History of Medicine, Lilybank House, University of Glasgow, Glasgow

Penicillin: promise, problems and practice in wartime Edinburgh

S Gardiner PhD candidate, Centre for the History of Medicine, Lilybank House, University of Glasgow, Glasgow

ABSTRACT While medical historians have paid ample attention to the introduction Correspondence to S Gardiner of antibiotics and their impact on hospital-based practice during and after the Centre for the History of Medicine Second World War, the multiple issues surrounding their use in Scottish hospitals Lilybank House are sorely lacking in current discussions. Drawing on an extensive yet underused University of Glasgow range of materials including patient treatment records, oral histories and medical Glasgow G12 8RT correspondence, this paper explores the introduction of penicillin for civilian UK treatment at the Royal Infirmary of Edinburgh during the closing stages of the e-mail [email protected]. War. It highlights the success of the drug in clinical treatment as well as its ac.uk shortcomings, offering an alternative view of its initial impact on surgical practice.

Keywords antibiotic resistance, Edinburgh, infection control, penicillin

Declaration of Interests No conflicts of interest declared

Introduction the considerable and recognised threat posed by microbial resistance right from the beginning.1,2 Medical historians have paid considerable attention to the introduction of penicillin during the Second World War and its revolutionary impact on surgical practice Managing supplies: the penicillin and systems for infection control in hospitals worldwide.1,2 committee Scholars too have documented and debated the rising rate of wound infection and the emergence of antibiotic Early in August 1944, discussions emerged regarding the resistance as a global phenomenon during the post-war dissemination of penicillin for civilian use in Scotland’s era.3–5 Yet little has been said about the implications of hospitals. Until this point, penicillin had been in use at antibiotic therapy for clinical practice in Scotland and, the RIE for just a few months. It remained under tight more generally, it is recognised that there is a dearth of control and was reserved for the treatment of war historical knowledge of the clinical work undertaken in casualties and for the purposes of clinical trials.7 civilian hospitals during the Second World War.6 However, in early August 1944, the Deans of the four Scottish medical schools of the Universities of Edinburgh, This paper seeks to redress these imbalances within the Aberdeen, Glasgow and St Andrews (in Dundee) met historiography by exploring the introduction of penicillin with officials from the Department of Health for to the Royal Infirmary of Edinburgh (RIE) and examining Scotland (DoHS) to arrange for its incorporation into its impact on the treatment of civilian patients during the civilian treatment.8 The DoHS explained that the Ministry closing stages of the War. This paper utilises a variety of of Supply was providing some 120 million units (120 hospital records including previously unused patient ‘mega’ units) for the treatment of civilians in Scotland in treatment records together with correspondence, August 1944. It was agreed that this sum would be minute books, oral histories and excerpts from the distributed to the four schools as follows: Glasgow, 60 medical press. As in the treatment of war casualties, mega units; Edinburgh, 35 mega units; Aberdeen, 15 mega penicillin achieved great clinical results in civilian units; and Dundee, 10 mega units. At the request of the treatment at the hospital. However, the new therapy was DoHS, each Dean established and led regional penicillin shaped considerably and, in some respects, tainted by ‘committees’ through which supplies and priorities for economic problems with regard to both the quantity use were determined at a regional level.8 That it was and quality of supplies. Indeed, this paper will demonstrate envisaged that the Deans of the four university medical that such considerations exerted a strong influence over schools would play such a crucial role in incorporating the cases chosen for penicillin therapy, methods for penicillin into the Scottish healthcare system is indicative administering the drug and, sometimes, clinical outcomes. of the supremacy of academic medicine in Scotland and its pre-eminence over extra-mural teaching before history Complicating the traditional view that penicillin was 1948.9 The remit of the new Edinburgh committee was perceived as a ‘wonder drug’ or even a ‘miracle drug’ to distribute the drug to hospitals across the South- when it was first introduced, this paper will also highlight Eastern Defence District, an area probably covering

