A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA PART IV: HICKMAN AND THE "INTRODUCTION OF CERTAIN GASES INTO THE LUNGS"

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1 Brit. J. Anaesth. (1966), 38, 58 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA PART IV: HICKMAN AND THE "INTRODUCTION OF CERTAIN GASES INTO THE LUNGS" W. D. A. SMITH Department of Anaesthesia, Leeds University, England In 1800, having observed by chance that headaches and the toothache could be relieved by inhaling nitrous oxide, Humphry Davy made the suggestion that the gas might be used with advantage during surgical operations, but there is no record of his having tried the experiment (see Part I, Smith, 1965a). Others confirmed this property of nitrous oxide (see Part II, Smith, 1965b), and someone even thought of using it to relieve pain following dental extractions as early as 1820 (see Part HI, Smith, 1965c). There is no record of the crucial experiment having been performed before Public opinion in the early nineteenth century was not attuned to either the necessity or the possibility of anaesthesia as we know it today. The social climate, however, was changing, and a revival of interest in mesmerism, and its application for painless surgery, probably paved the way for the widespread acceptance of inhalation anaesthesia when it was later demonstrated successfully (see Cartwright, 1952, pp ; Davison, 1965, pp. 15, 75). During the course of a series of public demonstrations of the properties of laughing gas given by Gardner Quincy Colton, Horace Wells rediscovered its power of relieving pain. In 1844 he inhaled the gas before a colleague extracted a tooth, and he felt no pain. He repeated the experiment successfully in a few patients and then gave a public demonstration at the Massachusetts General Hospital. This failed; but William Thomas Green Morton was present, and in 1845 Morton gave a successful demonstration of pain relief during surgery, using ether, the identity of which he tried to conceal under the name Letheon. Anaesthesia had arrived, but its birth was marred by unseemly quarrels between Wells, Morton and Jackson (who also claimed the discovery of ether anaesthesia), and by Morton's initial secretiveness and attempts to patent his discovery. The part played by Dr. Henry Hill Hickman (fig. 1) in the history of anaesthesia stands out in contrast against this background, although he cannot be said to have influenced its development. Hickman was born on January 27, 1800, at Lady Halton, Bromfield, near Ludlow. He was admitted a member of the Royal College of Surgeons, London, on May 5, 1820, and of the Royal Medical Society of Edinburgh, and he started practice in Ludlow. In 1821 he married Eliza Hannah Gardner of Leigh Court, near Worcester (Wellcome, 1930, p. 21). FIG. 1 Henry Hill Hickman, M.R.C.SO ; from an oil painting in the Wellcome Historical Medical Museum. (By courtesy of "The Wellcome Trustees".)

2 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA IV 59 Hickman's starting point was the pain and suffering associated with surgical operations. He was motivated by a desire to prevent this rather than by considerations of prestige or commerce. It occurred to him that the state of "suspended animation" might afford relief. He experimented with animals and performed amputations on them, apparently without causing pain and with complete recovery. He sought openly the cooperation of scientists and his medical brethren, but they failed him. He appealed to Charles X of France, but without success, and he died two years later at the age of thirty. Hickman's experiments. In February 1824, Hickman wrote a letter to T. A. Knight, Esq., of Downton Castle, in which he recorded what was probably the first deliberate attempt to obliterate pain and consciousness during surgical operations by the administration of a gas. T. A. Knight was the local squire, an expert horticulturist and a Fellow of the Royal Society. Downton Castle is two miles from Hickman's place of birth. The letter read: The object of the operating Surgeon is generally considered to be the relief of his patient by cutting some portion of the human body whereby parts are severed from each other or relieving Cavities of the aggravating cause of the disease. There is not an individual who does not shudder at the idea of an operation, however skilful the Surgeon or urgent the case, knowing the great pain that die patient must endure, and I have frequently lamented, when performing my own duties as a Surgeon that something has not been thought of whereby the fears may be tranquillised and suffering relieved. Above all, from the many experiments on Suspended Animation I have wondered that some hint has not been thrown out, of its probable utility, and noticed by Surgeons, and, consequently, I have been induced to make experiments on Animals, endeavouring to ascertain the practicability of such treatment on the human subject, and by particular attention to each individual experiment, I have witnessed results which show that it may be applied to the animal world, and ultimately I think will be found used with perfect safety and success in Surgical operations. I have never known a case of a person dying after inhaling Carbonic Acid Gas, if proper means were taken to restore the animal powers, and I have no hesitation in saying that suspended animation may be continued a sufficient time for any surgical operation providing the Surgeon acts with skill and promptitude.... From a number of other» I have selected the experiments now sent; each is correctly noted in as few words as possible, which I think will prove a vast object With great respect... With this letter Hickman sent notes on seven animal experiments. In the first experiment a month-old puppy was enclosed beneath a glass cover and... in ten Minutes he showed great marks of uneasiness, in 12 respiration became difficult, and in 17 Minutes ceased altogether, at 18 Minutes I took off one of the ears, which was not followed by haemorrhage, respiration soon returned and the animal did not appear to be the least sensible to pain, in three days the ear was perfectly healed. On this occasion the puppy was deprived of oxygen as well as subjected to an increasing concentration of carbon dioxide. Four days later the same puppy... was exposed to a decomposition of the carbonate of lime by Sulphuric Acid. In 1 Minute respiration ceased. I cut off the other ear which was followed by a very trifling haemorrhage, and as before did not appear to suffer any pain, in four days the wound healed.... The third experiment was similar to the first. The fourth was similar to the second, except that a mouse was used. In the fifth he exposed an adult dog... to carbonic acid Gas... in large quantity; life appeared to be extinct in about 12 seconds. Animation was suspended for 17 minutes, allowing respiration occasionally to intervene by the application of inflating instruments. I amputated a leg without the slightest appearance of pain to the animal. There was no haemorrhage from the smaller vessels. The ligature that secured the main artery came away on the fourth day and the dog recovered without expressing any material uneasiness. The sixth experiment was similar, using a rabbit. In the seventh experiment: I filled a glass globe with the Gas exhaled from my own lungs; into it I put a kitten. In 20 seconds I took off its Ears and tail; there was very little haemorrhage, and no appearance of pain to the animal [Wellcome, 1930, pp ]. A portrait of Hickman experimenting with animals is shown in figure 2. Hickman's pamphlet. There is no record of precisely what passed between Hickman and Knight or between Knight and anyone else during the following six months: but Hickman re-wrote the letter, added an introduction and had it printed privately as a pamphlet which was dated August 14,1824. A reproduction of the title page is shown in figure 3. By this time Hickman had moved to Shifnal.

