Cosnett, JE

National Documentation Centre on Drug Use

DR. WILLIAM BROOKE O'SHAUGHNESSY The scene is Britain in 1831. MEDICAL BACKGROUND stopping as short a time as possible ..." Princess Victoria is 12 years All manner of physical, chemical and s arrived, with its nidus in Carbolic acid fumigation of railway passengers against cholera. universal was blood-letting. An authority wrote: "In commencing the treatment of cholera, no time is to be lost in endeav- ouring to bleed the patient ... the effect of blood-letting would appear to be almost miraculous ...". Of the other treatments, emesis was aimed at ridding the body of poisons, and vomiting was considered "the best of restoratives for torpidity of the blood". Calomel was almost univer- sally used, as a means of "unlocking the secretions". Other treatments included a large fraction of the pharmacopoeia of the time, mostly based on empiricism and superstition. The Lancet viewed this therapeutic miscellany with some scepticism when it declared. "All have the& seasons of celebrity and subsequent neglect". GLIMMERINGS OF SCIENCE A few doctors showed an inkling of scientific understanding. One thought that loss of water from the blood rendered it "difficult to circulation" and proposed that "distilled water be liberally poured into the stomach. Dr. Clanny of Sunderland analysed the blood of cholera patients and began his report with: "This blood, on applying the tongue to it, had no taste nor any particular smell ...". He found that the amount of water was decreased and the "colouring matter" increased, but he gave no specific advice about a remedy. In clear contrast to the ignorance, superstition, and empiricism that largely prevailed, one voice was heard, almost alone with its tone of reason and science. This was Dr. William Brooke O'Shaugh- nessy, a recent Edinburgh graduate, born in Limerick and aged 22 years at this time."' In his first paper on cholera, read before the Westminster Medical Society on 3 December, 1831, he wondered whether "the habit of practical chemistry which I have occasionally pursued might lead to the application of chemistry to its cure". So engrossed was he in the cause and cure of cholera that he travelled to Sunderland a few davs later. "for the purpose of making myself practically acquainted with the celebrated disease". Within 3 days he was writing to The Lancet:  "I have lost no time in endeavouring to obtain conviction on some points, and evidence on others ...". He reportea the appearance of two patients - clinical descriptions of cholera that have probably never been bettered: " O n  the bed lay an expiring woman ... presenting an attitude of death which ... I never saw paralleled in terror ... O n  the floor, extended on a palliasse ... lay a girl of slender make and juvenile height, but with the face of a superannuated hag. She uttered no moan, gave expression of no pain, but she languidly flung herself from side to side ... T h e  colour of her countenance was that of lead - a silver blue, ghastly t int;  her eyes were sunk deep into the sockets, as though they had been driven an inch behind their natural position; her mouth  was squared; her features flattened; her eyelids black; her fingers shrunk, bent, and inky i n  their hue. All pulse was gone at the wrist, and a tenacious sweat moistened her bosom. In short, Sir, that face and form I can never forget, were I to live beyond the period of man's natural age". O'Shaughnessy used this description to support his view that the cholera in Sunderland was a different disease from that which occurred in England before: "Would to God I could bring the sceptics here and show them the girl ...". In half- answer to his prayer The Lancet of 4 February, 1832, had a full-page, 3-colour sketch of such a patient (figure) - surely a landmark in medical illustration. On 20 December, 1831, O'Shaugh- nessy wrote: "I have been so busily confined in my laboratory that I have had little time for additional enquiries". Nine days later he wrote from London, asking The Lancet  to publish the "outlines" of his results, as follows: "The blood drawn in the worst cases ... is unchanged in its anatomical or globular structure ... It has lost a large proportion of its water ... It has lost also a great proportion of its neutral saline ingred- ients ... Of the free alkali contained in healthy serum, not a particle is present ... Urea ex is t s  i n  those cases where suppression of urine has been a marked symptom ... All the salts deficient in the blood, especially the carbonate of soda, are present in large quantities in the peculiar white dejected matters". These observations can hardly be faulted 150 years later. All the while the disease was spread- ing through England and Scotland, Famine in India,in the 1870s. appearing in London in January, 1832. There were reports of the "terrified populace" and the "dreadful distress which prevails in the neighbourhood of the various cases". O'Shaughnessy made a further, more detailed, report to the Central Board of Health, in which he confirmed his previous findings. Further he reported on the chemistry of the excreta and found that "the ingredients deficient in the blood were detected in the dejections or in other words, the addition of the dejection