by Jameel Barkat
100 years down the line, Insulin is still not flowing in the veins of the millions of people who desperately need it. Unfortunately, it remains inaccessible due to its exorbitant prices and unavailability, despite the fact that its discoverers decided not to patent it.
It was a nightmare to see the diabetic ward of any hospital in the nineteenth and early twentieth century as patients were collapsing into a coma due to high blood glucose levels. The only remedy available to hold onto the life of patients was the starvation method developed by the father of starvation, Dr Frederick Allen.
Starving diabetic patients was like reducing them to skeletons with life. The gloomy atmosphere of diabetic wards evaporated, exhilaration started circulating into veins and exuberance was displayed on the faces of diabetic patients after news of the discovery of Insulin spread throughout the world.
A Struggler’s Invention
By 1920, there was evidence given by scientists like George Zuelzer of Germany and Nicolae Paulescu of Romania that some extract from the pancreas was lowering the blood glucose in dogs they used for experiments. However, this crude extract from the pancreas was toxic with vast side effects.
Dr Federick Banting was a frustrated surgeon who was struggling to find a job and had a failed tryst with his first attempt of setting up his own clinic. One night, he was reading an article by Dr Moses Baron who had found atrophied pancreas in one patient whose pancreatic duct was blocked by a stone.
It is pertinent to mention that Banting had a very rudimentary knowledge of carbohydrate metabolism. However, the article was enough to stimulate an idea in Banting, which finally culminated in the discovery of Insulin.
Banting hypothesized that if we can ligate (tie) the pancreatic duct of dogs, we will be able to get rid of exocrine secretion, which at that time was thought to be the culprit in damaging the endocrine part having the anti-diabetic function. The next day, Banting sought an appointment with Professor JJR Macleod at the University of Toronto. Macleod was a renowned scientist of carbohydrate metabolism who gave a patient hearing to Banting’s hypothesis and agreed to allow him to work in his laboratory with some degree of acquiescence. Macleod saw some merit in Banting’s idea and was of the opinion that even negative results will also be helpful in further understanding of the then enigmatic anti-diabetic treasure extract from the pancreas.
Since it was time for summer vacations, Professor Macleod’s students, Charles Best and Nobel Clark had to toss the coin for deciding who will work with Banting in summer. Best lost the toss and had to work with Banting while Clark later regretted winning that toss, which perhaps deprived him of fame and becoming a part of the history of the marvelous discovery of Insulin.
Banting And Best
Banting and Best started their experiments by ligating the pancreatic ducts of dogs followed by extracting the fluid they named as isletin and subsequently injecting this extract into the diabetic de-pancreatized dogs. Their journey did not start on a good note as a number of dogs died due to infection while going through pancreatectomy (removal of the pancreas).
Best later recorded in his memoir that Banting, having an apprehension of using too many dogs from the University of Toronto’s animal facility, bought many dogs from the streets of Toronto and one time even used his necktie to catch and bring a dog to the lab.
Injecting the extract from the ligated pancreas into the diabetic dog was no less than a miracle as they had seen and recorded the dog’s high blood glucose levels plummeting. However, it was again the same problem of abscesses and other side effects. Banting and Best later found that extracts from normal bovine pancreas were also effective in lowering blood glucose. So, the question of ligated pancreas came to an end and the quest for purification of that effective constituent gained momentum.
A Failed Presentation
In December 1921, Banting and Macleod presented their work to the American Physiological Society Meeting at Yale University in New Haven. However, the inarticulate Banting poorly presented the work and failed to convince the jury and experts. Macleod chairing the session had to come to the defence of Banting from critical scrutiny of their work.
Returning back to Canada, doubts and misunderstandings started to seep in the mind of Banting who thought that Macleod was now robbing him of his credit. Banting in a hurry had pushed Macleod for the first human clinical trial and 14-year old Leonard Thompson became the first human to receive the crude extract of the pancreas. As expected, it did drop his blood glucose but with marked serious side effects. Thus, the first clinical trial was a failure and led to the demotivation of Banting. Macleod now sought the help of JB Collip, a brilliant chemist, in extracting pure internal secretion from the pancreas.
Collip’s work started on a disappointing and humorous note as he was not able to reproduce the results of Best and Banting and it later turned out that boy who was getting the pancreas for Collip from an abattoir was bringing back thymus and not pancreas due to the sweetbread culinary term used for both pancreas and thymus. Extract of thymus not lowering blood glucose was also an important result and compelling evidence of the presence of anti-diabetic hormone being exclusively present in the pancreas.
Collip, after receiving the correct sweetbread (pancreas), was finally able to extract a pure internal pancreatic secretion which was the first glimpse of Insulin.
Collip’s refusal to reveal his method of extraction outraged Banting and he grabbed his lapels to a point where Best had to intervene. That ugly moment was a display of nasty scientific competition. After Collip’s successful isolation of pure extract, ideal for human studies, Macleod was able to convince the world that they had discovered insulin. There came a twist in the story where Collip failed to repeat the success of his extraction method at a commercial scale production. Collip and his team really struggled to regain the knack of art of extracting insulin from the pancreas. Disillusioned, Banting was mourning the robbery of his due credit he thought by Macleod and Collip. Banting thought of leaving the laboratory and returning back to his clinic but Best’s emotional statement changed his plans.
Best: What will happen to me?
Banting: Your friend Professor Macleod will take care of you.
Best: I will also leave the laboratory if you will go.
After this, there was a moment of silence followed by Banting’s enthusiastic and emotional plea that they would not rest until insulin flowed in the veins of every diabetic patient. And they succeeded!
A Century Later
100 years down the line, we have come a long way in creating the best forms of Insulin. However, it is still not flowing in the veins of the millions of people who desperately need it. Unfortunately, it remains inaccessible due to its exorbitant prices and unavailability, despite the fact that its discoverers decided not to patent it. With hope, Banting’s wish will be achieved before a further 100 years have passed.
Declaration: I have used references from Bliss, M: The Discovery of Insulin. 1982 The University of Chicago Press, Chicago, USA.
(The author is a Kashmiri scholar who did his PhD from South Korea’s Daegu University on obesity and Type 2 Diabetes with a focus on the browning of white adipocytes, a novel strategy against obesity and its associated metabolic complications. He is now busy in his post-doctorate at the University of Gothenburg.)