3 60 BRITISH JOURNAL OF ANAESTHESIA There is not an individual, he believes, who does not shudder at the idea of an operation, however skilful the Surgeon, or urgent the case, knowing the great pain that must necessarily be endured; and it is frequently lamented by the operator himself, that something has not been done to tranquilise fear, and diminish the agony of the patient. With this view of the subject then, it is, that he submits his observations and experiments to the public in the brief form of a letter to a private gentleman of the highest talent as a man of science, who with others, thought them worthy to be laid before the Royal Society; and if one grain of knowledge can be added to the general fund, to obtain a means for the relief of pain, the labours of the author will be amply rewarded. At the end of the pamphlet he wrote:... and I feel so confident that animation in the human subject could be safely suspended by proper means, carefully employed, that, (although I could not conscientiously recommend a patient to risk his life in the experiment) I certainly should not hesitate a moment to become the subject of it, if I were under the necessity of suffering any long or severe operation [Hickman, 1824]. FIG. 2 Hickman experimenting with animals. From a painting in the Wellcome Historical Medical Museum. (By courtesy of "The Wellcome Trustees".) The introduction to Hickman's pamphlet read: LETTER OH SUSPENDED ANIMATION, EXPERIMENTS At the particular request of gentlemen of the first OPERATIONS OS ANIMALS, rate talent, and who rank high in the scientific world, it is, that the author of the following letter is induced to lay it before the public generally, but more par aavnii T*i ticularly his medical brethren; in the hope that someone or other, may be more fortunate in reducing the f&ntnau fttttywt, object of it beyond a possibility of doubt. It may be said, and with truth, that publications are too frequently the vehicles of self-adulation, and as such, T. A. KNIGHT, ESQ. OFDOWNTON CASIX, suffer greatly from the lash of severe criticism; but the author begs to assure hi«readers, that his views are totally different, merely considering it a duty incumbent on him (as a medical practitioner, and servant to the public), to make known any thing which has not been tried, and which ultimately may add something towards the relief of human suffering, arising from B. UBCBB&Rs acute disease. The only method of obtaining this end is, in the author's opinion, candid discussion, and liberality of sentiment, which, too commonly is a deficient ingredient in the welfare of so important a profession, productive of serious consequences, not only to the parties themselves, but to the patient whose F t l u H a l b M n t f W. life is entrusted to their care. The duty and object, MM. however, of the Physician and Surgeon, is generally considered to be the relief of a fellow creature, by applying certain remedies to the cure of internal affecfig. 3 tions, or cutting some portion of the body, whereby parts are severed from each other altogether, or re- The title page of Hickman's pamphlet. (By courtesy lieving cavities of the aggravating cause of disease. of "The Wellcome Trustees".)

4 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA IV This pamphlet can be interpreted as reflecting a young single-handed country practitioner of integrity and imagination, who thought that he had discovered a satisfactory way of preventing pain and suffering during surgical operations. He experimented on animals with success, but he had qualms about taking the next step of trying out the method on man. One can imagine, that he saw clearly the implications of this revolutionary idea; that he had misgivings as to how it would be received by his contemporaries; and that he knew his own limitations, and felt that it would be in everyone's interests if his ideas could be discussed and extended by men of greater standing and experience and in an environment offering more facilities for experimentation. It is difficult to know what one would have done in Hickman's position. What he did about it was to write to T. A. Knight, Esq., F.R.S. What Knight did is not known. The introduction to Hickman's pamphlet implied that Knight gave the impression that he considered Hickman's findings worthy of being presented at the Royal Society. Duncum (1947, p. 84) described Knight as an indifferent patron who either did not attempt to interest his fellow members or did not succeed in doing so. Cartwright (1952, p. 286) concluded: Thomas Knight seems to have been interested in Hickman's work, but there is no reason to suppose that he made any active attempt to bring Hickman's experiments before the Royal Society or any other learned body.... He was 64 years of age... and beginning to be something of a recluse... he would have been sufficiently kindly and enthusiastic to urge Hickman on to further efforts, yet he would not have had the energy or continuing interest to make any move himself on Hickman's behalf. Sykes (1960) commented: What a pity Knight did not take more interest in it. He could so easily have had a word with Davy, his co-fellow, who lived until Davy would certainly have suggested nitrous oxide. Appeal to Charles X of France. In 1828, Hickman went to Paris to seek the support of "His Most Christian Majesty Charles X, King of France". Permit me, Sire, to state that I am a British Physician, Member of the Royal College of Surgeons, London, who has visited Paris in pan for the purpose of bringing to completion a discovery to which I have been led by a course of observations and experiments on suspended animation. This object has engaged my practical attention during several years: It appears demonstrable that the hitherto most agonizing, dangerous and delicate operations may now be performed with safety, and exemption from pain, on brute animals in a state of suspended animation. Hence it is to be strongly inferred, by analogy, that the same salutary effects may be produced on the human frame, when rendered insensible by the means of the introduction of certain gases into the lungs: I have discovered a number of facts connected with this important subject, and I wish to bestow them on Society.... Presuming thus, Sire, to attract Your Majesty's thoughts to this interesting subject, I have resorted to the French Capital for the completion of my discovery, hoping to have the honour of placing it under Your Majesty's Royal and gracious auspices I have ventured on the liberty of praying Your Majesty to be pleased, by an express intimation, or command, on the subject, to permit me to develop my ideas on operations in a state of suspended animation, in the presence of your Majesty's Medical and Surgical schools, that I may have the benefit of their eminent and assembled talent, and emulous co-operation. It is also my desire, at a fit opportunity, to solicit the honour of presenting to Your Majesty... a Book containing an account of my discovery which, as far as I know or can learn, has entirely originated with myself.... [Wellcome, 1930, p. 41]. It is not known whether this "Book" was a copy of the pamphlet already referred to, or whether it also contained details of subsequent thoughts and experiments on the subject. This letter was referred to M. Gerardin, who was asked to report upon it to the section of Medicine of the Academie Royale de Medecine. As a result of his report a committee of five was appointed, which included Richerand, but there does not appear to be any record of the action taken. Presumably the committee was not impressed, because Hickman soon returned to England, and set up practice in Tenbury, where he remained until he died two years later. The inspiration, nature and growth of Hickman's ideas. The story of Hickman is incomplete. Facets of it have been treated as having the semblance of clues. Duncum (1947, pp ), for example, speculated as to how much Hickman may have known and been influenced by the works of Beddoes and Davy.... to what extent was he familiar with Davy's suggestion that the gas might be applied in surgery to obviate pain? In addressing himself to Knight, Hickman implied that before beginning his experiments he

