history 179 doi:10.4997/JRCPE.2012.219 1811–1870). RCPE 1811–1870). [email protected]

2012; 42:179–83 2012; Edinb Physicians Coll J R JAW Wildsmith to JAW Correspondence Road, Castleroy 6 Ferry, Broughty UK 2LQ, DD5 Dundee e-mail © 2012 Royal College of Physicians of of Physicians of College Royal © 2012

James Young Simpson ( Young James Figure 1 Collection. earlier developments had a Scottish connection, and and connection, Scottish a had developments earlier here. reviewed their contributions are In 1884 a young Viennese doctor, Carl Koller, was the first to recognise recognise to the first was Koller, Carl Viennese doctor, In 1884 a young oduction Paper Professor Emeritus, University of Dundee, Nethergate, Dundee, Scotland, UK Scotland, of Dundee, Nethergate, Dundee, Professor Emeritus, University JAW Wildsmith JAW Some (mostly Scottish) local anaesthetic heroes anaesthetic local Scottish) (mostly Some Intr a become could anaesthesia of form any Before had to be requirements practical possibility several the conceptmet: for be to had relief pain of to identify an mind had and a prepared developed, a from be administered which could agent effective soporific and The analgesic suitable delivery system. observedand were oxide nitrous of ether and effects 1844 when a Connecticut dentist, reported long before the employ to first was the (1815–1848), Wells Horace insight was to realise great Wells’s clinically. agent latter painless allow would inhalation oxide nitrous that stumps of his patients’ teeth rotting of the removal made dentures prior to the fitting of the effective Unfortunately, materials of the time. the new possible by failed his attempt to demonstrate the method publicly scepticism and through a combination of his audience’s com- the final the lack of a suitable delivery system, anaesthesia. effective for the requirements of ponent in 1846 anaesthesia ‘discovery’ of the for the credit Thus William Morton partner, former Wells’s to goes usually ether) more (diethyl agent an found who (1819–1868), the although systems, to cruder administration suited Wells. to go should the concept for credit applied development for requirements basic same The but a fascinating aspect is that both to local anaesthesia, conceived concept and administration system were Decades suitable agent was identified. a long before (like mind recognised a prepared before to elapse were of an described effects that the previously Wells) clinical specific the solution to a were drug available in those of the individuals involved Many problem. ABSTRACT cocaine and thus introduced of the alkaloid topical effects the significance of the Most subsequent development to clinical practice. drug-induced local anaesthesia not becoming interest with British and the United States, took place in Europe of doctors because a number This is surprising years. twenty over for apparent had made important contri- or with Scottish connections, in Scotland, working reviews paper This techniques. anaesthetic local of evolution earlier the to butions Arnott, James Wood, Alexander Simpson, Young of James work the relevant of John Alexander Hughes Bennett and the role and Richardson Ward Benjamin of the techniques. promotion William Struthers in the later Benjamin Arnott, James Wood, Alexander Simpson, Young James rds Keywo Ward Richardson, Alexander Hughes Bennett, John William Struthers John Bennett, Hughes Alexander Richardson, Ward declared. interest conflicts of ions of Interests No Declarat JAW Wildsmith

The concept is born

The term ‘local anaesthesia’ was first used in 1848, less than two years after the adoption of ‘anaesthesia’, to describe the effects of the inhalation of ether. James Young Simpson (Figure 1) published a paper in The Lancet1 providing early insight into the potential benefit of producing local rather than general anaesthesia:

But if we could by any means induce a local anaesthesia without that temporary absence of consciousness which is found in the state of general anaesthesia, many would regard it as a still greater improvement in this branch of practice. If a man, for instance, could have his hand so obtunded that he could see and yet not feel the performance of amputation upon his own fingers, the practice of anaesthesia in surgery would, in all likelihood, advance and progress still more rapidly than ever it has done.’

Simpson also reviewed earlier attempts at producing ‘peripheral insensibility’, including nerve compression, and described his own unsuccessful experiments with the topical application of and other substances.