198 history

22 199 In 1945, 1945, In Likewise, Likewise, 22 24–26 29 28 Indeed, the medical literature of literature the medical Indeed, Penicillin usage in wartime usage Edinburgh Penicillin This allowed one British clinician This allowed 23 27 22 while penicillin would eventually revolutionise the the revolutionise eventually while penicillin would was a delay there War during the of syphilis, treatment the full extent of its as treatment the new in introducing organism in the condition the causative activity against unknown. remained The inclusion of ulcerative colitis on the list of conditions list of the on colitis ulcerative of inclusion The ‘vexed the highlights treatment for inappropriate aetiologythe was that question’ during condition this of the interwar period. to state in January 1945 that Paul Ehrlich’s discovery of discovery in Januarystate to Ehrlich’s Paul 1945 that ‘greatest the to that day 1907 remained in Salvarsan [syphilis]’. of in the treatment advance the pre-penicillin period was awash with narratives with narratives period was awash the pre-penicillin with Bacillus condition, the of nature infectious the about dysenteriaea potential cause. highlighted as Such specific guidelines regarding where and when and where Such specific guidelines regarding bound were penicillin in what ways and should be used the to chief concern Of economy. of up with issues Ministryimplement economy to need the was Health of minimising and sensibly it using by penicillin with The memorandum also provided advice regarding how how advice regarding provided also The memorandum systemically, and locally both the drug administer to dosages. of the size and frequency often recommending encouraged they deep wounds and burns for example, For abscesses, For penicillin cream. a of local application the a solution containing sterile water recommended they at least 250 units of penicillinand per cubic centimetre. use the endorsed they of dryIn the treatment wounds, blown sulphonamide-penicillin powder, of a mixed insufflator. an using wounds to on directly member of the to the RIE and surgeon Learmonth, an the use of touted Committee, Penicillin Edinburgh of method economic most the being as insufflator an produced in that they penicillin powders applying be treated. to the area over ‘frosting’ even The Ministry of the use against of Health advised which organisms by caused conditions penicillin treat to the to be susceptible to that time known not at were colitis), and ulcerative drug (such as intestinal infections syphilis. and endocarditis bacterial excluding while also septicaemia, acute osteomyelitis and severe carbuncles); carbuncles); severe and osteomyelitis acute septicaemia, and pneumococcal streptococcal, haemolytic to those resistant (especially infections meningococcal Several gangrene. gas and treatment); sulphonamide when supplies ‘special consideration’ merited conditions and in burns sepsis infections; eye as such it, for allowed traumatic gonorrhoea; sulphonamide-resistant wounds; thoracic and fractures compound example, lesions (for associated with tuberculosis complications injuries); to resistant infections skin and empyema); acute as (such The Ministry of Health treatment. of other forms to authority penicillin the local committees the granted use penicillin on conditions other than those highlighted were supplies providing again in the memorandum, sufficient.

12,13 15–17 This 12 Learmonth, in Learmonth, 2 Its membership membership Its 8 Under the new new the Under 20,21 14 Despite these increases, Despite these increases, Indeed, the opening line Indeed, 198–205 18,19 15,22 2016; 46: 2016; 7,10,11 © 2016 RCPE J R Coll Physicians Edinb Coll Physicians J R collaboration with another bacteriologist, JP Duguid, had JP Duguid, collaboration with another bacteriologist, into the drug’s an investigation conducted recently the inflicted during war wounds efficacy in treating 1944. June of landings D-Day of this publication stressed the need for economy in economy for need the stressed publication this of provide of its contents using penicillin and the remainder rationed was in which the drug insight into the ways an in into civilian treatment first incorporated when it was all that Advising UK. in the elsewhere and Edinburgh the inhospital, penicillinadministered shouldbe ‘suitable’ as conditions the following noted memorandum (such as infections staphylococcal treatment: for The total share for civilian treatment in all hospitals civilian treatment for The total share to 50 mega units in Januaryincreased 1945 and 75 mega month. units in the following By September 1943, however, the net yield amounted to the net yield amounted however, By September 1943, patient. one just treat to enough unit, mega one only is indicative of the difficulties faced in British university British university in difficulties faced the of indicative is penicillin of quantities ample in producing laboratories deep-tank by production mass of method US the before in 1945. adopted was fermentation comprised: Professor Sydney A Smith, Dean of the A Smith, Sydney Professor comprised: Officer Medical Clark, WG School; Medical University’s of Professor TJ Mackie, Edinburgh; of Health for Bacteriologist and Bacteriology at Edinburgh University Surgeryof and Professor and JR Learmonth, to the RIE; the RIE. to Surgeon demand continued to considerably outweigh supply. This supply. outweigh considerably to continued demand the 1945, a brief period in early for explain why, may ‘sub-standard’ issuing Committee considered Penicillin than lower penicillin penicillin potency as of a (defined use. topical for hospitals its to milligram) per units 150 abandoned. soon were plans These Despite the fact that penicillin was still a relatively new new penicillin Despite the fact that was still a relatively possessed already team Edinburgh the technology, use and even to handle, of how considerable knowledge team at bacteriological Mackie’s the drug. produce small amounts growing had been Edinburgh University mid-1942. since RIE the at clinical use penicillin for of Awareness of the need to ration penicillin of the became Awareness Edinburgh when the 1944, in October apparent widely Ministryrecent a of Committee circulated Penicillin on the ‘Recommendations Health memorandum entitled with penicillin’ all civilian patients to of treatment hospitals under its authority. Lothian and the Scottish Borders. the Scottish Lothian and arrangements, from August of that year, penicillin supplies of that year, August from arrangements, department before University in Mackie’s kept were These region. the across hospitals to distributed being the itself but also RIE the only not included hospitals Hospital, Bangour Diseases, Infectious for City Hospital for Hospital Royal the Hospital, General Western the Margaret Princess the and Leith Hospital Sick Children, the the RIE obtained month, first In that Hospital. Rose civilian use in for of the supplies reserved largest share 35 mega units. eight out of receiving these hospitals, S Gardiner