5 62 BRITISH JOURNAL OF ANAESTHESIA had studied at least some part of the literature relating to therapeutic inhalation and pneumatic chemistry and this, coupled with the fact that in 1824 he was living in Beddoes' birth place, Shifnal, makes it hard to believe that he was entirely unaware of work carried out at the Pneumatic Institution only twenty-five years earlier. It is quite possible, however, that up to the time when this pamphlet was published, and even to the end of his short life, Hickman had neither had an opportunity of examining a copy of Davy's Researches nor heard any definite account of the letter's suggestion, which indeed had made little if any impression upon Davy's immediate contemporaries. If this were so it would explain why Hickman, who appears to have been so candid in all his actions, should have made no reference to Davy's researches in writing his own. Cartwright (1952, p. 281) wrote: It is a strange but exasperating fact that details of Hickman's life and work seem, at first sight, to indicate that his work was influenced by that of both Beddoes and Davy; yet, when the detail is carefully examined, the evidence is found to be evanescent. He acknowledged that Beddoes was born in Shifnal where Hickman practised when he published his pamphlet, but he pointed out that Hickman's animal experiments were carried out in Ludlow before he moved to Shifnal: "... therefore the evidence of any relationship with Beddoes through the Shifnal association fails to hold good". With regard to the possible influence of Davy he wrote (p. 282): In the same way, the fact that he [Hickmanl addressed his letters to Knight is enticing, and at first sight suggests a relationship with Davy. He was... a dose friend of Davy, with whom he first became acquainted in the spring of Davy, for a number of years, spent part of every autumn at Downton Castle, for the sake of the grayling fishing, and his letters betray his personal affection for Knight and his enjoyment of Knight's hospitality. He continued, however, "But there is, in fact, no evidence that Hickman's experiments were ever forwarded to Davy." In Hickman's original letter to Knight he referred to the use of "carbonic acid gas", and in his early experiments he used oxygen deprivation, carbon dioxide accumulation and carbon dioxide inhalation. In his next letter, dated some six months later and printed as a pamphlet, he wrote of "... the facility of suspending animation by carbonic acid gas, and other means..." Over three years later, when he approached King Charles X, he used the words "... when rendered insensible by means of the introduction of certain gases into the lungs". The change from "carbonic acid gas" through "carbonic acid gas, and other means" to "certain gases" suggests that he may have extended his ideas, and perhaps his experiments, further than one can know from the evidence now available. Cartwright (1952, p. 302) asserted: Hickman was using a perfectly ordinary term in its correct contemporary sense; suspended animation simply meant asphyxia, and it is so used in the eighteenth and early nineteenth century medical literature. In support of this view he quoted Nisbett (1801) who, under the heading "On Suspended Animation", wrote: "Accidents frequently occur from suffocation, drowning, and strangulation, which give an immediate check to the principle of life but do not for some time, entirely extinguish it". Cartwright inferred that "There can be no justification for arguing that Hickman properly used anaesthesia as we know it today, for his declared intention was to obtain his results by means of asphyxia". An interpretation of Hickman's work based upon equating suspended animation with asphyxia may be misleading. There is confusion over the meaning of the word. Modern writers differ in their precise use of it (compare Best and Taylor, 1961; Blakiston,1956; Little, Fowler and Coulsen, 1933; Wright, 1961). In 1869, Evans expressed his exasperation at the use of the word asphyxia, in relation to nitrous oxide anaesthesia, thus: "I can call to mind no word in modern medical literature which is used with less definiteness of meaning, which is more frequently misused, than this word asphyxia". Even in Hickman's day asphyxia could have a broad meaning. Richerand (1807, p. 161) had this to say: Although the term asphyxia merely signifies the absence of the pulse, yet the name is applied to every apparent loss of vitality, produced by an external cause that suspends respiration, as drowning, strangling, disorygenation of the air we breathe, etc. The only existing difference between real death and asphyxia is, that in the latter state, the principle of life can be re-animated, while in the former it is completely extinct.* * The precise wording of this paragraph varied slightly with the translator in subsequent editions, but the sense of it remained the same (see Richerand, 1819, p. 210).

6 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA IV 63 The introduction of "asphyxia" into the context of "submersion, strangulation, and several kinds of noxious airs" was explained by Goodwyn (1788). Thus we have traced the connexion of the symptoms, and the consequent cessation of the heart, to the obstruction of respiration, as to their proper cause.... As the gradual diminution of the pulse is a constant symptom of this disease, it was first called syncope: but, from some peculiarities afterwards observed, physicians thought proper to distinguish it from milder kinds of syncope and called it asphyxia; and this name has been generally retained. The contemporary use of the word asphyxia, as described by Richerand, is consistent with the view that it would have been used to describe an observed state rather than its cause or causes. Doubtless mention of suspended animation would have conjured up visions of the smothered, the drowned and the strangled, but it is possible that if Hickman had observed the state of anaesthesia as we know it today, he would also have described that as suspended animation, and so might his critics. The word asphyxia does not occur in any of Hickman's writings, but in his pamphlet he mentioned "a torpid state", and "a dog was several times rendered insensible by carbonic acid gas", and in his letter to King Charles X he wrote "when rendered insensible by means of the introduction of certain gases into the lungs". If Hickman equated suspended animation with anything it was with the torpid state or with insensibility. As Hickman may have used Richerand's Elements of Physiology when he was a student, the following passages quoted from it may have been familiar to him: Of the various non-respirable gases, some seem to produce asphyxia only by depriving the lungs of vital air necessary to the support of life, while others evidently affect the organs and the blood in them with a poisonous and deleterious principle... and later... carbonic acid; in the kind of asphyxia occasioned by this gas, which is of all the most frequent... the blood preserves its fluidity, the limbs their flexibility, and the body its natural heat, or even an increased degree of heat, for some hours after death fricherand, 1807, p. 163; see also Richerand, 1819, p. 211]. When Hickman described experiments in which he denied animals access to fresh atmospheric air, he did not indicate whether he thought that suspended animation was caused by deprivation of "vital air", by the accumulation of carbonic acid gas, or by both. On the whole he referred most frequently to the use of carbonic acid gas, and he did not say that his reason for using it was to asphyxiate the animals or to deprive them of vital air. On present evidence one cannot infer that he attributed the effects of carbon dioxide inhalation to any particular mechanism, nor can one exclude the possibility that he thought that carbonic acid gas had some specific action of its own. For the surgical operations performed in those days, Hickman would have been satisfied with insensibility of only a few minutes duration. Having produced insensibility in animals by administering carbon dioxide, it would not be surprising if he had at least speculated about the possibility of using other gases for the same purpose. There is no reason why he should not have thought of trying nitrous oxide. It was probably included in his course of chemical lectures when he was a medical student. Even if Hickman had never heard of Davy's association with nitrous oxide, which is unlikely, bis attention could have been drawn to nitrous oxide before he went to France, by the publication in the Lancet* of the Royal Institution Lectures by Brande (1827) (see Part n, Smith, 1965b). As a country practioner Hickman may not have had easy access to a medical library,f but if he had passed through London on his way to France he might have had time to browse in a bookshop, such as James Lackington's in Finsbury Square}: (Trevelyan, 1964). If he had looked at the latest text book on physiology (Bostock, 1826), he would have found The Lancet was advertised in and cost a penny less than the Shrewsbury Chronicle, in which the greater part of Hickman's pamphlet was reproduced (see below). It is probable that Hickman would have subscribed to the Lancet. tfelton's (1811) Description of the Tenon of Ludlow (p. 27) contains a reference to an extensive circulating library in King Street, Ludlow. This was advertised in the back of die book under the name of W. Felton. He also sold music, musical instruments, grand and square pianos, pens, quills, ink, sealing wax, etc Dictionaries, educational books on all subjects, Bibles, etc., Anglers, Downing's Cattle Doctor, and maps. X The London Institution, referred to in Doctor Syntax in London, in relation to a lecture on nitrous oxide (see Pan II, Smith, 1965b) was close by.

