Professor Sir Philip Randle
Researcher into metabolism
Saturday 02 December 2006
Philip John Randle, biochemist: born Nuneaton, Warwickshire 16 July 1926; Medical and Surgical Officer, UCH 1951; Research Fellow in Biochemistry, Cambridge University 1952-55, University Lecturer in Biochemistry 1955-64; Fellow, Trinity Hall, Cambridge 1957-64, Director of Medical Studies 1957-64; Professor of Biochemistry, Bristol University 1964-75; Professor of Clinical Biochemistry, Oxford University 1975-93 (Emeritus); Fellow, Hertford College, Oxford 1975-93 (Emeritus); FRS 1983; Kt 1985; Fellow, UCL 1990; married 1952 Elizabeth Harrison (died 2004; two daughters, and one son and one daughter deceased); died Oxford 26 September 2006.
Philip Randle was one of the world's foremost researchers into mammalian metabolism. Many of his findings were concerned with insulin's role in metabolism and with the control of secretion of the hormone from the pancreatic islets of Langerhans beta-cells. The ideas generated by his investigations laid the foundations for countless subsequent other studies and have a direct bearing on the understanding of diabetes.
Randle was born in Nuneaton, Warwickshire, in 1926 and went to school at King Edward VI Grammar School, Nuneaton. He read Natural Sciences at Sidney Sussex College, Cambridge, gaining a First in Part II Biochemistry, and then Medicine at University College Hospital before returning to Cambridge to carry out his first research studies on insulin, under the supervision of Professor Frank Young. He was awarded his PhD in 1955 for a thesis entitled "Studies on the Metabolic Action of Insulin" and was immediately appointed Lecturer in Biochemistry at Cambridge University.
In 1964, Randle was appointed founding Professor and Chairman of the Department of Biochemistry at Bristol University. Under his leadership, the new department became one of the strongest in Britain and remains so to this day.
He went to Oxford as the first Professor of Clinical Biochemistry in 1975, and spent the rest of his career as head of the Nuffield Department of Clinical Biochemistry. Randle was content for the NDCB to remain a small unit, in contrast to Bristol. He took with him Steve Ashcroft, with whom he continued his interest in the control of insulin secretion, and Alan Kerbey, with whom he studied the regulation of the key metabolic enzyme pyruvate dehydrogenase, which had become a major interest for Randle because of its central importance in the inhibition of glucose utilisation by fatty acids. Dick Denton, another early research student of Randle's, who had been closely involved with Randle in work on adipose tissue, remained behind in Bristol, where he pursued and expanded the study of the metabolic effects of insulin.
The NDCB, despite its small size, was highly productive and gained an outstanding reputation in diabetes research under Randle's leadership. Randle retired officially in 1993 but maintained an active interest in the topics that had occupied him throughout his career and continued to act as editor for scientific journals.
His best-known contribution to diabetes research is probably the glucose-fatty acid cycle. This innovative hypothesis, first put forward in a paper in The Lancet in 1963 with Eric Newsholme, Nick Hales and Peter Garland, was based on the demonstration that fatty acids reduce the oxidation of sugar by muscle. Randle and his colleagues speculated that increased fat oxidation was responsible for the insulin resistance (i.e. failure of insulin to adequately increase glucose utilisation by muscle) associated with obesity and Type 2 diabetes.
A biochemical mechanism was proposed to account for this effect and in a succession of papers, evidence was presented to support the idea. Thus the new possibility was suggested that, instead of being solely a disorder of carbohydrate metabolism, the primary event in the development of insulin resistance could be excessive release of fatty acids from fat tissue. The fundamental importance of the glucose-fatty acid cycle in normal physiology is now fully accepted.
Randle also proposed a second major hypothesis in the 1960s to explain how increases in blood sugar levels may result in increases in the secretion of insulin. Based on their observations of the ability of various sugars to stimulate insulin secretion in vitro, Randle and Hal Coore proposed that it was the metabolism of glucose within the beta-cell that was in some way coupled to triggering insulin release.
This metabolic model for glucose-stimulated insulin release, given the name of the substrate-site hypothesis, was supported by a long series of studies with Ashcroft, first in Bristol and later in Oxford, and is now fully accepted. The details of the biochemical mechanisms involved have been elucidated, the molecular components identified and modern techniques of molecular biology and genetics brought to bear on analysis of the possible contribution of mutations in these components to the development of diabetes.
Philip Randle was an impressive figure, both physically and mentally. He possessed an extraordinary memory for facts. At scientific meetings, he could be formidable in his ability to quote chapter and verse to support his arguments. But he was also capable of great kindness and support for those he took under his wing, scientifically.
He received many honours for his research work. He was the first recipient of the Minkowski Prize of the European Diabetes Association in 1966; he was elected to the Royal Society in 1983; and he was knighted in 1985. In all his activities he was supported by his wife, Elizabeth, whom he married in 1952 and who died two years ago. He also suffered the loss of a son, Peter, who died in 1971 while still in his teens, and a daughter, Susan, who died last year. His two daughters Sally and Rosalind survive him.
Steve Ashcroft and Dick Denton
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