Chapter II: Part 2

In the operating theatre, thronged with students, were the late Sir John Erichsen, the present Lord Lister, and many other famous surgeons. Mr. Barton relates an amusing incident which happened prior to the operation. Before the patient was brought in, the anæsthetist asked the students who crowded the benches in the theatre from floor to ceiling for some volunteer who would submit himself to be anæsthetised. A young man, Sheldrake, of very powerful build and a good boxer, at once offered to take the new anæsthetic, and came into the arena. “He lay on the table, and the anæsthetist proceeded to administer the ether. After the administration had proceeded for about half a minute, the subject of the experiment suddenly sprang up and felled the anæsthetist with a blow, and, sweeping aside the assistants in the arena, sprang shouting up the benches, scattering the students, who fled like sheep before a dog. He fell at the top bench, where he was seized and held down till he regained his senses. The whole scene hardly occupied a minute.”

One of the earliest employed for the administration of Ether]

[Sidenote: New method of administration]

Before operating, Liston addressed a few words to those present as to the nature of the experiment about to be tried. The ether was administered by Mr. William Squire in an apparatus he had devised, which consisted of a large bell-shaped receiver containing the ether, to which was attached a long tube and mouthpiece. The patient, a middle-aged man, who was suffering from malignant disease of the skin and tissues of the calf of the leg, for which amputation of the thigh was deemed necessary, passed easily into complete insensibility, and Liston rapidly removed the thigh, the cutting operation being declared to have lasted only thirty-two seconds. In a few moments the patient completely recovered consciousness, and apparently did not know that the limb was off. When the towel was removed from the uplifted stump so that he could see it, he burst into tears and fell back on his pillow. Both surgeon and patient were much affected, and the scene in the theatre was most impressive. All appeared to see what an incalculable boon was in store for the human race, and Liston could scarcely command his voice sufficiently to speak.

[Sidenote: A story of Liston]

Some amusing stories are related of Liston, who was a very big, powerful man. His fine physique was often useful in the pre-anæsthetic days, when a patient’s nerve gave way at the last moment at the sight of the crowded theatre and the operating-table with its straps. It is said that on one occasion a patient, losing his courage at the last moment, rushed shrieking down the long corridor of the hospital, with Liston at his heels. The man locked himself in a room, but the surgeon with his shoulder broke in the door, and half-dragged half-carried the poor wretch back to the operating theatre, where the operation for stone was successfully performed.

[Sidenote: First surgical operation under ether in Scotland]

The practice of using ether was soon followed in other hospitals, and not only medical men but distinguished laymen crowded to witness its use. In Scotland, Dr. Moses Buchanan, Professor of Anatomy in Anderson’s University, was the first to have news of the event, and immediately after his lecture that day he experimented with ether inhalation. On the following day, in the operating theatre of Glasgow Royal Infirmary, a patient was placed under the anæsthetic and successfully operated on for fistula. So rapidly, indeed, did the practice spread from one centre to another, that by the end of the first quarter of 1847 the use of the new anæsthetic may be said to have become general in all operation cases.

[Sidenote: Simpson proves value of ether in midwifery]

The value of ether in midwifery practice still remained to be proved, and Sir James Simpson was the first to suggest and test its use in this department. On January 9th, 1847, he first administered ether to a patient in order to facilitate the operation of turning. The result, he reported, was most satisfactory and important, for it at once afforded evidence of the one great fact upon which the whole of the practice of anæsthesia in midwifery is founded, viz., that though the physical sufferings of the patient could be relieved by the inhalation of ether, yet the muscular contractions of the uterus were not interfered with.

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 C_{4}Cl_{5}, 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, C_{2}HCl_{3} (or, using the present system of atomic weights, CHCl_{3}).

[2] Now the “American Journal of Pharmacy”

[Sidenote: 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.

[Sidenote: 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.

[Sidenote: 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.

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.

[Sidenote: On the eve of the great discovery.]

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 the 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.”

[Sidenote: Simpson achieves success]

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. 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.

LOCAL ANÆSTHETICS

Local anæsthesia, already alluded to as probably the earliest form of numbing sensibility to pain, was practised in antient times by the inunction of various narcotics, but after the seventeenth century the practice seems to have almost entirely gone out of use. The latter end of the nineteenth century, however, marks a new era in this department.

