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The Contrasting Strategies of Almroth Wright and Bradford Hill to Capture the Nomenclature of Controlled Trials

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The Contrasting Strategies of Almroth Wright and Bradford Hill to Capture the Nomenclature of Controlled Trials 6 Whose Words are they Anyway? The Contrasting Strategies of Almroth Wright and Bradford Hill to Capture the Nomenclature of Controlled Trials When Almroth Wright (1861–1947) began to endure the experience common to many new fathers, of sleepless nights caused by his crying infant, he characteristically applied his physiological knowledge to the problem in a deductive fashion. Reasoning that the child’s distress was the result of milk clotting in its stomach, he added citric acid to the baby’s bottle to prevent the formation of clots. The intervention appeared to succeed; Wright published his conclusions,1 and citrated milk was eventually advocated by many paediatricians in the management of crying babies.2 By contrast, Austin Bradford Hill (1897–1991) approached his wife’s insomnia in an empirical, inductive manner. He proposed persuading his wife to take hot milk before retiring, on randomly determined nights, and recording her subsequent sleeping patterns. Fortunately for domestic harmony, he described this experiment merely as an example – actually to perform it would, he considered, be ‘exceedingly rash’.3 These anecdotes serve to illustrate the very different approaches to therapeutic experiment maintained by the two men. Hill has widely been credited as the main progenitor of the modern randomised controlled trial (RCT).4 He was principally responsible for the design of the first two published British RCTs, to assess the efficacy of streptomycin in tuberculosis5 and the effectiveness of whooping cough vaccine6 and, in particular, was responsible for the introduction of randomisation into their design.7 Almroth Wright remained, throughout his life, an implacable opponent of this ‘statistical method’, preferring what he perceived as the greater certainty of a ‘crucial experiment’ performed in the laboratory. In this chapter I shall examine the rhetorical strategies employed by Wright and Hill. The principal aim of this chapter is to emphasise the fundamental importance of rhetoric to workers in the emerging scientific discipline of therapeutic trial methodology. Unlike my analyses elsewhere, this does not focus uniquely upon the term ‘controlled’ but is a wider examination of the means by which the two protagonists attempted to capture the vocabulary, and hence the fundamental understanding, of the recently-described 141 Editors Control and the Therapeutic Trial - 9789401204941 Downloaded from Brill.com09/24/2021 01:41:05PM via free access Martin Edwards Figure 6.1 Almroth Wright (1861–1947). Courtesy: Wellcome Library, London. statistical therapeutic trial. The importance of this is far more than semantic; defining the words used to describe trial methodology allowed the protagonists to define, very differently, the very nature of therapeutic trials, the assumptions along which they must proceed, and the uses to which they may be put. This serves to emphasise the extraordinary potential, offered to workers involved in creating a discipline, of defining the nomenclature of that discipline; and particularly potent is Bradford Hill’s adoption of the powerful term ‘controlled’. Wright invented a number of new words to supplement what he regarded as the deficient vocabulary of statistical experimentation. Bradford Hill, by contrast, adopted common words and phrases to describe new concepts. Wright’s new words, and Hill’s co-opted old ones, were ostensibly intended merely to provide precise terms for concepts where none had previously existed. Closer inspection reveals, however, that in naming these 142 Editors Control and the Therapeutic Trial - 9789401204941 Downloaded from Brill.com09/24/2021 01:41:05PM via free access Whose Words are they Anyway? Figure 6.2 Austin Bradford Hill (1897–1991) Courtesy: Wellcome Library, London. concepts Wright and Hill each subtly redefined them. An RCT designed and conducted using Wright’s nomenclature would have been a far more constrained and circumscribed affair, with a far narrower range of uses, than one employing Hill’s vocabulary. This analysis is intended to demonstrate the central importance of capturing the nomenclature of the RCT as a strategy to dictate the appropriate applications for such a trial and to dictate the people properly qualified to perform it. Wright described his ideas and nomenclature between 1912 and 1944, the early part of which occurs prior to Hill’s work, but Wright’s notions appear to have changed little over these three decades and although the two did not openly debate the virtues of statistical experimentation, their statements can be directly compared and contrasted. 