to the blood, in due proportion, would have restored the latter to ' i t s  normal consti tution" [original em- phasis]. He stressed that the changes "should not be regarded as primary causes" but rather as the "result of an external impression ... we still remain in darkness as to the mode in which that impression is communicated ...". Pursuing his theme logically to the "therapeutic conclusions", he wrote: " ... the indications of cure ... are two in number - viz. 1st to restore the blood to its natural specific gravity; 2nd to restore its deficient saline matters ... The first of these can only be effected by absorption, by imbibit ion,  or by  the injection of aqueous fluid into the veins. The same remarks,  w i t h  su f f ic ient ly  obvious modifications, apply to the second ... When absorption is entirely suspended ... in those desperate cases ... the author recommends the injection into the veins of tepid water holding a solution of the normal salts of the blood". In his final remarks O'Shaughnessy wrote: "I am therefore entitled to conclude that the exudation of the colourless part of the blood cons t i tu tes  one of the  chief  diagnostic characteristics of the malig- nant cholera ... in thefluidity, alkalesence and albuminous nature of the dejections we have the means of forming a certain and chemical diagnosis between this disease and others with which ... it may be confounded". THE FIRST INTRAVENOUS INFUSION The first practical application of O'Shaughnessy's advice was reported by Dr. Robert Lewins, MD, FRCP, of Leith in a letter dated, 15 May, 1832. He described witnessing the intravenous injection of a saline solution in a cholera patient. He wrote: "To Dr. Thomas Latta, o f  this place, is due the merit of first hav& recourse to this practice. He has tried it in six cases ... The most wonderful and satisfactory effect is the immediate  result  of the  injection ... a large quanti ty must  be injected, from 5 to 10 lbs. in an adult, and repeated at longer or shorter intewals as  the state of the pulse and other symptoms may indicate". A more detailed and formal report was sent by Dr. Latta to the Central Board of Health, and published in The Lancet of 2 June, 1832. He wrote: "So soon as I learnt the result of Dr. O'Shaughnessy's analysis I attempted to restore the blood to its natural state ...". The first patient was -an aged woman on whom all the usual remedies had been tried without success: "She  had apparently reached the last moment of her earthly existence, and now nothing could injure her - indeed so entirely was she reduced that I feared I would not be able to get m y  apparatus ready ere she expired. Having inserted a tube into the basilic vein, cautiously - anxiously, I watched the effects; ounce after ounce was injected but no visible change was produced. Still persevering, I thought  she began to breathe less laboriously, soon the sharpened features, and sunken eye, and fallen jaw, pale and cold, bearing the manifest impress of death's s ignet ,  began to g low w i th  returning animation; the pulse, which had long ceased, returned to the wrist' at first small and quick, by degrees it became more and more distinct, fuller, slower and firmer, and in tke short space of half an hour, when six pints had been injected, she expressed in a firm voice that she was free from all uneasiness, actually became jocular, and fancied all she needed was a little sleep; her extremities were warm, and every  feature bore the aspect of comfort and health. This being m y  first case, I fancied m y  patient secure, and from m y  great need of a little repose, left her in charge of the hospital surgeon; but I had not been long gone, ere the vomiting and purging recurring, soon reduced her to her former state of disability ... and she sunk in five and a half hours after I had left her ... I have no doubt the case would have issued in complete reaction, had the remedy, which had already produced such effect,-been repeated. Dr. Latta prepared the intravenous fluid as follows: "I dissolved from two to three drachms of muriate of soda and two scruples of the subcarbonate of soda in six pints of water, and injected it at temperature 112" F a h .  (This is approxi- mately 58 meq / l  sodium; 49 meq / l  chloride; 9 meq/l  bicarbonate."') Latta emphasised that "the watery diarrhoea may return with violence ... therefore so soon as the pulse fails, and the features again shrink, the venous injections must be repeated ... The injection should be carried on very slowly ... it should not exceed 2 or 3 ounces per minute". He described the apparatus as "a small silver tube" attached by a flexible tube to "Read's patent syringe". He cautioned against accidental injection of air, and advised that phlebitis could be prevented by "treating the vein with much delicacy". In subsequent letters Latta and several colleagues from Leith described further cases, some with dramatic response to injections. In reply to a query from the Board of Health, Lewins admitted that ten of the fifteen who had been injected died, but "under such circumstances that do not detract from the general merits of the practice". While O'Shaughnessy did not personally treat patients, he wrote to The Lancet: " ... the results of the