7 64 BRITISH JOURNAL OF ANAESTHESIA several pages devoted to respirable gases. If he had not known it already, he could have learned that Lavoisier demonstrated the specific toxic effects of carbon dioxide by showing that animals confined in a small volume of oxygen survived if carbonic acid gas was removed, by potash, as fast as it was produced, whereas without the potash they died. He could also have learned that, "Of gases, which although not capable of supporting life are still respirable, the one which is least injurious to the system appears to be nitrous oxide". Thompson (1912) went so far as to write that Hickman:... commenced a series of experiments on animals, first by producing semi-asphyxiation by exclusion of atmospheric air: then by causing them to inhale small quantities of carbon dioxide and later of nitrous oxide gas. He did not give evidence to support the idea that Hickman actually used nitrous oxide, but he did offer evidence that Hickman might have mentioned it to the French committee which examined his proposals. The subject came to light at a meeting of the Royal Academy of Medicine in Paris on February 23, 1847, to discuss the rival claims of Wells, Morton and Jackson, to have discovered anaesthesia, from which Thompson (1912) quoted the following extract: A letter was read from Dr. H. Wells of Connecticut, U.S.A., claiming the merit of the first application of the system to surgical operations. The protoxide of azote Mr. Wells now prefers to ether.... M. Gerardin then said that fifteen or eighteen years since a letter had been received from an English Physician who asserted that by inhalation of laughing gas he could render patients insensible to pain during surgical operations. This letter caused a certain sensation in the Academy, some members treating it with contempt. But Baron Larrey* defended it, and offered to try the experiment. M. Gerardin would look into the Archives of the Academy for the letter. On March 2, 1847, M. Gerardin reported that:... he had found the letter addressed to the late King Charles X by a Dr. Hickman, and dated September * As a military surgeon Baron Larrey would have been only too conscious of the pain and suffering associated with surgery. He performed two hundred amputations at a single battle (see Guthrie, 1945). On the other hand, he knew that amputations could be performed without pain because he observed this in soldiers who had lain for some time in the snow (see Davison, 1965, pp. 77, 165). He had also observed men brought to hospital in a state of suspended animation after sleeping in ill-ventilated rooms heated by stoves (see Cartwnght, 1952, p. 284). 26th, In that letter the author recommended the inhalation of several vapours for the purpose of producing unconsciousness during surgical operations. The evidence was inconclusive. Subsequent use of carbon dioxide as an anaesthetic. Since Hickman's day, the anaesthetic action of carbon dioxide has been the subject of animal experimentation from time to time (Nunneley, 1849; Ozanam, 1858; Leake and Waters, 1928, 1929; Graham, Hill and Nunn, 1959). Its clinical use was tried once, misguidedly, by Ozanam in 1862 (Ozanam, 1862, 1863; Brit. med. J., 1863). Significantly, attempts to use this form of anaesthesia clinically do not appear to have been repeated, although Rottenstein (1880) referred to it having been used once in a patient who succumbed, but he gave no details. Ozanam's surprising rationale for using carbon dioxide anaesthesia was set out in a letter he wrote to the President of the Royal Medical and Chirurgical Society in 1863 (fig. 4). Ozanam (1863) believed that ether, chloroform and amylene decomposed in the blood to form carbon dioxide and toxic substances such as cyanides, which he considered to be one of the causes of sudden death after anaesthesia. His argument led relentlessly to the conclusion: II faut done remplacer ces corps dangereux par une substance indecomposable, irreductible qui jouisse neanmoins du pouvoir d'enlever la sensibilite. Cette substance, c"est le gaz acide carbonique. Depuis la publication de mon travail j'ai pu appliqiter Us inhalations de gaz acide carbonique sur I'homme el opher comrne avec le chloroforme'. The patient was a young man to whom a mixture of three-quarters of carbon dioxide and onequarter of air was administered for the incision of a deep abscess of the thigh. Acceleration of respiratory movements and abundant facial sweating were observed during the induction of anaesthesia, which took about two minutes. Duration of anaesthesia was not reported, but the patient remained motionless and return of consciousness was described as immediate on withdrawing the carbon dioxide (Ozanam, 1862) Apart from the effects of carbon dioxide, the patient would also have been grossly hypoxic. Hickman's dream of painless surgery came true in the years immediately following 1844, but

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9 66 BRITISH JOURNAL OF ANAESTHESIA safer agents were used than his early choice of carbon dioxide. Ozanam's trial of carbon dioxide on man showed that if Hickman had tried it he might have had at least an initial success. The subsequent silence on the subject, and Rottenstein's warning, suggest that the final outcome might not have been so fortunate. FRESH LIGHT ON HICKMAN Early years. Hickman was baptized on January 30, 1800, only three days after he was born. This has been interpreted as suggesting that he may not have been expected to live. Cartwright (1952, p. 266) wrote that Henry Hill Hickman was the third child of John and Sarah Hickman, and that of their four children, Henry Hill was the only one to survive infancy. In view of this family history he suggested that Hickman probably died of consumption (p. 299). The parish registers of Bromfield and Stanton Lacey,* however, indicate that Henry Hickman was the seventh child of thirteen children (Devey, G. B., 1964, personal communication). Neither Henry nor his siblings were registered as having more than one Christian name. Henry's second name, Hill, may have been added later.fof the six older children, the second child, Richard, died four years after baptism, and the fifth child, Kate, survived for about a year. The others were Benjamin (baptized 1792), John (baptized 1794), Sarah (baptized 1795) and Thomas (baptized 1797). In the back of a small book printed privately in Ludlow c (Bullock) are listed 326 subscribers, including Mr. J. Hickman, Mr. B. Hickman, Mr. T. Hickman and Mrs. Hickman. These were probably Henry Hickman's elder brothers and his mother. At that time Benjamin would have been twenty-six and Henry would have been away as a medical student. * These registers, for the period c to 1812, were printed in about 1903 by the Shropshire Parish Register Society (Devey, G. B., 1964, personal communication). t If so, it is just possible that he may have been so named after some local person having that name, and that a search for Hill-Hickman friendships might lead to fresh evidence. A Henry Hill was buried at Bromfield on November 28, 1792 (Robinson, F. S., 1965, personal communication). A Dr. Caleb Hill practised in Ludlow and was an alderman of the borough in He died in 1762 (Morley, E., 1965, personal communication). Education. It is not known where Hickman went to school. The records of the Ludlow Grammar School do not go back before 1850 (Merchant, G. E., cited Robinson, F. S., 1965, personal communication). It is not known at what age he started his medical training nor at what schools and hospitals he received it. He neither matriculated nor graduated at Edinburgh University, although he may have attended lectures at the Edinburgh Extra-Academical School of Medicine and Surgery (Simpson, S. M., 1964, personal communication). There is no evidence to suggest that Hickman was likely to have come under any noteworthy scientific influences before he began his medical training, and one might suppose that his orientation towards medicine would have been more clinical than academic. One should not, therefore, read too much into the passages in his letters to Knight:... Above all, from the many experiments on suspended animation I have wondered that some hint has not been thrown out, of its probable utility.... I have never known a case of a person dying after inhaling Carbonic Acid Gas, if proper means were taken to restore the animal powers... it is well known that carbon has a most powerful antiputrescent quality.... The facility of suspending animation by carbonic add gas, and other means, without permanent injury to the subject, having been long known... etc. These need not be taken to imply that he had studied any of the literature relating to therapeutic inhalation and pneumatic chemistry. He may have been doing little more than quoting from notes made during his training. Knowledge of Beddoes and pneumatic medicine. Hickman may have heard something about pneumatic medicine and about Beddoes' Pneumatic Institution as a result of his association with Shifnal, which is where Beddoes was born. The fact that he began his experiments in Ludlow need not necessarily rule out this possibility. We do not know why he moved to Shifnal, and he is unlikely to have gone there without first finding out something about the place. Although he did not set up practice in Shifnal* until some time in 1824, he may have had friends there much earlier. Beddoes, however, died in If Hickman gained knowledge of his work on pneumatic medi- * His practice was in Church Street, Shifnal (Pigot & Co., Shropshire, 1828).

