Control and the therapeutic trial: the influence of insulin

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)

The Pharmacopoeia Londinensis

The Pharmacopoeia Londinensis was originally published in Latin by the Royal College of Physicians in 1618 and translated into English by Nicholas Culpepper in the middle of the seventeenth century. To celebrate its 400th anniversary an illustrated version of the book is to be published later this year.
I am delighted to be one of a number of contemporary botanical artists asked to contribute to this exciting project. I have selected to paint the beautiful and intriguing ‘Rosa damascena’ or the damask rose. A strongly scented rose it is famous for its use in perfume with the fresh petals either distilled as rose water or as one of the worlds most expensive essential oils, 100ml costs more than £1500.00, the petals are also used dried and the hips used fresh or dried. Rosa damascena essential oil is composed of hundreds of components, including citronellol, citral, carvone, citronellyl acetate, eugenol, ethanol, farnesol, stearpoten, methyl eugenol, nerol, nonanol, nonanal, phenylacetaldehyde, phenylmethyl acetate, and phenyl geraniol. There is evidence of its use medicinally going back to the seventh century with a particular link to Iran and the Middle East. Recent studies of the pharmacological effects of the damask rose show it has not only antibacterial and anti oxidant effects, but also anti-viral, anti-depressant, anti-diabetic, analgesic and hypnotic properties.

Detail of Rosa damascena  –  watercolour

All of the medicinal plants painted for this publication and accompanying exhibition can be found growing in the Royal College of Physicians medicinal garden near Regents Park in London. A lecture on the Pharmacopoeia Londinensis and tours of the garden will be part of the RCP/BSHM special event on 11th June 2018. See https://www.rcplondon.ac.uk/events/medicinal-plant-lecture-historical-sidelights-and-poynter-lecture

I was particularly interested in taking part in this medicinal plant project as I have a multidisciplinary art practice with a strong research base informed by my career as a horticulturalist working in therapeutic community gardens.  I use plants as a way of telling stories about our relationships with the natural world.


Ishtar

Julia Groves
info@juliagroves.co.uk
www.juliagroves.co.uk

Finding the “missing link”

Historians will be familiar with the challenges of researching an archive: sifting through a pile of dusty records, drawing a blank in a confusing catalogue, or scoring hundreds of hits searching an electronic database. With the help of an archive expert, however, the rewards outweigh the effort required.

When preparing for my presentation on English medical researcher Dr Annie Homer at the recent BSHM Congress in Edinburgh, I wanted to find out more about her time in Canada at the start of the First World War. In particular, she had served as the Assistant Director of the University of Toronto’s Antitoxin Laboratory, the forerunner of the Connaught Laboratories.

Extract from Antitoxin Laboratory Record of Diphtheria Antitoxin Refining, dated Sept 28th, 1914 [SPC Archives 83-006-01]

I contacted Dr Christopher Rutty, professional medical and public health historian, and consultant to Sanofi Pasteur Canada’s Connaught Campus in Toronto, where the original buildings and archive documents are preserved as part of the country’s medical heritage. By return e-mail, Chris sent me a copy of a lab notebook, which contained several pages written in Homer’s distinctive hand, revealing her work at the start of the war. The preservation of this “missing link” was a stroke of good fortune.

The Connaught Laboratories, University of Toronto, officially opened on Oct 25th, 1917 [SPC Archives 0591]

The Connaught Laboratories were established in 1917 to make up a shortfall of tetanus antitoxin needed by the Canadian Expeditionary Force, and became the site of pioneering advances in the production of vaccines, heparin and insulin. More information is available via The Legacy Project which can be viewed online at www.thelegacyproject.ca

Edward J Wawrzynczak

Christmas and the Chemist: The Pretty Thermometer and other marketing ploys from the nineteenth century

“Gentlemen – I have the honour to wish you a scientific Christmas and a drug-devouring New Year”
– Fred Reynolds, co-founder of the British Pharmaceutical Conference[i]