The concept is developed and an administration system devised Figure 2 Alexander Wood (1817–1884). RCPE Collection. The concept of a peripheral approach to pain relief was developed further by one of Simpson’s contemporaries letter from James Arnott, an Aberdeen-trained physician in Edinburgh, the physician Alexander Wood (Figure 2), working in Brighton.3 Arnott was interested principally who was interested in improving the treatment of in the treatment of inflammation, but had noted that neuralgia. Others had tried applying morphine to the cooling had an analgesic action and suggested that it skin over the site of pain using a scarifying process might be the local anaesthetic which Simpson sought. similar to inoculation, but Wood reasoned that it might However there is no evidence of any response then or be more effective to inject the morphine close to the subsequently from Simpson, even though he continued nerve supplying the painful area.2 Both syringes and to be interested in analgesia induced by topical hollow needles had been developed by others, but application, studying the use of both chloroform and Wood was the first to combine them for drug carbon dioxide for this purpose. A possible explanation administration. He achieved some benefit, but through for Simpson’s lack of response might be that Arnott made the systemic absorption of morphine, not from any local some very critical comments regarding the risks of effect. However, in recognition of his work, Wood has Simpson’s beloved chloroform. A subsequent pamphlet been referred to, very appropriately, as the ‘father-in- cannot have helped endear Arnott or his method to the lore’ of local anaesthesia. Wood and Simpson had much great man, being lengthily, but very critically titled: in common apart from their insights into local anaesthesia: they lived and worked in Edinburgh, each was Question considered – Is it justifiable to administer subsequently President of the Royal College of Physicians chloroform in surgical operations, after its having of Edinburgh and they both lacked a drug which worked proved suddenly fatal in upwards of 50 cases when by the route of application they employed. pain can be safely prevented, without loss of consciousness, by momentary benumbing cold?4 Refrigeration anaesthesia developed Arnott did not pursue the matter, becoming more Given his knowledge of the early, even antiquarian, interested in the therapeutic aspects of cooling and now literature, it is perhaps surprising that Simpson’s paper being considered the pioneer of cryotherapy for cancer. on local anaesthesia made no mention of previous However, others did undertake further study of the history observations on the analgesic effects of cold. In the next analgesic effects of cold, and Arnott’s method (known as edition of The Lancet, this omission was corrected in a ‘congelation’ after he demonstrated it in Paris) was used

180 J R Coll Physicians Edinb 2012; 42:179–83 © 2012 RCPE history 181 1848–1901). Image 1848–1901). Some local anaesthetic heroes anaesthetic local Some ared mind Alexander Hughes Bennett ( Figure 3 Medical Society. courtesy of the Royal The prep the of nineteenth centuryIn most aspects surgery, of was a source of general anaesthesia availability not was this but comfortsurgeon, and patient both to recovery during Vomiting in ophthalmology. the case chloroform with ether or general anaesthesia from suture surgical the rupture to enough severe be could globe. the of contents the of extrusion cause line and worse be could operating of consequences the Thus to returned had surgeons some so nothing, doing than the avoid to in order patient conscious the on operating to ether and an alternative The need for problem. Arlt (1812– Ferdinand by was recognised chloroform who Vienna, of Ophthalmology in Professor 1887), recognise the implications of their own observations implications of their own the of recognise to translate these effects The failure local effects. cocaine’s of a mystery more even into clinical practice is perhaps and oxide of nitrous the effects to utilise than the failure general of introduction The . the to prior ether acceptance of an entirely did at least require anaesthesia as had, ‘local anaesthesia’ but the term concept, new methods and been coined veryafter, soon above, noted The significance of been sought. had its production for better been observation have might Bennett’s is a cocaine that his evidence although appreciated, his contributed to have substance may toxic highly this himself. to do failure

