Lives of the fellows

James Harrison Renwick

b.4 February 1926 d.29 September 1994
MB ChB St And(1948) MRCP(1951) PhD(1957) MRCP Glasg(1962) FRCP Glasg(1970) DSc Lond(1970) FRCP(1974) MFPHM(1974) MRCPath(1982) FRCPath(1982)

Jim Renwick will be remembered for his contribution to two quite different fields - human genetics and teratology. Born in Otley, Yorkshire, he gained a scholarship to study medicine at the University of St Andrews. The first baby he delivered as a medical student had anencephaly and this experience had a profound influence on his subsequent career. He purchased his first copy of the Annals of Eugenics in 1949 and he avidly looked forward to new issues. After qualifying in medicine he spent some of his National Service in Japan, where he became involved with J V Neel and Newton Morton in the Atomic Bomb Casualty Commission in Hiroshima.

He was attracted to the numerical aspects of human genetics, particularly data on human pedigrees for linkage analysis. He particularly wanted to make a contribution which, however small, made vital ratchet-type, non-slip advances, unlike the papers on diabetes, schizophrenia or duodenal ulcer of the period 1949 to 1972. He chose the nail-patella syndrome for its 100% penetrance, easy diagnosis and compatibility with normal reproductive life. Large pedigrees were therefore possible. Together with Sylvia Lawler [q.v.] he was able to show that the gene causing nail-patella syndrome is genetically linked to the ABO blood group locus. Their classical paper (Renwick and Lawler, Annals of Human Genetics 19:312-331,1955) was one of the earliest unequivocal demonstrations of genetically linked autosomal human genes.

Renwick knew his team’s thorough analyses, at that time exhaustively done by hand, were encouraging the collection of linkage data all over America and Europe. By the time he started to computerize the data and analyses in 1957 linkage was no longer an obscure activity. In 1959 Victor McKusick of the department of medical genetics at the Johns Hokins University, who had similar dreams of mapping human gene loci, invited Renwick to the largest computer configuration in the world which was being used in the United States space programme.

By 1961 the first fully efficient computer programme for genetic linkage was functional. The whole programme computerized the fully efficient likelihood methods of mathematician Cedric Smith of the Galton Laboratory, University College, London. By 1969 the success of the programme to detect new linkages inspired McKusick to propose a human genome project to match the ‘moon-shot’. Thus Renwick was the practical link between Cedric Smith’s methods of extraction of likelihoods and the modern genome project. Although molecular biology dominates the genome project, pedigree analyses are essential for the identification of possible gene loci, and Renwick’s work on genetic linkage was the crucial forerunner of the whole genome project.

Renwick pursued a stubborn and uncompromising quest for truth and absolute accuracy. A paper in the journal Science, which included him as an author, but which he had not seen, was perhaps the trigger for a change of interest. Renwick’s second career was in teratology, the study of the causes of human congenital malformations. In 1968 he became reader in human genetics and teratology at the London School of Hygiene and Tropical Medicine, and in 1979 he was appointed to a chair.

His teratology research initially focused on the malformations of anencephaly and spina bifida. In 1972 Renwick discovered a close correlation between variations in births of children with spina bifida and anencephaly and geographical, seasonal and annual variations in the incidence of potato blight. Potato blight is a fungal infection of the potato tuber, in which the uninfected parts of the potato produces a variety of anti-fungal chemical substances. Renwick’s hypothesis, which attempted to explain an array of apparently unconnected observations about the epidemiology of spina bifida and anencephaly, was that one of these anti-fungal substances, solanidine, when taken by a susceptible mother in early pregnancy, would interfere with the normal development of the embryo. Public anxiety about the consumption of blighted potatoes was followed by a rapid improvement in the quality of British potatoes, and an ill-informed ministerial statement by Keith Joseph that anxious mothers-to-be would be well advised to cut out and discard unhealthy looking parts of a potato, thereby completely missing the point of the hypothesis, namely that the danger lay in the healthy part of the vegetable. Subsequently it was shown that pre-conceptional vitamin supplements helped to prevent spina bifida and anencephaly, and the relevance of potato blight to these malformations remains unknown.

Previously most research into the causes of congenital malformations had focused on the way the embryo developed, how this might be affected by drugs, and the influence of genetic factors. However Renwick’s work resulted in an appreciation of the huge potential importance of environmental (and therefore avoidable) factors as possible causes of birth defects.

Throughout his second career in human teratology, Renwick found himself struggling in a difficult descriptive field which he was attempting to convert into a science. One striking discovery was his finding that the total foetal mass lost to a litter of a rodent was proportional to the cube of the dose of caffeine administered. The same cube law applies to mice, rats and also to rabbits. There is a known birth weight loss in man also due to caffeine.

A truly aggressive determination to study a problem in depth, meticulous attention to detail, scrupulous accuracy and honesty, great generosity and impatience with shoddy work and those who did not adhere to his high standards were his hallmarks. After his retirement he became ill with lung cancer. He had never smoked and believed his cancer arose as a result of exposure to radiation in Japan after the war. He married twice and had four children.

T J David

[, 1995,310,187; Bull.Roy.Coll.Path., 1995,90; The Independent, 13 Oct 1994; Times, 18 Oct 1994]

(Volume X, page 412)

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