VALLANCE-OWEN, John (1920-2011) was an English physician who invented the concept of synalbumin insulin antagonism. The starting point was that in the early 1950s bioassays for insulin showed that, whereas juvenile diabetics [type 1] were insulin deficient, maturity onset patients [type 2] had either normal or supranormal levels of the hormone. To accommodate these facts, several investigators, including Vallance-Owen began a search for plasma factors which could inhibit the action of insulin.
Vallance-Owen found that when insulin was added to the plasma of normal subjects or untreated diabetics, he could recover most of the added insulin. However, when insulin was added to the plasma of diabetics on insulin, the added insulin had no additional effect, suggesting antagonism. Two years later he reported that the antagonist was associated with the albumin fraction and christened it ‘the synalbumin insulin antagonist’. These and other observations suggested to Vallance-Owen that;
The primary abnormality in essential diabetes mellitus may be increased insulin antagonism, presumably inherited. The type and time of onset of the diabetic state would depend on the degree of antagonism and on the resilience of the pancreatic beta cells. Since the antagonism is apparently mediated via the pituitary – adrenal system, it would be expected to increase under certain conditions such as pregnancy, infection and puberty .
SIA now became a marker of diabetes ‘without reference to carbohydrate intolerance’ and Vallance-Owen suggested that it, and by implication diabetes, was dominantly inherited. The more conditions in which it was measured in Vallance-Owen’s lab, the more impressive its pedigree seemed to become. Thus it was present in a high proportion of people with myocardial infarctions and in over 80% of women whose children had deformities of the limbs or spine. Methodological problems led to contradictory results and interpretation was always difficult because, according to Vallance-Owen, everyone was either positive or negative. It was initially suggested that the antagonist might be the B chain of the insulin molecule but its role in the pathogenesis of any form of diabetes was never established. It was eventually thought to be a methodological artefact resulting from lowering of the pH or the use of a certain kind of dialysis membrane. Be this as it may, during its 10 year life it spawned a plethora of papers.
Perhaps the best epitaph was that written by Berson and Yalow in 1970:
The story of the synalbumin antagonist provides an interesting case study in clinical investigation. Held to be the “primary abnormality in essential diabetes” by Vallance-Owen, synalbumin has totally captured the devotion of some authors, and yet has been completely rejected by others. The chronological history of synalbumin is replete with its ability to revive after each apparent death blow .
In fairness to Vallance-Owen it should be said that the end of the1950s was a great era of insulin inhibitors and every self-respecting investigator had his own. Harry Keen told me that he had suggested that kipper water – after boiling the fish – would have inhibitory properties and was able to demonstrate that it was indeed an extremely powerful insulin inhibitor in the rat diaphragm assay!
He had considerable talents as an administrator. In 1981, after Mintoff had sacked most of the doctors and replaced them from Jugoslavia, Vallance-Owen went to Malta where he became director of medical services and organised clinical teaching. In 1983, on the verge of retirement, he was invited to become the foundation professor of medicine at the Chinese University of Hong Kong where he had great success.
^ Vallance-Owen J, Lilley MD. Insulin antagonism in Plasma of Obese Diabetics and Prediabetics. Lancet 1961; 1: 806-7.
^ Vallance-Owen J. The inheritance of essential diabetes mellitus from studies of the synalbumin insulin antagonist. Diabetologia 1966; 2: 248-252.
^ Davidson MB, Poffenbarger PL. Role of synalbumin insulin antagonist in the pathogenesis of diabetes mellitus. Metabolism 1970; 19: 668-686.
^ Solomon A Berson and Rosalyn S Yalow. Insulin “Antagonists” and Insulin Resistance. In Ellenberg M and Rifkin H (eds) Diabetes Mellitus: Theory and Practice. 1970.