The concept of Christmas adverts feels very twenty-first century, particularly with the rise of emotionally intense adverts that use neuroscience to research how to effectively communicate with the consumer’s subconscious. Today it feels the real meaning of Christmas has lost out to excessive consumerist consumption, but the Victorian  ‘nation of shopkeepers’ also used Christmas for commercial gain. The rise of consumer capitalism has been addressed by Brewer and Porter with the identification, from the 1850s onwards, of the growth of advertising, department stores, international exhibitions, consumer psychology and industrial design.[ii] There was a marked transformation in shopping in the Victorian era and it is possible to identify modern advertising techniques.

This wider marketplace is of great significance to the medical marketplace, particularly as the emergence of the chemist and druggist was part of the commercialisation of society. The world of medicine was a commercial venture and there is evidence found in the trade periodical The Chemist and Druggist that the pharmaceutical trade started to utilise the Christmas season for their own commercial gains. It was reported in the periodical by a critic that “Christmas always gives the chemist an opportunity to disguise the real nature of his mission, and bring himself in line with the festive spirit of the occasion.”[iii]

The late 1880s seemed to be a turning point for appropriating the Christmas season for commercial gains – with more references in The Chemist and Druggist to ‘Christmas prices,’ ‘Christmas Decoration,’ and ‘Suitable Christmas Presents.’ As ever, Burroughs Wellcome & Co were at the forefront of marketing, and promoted their products at “special Christmas prices,” or specifically as Christmas presents.

Figure 1 – Burroughs, Wellcome & Co Christmas advertisement[iv]

In the late 1880s Burroughs, Wellcome & Co produced a Medical Pocket Diary, which formed ‘a very suitable Christmas card for chemists to send to their medical patrons.’[v]  Their ‘ABC Medical Diary’ was similarly marketed as a gift for the medical profession.[vi]

Fig 2 Burroughs, Wellcome ABC Medical Diary advertisement [vi]

The Christmas novelty can be found in the periodicals’ advertisements throughout the late nineteenth century but predominately for toiletries, perfume, or ‘scientific’ devices. Below are some adverts placed by manufacturers making explicit reference to the festive season as a means to promote their products to the retail trade:

xmas-presents2

Figure 3 –  Perfumes were popular products sold in chemists’ shops.
“Chemists will find PETAL DUST the best selling line for the Christmas Season”

 

beechams

Figure 4 – A Beecham’s advert that includes a New Year’s puzzle and festive poem[vii]

 

christmas-gift

Figure 5 – Blondeau et Cie used Christmas to promote their Vinolia products.
Retail chemists’ shops were encouraged to buy a specific amount in order to receive a “Christmas Gift” [viii]

Taking advantage of the Christmas season was not just a commercial opportunity for large manufacturing chemists. Smaller local chemists were also able to cash in.The Chemist and Druggist reported in December of 1896[ix] that:

“At this season of the year chemists are not behind their neighbours in attracting customers”:-

And listed a whole range of chemists marketing ploys:

Mr Herbert W. Seely, Southgate, Halifax, is presenting his customers with a pretty thermometer.

Mr F.G.da Faye, chemist and mineral-water maker David Place, Jersey, is distributing letter-racks gratis to his customers and giving one to every applicant.

The “Christmas Welcome” presented by Messrs. Fukker & Co., chemists, Norwich, is an original conception containing poetry, tales, conundrums, and other seasonable reading, interspersed with advertisements. It is a good idea well carried out. 

Messrs. F.H Prosser & Co, pharmaceutical chemists Spring Hill, Birmingham, publish an almanac and price-list which extends to 184 pages plus insets. There are notes on domestic medicine, and, most wonderful of all, advertisements of a dozen local chemists.

Mr. J. L. P. Hollingworth, chemist and druggist, 21 New Street, Barnsley, and Cudworth, announces that to every person spending Is. and upwards at his establishment he will present a sixpenny Christmas Annual.

