Category Archives: medical history

Recycling Penicillin from Urine in Post-War Germany

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Limited supplies of penicillin and Allied restrictions on German access to the drug in the immediate aftermath of World War II led to its recovery from the urine of treated patients. Susanne Krejsa MacManus explains.

German research on penicillin started only in 1942 and then on a very small scale.[1]  Gerhard Domagk (1895-1964), the German scientist who in 1935 had developed sulfonamides, had advised the Nazi government to concentrate on improving of “his” type of antibiotics instead of trying to get its own penicillin production going.

It took Germany till the end of 1943 to really understand the importance of penicillin, but because of the efforts of the Allies to restrict information and materials,[2] German scientists were not able to learn about the right mould, nor could they develop the process to get a good supply.

From autumn 1945, British and American forces increased the amount of penicillin flown into hospitals in Berlin – mostly for their own soldiers as a treatment for sexually transmitted diseases. But the occupying forces faced a dilemma: on one hand, they had to look after the health of the population of the occupied areas; on the other hand, there was a hostile atmosphere against the German population – at least in the first months after the end of the war. Germany was categorised as a “defeated enemy” – in contrast to Austria which was categorised as a “victim”.

There was even a third aspect. The German pharmaceutical industry was known as being innovative and effective. The occupying forces hoped for “penicillin made in Germany” and encouraged companies like I.G. Farben, Hoechst and Chemie-Grünenthal to start such an undertaking.

The USSR did not have penicillin production of its own, although they claimed two of their scientists had invented the antibiotic long before Alexander Fleming. As early as early May 1945, Soviet forces who were eager to get penicillin as part of German reparations were pushing the German company Schering .[3]

Since one of Schering’s production sites lay in British territory, the company got support from the British element of the occupation forces for building laboratories and getting raw material (as this ad shows.).[4] 

Salzburger Nachrichten, 9/1/1946  Schering AG produces penicillin Berlin,  As the British broadcast has reported, the Germany pharmaceutical company Schering AG in Berlin will manufacture penicillin for Germany. The British military government has promised its support to the company in procuring the laboratory and the necessary material, so far as it is available in Germany.

But sufficient output was not available before the end of 1946/the beginning of 1947.

Two-thirds excreted

During their struggle to set up a production site, scientists at Schering recalled that two- thirds of penicillin given by injection left the body very quickly, so quickly that injections had to be repeated every few hours.[5] “If we could get the urine of patients treated with penicillin”, the scientists speculated, “we might be able to reclaim and concentrate this substance.”

The British and American forces permitted them to collect the urine from their hospitals on the condition that they got their share of the recycled substance. From March 1946, Schering’s scientists organised milk-churns and bicycles and went from hospital to hospital to collect patients’ urine. The recycling process was successful, and in spring 1947 it was extended into American and British areas of West Germany. In April 1949, nearly 5000 liters of urine from 3153 patients were collected from hospitals. This activity lasted till 1950, when the manufacturers’ penicillin production was sufficient to meet demand.

Recycling penicillin from urine was not a new idea, but its use on this scale was was exceptional. It showed that the German researchers had clearly understood the character of penicillin being excreted from the organism so quickly. Secondly, the process of recycling penicillin purified the substance, which at the initial injection had produced sharp and unpleasant feelings for the patient. And third, it shows how Schering’s researchers could act on their own initiative, without having to ask boards and committees for permission as they would have to do today.

Susanne Krejsa MacManus PhD is an independent journalist, author and archivist in Vienna. She is a member of the History of Medicine/Medical Humanities working group of the Commission for History and Philosophy of the Sciences at the Austrian Academy of Sciences (ÖAW).

References

[1] I. Pieroth: Penicillinherstellung – Von den Anfängen bis zur Großproduktion, Heidelberger Schriften, 1992, p. 103.

[2] P. Rostock: Die Wunde, Berlin: De Gruyter, 1950, p. 290.

[3] J.-P. Gaudillière, B. Gausemeier: Molding National Research Systems, OSIRIS 2005, 20:180-202.

[4] Schering A.G. Berlin produziert Penizillin, Salzburger Nachrichten, 9. 1. 1946, p. 2.

[5] J.H. Humphrey: Excretion of Penicillin in Man, Nature 3920, 1944, 765.

 

 

Being right is not enough

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Scientific debate can be soured by the tendency for evangelical pioneers to see any questioning as opposition bordering on evil.   Their aggressive attitude can delay innovation, a lesson perhaps for our own times and a reason for studying history, says Mike Davidson.  

Ignaz Semmelweis

My wife and I saw the production “Dr Semmelweis” at the Bristol Old Vic. At last, a chance to experience live theatre with a full audience; it also fulfilled my interest in the history of medicine. The writers, Mark Rylance and Stephen Brown, were influenced by the 1952 biography Semmelweis (1818-1865) by Louis-Ferdinand Céline, a work I am unfamiliar with.

