Lives of the fellows

Denis Anthony Mitchison

b.6 September 1919 d.2 July 2018
CMG MB BChir Cantab(1943) MRCS LRCP MRCP(1965) MRCPath(1965) FRCP(1970) FRCPath(1977)

Denis (‘Denny’) Mitchison was a bacteriologist who helped establish the standard short course chemotherapy regimen. He developed the first generally accepted definitions of drug resistance in tuberculosis (TB) and delineated a theoretical framework for modern TB chemotherapy. His work helped save millions of lives worldwide.

Denny was born in Oxford, the eldest son of Richard Gilbert Mitchison, a London barrister who later became a Labour MP and life peer. His mother, Naomi Mitchison, was a radical feminist writer and activist. Important influences were Denny’s maternal grandfather, J S Haldane, a professor of physiology, and his uncle, J B S Haldane, a population geneticist.

Denny attended the Dragon School in Oxford and later went to Abbotsholme School in Staffordshire, where he learned to shear a sheep and excelled at carpentry as well as his academic studies. Going up to Trinity College, Cambridge in 1936, he obtained a first class degree in natural sciences and met his first wife, Ruth (née Gill), the daughter of a patent agent. They married in 1940 and both qualified as doctors working in challenging conditions during the War while bringing up their two older children.

In 1947 Denny’s career took a key turn as he became involved in the first randomised controlled clinical trial involving TB at the Brompton Hospital, London under Philip D’Arcy Hart [Munk’s Roll, Vol.XII, web], which proved the effectiveness of streptomycin as compared to bed rest. Another trial in 1948 demonstrated that the use of streptomycin in combination with para-aminosalicylic acid (PAS) diminished the emergence of drug resistance and achieved better long term results than the use of streptomycin alone. Further clinical trials, including the more effective drug, isoniazid, laid the basis for scientifically-validated triple drug TB treatments, replacing the traditional subjective opinions of individual consultants.

In 1956 Denny was appointed head of a new Medical Research Council (MRC) unit on drug sensitivity in TB to coordinate bacteriological studies on a firm statistical basis.

The focus of concern was now shifting from the richer nations to the Third World, where TB remained a massive problem and resources were limited. Working with his long term collaborator, Wallace Fox [Munk’s Roll, Vol.XII, web], a major study was undertaken in Madras, India from 1956 to 1959. This proved that a combination of isoniazid and PAS could be used to treat patients effectively at home without requiring the much more expensive treatment at traditional sanatoria. The results were profound as sanatoria closed worldwide with huge cost savings while relatively cheap domiciliary treatments for TB were developed.

Back in London, Denny continued to lead his MRC unit at Hammersmith Hospital, London, becoming a professor at the Postgraduate Medical School in 1968. From the 1960s onwards he provided the scientific expertise behind numerous clinical trials in Hong Kong, Singapore, India and East Africa, while developing sputum microscopy as a more accurate diagnostic tool to detect tubercle bacilli, indicating that a patient was still infectious. This was cheaper and more accurate than X-ray assessment. Rigorous statistical analysis underpinned this research.

A major risk was that patients might not be cured through failure to take their prescribed medication properly or to complete the course. Worse, such patients would harbour and spread forms of drug resistant TB, creating a more intractable future problem. In poor nations direct medical supervision of drug treatment over a long period was too costly. To deal with this Denny developed a new standardised short course regimen for TB that reduced overall treatment duration from 18 to six months using a combination of drugs, including rifampicin and/or pyrazinamide, with the initial treatment being directly supervised. When this short course regimen was applied in study in Tanzania between 1982 and 1986 cure rates of up to 90% were reported.

After Denny had reached age 65, his MRC unit was closed down in 1985 as a result of a short-sighted view that TB was no longer a significant problem, at least in the UK. Unfortunately, just at that time, the spread of HIV/AIDS through the world opened the way to a resurgence of TB infection among patients whose immune systems had been compromised.

Denny continued his research at St George’s Hospital, Tooting with his former student Amina Jindani and others. Useful work followed, including the development of important new techniques for measuring the early bactericidal effectiveness of new drugs, which became standard practice as an initial step in phase two clinical trials. Denny continued working until 2015 when, aged 95, he finally retired.

During the course of his scientific career Denny published some 250 papers on TB chemotherapy and he served on the scientific advisory committee of the Global Alliance for TB Drug Development. He received many awards, including the British Thoracic Society medal, the International Union Against TB medal, the Stop TB Kochon prize and the CMG. Denny used to express the view that modern over-regulation was rendering clinical trials too complicated and expensive, thereby harming progress. He did not tolerate fools gladly and was often outspoken but, nonetheless, he was held in great affection and esteem by colleagues for his usual benevolence and good humour.

Although his work was central to his life, Denny was widely read, enjoyed classical music and used his carpentry skills on many DIY projects at his home near Richmond Park. He spent time with his extended family in his mother’s house at Carradale in the Scottish Highlands, often walking the hills with his two brothers, Murdoch and Avrion, both professors of zoology.

Denny’s wife, Ruth, worked with him at Hammersmith Hospital from 1967 to 1979, before succumbing to multiple sclerosis and dying in 1992. In 1993 Denny married Honora (née Carlin), a retired advertising executive, and they enjoyed many happy years before she died of pneumonia in 2012. Denny had four children by Ruth, but his older daughter, Susan, and his older son, Graeme, a Cambridge mathematician, predeceased him. Denny died at the age of 98 and was survived by his two younger children, Terence, a solicitor, and Clare, a public health researcher, as well as four grandchildren and two great-grandchildren.

Terence Mitchison

[Holme CI. ‘Trial by TB: a study into current attempts to control the international upsurge in tuberculosis’ Proceedings of the Royal College of Physicians of Edinburgh January 1997 Vol.27 No.1 Supplement No.4 http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.621.7284&rep=rep1&type=pdf – accessed 21 March 2019; The Telegraph 18 July 2018 www.telegraph.co.uk/obituaries/2018/07/18/denis-mitchison-groundbreaking-tuberculosis-researcher-obituary/ – accessed 21 March 2019; BMJ 2018 362 3518 www.bmj.com/content/362/bmj.k3518 – accessed 21 March 2019; The Lancet 2018 18 954 www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(18)30509-7.pdf – accessed 21 March 2019; The Union: International Union Against Tuberculosis and Lung Disease In Memoriam: Prof Denis A Mitchison 6 July 2018 www.theunion.org/news-centre/news/in-memoriam-prof-denis-a-mitchison – accessed 21 March 2019; UCL Home UCL-TB In Memory of Professor Denis Mitchison 8 August 2018 www.ucl.ac.uk/tb/news/2018/aug/memory-professor-denis-mitchison – accessed 21 March 2019; Stop TB Partnership Obituary – Professor Denny Mitchison www.stoptb.org/news/announcements/2018/a18_001.asp – accessed 21 March 2019; St George’s University of London Professor Denis Mitchison 1919-2018 www.sgul.ac.uk/news/news-archive/professor-denis-mitchison-1919-2018 – accessed 21 March 2019; Times Higher Education Denis Mitchison 1919-2018 www.timeshighereducation.com/people/denis-mitchison-1919-2018 – accessed 21 March 2019]

(Volume XII, page web)

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