practice described by Drs. Latta and Lewins exceed m y  most sanguine expectations. When we consider that no practitioner would dare to try so novel an  experiment,  except i n  cases beyond hope of relief by an ordina y mode of treatment, and consequently desperate to the last degree, even a solitary instance of recovery affords matter for congrat- ulation". He emphasised that "although by the injection of water and salts ... we may restore the deficient fluids of the body, and bring back the blood to its normal state, ... we must still remember that the unknown remote cause, and other agents, ... still are in operation, and require to be remedied before a perfect cure can be performed". The Lancet of 2 June, 1832, carried a leading article in which the history of intravenous injections was reviewed. The intravenous saline treatment of a cholera patient was described as "more like the workings of a miraculous and supernatural agent ...". It seems there was no previous record of water and salts being given deliberately to restore constituents lacking in thk blood, though there is record of blood transfusion, and of the injection of 6 ounces of water into a Russian cholera patient, with death in 2 hours. Over the ensuing months there was a flurry of reports of cases treated with intravenous saline in Britain. Almost all reported dramatic, but often temporary, improve- ment, but relapse was frequent as the purging continued. Various modifica- tions of the intravenous fluid were tried, even "milk, boiled once, skimmed and strained". Some patients were reported to have rigors or laboured respiration after the saline injections. Of the first 25 reported cases so treated, 8 recovered. There was much severe criticism, often outside medical journals. This provoked Dr. Latta to defend his treatment against "members of the medical profession guilty of scribbling on medical matters in the news-papers of the day". " THE TREATMENT FAILS TO PROSPER This pandemic subsided in Britain during 1832 but it continued across America. Despite further pandemics in 1852 and 1863 the use of intravenous saline was not accepted. Why did the treatment not prosper when it had the foundations of rational therapy, support- ed by many reports of its successful application? Firstly, it was only applied in patients who were deemed moribund; so, while the proponents were satisfied that lives were saved, others, and the public, thought that deaths were hast- ened by the treatment. Not realising that severely dehydrated patients can no longer lose fluid, it was felt by some that rehydration provoked more purging. Secondly, the treatment was not repeated sufficiently to maintain fluid balance. Thirdly, the fluid was not only unsterile but also chemically impure and very hypotonic. So, the more fluid that was given, even with good intentions, the greater was the chance of bafteraemia, pyrogen reactions, and haell~olysis. However sound the rationa1e:'fhe idea was much ahead of contemporary knowledge of physiological chemistry and microbiology. Another reason for lack of persistence with the concept was that, after the epidemic subsided in Britain, the main protagonists were no longer on the scene when the disease struck again."' Latta died in 1833. In that year, O'Shaughnessy joined the East India Company and went to India. There he interested himself, not with cholera, but with chemistry, electricity, and  telegraph^.'^' He was knighted in 1856, not for work in medicine, but for establishing a telegraph service between the main centres of India which was said to have influenced the result of the Indian mutiny.'" William O'Shaugh- nessy's third claim to fame was that, on returning from India, he introduced cannabis to England and Europe as a potent medication and analgesic for the treatment of tetanus, rheumatism, and epilep~y.'~' He died in 1889, but obituary notices make no mention of his pioneering re~earch'~' - his analyses of the blood and excreta of cholera patients, his deduction of the mechanism of the changes in composition, and his proposal of rational treatment, which was put into practice by Thomas Latta and Robert Lewins of Leith. All this when O'Shaugh- nessy was 22 and 23 years old, and when chemical pathology was an embryonic science. Dr. Lewins, in reporting Latta's second case, wrote to The Lancet on 18 May, 1832: "Verily, Sir, this is an astonishing method of medication, and I predict will lead to wonderful changes and improvements in the practice of medicine". He was right. Yet the names of O'Shaughnessy, Latta, and Lewins cannot be found in any major work on general medical history. REFERENCES 1. van Heyningen WE, Seal J.R. Cholera:  T h e  A m e r i c a n  Sc ient i f ic  Exper i ence  1947-1980. Boulder, Colorado: Westview Press, 1983: 1-25. 2. Ibid. 3. Ibid. 4. Ibid. 5. Nahas GG. Marihuana - Deceptive Weed. New York: Raven Press, 1973: 7. 6. van Heyningen WE, Seal J.R. Cholera:  T h e  A m e r i c a n  Sc ient i f ic  Exper i ence  1947-1980. Boulder Colorado: Westview Press, 1983: 1-25. 

An eminent Limerick doctor: Dr. William Brooke O'Shaughnessy.

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An eminent Limerick doctor: Dr. William Brooke O'Shaughnessy.

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