On September 15th, 1884, considerable interest was aroused by a communication made at the Ophthalmological Congress at Heidelberg, by Karl Koller, of Vienna, in which he demonstrated the effects of cocaine as a local anæsthetic.

[Sidenote: The discovery of Cocaine]

The alkaloid now known as cocaine was isolated by Gädeke, from the leaves of the _Erythroxylon Coca_ as far back as 1855. He called it ethroxylene. Four years later a further investigation of the plant was made by Nieman, who noticed that the leaves produced a numbness of the tongue; and in 1874 Hughes Bennett demonstrated that cocaine possessed anæsthetic properties. In 1880, Von Anrep, who made a careful investigation of the drug, hinted that the alkaloid might be of use in general surgery as a local anæsthetic, and Koller undertook a series of experiments on animals in the laboratory of Professor Stricker, in which he found that complete anæsthesia of the eye, lasting, on an average, ten minutes, followed the introduction of a two per cent. solution of the alkaloid.

The immense value of such an anæsthetic in ophthalmic operations was universally recognised, and it at once came into general use. In painful conditions of mucous surfaces, and for minor operations, cocaine has been found of great service, and as a local anæsthetic it has a large field of usefulness. Since the introduction of cocaine, other substances have been brought forward, which, after extensive trials, have proved to be of real clinical value. Of these may be mentioned eucaine, a synthetic product (benzoyl-vinyl-diaceton-alkamine) discovered by Merling, and first studied by Vinci in Liebreich’s laboratory. Of the two forms of this drug used, which are known as A and B, the latter was soon found to be the only one suitable for producing local anæsthesia. Its properties are similar to those of cocaine, with the exception that it produces no vaso-constriction, and it is claimed that it is equal in anæsthetic power, whilst its toxicity is very much less.

[Sidenote: Stovaine and Tropa-cocaine]

Stovaine, or benzoyl-ethyl-dimethylaminopropanol hydrochloride, more recently introduced, is a synthetic product elaborated by Fourneau, and derived from tertiary amyl alcohol. It is much less toxic than cocaine, but its comparative value still remains to be proved by further trial. Tropa-cocaine, a drug closely allied to cocaine, and derived from the leaves of the Java coca plant, has recently been much used in Germany, but it does not appear to possess any advantages over cocaine or eucaine.

Novocaine, or para-amido-benzoyl-diethylamino-ethenol hydrochloride, has lately been found to possess satisfactory properties as a local anæsthetic in dental operations. It is said to be free from the toxic and local irritant action common to other local anæsthetics.

THE NECESSITY FOR ABSOLUTE PURITY IN CHLOROFORM

[Sidenote: Administration of Chloroform]

[Sidenote: Purity an essential]

[Sidenote: Danger of impurities]

Considerable attention has been directed to different methods of administering chloroform, and various forms of apparatus have been devised which claim to reduce to a minimum the dangers of anæsthesia. Assuming a most skilled and competent administrator, an ideal method of administration, and a suitable patient, an unsatisfactory result can only be attributed to the chloroform employed. Purity of chloroform is a most important factor in contributing to safe anæsthesia. The physician claims that absolute purity shall characterise all medicinal agents, and the justice of the claim is acknowledged by the trend of recent legislation. Purity is a prime essential of any anæsthetic. The presence of impurities largely increases the risk inseparable from the use of chloroform. The train of symptoms observed during the normal process of anæsthesia may be masked and altered, and dangerous results may supervene under the most competent, careful and observant administrator.

[Sidenote: Expert testimony]

That some of the chloroform offered to the profession may reasonably be regarded with suspicion is evidenced by the words of a prominent obstetrician, based on the experience of 40 years in the use of chloroform; this authority expresses himself as follows: “I may say I fear the chloroform in common use is often far from being as pure as it should be, and is sometimes very defective in this respect.”

