Russell Morse Wilder
Russell Morse Wilder (1885 -1959) came from a medical family. In 1910, while a medical student, he went to Mexico with Dr Howard Ricketts (1871-1910) to study tabardillo, a typhus like disease. Ricketts had previously shown that Rocky Mountain spotted fever was transmitted by a tick and he and Wilder showed that tabardillo was transmitted by the human body louse. They isolated the organism from lice and patients and showed that it could be transmitted to monkeys. During the studies Ricketts died from typhus and Wilder returned to Mexico to finish their work.
In 1914 he studied in Vienna for eight months where his interest in diabetes was kindled. On his return he became resident physician in the Presbyterian hospital of Chicago where he worked with Rollin Woodyatt (1878-1953) on the rate of metabolism of ketones in dogs. He became a member of the staff of the Mayo clinic in 1919 and was put in charge of all diabetic patients, at that time about 100 a year. In 1919-20 he did extensive metabolic studies on a single patient with the physiologist Walter Boothby (1880-1953). Their patient, Bessie Bakke, had developed diabetes acutely in 1918 at the age of 26 and was an investigator’s dream because during her 74 days in hospital she co-operated totally and ‘maintained perfect serenity throughout her stay.’ She was tried on 12 different diets. On high protein and fat (meat, butter, eggs, and soy bean bread, containing less than 1gm of carbohydrate), a dangerous acidosis developed and could only be countered by reverting to a low protein-high fat diet. This paper is credited with having given the scientific imprimateur to high fat diets. Wilder was also the first to test a ketogenic diet in epilepsy.
He was one of the North American physicians chosen to investigate the clinical use of insulin and in 1922 made an important contribution on the physiology of hypoglycaemia. He and colleagues reported studies on three diabetic patients and one normal subject, Wilder himself. Walter Boothby had found that an injection of adrenaline produced a 30 – 40% increase in basal metabolic rate. Boothby and Wilder then found that an injection of insulin also produced a transient increase in metabolic rate but that this only happened when the blood sugar fell below the fasting level. By a lucky chance Wilder suffered from hay fever for which he used to give himself injections of adrenaline. He had therefore experienced the palpitation, sweating and feeling of anxiety so that when he experienced the same symptoms after an injection of insulin, he suggested that ‘this may have been caused by a spontaneous discharge of the patient’s own epinephrine and that herein we may be dealing with an automatic protection mechanism against hypoglycaemia.’ Wilder recounted these findings in a lecture in Boston where Walter Cannon, the originator of the concept of the fight-flight reaction, was sitting in the front row. Cannon had also noted that some of the symptoms of hypoglycaemia - particularly pallor, sweating, tremor, dilatation of the pupils and palpitations - were similar to those which followed an injection of adrenaline. He regarded the bodily reaction to hypoglycaemia as ‘another remarkable example of automatic adjustment within the organism when there is a disturbance endangering the equilibrium.’
Wilder was one of the pioneers of treating insulin requiring patients as outpatients. As he explained, “[when] the depression reached its height, many of the diabetic patients were loath to add hospital bills to their clinic charges. Therefore it became expedient to provide outpatient care for those whose diabetes was uncomplicated…. The outpatient care of the diabetic patients, although forced on us by necessity, proved to be a blessing. It enabled us to see these patients frequently and to give them more effective training than was possible in a hospital.” He wrote a patient handbook "A Primer for Diabetic Patients" which was first published in 1921 and went to 9 editions, the last in 1950.
In 1927 Wilder and colleagues were the first to describe an insulinoma. The opening sentence of their paper read, ‘We have recently studied, both clinically and at necropsy, a case of severe spontaneous hypoglycemia. This is attributed to a tumor of the islands of Langerhans with metastasis in the liver and lymph nodes. The condition has not been described heretofore and in this sense it represents a new disease.’ The patient was a 40 year old orthopaedic surgeon with an 18 month history of attacks of faintness, confusion and stupor which had become more frequent and severe. Even a short fast resulted in a coma and his wife had ‘to watch when he slept and put candy into his mouth at the first sign of unusual behaviour’. His cousin had had similar symptoms and died 6 years earlier. It seems likely that both had multiple endocrine neoplasia since Wilder’s patient also had renal stones.
In 1934 the work of Wilder and his ophthalmologist colleague Henry Wagener (1890-1961) challenged the orthodox view that diabetic retinopathy was due to arteriosclerosis. They found young patients with retinopathy who had normal blood pressure and no signs of arterial disease and concluded that, ‘The very existence of retinitis in cases in which patients have no other signs of vascular disease must mean that diabetes alone does something to injure the finer arterioles or venules of the retina, probably the latter.’
He retired from the Mayo clinic in 1950 to become the first director of the new National Institute of Arthritis and Metabolic disorders but had to give this up because of coronary artery disease. Wilder was a modest man and in one of his last addresses at the American Dietetic Association in 1959, he said, "I can lay no claim to any great discovery but I was a member of the crew and several of the ships engaged in exploration of the Islands of Langerhans and I must admit to a degree of pleasure in recalling these adventures."
An obituary of Russell Morse Wilder by Randall G Sprague can be accessed at: http://diabetes.diabetesjournals.org/content/9/5/419.full.pdf+html
^ Wilder RM, Boothby WM, Beeler C. Studies of the metabolism of diabetes. J Biol Chem 1922;51:311-356. Carol Beeler was Wilder’s technician.
^ Russell M Wilder. Recollections and reflections on education, diabetes, other metabolic diseases, and nutrition in the Mayo clinic and associated hospitals, 1919 - 1950. Perspectives in Biology and Medicine 1958;1:237-277.
^ Wilder RM, Allen FN, Power MH, Robertson HE. Carcinoma of the islands of the pancreas: hyperinsulinism and hypoglycemia. J Am Med Ass 1927;89: 348-355.
^ Wilder, R. M. Adventures among the Islands of Langerhans. J Am Dietetic Assoc. 1960;36:309.