10 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA IV 67 cine from local sources, he would probably have done so in conversation with Beddoes' relatives or acquaintances, and there is no particular reason why his informants need have Lived in Shifnal. Even if we knew that Hickman did learn about pneumatic medicine in this way it would be a formidable task to determine who might have informed him.* On present evidence, however, no conclusions are justifiable as to whether, when, where or how Hickman may have gained knowledge of Beddoes' work. Experiments. There is a local belief that Hickman carried out his experiments on dogs and mice at a place called Pouches Pool. This was burned down about five years ago, but was situated just off and to the west of the main Bromfield-Ludlow road. It is possible that the original of figure 2 was painted at Pouches Pool. The windows depicted are thought to be consistent with this and there were trees close by the buildings, but no positive identification has been made (the Misses Tew, cited Robinson, F. S., 1965, personal communication). His practice was in Corve Street, Ludlow (Pigot's London and Provincial New Commercial Directory 1822/3). The impact of Hickman's pamphlet. At the time that Wells, Morton and Jackson were competing for recognition as the discoverer of anaesthesia, Dudley (1847) wrote to the Lancet: I am in a position to prove that a similar system was brought before the public nearly twenty years ago by Dr. Hickman, then residing at Shiffnal... where he successfully performed various experiments with it on animals.... He went to Paris in 1828, in which year he presented a memorial to the King of France, Charles X, praying for permission to perform his experiments before the medical officers of that metropolis. A copy of his memorial is now before me, and also a letter from the widow of the memorialist... the prosecution of his enquiries was cut short soon after by his decease, previous to which he published an account of his invention either in a pamphlet, or in the form of an essay in the medical publications of the day. I well remember that the system was treated with great severity in the medical reviews, and was generally condemned as a wild and visionary theory, which was deemed practically useless, if not dangerous and impossible.... * It may be noted that there was a Mr. Beddoes of Delbury among the subscribers to Bullock (c. 1818). Delbury is about seven miles from Bromfield and about the same distance from Cheyney Longville, where Thomas Beddoes spent his boyhood (Cartwright, 1952, p. 50). Cartwright (1952, p. 291) inferred that Hickman's paper did not arouse any great attention, because no obvious reference to it had been discovered in any of the more important journals. He did, however, trace a note about Hickman's pamphlet in the Gentleman's Magazine for January-June 1825, and this ended:... and says he should not hesitate a moment to become the subject of the experiment he recommends, if he were under the necessity of suffering any severe operation. Notwithstanding Dr. ITs confidence, it may be doubted whether the pain of his operation, and especially in the recovery, would not equal or perhaps surpass that experienced in the usual mode of operation. There is also a letter in the Lancet of February 4, 1826, (Antiquack, 1826), under the heading "Surgical Humbug", which criticized Hickman's pamphlet. Apart from being noted by Callisen (1831), it appears to have been overlooked. It is reproduced in figure 5. The letter may contain clues as to the identity of its author, but if so, they are no longer obvious.* Taken in conjunction with the note in the Gentleman's Magazine and the sorry tale of the lack of interest shown in Hickman's work in England and France, Antiquack's letter appears to confirm that the time was not ripe for the reception of the idea of surgical anaesthesia. If this was so in 1826, it is unlikely to have been less so when Davy's researches were published in Hickman, Knight and Davy. Beneath the heading "Surgical Humbug" of Antiquack's letter, the contents of the title page of Hickman's pamphlet are given in italics (fig. 5). Comparison of this with the reproduction of the title page (fig. 3) reveals that it contains an extra clause: "... and read before it by Sir H. Davy". On examination of the original pamphlet, which has been handed down through Hickman's granddaughter to the Wellcome Historical Medical Libraryf, it is immediately obvious that AND READ BEFORE IT BY SIR HUMPHRY DAVY Was printed On the title page of the pamphlet, but the words were crossed out by hand, using a series of short The reference to Dr. Smith of Upton Majma is obscure. No obvious references to him have been found in the Shrewsbury Public Library (Messenger, M. F., 1965, personal communication). t The only known copy (Fulton and Stanton, 1946, p. 14; Cartwright, 1952, p. 287).

