Lives of the fellows

Thomas Hamilton Bothwell

b.27 February 1926 d.12 November 2016
MB BCh Wits(1947) MRCP(1952) MD(1953) DSc(1965) FRCP(1968) FRS South Africa(1973) Hon FACP(1975) Hon MD Cape Town(1986) FRCP Edinb(1992) Hon MD Natal(1993) Hon FCP South Africa(1994) Hon DSc Wits(1994)

As a twenty-one-year old medical intern in Johannesburg, Tom Bothwell encountered his first patient with severe iron overload due to idiopathic haemochromatosis. Always wanting to know why, he managed to scrounge some radioactive iron to show that the overload was due to excessive iron absorption. So began a lifelong fascination with iron, which saw him discover many of the basic tenets of iron metabolism that laid the foundation for later discoveries, ranging from molecular biology to food fortification.

Tom Bothwell was born in Johannesburg, South Africa, the son of Robert Cooper Bothwell and Jessie Isobel Thomson Bothwell née Hamilton. Robert had emigrated from Scotland in 1909, but ten years and a world war were to pass before he was able to marry his fiancée and bring her back to South Africa. Tom was a scholar at St John’s College, Johannesburg and entered the medical school of University of the Witwatersrand (Wits) at the tender age of 16. He graduated in 1947 and was awarded the bronze medal of the South African Medical Association for the most distinguished graduate. Because he was too young to register as a doctor, he spent six months as a demonstrator in the department of physiology. It was here that he met his future wife, Alexandrine Moorman (‘Alix’) Butterworth, who was in her second year of medicine. However, like his father before him, nearly ten years, overseas study and many letters were to pass before they married.

Iron overload was not new to Wits Medical School in 1948. Archie Strachan, professor of pathology, had described iron overload in the adult black population in 1925 and Bothwell was able to demonstrate the profound differences in absorption and distribution of iron in idiopathic haemochromatosis and ‘Bantu siderosis’. The source of the iron overload in Africans was shown to be traditional beer brewed in iron containers. Bothwell’s laboratory was a small room off one of the wards from which the smell of drying faeces (an essential step in the measurement iron absorption at that time) is said to have puzzled many a matron. His endeavours were supported by grants from the South African Council for Scientific and Industrial Research (CSIR) under Sir Basil Schonland. Bothwell continued his iron research as a medical registrar and took his first steps in the emerging field of ferrokinetics. A seminal discovery was that, in haemochromatosis, the absorbed radioiron accumulated in the liver rather than in haemoglobin. During this time, he also obtained his membership of the Royal College of Physicians and a doctorate of medicine from Wits.

In 1954 Bothwell was awarded a Nuffield travelling fellowship to the University of Oxford under Leslie Witts [Munk’s Roll, Vol.VII, p.618]. This provided the opportunity to widen his nascent ferrokinetic studies to included a range of haematological conditions. He also developed a robust method for measuring iron in serum that was the standard for many years. While at Oxford, Tom attended the fifth congress of the International Society of Haematology in Paris, where he met Clem Finch of the University of Washington, Seattle. This was the beginning of a long and rewarding partnership that started with a Lederle research fellowship and a year working with Finch in Seattle. Tom described his year in Seattle as one filled with ‘excitement’. The availability of radioisotopes was to be the catalyst that started a revolution in haematology research and enabled the study of how iron moves through the body. Undoubtedly their seminal contribution to iron metabolism was the demonstration that iron absorption is related inversely to the size of iron stores and directly to the rate of erythropoiesis. Fifty years were to pass before the discovery of the iron hormone, hepcidin, provided an explanation for this relationship.

Back in the department of medicine at Wits in 1956, Tom again turned his attention to iron overload in black South Africans. Starting with an improvised laboratory in a closed-off verandah and CSIR/Medical Research Council funding for his iron and red blood cell metabolism unit, Tom documented the pathogenesis and sequelae of this unique condition. Of great importance was the discovery that the iron overload (of any cause) induced irreversible oxidation of ascorbic acid (vitamin C), leading to clinical scurvy, a condition that had plagued the early mining industry in South Africa. This also had important implications in the management of iron overload in thalassaemia. Furthermore he, together with Harry Seftel, was the first to demonstrate the association of vitamin C deficiency and osteoporosis.

While the mechanisms of iron absorption and iron overload occupied the young researcher, it was the broader problem of iron nutrition that was to dominate Tom Bothwell’s research in later years. His robust method of measuring iron in tissues was applied by the Expert WHO Committee on Nutritional Anemia to a worldwide collaborative survey of liver iron stores. The high prevalence of iron deficiency in some populations, particularly India, suggested that nutrition, rather than blood loss, was the basic cause. A long series of iron absorption studies utilising dual iron radioisotope counting was to prove that the mix of promoters and inhibitors of non-haem iron absorption in the diet greatly influenced iron absorption and hence the iron nutritional status of a population. Inevitably these findings brought Bothwell into the field of iron fortification, culminating in a highly successful double blind fortification trial showing the efficacy of iron EDTA (ethylenediaminetetraacetate) in an iron deficient Indian population.

His work with the International Nutritional Anemia Consultative Group and latter with Sustain, the alliance for improved food and farming, produced a series of monographs on iron nutrition and fortification which drive world iron fortification projects. His years in iron research produced over 300 papers, monographs and chapters in books, two books and 18 doctorial theses. His book Iron metabolism in man (Oxford, Blackwell Scientific), published in 1979 and co-authored with Clem Finch, Jim Cook and Bob Charlton, remains an essential reference. He was the recipient of numerous awards and honours, including three honorary doctorates, the gold medal of the South African Medical Research Council and a Sims travelling professorship. He was the first honorary member of the International BioIron Society and was an invited lecturer at over 50 international congresses.

Over and above Tom Bothwell’s work as a research scientist, he was an able administrator and a brilliant clinician. He was academic head of the department of medicine at Wits for 24 years, responsible for undergraduate and postgraduate medical education in four teaching hospitals with over 1,200 medical inpatients covering disease profiles associated with the affluent West to the deprived, developing world. He served on numerous local, international and university committees and was a member of the councils of the university and St John’s College, his old school.

As a clinician, Tom Bothwell is remembered as being the doctor we all aspired to be. Although he appeared to be aloof, those who worked closely with him soon discovered his considerable charm. Many remember being called ‘maestro’, often ironically, and being told ‘Down boy!’ in response to some overenthusiastic suggestion. He had a remarkable bedside manner and, during a ward round, would sit on a chair next to a patient’s bed to quietly explain some important aspect of their medical management. Although an eminent scientist, Tom Bothwell fully understood the human side of medicine.

In spite of his enormous workload, Tom did not take work home. Home was a welcoming place revealing impeccable taste and a wide range of interests, music, books and art. Alix was there and so were their three children – Robert, now a psychiatrist, Janet, a dermatologist, and Ann, a teacher, and later four grandchildren.

Patrick MacPhail

[Bothwell TH. Iron in the Soul. Proc. R. Coll. Physicians Edinb. 1991;21:72-81; MacPhail P. The scientific writings of Tom Bothwell and his contribution to iron metabolism Adler Mus Bull. 2006;32(1):18-21; Bothwell TH, Pirzio-Biroli G, Finch CA. Iron absorption. I. Factors influencing absorption. J Lab Clin Med 1958 Jan;51(1):24-36]

(Volume XII, page web)

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