[Sidenote: Effects of impurities]

Impurities may result from the process of manufacture, or from decomposition. Conspicuous amongst these undesirable elements are chlorine, hydrochloric acid and carbonyl chloride (phosgene), which irritate the lining membrane of the respiratory tract and interfere with the normal process of respiration. Such irritation may result in arrest of cardiac action or may produce a severe form of bronchitis. It is obviously of great importance that chloroform should be free from irritating properties, that the respiratory passages should not be obstructed, and that during anæsthesia the breathing and the circulation should approximate the normal. Superadded to these results, produced by local irritation, is the effect of other impurities which exert their action after absorption. These latter markedly increase the cardiac depression which has been shown to follow the administration of pure chloroform. Such an action is difficult of detection, and is, probably, in large degree responsible for a considerable number of the accidents reported.

[Sidenote: Contradictory results]

[Sidenote: Recent research]

[Sidenote: Ethyl chloride]

Of recent years increased knowledge has elaborated exact tests, which ensure the absence of these impurities. Nevertheless, anæsthetists of wide experience have obtained results which could not be reconciled with the use of pure chloroform. It has been observed that different chloroforms, all of which answer the official tests for purity, give effects which are difficult to harmonise, and the interpretation of which only appears satisfactory on the assumption that the chloroforms differ in composition. Whilst one chloroform acts most satisfactorily, another produces, during the early stages of administration, a marked excitement and an irregularity of breathing, which prolongs the period of induction. Further investigation has therefore been deemed necessary, and a comprehensive and careful research has elucidated the cause of these hitherto unexplained phenomena (Wade and Finnemore, “Journal of the Chemical Society,” 1904, 85, 938). In the chloroforms which produced anæsthesia in a satisfactory manner, has been demonstrated the presence of ethyl chloride in minute and varying quantities. When the undesirable effects were noted, no ethyl chloride was detected in the anæsthetic. A physiological test conclusively proved that ethyl chloride was the factor which determined these differences.

[Sidenote: Value of the investigation]

A chloroform which had previously given undesirable effects, and in which the presence of ethyl chloride could not be demonstrated, was modified so as to contain a small proportion of the latter. The chloroform then proved a most satisfactory anæsthetic, and there was entire absence of the excitement and respiratory irregularity previously observed. The results of this research are of the utmost value. In the initial stages of the induction of chloroform anæsthesia, the presence of a small quantity of ethyl chloride has a beneficial effect, leading to the absence of mental excitement, and steadies the breathing. The respiration is stimulated and becomes regular and deep. In these circumstances, satisfactory anæsthesia is induced with rapidity and ease.

A CHRONOLOGICAL TABLE OF CHIEF EVENTS AND DISCOVERIES IN THE HISTORY OF ANÆSTHESIA

NITROUS OXIDE

Joseph Priestley 1776
Humphry Davy 1800
Horace Wells (Colton, Riggs, Evans, Best) 1844

ALCOHOL

Collier 1835–42

ETHER

Michael Faraday 1818
W. E. Clarke 1839
Crawford W. Long 1842
E. E. Marcy 1844
W. T. G. Morton 1846
Charles T. Jackson 1846
First surgical operation in America October 16, 1846
First surgical operation in Great Britain December 21, 1846

(Warren, Hayward, Bigelow, Boote, Robinson, Liston, Buchanan,
Louget, Snow, Simpson, Bernard, Clover)

CHLOROFORM

Guthrie 1831
Waldie 1847
James Young Simpson 1847
First surgical operation under chloroform,
in Edinburgh November 15, 1847

(Soubeiran, Liebig, Dumas, Flourens, M. Duncan, G. Keith,
Snow, Nunneley, James Arnott)

COCAINE

Gädeke 1855
Hughes Bennett 1874
Von Anrep 1880
Koller 1884

‘WELLCOME’ BRAND CHLOROFORM

[Sidenote: Ethyl chloride]

[Sidenote: Conforms to B.P.]

‘Wellcome’ Brand Chloroform represents the results of the most recent researches. It embodies the essentials of purity and uniformity, the necessary basis of a satisfactory chloroform. Some chloroforms which satisfy official standards have yet been shown to vary in composition and in effect, the result depending on the occurrence in the preparation of a small and varying quantity of ethyl chloride. ‘Wellcome’ Brand Chloroform is of constant composition and gives uniform effects. It conforms in every respect to the requirements of the B.P., and contains a small and definite proportion of ethyl chloride, which has been found to assist the satisfactory induction of anæsthesia.

