William Bosworth Castle, a lifelong New Englander, is remembered for his pioneering work on ‘intrinsic factor’, the substance elaborated by the stomach which is necessary for the absorption of vitamin B12-Castle first discovered m 1928 that the condition of permicious anaemia, now known to be due to vitamin deficiency, was caused by a lack of secretion of ‘intrinsic factor’ by the stomach. He was also responsible for stimulating Linus Pauling to the then original idea that sickle cell anaemia might be a molecular disease.
He made important contributions to the treatment of tropical anaemias, particularly those associated with hookworm infestation and tropical sprue, and was also influential in determining the causes of haemolytic anaemia and the value of splenectomy in treatment. For a whole generation he was the leading figure in American haematology and his death, at the age of 91, marked the end of an era. As one of his pupils so aptly remarked: ‘Where Dr Castle sat, there was the head of the table.’
Bill Castle was born in Cambridge, Massachusetts, the son of William Ernest Castle, professor of zoology at Harvard University, and Castle’s own career was spent entirely at Harvard. He graduated in medicine in 1921 and went on to internships at the Massachusetts General Hospital, and then to become instructor in physiology at Harvard Medical School.
In 1925 he became assistant resident at the Thorndike Memorial Laboratory, where he was to spend his professional life. Here he met and was influenced by George R Minot [Munk's Roll, Vol.V, p.286] and William Murphy, who were at that time pioneering the successful liver treatment of pernicious anaemia, then a universally fatal disease. Their achievement won them - with George Whipple - the Nobel prize for medicine in 1934. It was in this inspiring environment that Castle was encouraged to undertake the work that established his international reputation.
The question that intrigued him was why patients with pernicious anaemia had to eat large amounts of liver every day to regain health, whereas normal individuals could simply eat a normal diet. He then showed, in a series of experiments upon himself, that meat digested in his own normal and then regurgitated stomach would be effective in restoring blood formation in a pernicious anaemia patient whereas meat alone would not.
It was this simple but crucial experiment that led to his suggestion that there was a factor in the stomach - ‘intrinsic factor’ - that was necessary for blood formation. Later studies showed that his ‘intrinsic factor’ was a complex polysaccharide which was essential for the absorption of vitamin B12.
Castle served as associate director of the Thorndike Memorial Laboratory from 1932-48 and he then succeeded to the directorship, which he held until 1963. He was elected to the fellowship of the College in 1964. He retired in 1968 as Francis Weld Peabody faculty professor at the Harvard Medical School.
Bill Castle was a tall, imposing figure who was characterized by an endearing modesty. He was totally immune to the attractions of medical or scientific politics. He did everything himself, even to the extent of repairing the plumbing in the Thorndike Laboratory, which was often in need of repair. There was more than one brash young investigator who, ignoring the boiler-suit clad figure who was repairing the drains, was subsequently disconcerted to discover that the plumber was the director of the laboratory.
In later years, as a much sought after visiting professor, he enjoyed particularly listening to young men presenting their data. On one memorable occasion, at the Royal Postgraduate School at Hammersmith, a young man suggested to him that the electron microscope appearances that he was describing resembled a doughnut. He asked Castle whether Americans knew what a doughnut was. To which Castle, drawing himself up to his formidable height, responded: ‘Didn’t you know that we invented the doughnut?’
Bill Castle was a man of total integrity. A stimulating teacher, inspiring colleague, and a legend in his own time, he belonged to that great generation of Harvard physicians and haematologists who did so much to create order out of the medical uncertainties that they inherited.
Sir Christopher Booth
* Elected under the special bye-law which provides for the election to the fellowship of "Persons holding a medical qualification, but not Members of the College, who have distinguished themselves in the practice of medicine, or in the pursuit of Medical or General Science or Literature.."
[Annals of Internal Medicine, 1978,89,no.6,1003-4]