11 SURGICAL HUMBUG. Letter on Suspended Animation, containing Experiments showing that it may be safely employed during Operations on Animals, with a view of ascertaining its probable utility in surgical operations on the Human Subject, addressed to T. A. Knight, Esq. of Downton Castle, Herefordshire, one of the Presidents of the Royal Society, and read before it by Sir H. Davy. By Dr. H. HICK- MAN, of Shifjnal, member of the Royal Medical Societies of Edinburgh, and of the Royal College of Surgeons, London. Ironbridge. Smith. To the Editor of THE LANCET. " Oh! for a Hymn, Loud as the virtues thou dost loudly vaunt, Not practise." BYRON. SIR, A few days since I took up a fragment of an old Shrewsbury paper, in which I observed a paragraph from the above letter, inserted most probably by the author, who endeavours to show, by a series of experiments on mice and dogs, that it would be advisable before performing important operations on human subjects, to expose them for a short time to an atmosphere of carbonic acid gas, by which means they may be rendered incapable of feeling pain during the operation. Now giving this learned Theban full credit for his charitable intentions towards that unfortunate portion of his fellow creatures who may be doomed to come under his care, or to solicit his advice in any surgical case, can he for a moment suppose that any medical man of sense and judgment will be so far led away by a proposal so utterly at variance with all he has ever heard, saw, or read, of the deleterious effects of respiring the fixed air, even for a short time, as to believe, for a moment, that this letter was published with any intention of benefiting mankind; or, that it was not intended, like the wonderful but more innocent challenges and assertions of the celebrated Dr. Smith, of Upton Magna, to serve as a decoy by which the credulous may be induced to give up their senses as well as their cash to men, who though perhaps not greater fools, are at any rate greater knaves than themselves. I must now beg Dr. Smith's pardon for making use of his name in such company, for I have no hesitation in saying, that I consider an open and downright quack to be as far superior to a plausible quacking physician, as a declared enemy is superior to one who conceals himself under the mask of friendship, that he may inflict the deeper injury. As for that large portion of society, who do not belong to the medical profession, does he suppose that they would not laugh him to scorn if he were to recommend a man who was about to have a tooth drawn to be previously hanged, drowned, or smothered for a few minutes, in order that he may feel no pain during the operation? While writing this sapient puff, (for it claims no other appellation,) did he think, if he ever thought at all, which for his own sake I hope he did not, that animation was to be suspended by the means proposed, without occasioning sensations far more horrible than the pain inflicted by ordinary operations; or, does he suppose that after amputating a limb, (granting to him for the sake of argument that animation may have been suspended during the operation,) does he, I ask, think that the stump will heal without pain, or inflammation, as he affirms was the case in his first experiment on puppies' ears; although he must know (provided he knows any thing about it) that it is by an inflammatory process the parts divided by an operation are again united, and that inflammation forms an important part in the healing process, in all instances. The Doctor concludes his noble, disinterested, and scientific letter in these words, " Although I could not conscientiously recommend a patient to risk his life in the experiment, (after having a littl: before assured us that it was perfectly safe,) I certainly should not hesitate to become the subject of it, if I were under the necessity of suffering a long or severe operation." How magnanimous, what a noble declaration, as though he does not know, that if he were weak enough to make such a proposal, (which in this case I know he would not be, when really about to undergo an operation,) that it would, I sincerely hope, and believe, for the credit of the profession, be utterly impossible to find any surgeon so great a fool, and so unwarrantably bold as to undertake that operation on such terms. Now I do fervently hope that the letter itself may be a complete hoax, and not written by Dr. Hickman; for, in this age of science and gentlemanly acquirement, I feel assured, that no man who has any claim to the honourable appellation of a Doctor of Physic would so far disgrace both his profession and himself by writing such a tissue of quackery, which he himself, and every medical man must know is (to say the least of it) humbug. The writer, whoever he may be, seems to be perfectly well acquainted with the generality of his countrymen, and must suppose that the majority are not competent to judge in such cases; or, he would not have dared to offer so gross an insult by laying such trash before them; -but, I may be wrong, perhaps he compares mankind to the audience of a pantomime, who always applaud that actor most who plays the fool best. I shall now conclude with a few words from a late poet, which the Doctor's conscience will teach him to apply, and to feel "What I have spoken Remains to speak of me." I am, &c. ANTIQUACK. FIG. 5 Letter from "Antiquack" to the Editor of the Lancet (1826).

12 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA IV 69 backward-sloping ink strokes. At a casual glance, the effect produced in reproductions is that of some decorative device, but the ink strokes are obvious enough on careful examination. The printed words are not decipherable in published reproductions, but their lengths can be seen to be consistent with the above. No such communication by Sir Humphry Davy was published; nor was it recorded in the Minutes of the Royal Society meetings, which I have searched from February 26, 1824, to February 23, 1826 (Journal Book of the Royal Society, Volume 44). Antiquack's letter opened with a reference to having observed a paragraph of Hickman's letter in a fragment from an old Shrewsbury paper. The two local papers published at that time were the Shrewsbury Chronicle, which is still published, and Eddows's Salopian Journal, now defunct (Hobbs, J. L., Shrewsbury Public Library, 1964, personal communication). I have searched these two papers and found that Hickman's second letter to T. A. Knight was published in the Shrewsbury Chronicle on June 3, The title page and the introduction to the pamphlet were omitted, but the editor inserted a short preface which was in the spirit of the pamphlet. Dr. Hickman, of Shiffnal, has published a Letter, shewing that Suspended Animation may be safely employed during Operations on Animals, with a view of ascertaining its probable utility in Surgical Operations on the Human Subject. We extract the following in the hope of furthering the writer's desire for liberal experimental inquiry. There does not appear to have been any correspondence about suspended animation in the Shrewsbury Chronicle between June 3, 1825, and February 1826, when Antiquack's letter was published. Antiquack's letter, as printed, revealed a greater knowledge of Hickman's pamphlet than could have been obtained from the extract published in the Shrewsbury Chronicle, let alone from a single paragraph from it. This suggests that at some time between June 3, 1825, and February 1826, either Antiquack or the editor of the Lancet obtained details of at least the title page, directly or indirectly, from a copy of Hickman's pamphlet. It is not known when that copy left the printer, or through what channels the information contained on the tide page reached the Lancet. It is unlikely that the line "and read before it by Sir Humphry Davy" would have been deleted, but it is noteworthy that this does not seem to have inhibited Antiquack in any way. In the hope of tracing an unamended copy of the pamphlet, the Librarian of the Royal Society, the present editors of the Shrewsbury Chronicle and the Lancet, and the librarian