Andrews. Andrews. 8 Its rapid evap- Its rapid 7 Unfortunately, the Unfortunately, 5,6 9 2012; 42:179–83 2012; unities and missed opport In addition, almost hidden away in the list of his away almost hidden In addition, 9 Right calf of leg injected. After no movement on After no movement Right calf of leg injected. entire of movements calf left pinching on irritation, including right leg. body, J R Coll Physicians Edinb Coll Physicians J R © 2012 RCPE technique was cumbersome (involving the infusion of an the infusion (involving was cumbersome technique bladder thin-walled a through mixture ice/water/salt to have site) and seems placed on the operative Subsequently, effects. inconsistent and slow produced another the attention of attracted the basic method Sir) Benjamin Dr (later of anaesthesia, pioneer early in London worked who (1828–1896), Richardson Ward St from qualifying and after studying in Glasgow Richardson was a friend and colleague of the first of colleague and friend a was Richardson took (1813–1858) and Snow John anaesthetist specialist development. its to approach scientific equally an by of local anaesthesia concept Attracted to the and eventually he sought a better method refrigeration, ether. utilising diethyl a spray developed The significance of this clear demonstration of sensoryThe significance of this clear demonstration also failed to although other workers block was missed, When Simpson and Wood were developing their their developing were Wood and Simpson When worked have which would cocaine (the drug concepts, although named, or isolated been not them) had for chewing of effects ‘exercise-sustaining’ the of reports from Europe of Erythroxylon coca had reached the leaves America. South the time of the Spanish conquest of place taken had study formal little if any However, leaves sufficient quantities of both of lack the of because isolation allow that would the chemical techniques and Albert until 1860 that not was It principle. active the of Wöhler’s in Friedrich working (1834–1861), Niemann was the (1800–1882) chemistry laboratory in Göttingen, white crystalspure isolate first to named (which he the first to note also he was leaves; coca cocaine) from on the tongue. effect numbing a had they that Cocaine in both dental and general surgery. general and dental in both experiments with cocaine is the following report: report: is the following experiments with cocaine oration provided a more definitive and rapidly acting and rapidly definitive a more oration provided more being even chloride, of cold (ethyl application 1880). after agent cooling the as substituted was volatile, Limited availability of the raw material may have have may material raw the of availability Limited people made but several study, to restrict continued One of notable. are in retrospect, observationswhich, Edinburgh graduate, these individuals was a young of the son 3), Alexander Hughes Bennett (Figure In 1871, University. Edinburgh at Physiology of Professor while working alkaloids plant of range a studied Bennett He observed laboratory. his MD thesis in his father’s for and animals of range a in injecting cocaine of effects the that certainlyalmost was record to person first the respiratory and convulsions produced doses large arrest. JAW Wildsmith

believed that a local anaesthetic suitable for ophthalmic work would be of great benefit. This led Carl Koller (1857–1944), then a young Viennese doctor with aspirations of becoming an ophthalmologist, to test the conjunctival application of a number of substances, but they were all ineffective.10

In 1884 Koller’s close friend, Sigmund Freud, became interested in cocaine, hoping that it might have therapeutic applications. Freud reviewed the literature, planned a series of studies of systemic effects and asked Koller to help. It was while demonstrating (to a third party) the tongue numbing effect of ‘tasting’ cocaine that Koller realised that it might be the local anaesthetic which he had sought earlier. Conjunctival instillation in animals led quickly to personal experimentation and on to successful use in operative surgery before the discovery was announced at an Ophthalmological Conference in Heidelberg.11 Almost forty years earlier the news of general anaesthesia had taken six weeks just to cross the Atlantic, but the news of local anaesthesia was around the world in a few days courtesy of the electric telegraph. It was a landmark event, prompting the comment:12

The loneliest doctor in the world is the ophthalmologist who hasn’t written an article on cocaine. Figure 4 John William Struthers (1873–1953). Image courtesy of the Royal College of Surgeons of Edinburgh. Subsequent development

The new discovery was met with great enthusiasm in His monograph (1906)… was for long the best both Europe and the United States, with most of the source of information on the subject in English. nerve block techniques we know today being developed on one or other continent within a couple of years of Struthers’s book notes that most of the development of Koller’s discovery. However, cocaine is a poor local local anaesthesia had been in France, Germany and the anaesthetic for anything but topical application in United States, but there is (unfortunately) no indication relatively small doses, and wider use was limited by its of how he became interested in this aspect of anaes- toxicity, its addictive nature and the difficulty of sterilising thesia. Because of World War II Struthers worked long solutions. It was only when new local anaesthetic drugs after the normal retirement age so he may have had were synthesised, particularly procaine (in 1904), that some influence on HWC Griffiths and John Gillies in the more major nerve blocking techniques could be their choice of spinal anaesthesia (one of the techniques used in relatively safety. None of this development took described in Struthers’s book) for their seminal study on place in Britain where local methods do not seem to have induced hypotension published in 1948.16 From this been used much until well into the first decade of the work the Department of Anaesthesia in the Royal twentieth century. In Dundee Royal Infirmary, for example, Infirmary of Edinburgh developed a major interest in there is no record of spinal anaesthesia being used until it local anaesthetic techniques during the second half of is mentioned in the Annual Report for 1908–9.13 the century.

