David Weatherall was an international authority on the genetic underpinnings of thalassaemia, a principal architect of the field of molecular medicine in the late twentieth century, and Regius Professor of Medicine at Oxford University.
David’s father, Harry Weatherall, was a laboratory manager at a manufacturer of animal feed and soap, as well as an organist and choir master. David’s mother, Gwendoline (née Tharme), was an amateur singer. David was born on 9 March 1933 in Liverpool and attended Calday Grange Grammar School on the Wirral Peninsula, followed by Liverpool University Medical School, from which he graduated in 1956. A house job under the supervision of Cyril Clarke (Munk’s Roll, Vol. XI, p.112) appears to have triggered David’s interest in genetics.
A member of the cohort subject to mandatory National Service, David was sent to southeast Asia as a young Army ‘medical specialist’ and put in charge of a children’s ward in a military hospital in Singapore. Here he encountered a child with unexplained anaemia. Working in a university laboratory in Singapore, David identified thalassaemia as the cause of the anaemia, one of the first demonstrations of this disease in an Asian individual. The resulting case report in the British Medical Journal (in 1960) was David’s first scientific publication. Summoned to the office of a superior Army officer who had become aware of this publication, David was admonished for publishing information about Army personnel without permission from the War Office (the patient was a member of a Gurkha family), and the threat of court martial was raised if he did it again. He did - publishing a second paper, on neonatal jaundice (based on work at a hospital in Taiping, north Malaya) - and was not court-martialled.
After leaving the Army, David learned about a vacant research fellowship in Baltimore, under the supervision of the geneticist, Victor McKusick (Munk’s Roll, Vol. XII, Web). Despite initial unhappiness in Baltimore, possibly related to low winter temperatures, David’s academic career continued to flourish, as exemplified by further publications and completion of a doctoral dissertation in 1962 for Liverpool University, on haemoglobinopathies in the Black population. At a successful oral examination for the doctorate, one of the examiners asked the candidate whether he had contemplated switching to psychiatry, which the examiner seemed to feel was a less risky career pathway than studying ‘obscure’ diseases. Wishing to increase his knowledge of haematology, David pursued a fellowship in this subject in Baltimore during 1963-5 (his second extended stay there), before returning to Liverpool.
Besides meeting his future spouse (Stella Mayorga-Nestler) in Baltimore, David also ‘acquired’ a future longstanding co-worker there - John Clegg, a protein chemist whose PhD work at Cambridge had been supervised by Frederick Sanger. In a series of studies during the 1960s, Weatherall and Clegg showed that synthesis of alpha and beta globin chains of haemoglobin (which are normally produced in similar amounts), is deranged in thalassaemia, with reduced production of these respective chains in alpha and beta thalassaemias. Structural abnormalities of the resulting haemoglobin molecules have several consequences, including shortened lifespan of erythrocytes, and anaemia of various degrees of severity.
In 1971, David gave a talk at an Association of Physicians meeting in Sheffield, about his work on characterisation of a mutant haemoglobin (Constant Spring). This talk impressed members of the audience, who included Paul Beeson (Munk’s Roll, Vol. XII, Web). Some two years later, Beeson was contemplating returning to the USA, a move that would vacate the Nuffield Chair of Medicine at Oxford, of which he was the current holder. David’s interest in the Chair was explored and, following a dinner and discussions at Oxford, he was offered the position. He received no confirmatory paperwork, however, and after several months had elapsed, asked the office secretary in Liverpool to telephone Oxford to seek clarification. She received a message that “It [the appointment] was announced in The Times. What more does he want?” In articulating his plans for the job, David emphasised clinical work and teaching, a perspective reflecting the fact that he was an excellent clinician as well as a visionary scientist.
David moved from Liverpool (where he was, by then, Professor of Haematology) to the old Radcliffe Infirmary in Oxford in 1974. In 1979, the Nuffield Department of Medicine moved to the John Radcliffe Hospital in Oxford. During the late 1970s and early 1980s, David’s research programme embraced nucleic acid technology – including Southern blotting and DNA sequencing – a development that allowed detailed study of genetic abnormalities in thalassaemia. An ecological niche became available in the 1980s, following the retirement of Geoffrey Dawes (Munk’s Roll, Vol. X, p. 99) from directorship of the Nuffield Institute for Medical Research on the John Radcliffe Hospital site. David was able to colonise this niche by founding an Institute of Molecular Medicine, which began operation in 1989, and to which his surname was prefixed in 2000. David was elected to the Regius Chair of Medicine at Oxford in 1992 and retired from this post in 2000, though continued to work on a thalassaemia-related project linked to Sri Lanka. During 2002-2012, David was Chancellor of Keele University.
As a clinical lecturer at Oxford during 1975-1981, the present author was able to benefit from David’s example and guidance during one’s transition from postgraduate clinical training to a nascent academic career. Ingredients of David’s success included a ferocious work drive (exemplified by a vast output of published work), a broad perspective that embraced the whole of medicine, compassion as a clinician, and kindness to junior staff. While taking on large projects that might have diluted (though did not) David’s effectiveness as a scientist – including editing the first three editions of the Oxford Textbook of Medicine (along with John Ledingham and David Warrell) – he appears to have shown minimal interest in other potential activities such as RCP politics, ‘commercialisation’ of the results of his research, or premature clinical applications (notably, gene therapy). David was interested in music (particularly that of Mozart) and Asian food. A person of great humility, David attracted recognition and honours, including Fellowship of the Royal Society, two knighthoods (the second being Knight Grand Cross), and a Lasker award. He was survived by Stella and their son, Mark, who is a neurologist.
Martin F. Heyworth
[Br Med J 1, 1711-3, 1960; Lancet 2, 835-7, 1960; Oxford Medicine, May 2019, pp. 5-8; David Weatherall – Scientist - Web of Stories (info@webofstories.com); 2010 Lasker-Koshland Special Achievement Award in Medical Science, David J. Weatherall]