Robert Turner (1938-1999)

Robert Turner was a classic physician-investigator whose work over three decades spanned the radioimmunoassay and physiology of insulin, the pathogenesis of type 2 diabetes and a landmark trial in its management. He studied medicine at Cambridge and worked with Sir John Nabarro at the Middlesex Hospital, where he developed a lifelong interest in the role of insulin secretion and action in the pathogenesis of diabetes and devised a charcoal-based insulin assay. At a time when the diabetes community firmly believed that type 2 diabetes was a disease of insulin resistance, he and a few other visionaries located the problem in the beta cell. With Rury Holman he devised a model of disordered glucose-insulin homeostasis, and with David Matthews he did pioneer work on pulsatile insulin release and developed the widely used HOMA model of insulin homeostasis. His master-work was however the UK Prospective Diabetes Study, a prospective intervention trial in newly-diagnosed type 2 diabetes which took twenty years to complete. Patients were randomized to intensified or conventional glucose control with sulfonylureas, insulin, or (later) metformin. A blood pressure control arm was later added. The study demonstrated the key roles of glucose control and antihypertensive therapy, thus defining the course of diabetes management for a generation.

Early Career

Robert studied medicine at Downing College, Cambridge and did his clinical studies at the Middlesex Hospital, London. His interest in diabetes developed whilst working as a Leverhulme Fellow for Dr John Nabarro. He developed methods for physiological studies to investigate insulin secretion in vivo in man and development of a charcoal separation phase insulin assay with Roger Ekins, a pioneer of radioimmunoassay.

After two years of research at the Massachusetts General Hospital in Boston USA, he returned to Oxford as a clinical lecturer to Professor Paul Beeson. He initially occupied two small rooms in the Sir Hans Krebs Metabolic Research Laboratories with one technician and one research nurse. He was later joined by Dr Rury Holman, and the Diabetes Research Laboratories (DRL), ,created in 1976, and became one of the largest and most successful clinical research units in Europe. These were originally located at the Radcliffe Infirmary, Oxford and later formed a cornerstone for the building and development of the present Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM).

Insulin & Glucose

Robert appreciated at an early stage that type 2 diabetes was a disorder of insulin-glucose homeostasis, in which insulin levels rose in phase with, but always lagging behind, rising basal and stimulated levels of glucose. His work, with that of Rury Holman, paved the way to successive models of the dynamic interaction between glucose and insulin[1], and led on to the development of the famous HOMA model[2]. The demonstration (with Steve O'Rahilly) of defective beta cell function in first degree relatives of people with type 2 diabetes[3] further underscored his conviction that beta cell dysfunction lay at the core of type 2 diabetes, at that time a lonely and unpopular view.

Other Research Interests

Robert was early to recognise the revival of diabetes genetics in the age of molecular biology. He actively promoted this line of investigation in the Diabetes Research Laboratories, and started Steve O'Rahilly and Andrew Hattersley on their careers as well as bringing Anna Gloyn to Oxford.

With Anne Clark and others including Garth Cooper he investigated the long-neglected role of amyloid in the pancreatic islets and proposed a role for IAPP/amylin in the pathogenesis of type 2 diabetes[4].

With George Alberti and Derek Hockaday he pioneered the treatment of diabetic ketoacidosis with repeated small doses of insulin, an approach that translated basic research on the hepatic suppression of glucose production into a new approach to therapy that revolutionized the management of this feared diabetic emergency[5].

UKPDS

The University Group Diabetes Program (UGDP) set out to determine the role of improved glucose control in general, and oral hypoglycaemic agents in particular, upon vascular outcomes in diabetes. This bold endeavour resulted in confusion when the intervention appeared to show no benefit in improved glucose control and positive harm in cardiovascular outcomes with the use of tolbutamide and phenformin. See The University Group Diabetes Program for more details.

The resulting controversy was so bitter that it took a brave and determined man to throw this area open to renewed investigation. Robert was such a man. No funding framework existed in the UK for a study on the monumental scale he proposed, and Robert himself scarcely envisaged the scale of the task. The study was therefore established on the basis of a series of short term grants, endlessly renewed. It is probably true to say that no other investigator could have proved so resilient, indeed unruffled, by an endless sequence of rejections, but Robert apparently lacked a receptor for the word "no".

UKPDS was designed to investigate the optimal treatment regimes for Type 2 diabetes and was one of the longest clinical trials in medical history lasting for 20 years with a further 10 years of post-study monitoring. Nurses, doctors, dieticians, technicians and statisticians operated from 23 clinical centres around the UK with Oxford as the co-ordinating and blood sample assay centre. UKPDS involved 5102 patients with newly diagnosed type 2 diabetes and the 20 year results were unveiled at the EASD meeting in Barcelona in 1998. Ably assisted by the organizational prowess of Rury Holman, Robert fought for the study every inch of the way, but ended by transforming the management of type 2 diabetes around the world for decades to come. See The United Kingdom Prospective Diabetes Study [UKPDS] for more details.

Sadly, Robert himself was denied much of the recognition he deserved because of his untimely death from a cerebral haemorrhage whilst attending a meeting in the USA.

Personal Insights

Robert was a somewhat shy and reserved person who led by example and had the great gift of identifying and fostering talent in others. His charm, modesty, kindness and consideration overlay a steely resolution; Robert was not for turning. This stubbornness served him well, and helps to explain the extraordinary breadth of his achievement. Add to this the capacity to frame his thinking and that of the people around him into simple and soluble questions, and the personal touch provided by his thoughtfulness and unstinting support for others, and you have the recipe for a great scientist, a great leader and a true gentleman.

References

  1. ^ Stumvoll M et al. The hyperbolic law - a 25 year perspective. Diabetologia 2005;48:207-9

  2. ^ Matthews DR et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985;28:412-19

  3. ^ O'Rahilly SP et al. Beta cell dysfunction rather than insulin insensitivity, is the primary defect in familial type 2 diabetes. Lancet 1986;ii:360-4

  4. ^ Clark A et al. Islet amyloid formed from diabetes-associated peptide may be pathogenic in type 2 diabetes. Lancet 1987;ii:231-4

  5. ^ Alberti KGMM et al. Small doses of intramuscular insulin in the treatment of diabetic "coma". Lancet 1973;ii:515-22

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