Andrew Cudworth

Andrew Cudworth (1939-1982) will be remembered for three major contributions to the understanding of type 1 diabetes. The first is as one of the discoverers of the HLA associations of type 1 diabetes, although Jørn Nerup and colleagues in Denmark were the first to publish their findings. The second was as the founder of the Bart's-Windsor Family Study of diabetes, the pioneer prospective study of first-degree relatives of a child with type 1 diabetes. The third contribution was his reintroduction of the terms type 1 and type 2 diabetes, which rapidly replaced earlier labels for these conditions.

Andrew Cudworth trained in medicine at Liverpool, qualifying in 1963, and joined the Army Cadet scheme - partly because he married young and needed the money. He spent the first 5 years of his medical career in the army, rising to the rank of major. He then left the army and returned to Liverpool as a medical registrar, passing the examination for the Royal College of Physicians of London in 1971. His interests were soon directed towards diabetes and immunology, and he worked in the laboratory of John Woodrow, one of the pioneers of HLA analysis.

The topic was immensely complicated at the time, owing to the proliferation of sera and differences in nomenclature, but Andrew rapidly achieved mastery of the new area, and independently discovered the HLA associations of what was then called insulin-dependent diabetes. His was the sad fate of being second past the post, however, for Nerup and colleagues published their findings in the Lancet in December 1974, followed only two weeks later by a letter from Cudworth and Woodrow confirming the association.

Cudworth was soon head-hunted for St Bartholomew's Hospital in London, which he joined in 1977. At that time he, like most others in the field, believed that childhood-onset diabetes was caused by acute viral infection superimposed upon HLA susceptibility. Around this time he met John Lister, a diabetes physician at Windsor Hospital, and learned that Lister had proposed the terms type 1 and type 2 diabetes 25 years earlier. Furthermore, he had a card index of all his patients, colour-coded according to their type of diabetes.

Cudworth seized upon the files and rapidly devised what became the Bart's-Windsor family study. One aim was to identify the HLA characteristics of probands and unaffected siblings, and thus to find ways of allocating risk in the latter. A second and more ambitious aim was to capture the causal virus by repeated serological testing, thus (as it was hoped) paving the way to vaccination against diabetes. This could only be achieved by a programme of regular visits and collection of blood samples from all members of the families concerned, visits which were carried out by a succession of research fellows (Andrew Gorsuch, Kate Spencer and Anne Tarn).

The quest for a virus was to prove fruitless, but the group teamed up with Franco Bottazzo, the discoverer of islet cell antibodies (ICA), who was also working in central London at the Middlesex Hospital. ICA were found to be present in ~5% of first degree relatives, and it was soon noticed that the vast majority of those who went on to develop diabetes were ICA positive. This landmark discovery paved the way to our current understanding of the long prodrome to clinical type 1 diabetes, and of the possibility of predicting - and potentially preventing - its onset. See the entry on Discovery of type 1 diabetes for further details.

Andrew Cudworth's subsequent rise to prominence was meteoric. His focus and drive were phenomenal, and his ability to secure research funding was legendary. He did important work on HLA haplotype sharing and its role in diabetes prediction, and in the the role of HLA Class II antigens in disease susceptibility; the latter work was undertaken in collaboration with Eva Wolf (later Tuomilheto-Wolf). His prominence in the European diabetes community was signalled by his appointment as Editor of Diabetologia, the journal of the EASD in 1980.[1]

A keen squash player, Andrew noticed problems with his forehand drive at around this time, the earliest manifestation of a right parietal lobe glioma. As might be expected, the progression of his disease was rapid and harrowing, but (supported by high-dose dexamethasone), he persisted in his work and forward planning right up to the very end, finally passing away on October 11th 1982 at the age of 43. The family study that he founded, redesigned and extended as the Bart's-Oxford Family Study of diabetes, is still going strong.

Si monumentum requiris circumspice

References

  1. ^ See the obituary by John Dickinson in Munk's Roll: http://munksroll.rcplondon.ac.uk/Biography/Details/1097

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