wastage, owing to the scarcity of supplies and widespread table 1 Conditions treated with penicillin at the Royal demand. These problems, they envisaged, could be Infirmary of Edinburgh, 1944–5. (Adapted from: LHSA. RIE counteracted by developing and spreading knowledge of penicillin treatment records, 1944–5. GD1/74/8/5. Note: 8 22 patients were recorded under two separate categories, the properties and best uses of the drug. James hence the total of 61 patients). Whorton has documented the development of ‘therapeutic rationalism’ in the USA during the 20th Condition(s) No. of patients century, which he defined as the ‘conservative and Osteomyelitis 17 informed use of drugs only in situations where the likely Septicaemia 6 benefits significantly outweigh the risks’.30 He writes that Gonorrhoea 6 these risks, particularly where antibiotics are concerned, Puerperal/suppurative mastitis 5 include toxicity, side effects and resistance.30 Building on Abscess/multiple abscesses 5 this, Scott Podolsky maintains that by the 1960s, and in Laceration 3 light of the escalating cost of prescription medications in Compound fracture 2 the USA, notions of ‘rational’ drug prescribing – Septic arthritis 2 particularly antibiotic prescribing – were now Varicose/necrotic ulcer 2 underpinned by issues of economy.31 However, in British Carbuncle, empyema, 1 hospitals, antibiotics were closely linked to issues of epithelioma, gangrene, (for each condition) economy right from the beginning, not because of the gonococcal iritis, gunshot wound, cost of the new therapy but because of the huge haemothorax, pneumonia, imbalance between supply and demand. The story of pyaemia, septic burn, septic penicillin in British hospitals was therefore centred as thumb, tendon sheath infection, much on ideas of economic rationalism as it was on ulcerative colitis therapeutic rationalism. Total 61

