconsciousness; the relaxation of the muscles renders the face devoid of expression, and with a placid appearance, as if the person were in a sound natural sleep. He is perfectly passive under every kind of operation. The breathing and the action of the heart proceed all the while with unimpaired regularity. It is, however, known by experiments on animals that if the inhalation be prolonged beyond the period necessary to produce these effects, the respiratory functions are interfered with by the insensibility extending to the nerves on which they depend. The breathing of an animal thus treated becomes irregular, feeble, or laborious, and death ensues. However nearly dead from inhalation of ether vapour the animal may be, provided respiration has not actually ceased, it always recovers when allowed to breathe fresh air. Of course, the etherization is never carried to this stage with human beings.

Air containing 2 grs. of chloroform in 100 cubic inches suffices to induce insensibility; but 5 grs. in 100 cubic inches is found a more suitable proportion. Dr. Snow, who strongly disapproved of the uncertain and irregular mode of administering chloroform on a handkerchief or sponge, contrived the inhaling apparatus already described. The air before reaching the mouth and nostrils of the patient passes through a vessel containing bibulous paper moistened with chloroform. This vessel he surrounds with water at the ordinary temperature of the air, in order to supply the heat absorbed by the conversion of the liquid into vapour, so that the formation of the latter may go on regularly. The same thoughtful arrangement formed part of the ether-inhaler he had previously contrived.

The extraordinary effects of ether and chloroform have introduced new and important facts into psychological science, and have illustrated and extended some of the most interesting results of physiological research. Let us trace the action of these substances, and explain it as far as may be. Nitrous oxide, ether vapour, and chloroform vapour are all soluble in watery fluids. The lungs present a vast surface bathed by watery fluids, and therefore these gases are largely absorbed; and by a well-known process, they pass directly into the blood, through the delicate walls of the capillary vessels. The odour of ether can be detected in any blood drawn from persons under its influence. Ether, or chloroform, thus brought into the general current of the circulation, is quickly carried to all parts of the body, and thus reaches the nerve-centres. On these it produces characteristic effects by suspending or paralysing nervous action: why or how this effect takes place is unknown. The nervous centres are not all acted upon in an equal degree—some require a larger quantity of the drug to affect them at all. The parts of the nervous system first affected are the cerebral lobes, which are known to be the seat of the intellectual powers. The cerebellum—the function of which there is reason to believe is the regulation and coordination of movements—is the next to yield to the influence. Then follow the spinal nerves, which are the seat of sensibility and motive power. This is as far as the action can safely be carried: the nervous centre called the medulla oblongata, which is placed at the junction of the brain and the spinal cord, still performs its functions—one of the most important of which is to produce the muscular contractions that keep the respiratory organs in action. We have seen, by the effects of further etherization in animals, that when this part of the system is affected, the animal dies from a stoppage of the respiration.

But, unfortunately, there have been instances in which death has been caused by the administration of ether and chloroform even under the most skilful management. But these occurrences were not the result of the inhalation having been carried so far as to stop respiration: in some cases the patient has died before the first stage of insensibility. These fatal cases have all been marked by a sudden paralysis of the heart—that organ has abruptly ceased to act. Why in these, certainly a very small percentage of patients, the action of the drug should at once take effect on the heart has not yet been explained. The rhythmic action of the heart depends upon nervous centres enclosed within its own substance, so that this organ is to a certain extent independent; but it is connected with the other nervous centres by the branches of a remarkable nerve which proceeds from the medulla oblongata, and also by another set of nerves which come from the chain of ganglia called the sympathetic nerve. The nerve connecting the heart with the medulla is a branch of that called the pneumo-gastric, and it is a well-established fact that the action of the heart may be arrested by irritation of this nerve. The comparatively few fatalities which have attended the use of anÆsthetics may, therefore, be due either to an immediate action on the nerve-centres of the heart, or possibly to a mediate action through the medulla and the pneumo-gastric nerve.

Soon after the introduction of ether the use of nitrous oxide was discontinued by the dentists, on account of the apparent uncertainty of its action. Within the last few years, however, its employment in the extraction of teeth has been revived by Dr. Evans, of Paris, who found that to insure certainty in its action, the great point is the inhalation of the gas in a pure state and without admixture of air. Nitrous oxide seems now to be extensively used by dentists, and thus Davy’s experiment of 1800 is repeated and verified daily in thousands of cases, and to the great relief of hundreds who probably never heard his name.

Other bodies, such as amylene (C₅H₁₀), carbon tetrachloride (CCl₄), &c., have been tried as substitutes for ether and chloroform; but having been found less efficacious or more dangerous, their use has been abandoned. It might be instructive to reflect how much unnecessary pain would have been spared to mankind had ether and chloroform been known and applied at an earlier age. We know not what other beneficent gifts chemistry may yet have in store for the alleviation of suffering, but it is unlikely that even ether and chloroform are her derniers mots. It should be remembered that the chemists who discovered and examined these bodies were attracted to the work by nothing but the love of their science. They had no idea how invaluable these substances would afterwards prove. The chemist of the present day, whose labour is often its own reward, may be cheered and stimulated in his toil by the thought that while no discovery is ever lost, but goes to fill its appropriate place in the great edifice of science, even the most apparently insignificant truth may directly lead to invaluable results for humanity at large.

What strange things the ancient thaumaturgists might have done had they been possessed of the secret of chloroform or of nitrous oxide! What miracles they would have wrought—what dogmas they would have sanctioned by its aid! But the remarkable effects produced by the inhalation of certain gases or vapours were not altogether unknown to the ancients—although these effects were then attributed to anything but their real cause. It is related that a number of goats feeding on Mount Parnassus came near a place where there was a deep fissure in the earth, and thereupon began to caper and frisk about in the most extraordinary manner. The goatherd observing this, was tempted to look down into the hole, to see what could have caused so extraordinary an effect. He was himself immediately seized with a fit of delirium, and uttered wild and extravagant words, which were supposed to be prophecies. The knowledge of the presumed divine inspiration spread abroad, and at length a temple in honour of Apollo was erected on the spot. Such was the origin of the famous Oracle of Delphi, where the Pythoness, the priestess of Apollo, seated on a tripod placed over the mysterious opening, delivered the response of the god to such as came to consult the oracle. It is stated by the ancient writers, that when she had inhaled the vapour, her eyes sparkled, convulsive shudders ran through her frame, and then she uttered with loud cries the words of the oracle, while the priests who attended took down her incoherent expressions, and set them in order. These possessions by the spirit of divination were sometimes violent. Plutarch mentions a priestess whose frenzy was so furious, that the priests and the inquirers alike fled terrified from the temple; and the fit was so protracted that the unfortunate priestess herself died a few days afterwards.