143 Editors Control and the Therapeutic Trial - 9789401204941 Downloaded from Brill.com09/24/2021 01:41:05PM via free access Martin Edwards Statistics in therapeutic experimentation Recent authors have traced increasingly early origins for manipulation of numbers in British medicine, implying a quantification project spanning some three centuries. Seventeenth-century British quantifiers such as Francis Bacon and John Graunt – who analysed bills of mortality – inspired the eighteenth-century project of ‘medical arithmetic’ involving systematic quantification of population morbidity and mortality.8 Regarding therapeutic experimentation, Ulrich Tröhler argues for the British origins of a quantitative, empirical approach to therapeutics from the beginning of the eighteenth century, arising in a community of like-minded, dissenting physicians who favoured meticulously recorded clinical observations and numerical quantification of case outcomes as the means to establish the most effective remedy.9 Rosser Matthews traces the origins of ‘statistics’ in their current meaning – mathematical techniques to allow comparison of data – in British therapeutic experimentation to the biometrical tradition associated with figures such as Francis Galton and Karl Pearson during the last third of the nineteenth century.10 This movement transformed statistics from the straightforward numerical description of social phenomena, into a mathematical discipline with techniques for analysing aggregated data. With the zoologist W.E.R. Weldon, Pearson and Galton founded the journal Biometrika in 1901, hoping to increase awareness of the value of mathematical statistics amongst the wider scientific community. Pearson, as Professor of Mathematics at University College London (UCL), ran a course on statistical theory, the only source for such instruction up to the 1920s. However, Matthews points out that throughout the 1920s and 1930s scientists in general, and medical practitioners in particular, remained sceptical of the application of statistical methods to their work. Edward Higgs11 has examined the incorporation of statistical methods into medical research through the establishment and efforts of the MRC Statistical Unit. He emphasises the importance of patronage relationships, exploited in particular by Major Greenwood (1880–1949), the first Director of the Statistical Unit. Greenwood and another key figure, George Udny Yule (1871–1951) had both received their statistics training from Pearson. Yule became Assistant Professor of Statistics at UCL in 1896 and a statistics lecturer at Cambridge in 1912, where he remained until his death in 1951. Greenwood undertook statistical work for the Ministry of Munitions during the First World War, where he met Walter Fletcher, the Medical Research Committee Secretary. The two developed mutual respect and a strong friendship, prompting Fletcher to persuade the Ministry to second Greenwood to the MRC in 1920, to chair the newly created Statistics Committee. The MRC’s Statistical Unit, formed in 1914, had not 144 Editors Control and the Therapeutic Trial - 9789401204941 Downloaded from Brill.com09/24/2021 01:41:05PM via free access Whose Words are they Anyway? performed well under what Fletcher perceived to be lacklustre direction by John Brownlee, and gradually became sidelined by the increasing activity of Greenwood’s committee. Brownlee’s death in 1928 enabled Fletcher to amalgamate the Statistical Committee and Statistical Unit as a single new MRC Statistical Unit under the leadership of Greenwood, who was by then Professor of Epidemiology and Vital Statistics at the London School of Hygiene and Tropical Medicine (LSHTM). Greenwood was succeeded in the chair at LSHTM, and as head of the MRC Statistical Unit, by Bradford Hill in 1945. The web of patronage appears to have extended deeper even than Higgs has described. Greenwood had enjoyed considerable support in his own career from Hill’s father, to whom he felt a debt of gratitude, which he repaid through his own patronage of Bradford Hill. Reflecting towards the end of his life, Bradford Hill considered that the help he received from Greenwood arose ‘out of gratitude to and affection for my father.’12 Indeed, he received sufficient patronage from Greenwood to conclude that, to him, ‘I owed my whole career’.13 Greenwood suggested that Hill study economics during his protracted convalescence (see below) and invited him to join him at the Statistical Committee in 1923, and again at LSHTM in 1933. However, the extent to which the Statistical Unit and Committee influenced the methodology of therapeutic assessment in the MRC prior to the Second World War, is debatable. Higgs considers that from the mid- 1920s, the MRC ‘could proceed with applying the innovations of Pearsonian statistics to medical research’14 and credits Greenwood and his subordinates with a wide and varied range of statistical examinations. Greenwood later reflected
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