[Sidenote: Proved value]

[Sidenote: Confidence in administration]

‘Wellcome’ Brand Chloroform is the result of prolonged laboratory experiment and careful clinical observation. Its reception by the profession verifies the theory upon which its production is based. It has been largely used in hospital and in private practice, and with gratifying results. Reports from most experienced anæsthetists agree in regarding ‘Wellcome’ Brand Chloroform as a distinct advance. Its constancy in composition gives confidence in administration, and its freedom from irritating and depressant principles removes the source of many of the accidents which have hitherto been regarded as grave objections to the employment of chloroform as an anæsthetic.

‘Wellcome’ Brand Chloroform is issued in 2 oz., 1/4 lb., 1/2 lb. and 1 lb. amber-coloured bottles; also in 30 c.c. and 60 c.c. hermetically-sealed tubes, as illustrated on the previous page.

‘WELLCOME’ BRAND ETHER

‘Wellcome’ Brand Ether is prepared specially for anæsthesia and is thoroughly pure and reliable. When the administration of ether is desired, this product will be found eminently suitable.

[Sidenote: Ideal packing]

The method of packing in hermetically-sealed tubes is especially desirable with such a volatile substance as ether, and the shape of the glass tube admits of the contents being readily transferred to the graduated bottles usually employed.

[Sidenote: Conforms to B.P.]

‘Wellcome’ Brand Ether conforms to the requirements of the British Pharmacopœia for _Æther Purificatus_, and has a specific gravity of 0·720.

‘Wellcome’ Brand Ether is issued in hermetically-sealed tubes containing 30 c.c. and 60 c.c., similar to the Chloroform packing illustrated on the previous page.

The anæsthetics issued under the ‘Wellcome’ Brand denote the highest degree of perfection and purity.

‘WELLCOME’ BRAND PRODUCTS

It is well known that considerable variation exists in the quality and activity of the medicinal chemicals of commerce.

[Sidenote: The need for reliable Medicinal Chemicals]

Purity and reliability are matters of the utmost importance to prescriber, dispenser and patient alike, and every opportunity should therefore be taken to ensure the supply of only those chemicals and galenicals which are known to be thoroughly pure and trustworthy.

In order that goods answering to this description in the highest sense may be at the disposal of the profession, Burroughs Wellcome & Co. manufacture and issue a series of fine chemicals, alkaloids, etc., to which they have recently added a series of standardised liquid and granular extracts and concentrated tinctures, under the distinctive title of the ‘Wellcome’ Brand.

[Sidenote: Standardised galenicals]

[Sidenote: Physiological standards]

The advantages of galenicals containing a definite proportion of active principle over those that vary in strength with every sample of drug employed are now fully recognised, and several such have been admitted into the Pharmacopœia. With regard to galenicals, Burroughs Wellcome & Co. have extended the standardisation by total alkaloid assay, and have never adopted the basis of total extractive, regarding it as misleading and useless. Total alkaloid estimations have been adopted in so far as they secured definite standards of truly representative activity, but the firm has not been content to rely on this means alone. As the result of extensive research, they are able to offer many other standardised preparations in addition to the official ones. Those galenicals which are known to be extremely variable in their character and action, and by their nature do not admit of exact control by chemical means, have been the subject of physiological research. Not being satisfied with the methods hitherto available, special processes of standardisation have been developed which give more complete control over the finished products. This subject is still one of continuous research.

The standards adopted have been chosen after the examination of very many different samples of drugs, and represent the average of the amounts of active principle found in preparations made from good specimens. Thus the dose remains the same as that of the older preparation, but the prescriber is certain of always obtaining the proper effect instead of one varying from time to time with the particular batch of extract of tincture used, and the advantage of this certainty, both to the reputation of the prescriber and the health of the patient, can hardly be over-estimated.