of the Shrewsbury Public Library were approached; but no copy of the pamphlet was traced. The Shropshire Magazine (1964) also inserted an appeal on my behalf. The chances of finding the copy or copies which T. A. Knight must have possessed appear to be remote. In his printed letter to Knight, Hickman wrote: "... the results of some experiments which I made, lead me to think that these conjectures are well founded, and to hope that you will think the results sufficiently interesting to induce you to do me the honour to lay them before the Royal Society". The unamended tide page, on the other hand, would lead one to believe that the results had been communicated to the Royal Society already, by Sir Humprey Davy. Hickman's pamphlet was dated August 14, 1824; yet the Gentleman's Magazine and the Shrewsbury Chronicle did not report upon it until the summer of The interval is rather too long to be explained simply by the time taken to print such a short pamphlet, although there may have been a delay in submitting the draft or in distributing the printed pamphlet. It is possible that Hickman came to understand that his work had just been or was just about to be communicated to the Royal Society by Sir Humphry Davy, and that he drafted the title page and the introduction accordingly. This possibility is the more likely in the light of the wording of the introduction, which now acquires new force: "At the particular request of gentlemen of the first rate talent, and who rank high in the Scientific world... ". This can be taken to imply that Hickman had discussed the matter with someone of high rank in the scientific world in addition to Knight; or that he believed that Knight had had a favourable discussion with at least one other Fellow of the Royal Society probably Davy. It may have been that Knight, with an outward show of optimism, promised to discuss the whole thing with his friend Davy when they next met. Hick-

13 70 BRITISH JOURNAL OF ANAESTHESIA man may have been forcing the pace a little, perhaps in order to keep Knight to his promise, but one can only guess at what happened. There is no evidence other than the above documents. The facts that Davy does not appear to have read any such communication before the Royal Society, and that the clause "and read before it by Sir Humphry Davy" was subsequently deleted from at least one copy of the pamphlet, on a date unknown, suggest either a misunderstanding between Hickman and Knight or between Knight and Davy, or a change of plan. Davy left London on June 30 and did not return from travels abroad until just before August 22, 1824 (Davy, 1839). This may have resulted in Knight not having had an expected opportunity for meeting Davy. About a year after his return, Davy's health began to deteriorate (Davy, 1839), and this could have discouraged Knight from approaching him again. It might also have increased the chances of misunderstandings, although these points should not be stretched too far. Even if it could be shown that Hickman's work was discussed with Davy, it cannot be assumed either that he would have remembered his suggestion about using nitrous oxide during surgical operations, or, if he had remembered it, that he would necessarily have said so. It was a quarter of a century since Davy had carried out his researches into nitrous oxide. The greater part of this work was completed during the year before Hickman was born. By 1825 Davy had become a different man. Cartwright (1952, p. 258) paints an unhappy picture of him at about this time:... trouble had been brewing in the Council of the Royal Society for some time past, and Davy had become irritable and intolerant of criticism; at the Royal Institution too, there was trouble, and Davy behaved in an autocratic fashion that provoked angry dissatisfaction. At one time he thought of retiring completely and he entered into negotiation for a house in Hampshire, but it came to nothing. His health was failing him, he was growing weaker and became easily tired, so that he found it a labour to indulge in his favourite field sports; after his re-election to the chair of the Royal Society in 1826 he delivered his last discourse to the Society; it was obviously done with great effort and those who were near him thought that he was going to have a seizure: afterwards he was so unwell that he was unable to attend the annual dinner. The discovery of Antiquack's letter in the Lancet, together with the contribution in the Shrewsbury Chronicle to which it referred, and the uncovering of the line deleted from the title page of the surviving copy of the pamphlet, have given a further glimpse of Hickman's attempts to gain support for his ideas, but they have not given a clear answer to any outstanding question. On the contrary, they increase the number of questions to be answered, but this may lead to an unravelling of more of the story. The visit to Paris. We know little of Hickman's means. Cartwright (1952, p. 271) described the Hickmans as "one of those old and undistinguished families which are the true backbone of England.... Such a family, never knowing the extremes of wealth or poverty, keeps upon its own even and middle path". Sykes (1960, p. 118) thought that Hickman was probably not very successful because he practised in three different places in his working life of ten years, but supporting evidence is lacking. No-one appears to have written about the professional competition that Hickman would have had to face in Ludlow, Shifnal or Tenbury. It is quite possible that he was given a helping hand by his family at the start of his career in Ludlow. We do know, however, that somehow he found sufficient money for his visit to Paris in order to appeal to Charles X Of France. Having failed to gain support in his own country, the next obvious step for Hickman to take may have been to stimulate interest in the French capital, which was a centre of medical and scientific thought at that time. It is improbable, however, that an unknown young country practitioner would have taken that step without detailed advice. Cartwright (1952, p. 296) implied this when writing about Hickman's letter to Charles X: 'It is magnificent in its courtly grace; a model of subservience, which must have owed its genesis to someone familiar with the forms and customs of pre-revolutionary France." From whom did Hickman find out the "form"? It might have been T. A. Knight. Cartwright (1952, p. 294) tentatively put forward the possibility that the Hickmans may have been friends of Joseph Glover who lived at Pool House in Astley Worcester. Joseph was the brother of John Glover, an English painter who enjoyed the patronage of the French royal family. Another possibility arises from the fact that Napoleon Bonaparte's brother Luden lived in

14 A HISTORY OF NITROUS OXIDE AND OXYGEN ANAESTHESIA IV 71 Ludlow from December 26, 1810 (Felton, W., 1811, pp ). He went to Rome in 1814, at which time Hickman would have been fourteen. A direct link between Lucien Bonaparte and Hickman or between Lucien Bonaparte and Charles X is unlikely, but it would be surprising if friendships did not grow up between Lucien's entourage and the local population, and these could be relevant. The material presented in Parts II and El (Smith, 1965b, c) lends support to the belief that Hickman could have been well aware of the existence and of some of the properties of nitrous oxide. One would have expected him, at some stage, at least to have considered its use. Whether he actually did so we cannot know from existing evidence, but M. G6rardin's memory may not have been at fault when he thought that an English physician had asserted that by inhalation of laughing gas he could render patients insensible to pain during surgical operations. The answer may have been, and may still be, contained in the "Book" which Hickman referred to in his letter to King Charles X of France. Hickman's ideas were ahead of his rime. He sought to provide relief from pain during surgical operations and he saw the possibilities of insensibility induced by the administration of "certain gases". He came near to the discovery