Their play is a dramatic interpretation of the work of Ignaz Semmelweis (1818–1865) on puerperal sepsis and his failure to convince his contemporaries of the need for ward hygiene to control the disease. This was in no small part a result of his uncompromising personality and ability to alienate even his strongest supporters and allies.

Semmelweis proposed the practice of washing hands with chlorinated lime solutions in 1847 while working in Vienna General Hospital’s First Obstetrical Clinic, where doctors’ wards had three times the mortality of midwives’ wards. His observations brought him into conflict with many within the contemporary scientific and medical establishment.

The play records Semmelweis’s descent into madness, haunted by the ghosts of the women he has not saved. The ghosts are portrayed as dancers and musicians on stage and within the audience, as he recollects events. Much of the narrative takes the form of flashbacks acted out for his wife. The opportunities for engagement squandered by Semmelweis due to his lack of understanding of human nature are highlighted.

Rylance’s performance as Semmelweis was central and powerful and the cast provided strong support. I found two female performances poignant, Thalissa Teixeira, as his wife Maria, and Jackie Clune, as nurse Muller. The female characters provide a more balanced view of history than concentrating on male pioneers.

Muller is a senior midwife who helps Semmelweis with his introduction of hygiene methods and provides clinical data to support his thesis. His lack of empathy for her guilt in accidentally causing an outbreak of sepsis that contributed to her ultimate suicide speaks volumes of the single-mindedness and unforgiving attitude of Semmelweis.

There is a very pertinent observation by Rylance in an interview published in the Financial Times on 12 January 2022: “He wasn’t just a victim. He was also a very difficult person: someone who got very angry about people not understanding him and became his own worst enemy. Which maybe a lot of pioneers are — they’re people who cut through and are not the most polite or politically savvy people.”

The production at Bristol has now ended but given the enthusiastic reception it got there, it may be staged again.

I recommend the play not only for a medical history enthusiast but for anyone who wants to experience a thought-provoking performance by a talented cast, playwrights, dancers and musicians.

Mike Davidson is President of the British Society for the History of Medicine.

Control and the therapeutic trial: the influence of insulin

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How do we decide whether a drug, or other treatment, actually works? Martin Edwards describes the rhetorical strategy adopted by the Medical Research Council to establish its authority.

Patients’ variations in response to disease and treatment can render it fiendishly difficult to know whether a therapy is benefitting a particular individual. For centuries, the gold standard was the assessment of a wise and experienced clinician but during the first half of the twentieth century, new methodologies arising from the laboratory, hospital and statistical theory challenged this traditional model.

The stakes were high, no less than the moral authority to adjudicate how the therapeutic efficacy should properly be ascertained. Between the wars, the debate in Britain was frequently vitriolic – particularly between the Royal College of Physicians, which prioritised clinical acumen, and the Medical Research Council (MRC) which advocated newer methodologies.

The University of Toronto in 1921 granted British patent rights over insulin to the MRC and thus offered the MRC control, not only over insulin manufacture and supply, but also how to assess its effects and proper usage.

In fact, the MRC’s approach to testing was, as with other drugs at that time, highly eclectic; it sent samples of insulin to trusted clinicians in prestigious hospitals without any protocol or scheme for investigation – the clinicians were simply asked to report their experiences with the drug.

An unanticipated consequence of the MRC’s control of insulin supply was that it was on the receiving end of public clamour for the drug. Heartrending letters to the MRC described young people, typically in their teens or early twenties, dying slowly and horribly from diabetes, and pleaded for supplies of life-saving insulin.

Patients even turned up at the MRC, supported by loved ones. Landsborough Thomson, MRC Council Secretary, recalled the MRC administration being swamped by these requests and unable to fulfil its normal functions.

Reserved for controlled studies

In response, the MRC under the direction of its chairman Walter Morley Fletcher adopted a standard response to such requests, stressing that insulin was a new drug which needed to be reserved for ‘controlled studies’. The meaning of ‘controlled’ was not defined nor did it refer to the presence of a comparison group – none of the MRC insulin trials used one – but rather vaguely implied proper conduct, regulation and scrutiny.

So successful was this rhetorical strategy that the MRC repeated it when restricting supplies of penicillin in the 1930s and streptomycin and influenza vaccine in the 1940s. In each case, it stated that the drug should be reserved for ‘controlled trials’.

Control is a powerful word with implications of authority, power, regulation and order. Without defining it, the MRC appended the word to their own studies in the interwar years, using it as a rhetorical device in the battle for authority to adjudicate therapeutic efficacy.