The Edme Malt extract Company (Limited), Mistley, wish the trade a very happy Christmas and prosperous New Year on a reply post- card — which to us is a new idea.

The Victorian era was also a time when shop windows and display cases became sophisticated advertising spaces to attract custom.

L0030356 A grocer's shop in England: doorway and shop window. Photogr Credit: Wellcome Library, London. Wellcome Images images@wellcome.ac.uk http://wellcomeimages.org A grocer's shop in England: doorway and shop window. Photograph. Photograph 1900 Published: [ca. 1900?] Copyrighted work available under Creative Commons Attribution only licence CC BY 4.0 http://creativecommons.org/licenses/by/4.0/

Figure 6 – A shop window, 1900 – Credit: Wellcome Library, London

The Chemist and Druggist evidently realised the importance of this phenomenon for the trade and published advice on how to create an attractive Christmas window.

“In the space between the stands and the window arrange neat boxes of perfumes, or anything suitable for presents; then bang from the top ” falling snow,” which may be made by small tufts of cotton wool attached deftly to fine white cotton, and woven together irregularly; … The side stands to be arranged with proprietary articles suitable for the season, as cough mixtures, etc. ….At the back of and over the doors scarlet chest-protectors might be fixed evenly, on which might be worked by pearl- coated pills, string together appropriately, “A Jolly Xmas!” [x]

Their advice seemed well received, a commentator on chemists’ shops in Dublin, Ireland remarked,
“The windows of a number of pharmacies are very neatly dressed with Christmas goods. I can see many instances where the craft have benefited by your valuable hints; an artistic arrangement taking the place of the odd medley which used to prevail”[xi]

With Christmas over a chemist reflected on the Christmas present-giving craze and looked hopefully towards a consumerist future:
“Before Christmas, we have been advising the trade to stock a certain class of goods suitable for presents, but surely it is a wise thing to have a good display of articles of this kind all the year through. In the matter of perfumes, for example, people are always wanting them. Birthdays come; presents are wanted then. Love is ever with us, and its path is strewn with perfume.”

Articles and advertisements from The Chemist and Druggist show that even in the nineteenth century Christmas was being exploited for commercial ends in the retail Pharmaceutical sphere- perhaps all a precursor to the extensive twenty-first century Boot’s Christmas Catalogue!

Only medical men could prescribe medicines under the 1815 Apothecaries Act- Chemists and Druggists were only allowed to supply these substances. So I will end with some Christmas humour from The Chemist and Druggist’s correspondence advice column, in which a chemist inquires,

“If I should meet with any accident on Christmas Day which should afflict me with headache on the morning of the 26th, may I without infringing the Apothecaries Act mix for myself a “short draught,” or must I apply to a duly qualified medical man?”[xii]

 

References

[i] The Chemist and Druggist, December 25th 1886, p.841

[ii] See: J. Brewer and R. Porter (1993) Consumption and the World of Goods (Routledge, London and New York) and N. Mckendrick, J. Brewer & J.H Plumb (1982) Birth of a Consumer Society: Commercialization of Eighteenth Century England (London, Europa Publications Limited)

[iii] The Chemist and Druggist, 26th December 1886, p. 913

[iv] The Chemist and Druggist, 22nd December 1888, p. ix

[v] The Chemist and Druggist, 24th December 1887, p.819

[vi] The Chemist and Druggist, 20th December 1890, p. 13

[vii] The Chemist and Druggist, 21st December 1889, p. iii

[viii] The Chemist and Druggist, 13th December 1890, p. 15

[ix] The Chemist and Druggist, 26th December 1896, p. 912

[x] The Chemist and Druggist, 22nd December 1888, p. 847-848

[xi] The Chemist and Druggist, 22nd December 1888, p. 841

[xii] The Chemist and Druggist, 15th December 1896, p. 514

Laura Mainwaring