Penicillin treatment at the Royal Infirmary of Edinburgh Table 1 shows that the ailments treated with penicillin at the RIE during this period were almost identical to those To keep a watchful eye on penicillin consumption in that the Ministry of Health had awarded priority status Edinburgh, the local Penicillin Committee requested that to. Osteomyelitis represented the most common clinicians kept records of the cases treated with condition in this series, as found in 17 patients.32 This is penicillin and the amount of the drug used in each case.15 perhaps unsurprising given the very successful results of Fifty-three of these treatment records from the RIE are a clinical trial of penicillin in osteomyelitis which was held at the Lothian Health Services Archive, and dated conducted at the RIE only a matter of months previously, between October 1944 and February 1945. Forty-six using penicillin obtained from US pharmaceutical patients in the series were admitted as inpatients and company Pfizer.12 In that study, a mortality rate of just the remaining seven were outpatients. The records 2.5% was demonstrated in 40 patients despite a 50% contain information on the name, age and condition of incidence of staphylococcal septicaemia. In osteomyelitis, each patient. They also cite dates of admission and penicillin represented a considerable advance over discharge, the duration, method and dose of penicillin sulphonamides which studies indicated had an associated treatment and the results of treatment.32 Their contents mortality rate of 10%.34 Only in one instance – the case give an illuminating insight into the types of patients that of ulcerative colitis – was penicillin used against the were chosen to be among the first civilian beneficiaries Ministry of Health’s wishes.22,32 The broad range of of penicillin in British hospitals, while their meticulous conditions represented in Table 1 highlights not only that detail demonstrates how the Ministry of Health’s the Ministry of Health’s guidelines for rational use were overarching aim of implementing economy operated at followed closely in Edinburgh, but also the degree of the individual patient level. flexibility afforded to regional penicillin committees in deciphering who else could be selected for therapy. That An indication of the age of the patients was given in 47 Edinburgh’s Committee chose a case of epithelioma for cases. The majority (29) were patients under the age of 30. treatment is an interesting observation and likely reflects From the 45 records giving specific ages, an average age of the longstanding association of cancerous conditions 31.5 years is noted.32 The relatively young age of this group with bacterial infection.35 is perhaps surprising considering the predisposition of the elderly to infection and the age-associated decline of the The exact quantity of penicillin used in this series immune system.33 Arguably, the decision to treat the amounted to 44,239,000 units. This sum represents history infectious ailments of these relatively young patients 81.2% of the total amount used at the hospital during reflected the need to minimise wastage by giving penicillin the period from October 1944 to February 1945 to those with a better chance of recovery. (54,500,000 units). It gives an average of 834,698 units

200 J R Coll Physicians Edinb 2016; 46: 198–205 © 2016 RCPE history 22 201 The Ministry of Health gave The Ministry of Health gave 36 Penicillin usage in wartime usage Edinburgh Penicillin ‘Eudrip’ apparatus for penicillin administration. penicillin administration. for ‘Eudrip’ apparatus One surgeon testified to the use of the Eudrip of the use testified to One surgeon 36 …my recollection is that it was a simple glass recollection …my hole a and cork with a cases, in some medicine bottle drip if home-made an almost and it, through bore that know probably you because, And okay? like, you the body, from the penicillin is very excreted quickly was to keep the problem so and penicillin, straight Figure 1 Figure Elsevier. from [36] with permission Reprinted from To operate the Eudrip No. 3, the model which found the model which found 3, operate the Eudrip No. To in a the penicillin solution was stored at the RIE, favour a glass through passing bottle before supply four-ounce Y-piece This the bottle. the neck of fitted into Y-piece, in which, of air into the bottle the inflow facilitated also passed which the solution by determined the rate turn, The rate of the patient. to reach the apparatus through the raising or lowering by could be adjusted flow Y-piece. No. 3 when penicillin first appeared: No. so too did it have implications for clinical outcomes in clinical outcomes implications for did it have too so this series. 1) was used to administer (Figure The Eudrip apparatus the in 1944 by Devised infusion. penicillin by University Edinburgh of staff surgical and bacteriological models in two available was apparatus this RIE, the and 3’). ‘No. 1’ and (‘No. detailed instructions for using both models in its using both models in its detailed instructions for suggesting that the Eudrip on penicillin, memorandum the UK during this period. across was used in hospitals