By the time the MRC’s trial of streptomycin in tuberculosis – reckoned by many trial historians to be the first randomised controlled trial – was published in 1948, the MRC had successfully co-opted the word as applying exclusively to its own studies. It offered the streptomycin trial as an exemplar of how therapeutic trials should be conducted, describing the methodology as ‘the controlled trial’. By then, ‘controlled’ referred technically to the presence of a control group, though the other powerful associations of the word continued to resonate.

We have depended on the ‘controlled trial’ ever since. The MRC’s adoption of the potent word ‘control’ arguably began with insulin. Had it not been for MRC control of British insulin supply, might we simply refer nowadays to a ‘randomised trial’?

This text is an abstract of a talk given to a session of the Apothecaries’ History of Medicine Fellows 8/12/2021 to commemorate the 100th anniversary of the discovery of insulin.

References/further reading:

  1. A Landsborough Thomson, Half a Century of Medical Research vol. 2: The Programme of the Medical Research Council (UK) (London: HMSO 1975) pp 40, 230
  2. Liebenau, ‘The MRC and the Pharmaceutical Industry: The Model of Insulin’, in J, Austoker and L. Bryder (eds), Historical Perspectives on the Role of the MRC (Oxford: Oxford University Press, 1989) 163-80
  3. Edwards, Control and the Therapeutic Trial: Rhetoric and Experimentation in Britain 1918-48 (Amsterdam: Rodopi Publishing, 2007)

A digital future for studying History of Medicine?

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Dr Mike Davidson reflects on his experience of completing a Masters of Letters (M.Litt.) degree via distance learning…

Saint Jerome in his study. Oil painting.. Credit: Wellcome Collection. Attribution 4.0 International (CC BY 4.0)

I recently completed a three-year distance learning M. Litt. in Scottish Heritage at the University of Aberdeen. Considering the current restrictions on conventional study and academic meetings by which many of us pursued our interest in the History of Medicine (HOM), I wondered if my experience offers a future option for HOM study.

I undertook the course to improve my academic skill-set, to write, and present my history of medicine research in a way that was appropriate for an academic audience. I could not find an appropriate postgraduate course within a 100-mile radius of my home willing to take on a student, part- or full-time, who did not have an undergraduate Humanities background. The University of Aberdeen ‘Masters in Scottish Heritage’ is a fully online, part-time course that anyone with a 2:1 honours degree or appropriate professional experience can apply to.

Teaching was delivered through MyAberdeen, an online Virtual Learning Environment. Screenshot courtesy of Dr Mike Davidson.

It provides the materials, tools and support needed for your studies. A potential weakness of distance learning course is library access, unless you can make local arrangements. I purchased some standard books for my library.

The recommended study time needed is 15 – 20 hours per week per term, more at assessment times. The total course fees were £8,700 paid in yearly allotments; other smaller regular payments are possible. The course comprised four taught modules of 30 credits, each over 12 weeks, two modules a year. There is flexibility in the time period to completion: students can prolong the course if personal circumstances demand.

The final year was a 20,000-word dissertation on a subject agreed with your supervisor. My dissertation title was “A Scottish doctor’s observations and experiences of the British West Indies; a comparative analysis of the pre-emancipation journals of Jonathan Troup (1764 – 1800).”

Each week of study had clear objectives, supporting material and notes relevant to the lecture or audio clips.  Lectures were delivered as downloadable PowerPoints. Videos and audio clips are a valuable addition to the course, these ranged from two experts debating a course topic to original archive visual material. Primo provides valuable, easy access to many online resources, including e-books, journal articles and academic databases.

Virtual discussion boards with classmates and tutors replaced seminars, Tutors started debate by offering a series of questions or statements relating to the week’s work. The discussion boards have potential downsides compared with face-to-face sessions. As it is a written format some students produced almost mini referenced essays rather than spontaneous comments. This dampens debate and can feel very intimidating. If you take part late in the week, you may find the subject has been done to death and you have little to add. You can become a silent participant if more confident or over-prepared colleagues dominate the board.

An example of the online discussion board. Screenshot courtesy of Dr Mike Davidson.

An undoubted weakness of an online delivered course is the loss of direct face to face mentoring opportunities. I resolved this by occasional planned visits to Aberdeen, including attending two weekend retreats for postgraduate history students and History department staff. The retreats were excellent, giving me an opportunity for networking, constructive criticism, presenting your own work to an academic rather than clinical historian audience.

Having finished the degree, I have been reflecting on whether this approach could not be adapted to gain a qualification in the History of Medicine?

I feel an online tailored modular course would offer aspiring healthcare historians’ a way of gaining appropriate researching and writing skills. Accumulation of credits would offer a path towards a formal qualification for those who wish. It just needs an academic institution to run with the idea. I suspect there is a market out there.

