James Bertram Collip

James Bertram Collip (1892-1965), always known as Bert, has been described as the forgotten member of the team which discovered insulin in 1921/2. He gained PhD in 1915 and was appointed to organize the Department of Biochemistry at the University of Alberta. In 1921 he was awarded a Rockefeller Travelling Fellowship which he had intended to spend in Toronto, London and New York. In the spring of 1921 he started in Toronto studying the effect of pH on blood sugar. In the autumn JJR Macleod asked him to help with the purification of insulin and he made rapid progress although later he described his role as ‘that which any well trained biochemist could [have been] expected to contribute’.

The first use of insulin was on January 11th 1922 when the house physician at Toronto General Hospital, Dr Ed Jeffery, injected what he described as 15cc of ‘thick brown muck’ into the the 14 year old Leonard Thompson who had been on the Allen starvation regime since 1919. This extract made by Charles Best was a failure but the experiment was resumed on January 23rd when he was given 5cc of a new extract prepared by Collip and then 10ml more over the next 24 hours. This time the results were spectacular. Thompson’s blood sugar fell from 520 mg/dl (29mmol/L) on the morning of January 29th to 120mg/dl (6.7mmol/l) at 5am the next morning. He continued on Collip’s potent extract for the next 10 days with marked clinical improvement and complete elimination of his glycosuria and ketonuria. Banting asked for details of how he had made the effective extract but Collip refused to tell him. This led to a confrontation in which Banting grabbed Collip by the collar. Clark Noble drew a cartoon showing Banting sitting on and trying to choke Collip which he entitled ‘the discovery of insulin’.

Collip returned to Edmonton in 1922 where he became professor of biochemistry. He also decided to qualify in medicine which he did in 1926. The discovery of insulin stimulated the search for orally active compounds with hypoglycaemic activity and Collip thought that because plants contained glycogen, they must contain something like insulin. He prepared extracts from various organic materials such as yeast, onion tips, lettuce, sprouted grains of barley and even lawn grass. These did appear to lower the blood sugar of rabbits, but only after a latent period of hours or days.[1] Collip proposed the name ‘glucokinin’ for the active ingredient of these extracts and in his experiments on rabbits, there was sometimes a fall in blood sugar but it was rather hit and miss and often took two or three days. His work led to a plethora of experiments on most known plants and seeds. These products were often claimed to be active but the claims could hardly ever be replicated, even eventually by Collip himself.

Arguably his most important contribution to endocrinology came in 1926 when he published a paper entitled, ‘The extraction of a parathyroid hormone which will prevent or control parathyroid tetany and which regulates the blood level of calcium.’ In it he showed that his extract not only cured tetany but that the effect was parallelled by a rise in the blood calcium level. This discovery led to a prolonged and bitter dispute about precedence with a small town surgeon and amateur chemist in Minnesota, Adolf M Hanson (1888-1959), who had described a similarly effective extract two years earlier in an obscure journal Military Surgeon. [2]

In 1928 Collip succeeded his mentor AB Macallum in the chair of biochemistry at McGill. Here he continued his endocrine research starting with the isolation of two hormones from the human placenta; one caused oestrus and was eventually developed as premarin. The other had a gonadotrophic effect and was probably identical with human chorionic gonadotrophin. In 1947 he became dean of medicine at the University of Western Ontario where he set up the Collip Medical Research Laboratory. He did not actually work in these labs but was always available for advice and those who worked there were extremely productive.

References

  1. ^ Collip JB. Glucokinin: a new hormone present in plant tissue. J Biol Chem 1923;56:513-543.

  2. ^ Alison Li. JB Collip, AM Hanson and the isolation of the parathyroid hormone, or Endocrines and Enterprise. J Hist Med Allied Sci 1992;47:405-438.

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