32 The case 22 Length of treatment Length of treatment 32,36 198–205 The MinistryThe Health of 37 There is thus ample evidence is thus ample evidence There . In this report, a daily dose of dose daily a report, In this . 32 22 As will be demonstrated below, As will below, be demonstrated 1 2016; 46: 2016; British Medical Journal © 2016 RCPE J R Coll Physicians Edinb Coll Physicians J R 120,000 units over at least seven days was recommended recommended was days seven least at over 120,000 units in systemic administration. notes did not always provide figures for total daily doses daily total for figures provide always not did notes 100,000 of the administration although each patient, for receiving in the 37 patients common relatively units was this figure to some However, infusion. penicillin by to treat needed minimum bare the absolute represented short far fell it was what of others, to and, infection of total dose if the average Moreover, necessary. deemed to each patient in this series amounted penicillin given 9.2 patient received the average to 834,698 units and 90,728 units of dose daily average an treatment, of days these figures. from can be deduced per day per case to show that reduced-strength doses of penicillin were penicillin of were doses reduced-strength that show to It elsewhere. probably and RIE the at administered being that this practice of giving sub- recognised is widely ‘underuse’ antibiotic as to referred also – doses standard and their microbes – has significant implications for resistance. for capacity was calculated for all patients in the series and gave an an gave and series the in all patients for calculated was of Methods patient. per 9.2 days of length average The 53 cases. in 51 of recorded were administration via intramuscular treated (32) majority of patients were osteomyelitis, of cases comprised This group infusion. Five other conditions. among and septicaemia, pyaemia penicillin by received conditions patients with similar intramuscular received Eleven intramedullaryinfusion. intervals regular at administered injections which were short time of period relatively a over typically and seven these 11, From less than 24 hours). (usually one of and patients (all six cases of gonorrhoea in a penicillin dissolved given iritis) were gonococcal oil or in a saline solution. and peanut beeswax of mixture with localised those typically patients, ten remaining The many In injection. by treatment local received abscesses, the of more or two by administered was penicillin cases, here. described methods These doses were likely weakened further the by weakened likely were doses These wartimeimpurities that plagued British-made penicillin. up the Ministrythat at that time, of Health noted Indeed, form tablet or in powder penicillin issued of 60% to could contain impurities. Just months before the beginning of the period under under the period of the beginning before months Just clinico-bacteriological combined a of report a analysis, penicillin, of properties into the therapeutic investigation in appeared Council, Research Medical the for produced the per case, although the total individual amounts given given total individual amounts although the per case, Typically, units. units to 4,200,000 40,000 from ranged penicillin this scale received the higher end of patients at administering, involved The infusion method infusion. by over and penicillin continuously of volumes large drip, by at bacteriostasis serum maintaining thereby days, several at all times. a satisfactory level recommended 100,000 to 120,000 units per day in cases day per units 120,000 100,000 to recommended receiving units 120,000 and infusion requiring injections. subcutaneous and/or intramuscular S Gardiner

the blood level up…. And if the patient was seriously infested with bacteria but without any clinical symptoms ill, you had to keep the blood level high, and you of infection. Just three deaths appear in the series, giving could only do that by an infusion. So my first a mortality rate of 5.7%. In all three instances, the introduction of it was it being given in this improved records intimated that the penicillin was administered drip-form, which was quite a novelty way of giving a too late.32 drug at that time, by infusion.38 Despite the overall successes achieved with the new It was the nurse’s duty to re-fill the supply bottle once treatment, ongoing issues with both the quantity and daily and, after use, the apparatus was washed with quality of penicillin were manifest in the patient records. distilled water before being autoclaved. The fact that the These issues, as mentioned above, resulted in the use of Eudrip No. 3 required relatively little attention from the impure, sub-therapeutic doses of penicillin which nursing staff in order to carry out its function gave it an undoubtedly contributed to questions surrounding advantage over the No. 1.36 Penny Starns has commented resistance. Indeed, the records provided concrete on the revolutionary impact of antibiotics on the nature evidence of microbial resistance. On at least six occasions, of nursing work. She argues that penicillin undermined some organisms – including those which are usually the traditional duty of care, hitherto regarded as a key susceptible to penicillin – resisted treatment. In three of component of nursing work. In her words, ‘[t]he days of these cases, although it had no effect on the eventual administering hot poultices and sponge baths were over, clinical outcomes, treatment was stopped despite the and in some instances good old-fashioned nursing care lingering presence of bacteria. Three patients developed was rendered superfluous’.39 This change was also staphylococcal abscesses during or after treatment. One occurring in Edinburgh in connection with penicillin and of these three records noted a ‘poor result’ in treating particularly so with the introduction of the Eudrip. A the abscess.32 nurse who trained at the RIE during the 1930s recalled the numerous practices (including administering These findings allow us to redefine the timeframe which poultices and providing fresh air) that were crucial to historians traditionally use for the phenomenon of the nursing of infectious conditions ‘without the aid of antibiotic resistance. Granted, as scholars traditionally antibiotics’.40 The arrival of penicillin therapy and the assert, microbial resistance did not rise to prominence Eudrip apparatus, in minimising the nurse’s role in the as a global threat until the 1950s.3–5 Yet, there was a healing process, ultimately shifted the power to facilitate notable degree of resistance to antibiotics right from the treatment from the nurse to the new technologies. beginning. Laboratory investigations conducted in Oxford as early as 1940 demonstrated the capacity for In this series, positive outcomes resulting from penicillin some bacterial strains to resist penicillin in vitro.44 These treatment were recorded in 48 cases (90.1%). The case notes, however, served as an early indication that treatment forms indicated that the patient had improved the phenomenon of resistance was entering the clinical notably and/or they had been discharged from hospital. sphere in Edinburgh. As early as April 1944, shortly Seven of these patients, most of whom were cases of before the period under analysis, experts advocated the gonorrhoea, were cured with penicillin having previously routine bacteriological testing of infective cases to failed to respond to sulphonamide therapy. One patient establish the cause of infection as a means of determining with a tendon sheath infection was successfully treated the efficacy of penicillin therapy in individual cases.37 with a sulphanilamide powder while receiving penicillin Evidence suggests that at the RIE, sensitivity testing was via intramuscular infusion. Before penicillin, tendon first performed in the wake of the D-Day landings in sheath infections, as one commentator noted in the June of that year. It is known that Learmonth and Duguid Lancet in 1947, ‘usually meant that the patient would be conducted in vitro analyses of swabs taken from left with a stiff claw which he would gladly see wounded soldiers arriving from Normandy to establish amputated’.41 The use of penicillin and sulphonamides the sensitivity of infecting strains to penicillin.14 One together shows that in wartime Edinburgh, penicillin was nurse who worked under Learmonth during the War deployed in what must be viewed as an early form of testified to the benefits of penicillin in wound care but ‘combination therapy’ – therapy involving two or more also to the need for routine testing at that time: antibiotics – which was popularised during the 1950s.42,43 Yes, [penicillin] made a tremendous difference. But On at least four occasions, penicillin was given as a there again, I can remember Sir James Learmonth prophylactic measure: in one case, before a saying so definite when penicillin came out, ‘Now let’s sequestrectomy; in another, before a leg amputation; in a hope these never become too common’. You see, we case of haemothorax, where it was noted to have been always took a small [sample] of whatever was causing used ‘with great success’ and resulted in the ‘complete illness or blood or what have you, urine sample and avoidance of infection’; and in a patient with severe made sure that the organism was sensitive to history lacerations to the hand which resulted in the ‘avoidance whatever we were giving. And his theory was that if of infection in what was an obviously heavily infected that wasn’t done routinely that the organisms would wound’.32 Presumably the latter denotes a wound become insensitive to the…And this has happened