Words by Dr Mike Davidson

‘Unfallstationen!’ – a short history of the emergency department

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Royal Free Hospital, Gray’s Inn Road. Accident ward.. Credit: Wellcome Collection. Attribution 4.0 International (CC BY 4.0)

The emergency department is seen as the ‘coal-face’ of any hospital, providing 24-hour-access medical assessment to members of the public.

Having just started my first job in emergency medicine, after working in general practice and in other hospital specialties, I have been struck by how distinct the challenges are facing staff in this environment. And for a specialty that is so publicly ubiquitous, it is hard to imagine that it is also one of the newest; in the UK only forming The College of Emergency Medicine as we know it, in 2005.

A brief look at the history of the accident and emergency department paints a picture of a speciality that has always adapted to the populations it serves.

Dominique Jean Larrey, a French surgeon in Napoloeon’s army, is seen as an early pioneer of many of the concepts of emergency medicine having developed a system of battlefield triage and emergency treatment. During the battles of the French Revolution in 1793 he commandeered the French flying artillery and made them into ‘ambulance volantes’ – literally meaning ‘flying ambulances’ – to transport the wounded from the battlefield rapidly.

He also improved the organisation of field hospitals and developed the technique of ‘triaging’ the wounded based on the seriousness of their injuries, rather than rank or nationality. Wounded soldier of enemy armies were also treated in his hospitals, demonstrating one of the central tenets of emergency medicine of care being open to all.

While Larrey may have been one of the first to define and formalise some of the concepts of modern-day emergency medicine, the offering to civilians began in the form of accident services set up by the citizens themselves in some cities. A 1905 article in The Lancet, describes attempts by the city of Berlin to set up municipal accident and emergency services.

Residents of a particular quarter within the city set up a ‘Sanitätswache’ – ‘first-aid station’ – by hiring out a building and setting it up with the instruments and dressing needed, and appointing surgeons to ‘staff’ them. These Sanitätswache were privately-run by committees and were subscription-fee only – a far-cry from open-access to all. Moreover, they had few visitors as they only operated at night, when accidents were less likely to happen due to the closure of factories and reduced foot-fall.

This concept was built upon by a new organisation of ‘Unfallstationen’ – ‘accident stations’ – to serve workers who wished to insure themselves against work-place accidents. Unlike the Sanitätswache, these were open during the daytime and proved to be popular among the general population, not just the workers at which they were aimed. They were still private enterprises with fees recuperated through cooperatives, or directly from individuals.

However they had their own issues, including criticisms that those with more serious injuries would be better off being conveyed straight to hospitals, many of whom had set up their services to see accidents, and had their own in-house surgeon.

Instead, a new society known as the ‘Berlin Rettungsgesellschaft’, the ‘Berlin First-Aid Society’, was created backed by the medical establishment to unite the Sanitätswache and Unfallstationen. The Rettungsgesellschaft introduced a central office with a special telephone communication service between local hospitals and the ambulance service, so that if more than one person was injured at a scene, enough surgeons and ambulances could be alerted to attend the scene.

Unfortunately, all three of the services relied on private subscriptions, and later a fight broke out over funding (sound familiar?), over whether they should be fully-funded by the municipalities which they served. The Lancet article ends with the future of civilian emergency services in Berlin hanging in the balance.

It was in the late 1800s and early 1900s that Anglo-American hospitals established ‘accident’ departments, although their official modern equivalents only becoming established in the 1960s. Prior to this, although hospitals would provide some level of accidental or urgent care this service was staffed by surgeons and general medical physicians who rotated in from other specialties. In the 60s and 70s, it became more common for surgeons and physicians to leave their respected specialties to focus primarily on emergency medicine.

In the US, emergency medicine was formally recognised as a specialty in 1979. In the UK, it was not until 2005, when The British Association for Emergency Medicine (BAEM), formerly the UK’s Casualty Surgeons Association, combined forces with the Faculty of Accident and Emergency Medicine (FAEM), a daughter organisation of six medical colleges, to form the College of Emergency Medicine, which became the Royal College of Emergency Medicine.

In spite of its relative youth as a recognised specialty, the importance of emergency treatment has been recognised in some capacity for hundreds of years, particularly in the field of battlefield medicine. And while we recognise it faces many modern pressures, Emergency Medicine’s long history of flexibility in the face of changing demands, is uniquely one of its strengths.

Words by Dr Flora Malein

 

Sources used:.

The College of Emergency Medicine [archived page].

Howard, MR. “In Larrey’s shadow: transport of British sick and wounded in the Napoleonic wars”. Scott Med J. 1994 Feb;39(1):27-9. doi: 10.1177/003693309403900109.

The Lancet, Volume 2, Part 2 (p. 1808-1809).

Suter RE. “Emergency medicine in the United States: a systemic review.” World J Emerg Med. 2012; 3(1): 5–10. doi:10.5847/wjem.j.issn.1920-8642.2012.01.001.