This was shortly after publication of a slim volume Conclusion entitled Local anaesthesia in general surgery, written by John William Struthers (Figure 4).14 Struthers was then a A number of doctors with significant Scottish connec- Clinical Tutor in The Royal Infirmary of Edinburgh; later tions played notable roles in the early history of local he was a Consultant Surgeon there and President of the anaesthesia. In Edinburgh, James Young Simpson coined Royal College of Surgeons of Edinburgh. The contem- the term and tried to produce it by topical application, porary importance of his book in promoting the use of Alexander Wood tried to achieve analgesia by perineural history local anaesthesia in Britain is evident from Struthers’s morphine injection, and over a decade later, in 1871, obituary in The Lancet:15 Alexander Hughes Bennett produced, but did not

182 J R Coll Physicians Edinb 2012; 42:179–83 © 2012 RCPE history 183 Proceedings of Proceedings London: Sigma London: Some local anaesthetic heroes anaesthetic local Some 1953; 265: 457–8. 265: The Lancet 1953; Victory over pain: a history of anaesthesia. Victory pain: over 18,19 1884; 2:990–2. The Lancet 1884; Robinson V. V. Robinson Becker HK. Carl Koller and cocaine. The Psychoanalytic Quarterly and cocaine. Carl Koller HK. Becker 32:309–73. 1963; the of anaesthesia producing for cocaine of On the use C. Koller eye. 1947. Books; in Dundee. anaesthesia of Highlights SW. McGowan at: Available 99–100. 6b: 1989; Anaesthesia Society HistoryThe of www.histansoc.org.uk surgery. in general anaesthesia on local Notes JW. Struthers 1906. & Sons; Wm Green Edinburgh: William John Struthers. Griffiths HWC, Gillies J. Thoracolumbar splanchnicectomy and Thoracolumbar splanchnicectomy Gillies J. Griffiths HWC, 3:134–46. Anaesthesia 1948; procedure. anaesthetic sympathectomy: the early years. 1: Volume transport. Edinburgh’s Hunter DLG. 1992. Thin; James Edinburgh: of the introduction (1857–1944) and Carl Koller Wildsmith JAW. 9:161–4. Regional 1984; cocaine into anesthetic practice. 1983; Regional Anesthesia Edinburgh men. Three Wildsmith JAW. 8:1–5.

12 10 11 13 14 15 16 17 18 19 Acknowledgements the National Library to thank staff at of like I would Edinburgh of of Surgeons College the Royal Scotland, help in in London for Collection Wellcome The and to in this of the material referred accessing much the detailed accounts of published more I have paper. Koller and Bennett Wood, Simpson, of work relevant elsewhere. The Edinburgh Medical Edinburgh Medical The 1866; i: 115–7. i: 1866; 1949; 4: 10–7. 4: 1949; 1873; 19:323–41. 1873; 2012; 42:179–83 2012; It was not until 1884 in Vienna that Vienna It was not until 1884 in 17 1855; 82:265–81. 1855; Painless tooth extraction without chloroform with with without chloroform tooth extraction Painless Medical Times and Gazette Medical 1860; 153:124–55. German. 153:124–55. 1860; London: John Churchill; 1854. Churchill; John London: Niemann A. [Ueber eine neue organische base in den cocablattern]. cocablattern]. den in base organische eine neue [Ueber A. Niemann Arch Pharm An experimental inquiry into the physiological AH. Bennett theobromine. and cocaine guaranine, caffeine, theine, of actions Edinburgh Medical Journal Simpson JY. Local anaesthesia, notes on its artificial production by by on its artificial notes production Local anaesthesia, JY. Simpson 1848; The Lancet and in man. animals, in the lower etc. chloroform 2:39–42. the direct neuralgia by method of treating New A. Wood points. painful the to opiates of application and Surgical Journal Arnott J. On cold as a means of producing local insensibility. The local insensibility. producing of means a On cold as J. Arnott 2:98–9. Lancet 1848; to administer is it justifiable The question considered: Arnott J. proved its having already after in surgical operations, chloroform when pain can be safely of 50 cases, in upwards suddenly fatal momentary by benumbing without loss of consciousness, prevented, cold? a pioneer in 1797–1883: (Aberdeen) M.D. Arnott, James HM. Bird Anaesthesia analgesia. refrigeration BlundellW. observations on local anaesthesia by congelation in general surgery. surgery. observations in general congelation on local anaesthesia by 1854. Churchill; John London: local method of producing and ready On a new BW. Richardson anaesthesia.

J R Coll Physicians Edinb Coll Physicians J R © 2012 RCPE 8 9 Carl Koller made the key connection between observed between connection key the made Koller Carl all the early Otherwise, application. and clinical effect Scottish had have might anaesthesia local of heroes connections. References 1 2 recognise, local anaesthesia by cocaine injection. Simpson injection. cocaine by anaesthesia local recognise, seen the importanceof Bennett’s might have Wood and Wood and dead was Simpson 1871 but by experiment, first Edinburgh’s for work medicine to up given had company. tramway 3 4 5 6 7