of clinical anaesthesia, but he did not influence its development If it had not been for Dudley's memory of him in 1847, and for the researches of Sir Henry Wellcome early in this century (Wellcome, 1930, p. 7), it is probable that his existence would have been forgotten. ACKNOWLEDGEMENTS This study began with Duncum (1947). Frequent reference was made to the work of Dr. F. F. Caifwright, who also gave personal encouragement and advice for which I am extremely grateful. I hope that I may be forgiven if my conclusions do not always coincide with his. The Wellcome Souvenir of the Henry Hill Hickman Centenary was an important foundation and much valuable assistance was given by Mr. E. Gaskell of the Wellcome Historical Medical Library. The late Mr. J. L. Hobbs and his successor, Mr. M. F. Messenger, of the Shrewsbury Borough Library were extremely helpful. Miss Gillian Comwell patiently and fruitlessly searched the old Hereford journals for evidence similar to that found in the Shrewsbury Chronicle. Many have replied promptly, and even enthusiastically, to my persistent queries. Some have been mentioned in the text, but I would Like to add the names of Mr. N. H. Robinson of the Royal Society Library who checked the printed records and arranged for me to search the Minutes of the Society; Mr. H. Dyson who arranged for a search of the Staffordshire Advertiser; Mr. Q Phipps who did likewise for the Berrow's Worcester Journal; Mr. J. F. W. Sherwood who drew attention to the Hereford Journal; Mr. Michael Moss who arranged for the appeal in the Shropshire Magazine on my behalf: also Major W. M. P. Kincaid Lennox; Miss Mary C Hill, County Archivist, Shrewsbury; Mr. M. Donnelly, County Branch Library, Ludlow; Mr. J. Norton, Ludlow Museum; Mrs. Richard Beesly; Mrs. de Waal and her father, Prebendary A. L. Moir, who made several useful suggestions; Miss R. Tompkinson and Miss E. Beddoes. Correspondence with Mr. E. L. Morley was more extensive than his mention in the text might suggest I am particularly grateful to Mrs. Florence S. Robinson, JJ\, who volunteered to make local enquiries, search old books, directories and maps, and who has gone out of her way to provide every possible assistance. REFERENCES Antiquack (1826). Surgical Humbug. Lancet, 9, 646. Best, C H., and Taylor, N. B. (1961). The Physiological Basis of Medical Practice, 7th ed., p London: Bailliere, Tindall and Cox. Blakiston's New Gould Medical Dictionary (1956), eds. Hoerr, N. L., and Osal, A., 2nd ed. London: McGraw Hill. Bostock, J. (1826). An Elementary System of Physiology, Vol. II. London: Baldwin, Crodok and Jay. Brande (1827). Lectures on chemistry XVII. On muriatic add, hydriodic acid and nitrous oxide. Lancet, 1, 455. British Medical Journal (1863). Carbonic acid as an anaesthetic. 1, 180. Bullock, J. (c. 1818). The Beauties of Ludlow. a poem. Ludlow: W. Felton. Callisen, A. C. P. (1831). Medicinischet Schriftsteller- Lexicon, 8, 489. Cartwright, F. F. (1952). The English Pioneers of Anaesthesia: Beddoes, Davy and Hickman. Bristol: Wright. Davison, M. H. A. (1965). The Evolution of Anaesthesia, Altrincham: Sherratt. Davy, J. (1839). Memoirs of the Life of Sir Humphry Davy. London: Smith, Elder. Dudley, T. (1847a). Alleged discovery of the influence of sulphurous ether in Lancet, 1, 163. (1847b). Painless surgical operations. Lancet, 1, 345. Duncum, B. M. (1947). The Development of Inhalation Anaesthesia: with special reference to the years London: Oxford University Press. Evans, T. W. (1869). Physiological action of nitrous oxide gas. Brit. J. dent. Scu, 12, 100. Felton, W. (1811). Description of the Town of Ludlow. Ludlow: Felton. Fulton, J. F., and Stanton, M. E. (1946). The Centennial of Surgical Anesthesia; an annotated catalogue of books and pamphlets bearing on the early history of surgical anesthesia. New York: Henry Schuman. Gentleman's Magazine (1825). Literature, Science etc. Surgical experiments. 95 (1), 628.

15 72 BRITISH JOURNAL OF ANAESTHESIA Goodwyn, E. (1788). The Connexion of Life with Respiration; or an Experimental Inquiry into the effects of Submersion, Strangulation, and Several Kinds of Noxious Airs on Living Animals: with an Account of the Nature of the Disease they produce; its Distinction from Death itself; and the most effectual Means of Cure, pp London: J. Johnson. Graham, G., Hill, D. W., and Nunn, J. F. (1959). Circulatory and respiratory responses of the dog to progressively increasing concentrations of inhaled carbon dioxide. J. Physiol. (Lond.), 149, 75p. Guthrie, G. (1945). A History of Medicine, p London: Thomas Nelson. Hickman, H. H. (1824). A letter on suspended animation, containing experiments showing that it may be safely employed during operations on animals, with the view of ascertaining its probable utility in surgical operations on the human subject, addressed to T. A. Knight, Esq., of Downton Castle, Herefordshire, one of the Presidents of the Royal Society, and read before it by Sir Humphry Davy. Ironbridgc. Leake, C. D., and Waters, R. M. (1928). The anaesthetic properties of carbon dioxide. J. Pharmacol, exp. Therap., 33, 280. (1929). The anesthetic properties of carbon dioxide. Anesth. Analg., 8, 17. Little, W., Fowler, H. W., and Coulson, J. (1933). The Shorter Oxford English Dictionary on Historical Principles, Vol. 1. O.UP. Nisbett, W. (1801). The Clinical Guide, 4th ed. Edinburgh: James Watson. Nunneley, T. (1849). On anaesthesia and anaesthetic substances generally: being an experimental inquiry into their nature, properties and action, their comparative value and danger, and the best means of counteracting the effect of an overdose. Trans. Provincial Med. Surg. Assoc, 16, 167. Ozanam, C. (1858). Des ancsthesies en general de leurs effets physiologiques et pathologiques et surtout de 1'clement chimique qui specialement produit l'anesthesie. Metz. (1862). De l'acide carbonique en inhalations comme agent anesthesique ef&cace et tans danger pendant les operations chirurgicales. CJi. Acad. Set. (Paris), 54, Ozanam, C. (1863). Manuscript letter from Dr. Charles Ozanam to the President of the Royal Medical and Chirurgical Society secured inside the copy of Ozanam (1858) which was sent with the letter. In the Library of the Royal Society of Medicine. Richerand, A. (1807). The Elements of Physiology, containing an explanation of the functions of the human body; in which the modern improvements of chemistry, galvanism, and other sciences, are applied to explain the actions of the animal economy (trans. Kerrison, R.), 2nd ed. London: Cotton. (1819). Elements of Physiology, 3rd ed. (trans. De Lys, G. J. M.). London: Thomas and George Underwood. Rottenstein, J. B. (1880). Traiti d'anesthesie chirurgicale contenant la description et les applications de la methode anesthesique de Mr. Paul Bert, p Paris: Librairie Germer Bailliere et Cie. Shrewsbury Chronicle (1825). On employing suspended animation during surgical operations. No. 2759, Friday, June 3, p. 88, columns 1-2. Shropshire Magazine (1964). Appeals for information. 16, No. 9, 71. Smith, W. D. A. (1965a). A history of nitrous oxide and oxygen anaesthesia. Part I: Joseph Priestley to Humphry Davy. Brit. J. Anaesth., 37, 790. (1965b). A history of nitrous oxide and oxygen anaesthesia. Part II: Davy's researches in relation to inhalation anaesthesia. Brit. J. Anaesth., 37, 871. (1965c). A history of nitrous oxide and oxygen anaesthesia. Part III: Parsons Shaw, Doctor Syntax and nitrous oxide. Brit. J. Anaesth., 37, 958. Sykes, W. S. (1960). Essays on the First Hundred Years of Anaesthesia, Vol. I, p Edinburgh: E. & S. Livingstone. Thompson, C. J. S. (1912). Henry Hill Hickman: a forgotten pioneer of anaesthesia. Brit. med. J., 1, 843. Trevelyan, G. M. (1964). Illustrated English Social History, Vol. 4: The nineteenth century, with 153 illustrations, selected by Ruth C. Wright, p Harmondsworth: Penguin Books Ltd. Wellcome Historical Medical Museum, London (1930). Souvenir: Henry Hill Hickman Centenary Exhibition , Wellcome Foundation Ltd. Wright, S. (1961). Applied Physiology, revised by Keele, C A., and Neil, E., 10th ed., p London: Oxford University Press.