53 203 However, 1,2 These issues 30,31 As the Penicillin Committee’s Committee’s As the Penicillin 49–51 Penicillin usage in wartime usage Edinburgh Penicillin Traditional historical accounts of penicillin historical accounts Traditional 6 By May 1946, the RIE’s supply of penicillin of had supply the RIE’s 1946, By May In the immediate post-war period, penicillin period, post-war immediate the In 52 49 exerted a strong influence on the nature of the early early the of nature the influence on strong a exerted penicillin the Although on the RIE. at penicillin therapy were these excellent clinical results, whole achieved supply. with problems extent by an to counterbalanced poor quality of wartime and the scarcity Undoubtedly, penicillin of resistance contributed to the phenomenon the after soon so within the clinical realm it emerged as introduced. was drug grown to some 700 mega units per month, approximately approximately units per month, 700 mega to some grown of cases for specifically reserved 250 of which were issue the free year, of that 1 June of As disease. venereal the point, this After ceased. DoHS the penicillin from of penicillin purchase to had hospitals other RIE and normal trade channels at a price (an estimated through the Government. by unit) regulated 15 shillingsper mega Penicillin therapy looked set to continue to be bound up be bound to continue to set looked therapy Penicillin Edinburgh, in post-war economy of with issues closely to supply with problems superseding costs with direct the leading concern. become in it emerged as penicillin therapy In examining the new World of the Second Edinburgh during the closing stages insight into some much-needed provides this paper War, in of wartime work nursing the nature clinical and historyinto the early and civilian hospitals antibiotics of practice in hospital-based their implicationsand for Scotland. powers diminished and as the RIE’s responsibility for for responsibility the RIE’s as and diminished powers to required longer no clinicians were penicillin grew, with the treated cases the of records detailed keep drug. distribution. In February, the DoHS began the process of process the the DoHS began In February, distribution. penicillin their duties of committees Scotland’s relieving ‘distributing designated specially place, their In control. for and receive to hospitals in up set were centres’ experience its considerable to Owing distribute supplies. distributing the RIE became one such in using penicillin, a major part in the dissemination of and it played centre duties All in the local area. penicillin to hospitals were dispensing and preparation the drug’s regarding pharmacy. to its assigned emphasise the euphoria generated by the drug when it drug the by generated euphoria the emphasise clinical sphere. the into introduced first was became available for use in Edinburgh in other forms in other forms use in Edinburgh for became available in late example, for of penicillin lozenges, with the arrival 1945. the findings outlined here offer an alternative view of the of view alternative an offer here outlined findings the despite that been shown It has historyearly penicillin. of this during clinical results penicillin great generating was into civilian treatment its introduction period, the necessity economic difficulties and by complicated use on rational This emphasis rationally. use the drug to nor of side- of cost considerations from did not result until the which did not come into play – issues effects issues surrounding ongoing post-war period – but from quality of supplies. the quantity and both Over Over 15,19 Issues of Issues Iatrogenic Iatrogenic 47 46

