Category Archives: medical history

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.

Mystery object – Frimley Sanatorium

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Mystery object 1: an illustration by a patient in a letter sent to the Lady Almoner at Frimley Sanatorium in 1952. Image source: Royal London Hospital Archives & Museum: RLHBH/AL/3/27/9

Mystery object 2: an image from the Wellcome Trust library that is related to Mystery object 1. Image Source: Wellcome Image Library.

Both the illustration and above object performed the same function.

Can anyone name them?

Answer to be published on Friday 17th July.

 

*** Update. See below for the answer ***

 

Mystery object 1 is an illustration of an object written by patient WA, a recovered tuberculosis patient, to the Lady Almoner at Frimley Sanatorium. WA refers to it colloquially as a ‘Brompton Muzzle’ that ‘were in common use to ease restricted breathing’. 

His illustration features an area for an absorbant sponge along the same lines as the absorbant sponge at the bottom of mystery object 2 which is an illustration of a Burney Yeo mask.

The Lady Almoner contacts the Dispensary in regards to the patient’s enquiry, and notes the following:

‘Dispensary say that they have a Burney Yeo’s improved inhaler which is a different shape but appears to fit over the mouth and nose and is on the same principle. Dispensary say that there should be no difficulty in obtaining this mask. It is in use in most hospitals’.

The Almoner replies, ‘I have made enquires in our Dispensary and I find that we have a small mask which serves the purpose that you describe. It is on the same principle, but is a square shape and much smaller.

The ‘Burney Yeo’ appears to be several iterations of a type mask used in the treatment of tuberculosis in which the patient inhaled an antiseptic liquid via an absorbant material.

If anyone knows of any other examples of the Burney Yeo mask or what the ‘solution’ that the patient inhaled might have been, please do comment below.

Images submitted by Dr Flora Malein.

 

Sources used:

The Royal London Hospital Archives and Museum

Wellcome Trust Library

Poems and Pandemics in the Plague Village

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Simon Armitage’s newly released poem, ‘Lockdown‘, recalls the Eyam plague of 1665/6, effectively evoking feelings that reverberate in our current situation, and remind us that we are not the first to find ourselves in such a position.

Elizabeth Hancock drags the body of a family member to the Riley graves. She lost her husband and all six children during the outbrak. Illustration from The Brave Men of Eyam by E.N. Hoare published by SPCK, 1881.

In Lockdown, the Poet Laureate touches on some of the most notable features of the story. ‘Thimbles brimmed with vinegar wine’, for example, refers to the practice of Eyam’s residents leaving coins in holes in the rock at the parish boundary. These would be exchanged for vital supplies by the neighbouring villagers, hinting at an understanding of antisepsis not widely acknowledged to be present at that time.

We find new resonance in the story of Emmott Sydall and Rowland Torre, betrothed lovers who found themselves on either side of the cordon sanitaire, seeing each other only from a distance until Emmott failed to appear one day, having tragically succumbed to the plague.

Such stories of ordinary individuals were passed down in the oral tradition, and whilst making it more difficult for historians to corroborate beyond births, marriages and deaths, this adds a somewhat mystical glow to this period.

Indeed, one of the key reasons the Eyam plague may stick in our consciousness more than the countless other local outbreaks of disease over the centuries, is the fascinating cocktail of physical reminders of the plague story around the village, combined with these legends of individual suffering.

Perhaps the Eyam plague is also memorable due to its particularly high death rate. As referenced in the poem, the village tailor received a parcel of cloth from London, believed to contain fleas carrying the plague. Certainly, the tailor’s assistant George Viccars, became the first victim in September 1665.

There was a steady rate of transmission, which slowed over the Winter, but exploded the following Summer, finally petering out in the Autumn of 1666. By then, around one-third of the villagers (260) were dead.

The ‘crisis mortality rate’ in Eyam has been estimated at twice that of the London outbreak, occurring at the same time. Whole families were wiped out, helpless to prevent the rampage of the infection.

Whilst this surge may simply have reflected the exponential nature of the spread within a non-immune population, it has also been suggested that the disease switched from the flea-borne bubonic type to the much more infectious pneumonic transmission.

Rev William Mompesson (right) converses with a parishioner. Illustration from The Brave Men of Eyam by E.N. Hoare published by SPCK, 1881.

Lastly, the image of the Rector, William Mompesson, leading his parishioners in their self-sacrifice, including through the death of his wife, has created a strong narrative of stoical heroism.

This was irresistible, in particular, to the Victorians seeking to retrospectively chronicle the events of 1665/6 with little written information to go on, save a few of Mompesson’s surviving letters.

What now of the plague village? Once again, Eyam is under lockdown. Public gatherings are prohibited, churches and inns are closed, and there is anxiety and uncertainty. On the other hand, supplies from neighbouring villagers have been replaced by those from supermarket delivery vehicles, and the Priests making the decisions, by Public Health officials.

Nevertheless, the community spirit has kicked in with local support schemes in operation, and, spontaneously, numerous villagers have remarked on the renewed empathy they have for their 17th century counterparts.

‘Plague Sunday’, which is celebrated in the village on the last Sunday of August, will certainly have added poignancy this year. Indeed, the Plague Sunday procession ends at Cucklet Delph, a natural amphitheatre used by Mompesson to address the village rather than cram everyone into the church.

This year, using this venue may well once again be for the reason of public safety rather than historical re-enactment.

Words by Dr William Parker, Eyam, Derbyshire

 

Sources/Further Reading

Clifford J (1989). Eyam Plague 1665-1666, self-published.

Mead R (1720) A Discourse on the Plague, Miller & Brindley. Available at http://www.gutenberg.org/files/32171/32171-h/32171-h.htm

Massad E et al (2004) The Eyam plague revisited: did the village isolation change transmission from fleas to pulmonary? Med Hypotheses 63:911-5.

Race P (1995) Some further consideration on the plague in Eyam, 1665/6. Available at http://www.localpopulationstudies.org.uk/PDF/LPS54/LPS54_1995_56-65.pdf

Wallis P (2005) A Dreadful Heritage: Interpreting Epidemic Disease at Eyam, 1666-2000. Available at http://eprints.lse.ac.uk/22546/1/0205Wallis.pdf

Wood W (1842). The History and Antiquities of Eyam, Whitaker & Company.