[Sidenote: Prolonged scientific research]

[Sidenote: ‘Ergotoxine’]

To attain the highest standard in these as in other preparations for medicinal use, extensive scientific research and many technical experiments have been made. Long-continued researches in the Wellcome Chemical and Physiological Research Laboratories led to the issue of ‘Hemisine,’ a physiologically standardised product which presents the active principle of the medulla of the supra-renal gland in a dry, soluble state. It is perfectly stable in all climates, and permits of the instant preparation of fresh reliable solutions possessing the characteristic hæmostatic and other properties of the supra-renal gland. Similarly, as the result of researches carried out at the Wellcome Physiological Research Laboratories, crystalline salts of a specific alkaloid, which produces the characteristic effects of ergot on the blood-pressure and the uterus, have been obtained in a state of chemical purity. To this alkaloid the scientific name “Ergotoxine” has been given. In ‘Ernutin,’ Burroughs Wellcome & Co. are enabled to present a preparation of uniform potency, containing the specific active therapeutic principles of ergot, chief of which is the alkaloid ergotoxine, in a state of purity which up to the present has never been approached. It is physiologically standardised by observation of its effects on the vaso-motor functions of the sympathetic nervous system.

[Sidenote: Aconitine]

ACONITINE as met with in commerce has been found to vary greatly in purity, and therefore in physiological effect. It is of the utmost importance that a definite strength should uniformly attach to so powerful a drug, and this is secured in the ‘Wellcome’ Brand product, which is free from pseudaconitine and japaconitine, and from the non-toxic aconine and benzaconine.

[Sidenote: Atropine Cocaine]

The alkaloid ATROPINE is, under this brand, issued free from hyoscine and hyoscyamine. COCAINE and its hydrochloride are prepared in a state of purity answering fully the most rigid tests.

[Sidenote: Aloin, Crystal]

ALOIN (CRYSTAL). This greatly improved product is barbaloin in well-defined crystals, and is free from resin.

[Sidenote: Bismuth Salicylate]

The bismuth salts have received much attention, a notable improvement being made in the quality of BISMUTH SALICYLATE. It is well known that there has been a lack of uniformity in the composition of this article, and that not infrequently preparations have been sold under this name which have consisted merely of a mixture of salicylic acid with the oxide or some salt of bismuth. ‘WELLCOME’ BRAND BISMUTH SALICYLATE is made from physiologically pure salicylic acid, and is uniform in composition.

[Sidenote: Stable and soluble]

The scale salt known as BISMUTH AND AMMONIUM CITRATE is a very unsatisfactory preparation. BISMUTH CITRATE (SOLUBLE), ‘WELLCOME’ BRAND, has the same therapeutic properties, but is much more stable in character. Being very freely soluble in water and yielding a bright solution, it is well adapted for the extemporaneous preparation of a solution corresponding to Solution of Bismuth and Ammonium Citrate, B.P., or for preparations in which the U.S.P. salt is used. Like the latter, which it is designed to supersede, it is not compatible with acid liquids.

BISMUTH AND LITHIUM CITRATE (SOLUBLE), ‘WELLCOME’ BRAND. This new combination, in the form of handsome colourless scales, is readily soluble in water. It is thus particularly convenient when the effects of both lithium and bismuth are desired, as in gouty dyspepsia.

[Sidenote: Sedative and hæmatinic]

BISMUTH AND IRON CITRATE (SOLUBLE), ‘WELLCOME’ BRAND, permits the sedative properties of the bismuth to be exerted on the digestive organs, while the iron, which is presented in a soluble, non-irritating and non-astringent condition, is readily absorbed to attack the anæmia which is the exciting cause in some cases of dyspepsia. The salt is in the form of yellowish-green scales, readily soluble in water.

[Sidenote: Definite composition]

IRON ARSENATE (SOLUBLE), ‘WELLCOME’ BRAND, differs from the insoluble amorphous powders, of indefinite composition, so often prepared under this name, in being a scale preparation readily soluble in water, and containing an amount of arsenic equivalent to 34–35 per cent. of anhydrous ferric arsenate.

[Sidenote: Soluble Manganese Salts]

A series of _soluble_ MANGANESE SALTS and combinations of the same with Arsenic, Quinine or Strychnine are unique forms in which this chemical may be prescribed with the best effect.

[Sidenote: Pilocarpine]

The ‘WELLCOME’ BRAND salts of PILOCARPINE, as a result of prolonged and costly investigations, are free from the less active isopilocarpine and the inactive pilocarpidine with which they are usually found to be associated. The melting point indicates the high purity of these salts.

[Sidenote: Quinine Sulphate]

A special feature is made of QUININE SULPHATE in the convenient form of _compact crystals_ occupying one-third the space of the bulky chemical ordinarily offered.