2 2,44 Taylor, for example, example, for Taylor, In this series, reactive reactive In this series, 47 47,48 198–205 2016; 46: 2016; According to Bud, negative reactions to reactions negative to Bud, According 32 45 of course, [penicillin is] given out right left and out right [penicillin is] given course, of centre. © 2016 RCPE J R Coll Physicians Edinb Coll Physicians J R the next two months, the DoHS envisaged that the the DoHS envisaged months, the next two at would hospitals in Scottish penicillin of used amount of number partlygrowing a because double, least to understood now syphilis) were (including conditions of use increasing The penicillin treatment. fit for be and control for systems new required penicillin inflammation around the site of the needle was recorded recorded was needle the of site the around inflammation and gonorrhoea of acute case In another cases. in two via was administered penicillin abscess, prostatic It was noted that this patient’s injection. intramuscular crippled’ ‘almost was he that the extent to stiffened leg after. days for theories often portray physicians as wrong-doers and wrong-doers as physicians portray often theories as such influenced some historians considerably have Illich. and Ivan Taylor Richard contends that the phenomenon of antibiotic resistance antibiotic resistance of phenomenon the that contends antibiotic use. widespread from resulted Supplies of penicillin for civilian treatment across across civilian treatment Supplies of penicillin for By February 1944. August after slowly grew Edinburgh the initial risen supplies had from monthly 1945, units. 75 mega units to 35 mega of allocation Conclusion A small number of cases highlight other issues issues of cases highlight other A small number RIE. the at penicillin in use of quality the surrounding to iatrogenesis’ ‘second level ascribes the term Taylor clinical treatment after side-effects experience of the including antibiotics. with drugs, These early warning signs of resistance – manifest as – manifest warning signs of resistance These early are – bacteriologically and clinically both were they on historical perspectives with some at odds somewhat often is disease that is, that theorythe iatrogenesis: of itself. treatment clinical from derived penicillin injections typically reflected the impurities the reflected typically penicillin injections that noted He within wartimecontained penicillin. and beeswax of injecting penicillin suspension in a particularly in treating the RIE, at oil – common peanut wartimepopular a was – designed practice gonorrhoea of injections the number reducing to counteract pain by have. to required each patient was that microbial resistance in Edinburgh at this early stage, stage, this early at in Edinburgh resistance microbial That of antibiotic overuse. not the result were however, in the penicillin storyearly so issues featured resistance that its use at on imposed despite the strict controls initially resistance microbial if anything, that, time shows by necessitated was But this underuse. from stemmed clinicians’ of out was and circumstance economic ability of natural the remember also must We control. consider and antibiotic treatment resist to bacteria may antibiotic practice while poor that argument Bud’s to nothing can be done certainlyresistance, encourage bacterial evolution. natural prevent S Gardiner

Acknowledgements

I am grateful to Professor Marguerite Dupree (University of Glasgow) and two anonymous reviewers for their valuable comments on a previous draft of this paper. I wish also to express gratitude to the Leverhulme Trust for providing the funds necessary to obtain permission from Elsevier to reproduce the image. Finally, I would like to thank Louise Williams of the Lothian Health Services Archive for helping me to obtain access to the patient records utilised in this article.

References

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