100 Years of Insulin: Why It’s the Greatest Medical Breakthrough of Its Time

This is the centenary year of the discovery of insulin, the greatest medical breakthrough of its time. It elevated Sir Frederick Banting to the status of international hero, honored with countless awards including a knighthood and a Nobel Prize. To this day Banting remains the youngest Nobel Laureate in Physiology or Medicine, receiving the Prize in 1923 at 32 years of age.

Prior to the discovery of insulin, a diagnosis of type 1 diabetes was a death sentence. Patients were typically pre-pubescent children presenting with weight loss, excessive thirst, hunger and glucosuria. The only effective treatment was a calorie-restricted diet that starved the body of carbohydrates that fueled the hyperglycemia and coma that inevitably preceded death. Intensive research in the three decades preceding Banting’s work identified the islets of Langerhans in the pancreas as the source of the internal secretion believed to regulate blood glucose.

Several research groups had demonstrated the ability of crude extracts of pancreas to reduce glucosuria in diabetic dogs, but the side effects resulting from impurities in the extract precluded progression to clinical trials.

Macleod, an expert on carbohydrate metabolism, was attracted to Banting’s skills as a surgeon, clearly a considerable asset when applied to grafting. Macleod supplied Banting with a laboratory, dogs, and an assistant, undergraduate student Charles Best. The promising results of the early experiments encouraged Macleod to extend funding, and to recruit biochemist James Collip to oversee the successful purification of the internal secretion, which MacLeod named insulin from the Latin, insula, meaning island, referring to the pancreatic islets.

A discovery is a lesser achievement than an invention, the former requiring a “find” of an existing entity, whereas the latter requires creation. Inventions are considered the pinnacle of scientific achievement, since they originate in the imagination of an individual(s), without whose insight they would not exist, such as Einstein’s theory of relativity or Darwin’s theory of evolution by natural selection.

The discoveries of insulin and the structure of DNA were areas of intensive research, and had Banting et al, and Professor James Watson and Professor Francis Crick failed in their endeavors, others would rapidly have succeeded, in the case of insulin within a few years and with DNA likely within a year.

Among the relatively recent medical discoveries including the smallpox vaccine, antibiotics, anesthesia, oral contraceptives and chemotherapy, the discovery of insulin was the most accessible of the low-hanging fruit. It was based on a straightforward premise understandable by any competent researcher: the islets of Langerhans in the pancreas produce the internal secretion (insulin), which controls blood glucose levels. Given that hyperglycemia resulting from insufficient pancreatic insulin production is the cardinal feature of diabetes mellitus, judicious preparation of pancreatic extracts would isolate insulin, which could be used to treat diabetic patients. The relative simplicity of the idea and the urgent need to develop effective therapies to treat diabetes attracted up to 400 research groups by 1920, who attempted isolation of insulin. They all failed. A confounding factor, accepted by many contemporary researchers, was that the external secretion degraded the insulin, accounting for its unpredictable potency, thus a means of isolating the insulin from the external secretion was required before the purification process could be applied to homogenized pancreas. This concept was wrong, as the external secretion was stored in the pancreas in an inactive form, but it led to delays in progress as researchers tried in vain to develop methods for removing the external extract.

This brief account glosses over the incompetence, failure, ignorance, conflict, misunderstanding, suspicion, fear and finally triumph that defined the project. The core conflict lay in Banting’s belief that Macleod was taking undue credit and stealing his data. While it was true that Macleod did not carry out any of the experiments, he did fund, support and advise on the project and was justified in referring to “our” experiments when presenting the data at conferences.

This transformed Banting’s already heightened feelings of simmering resentment into hatred and relations within the group were irrevocably damaged. The final insult to Banting’s already fragile ego was Collip’s rapid success in purifying the extract where he and Best had failed. Controversy relating to Nobel Prize awards is common, but it is unusual that a nominee threatens to refuse the prize in protest to sharing the award with a colleague. Banting would rather sacrifice the most prestigious award in science than share it with the charlatan Macleod. Wiser counsels soon prevailed and for the sake of the reputation of the University of Toronto he accepted the award, sharing half of his prize with Best.

What is Banting’s legacy? He is often described as a country boy who had difficulty adapting to cosmopolitan city life. He was also a decorated war hero who selflessly dedicated himself to helping his fellow soldier. Although naïve as a researcher he struck gold with his idea about diabetes, which precipitated the discovery of insulin. However, he was unable to rejoice in his discovery and the countless lives it saved, and later became frustrated with his inability to reproduce his success in the field of cancer research. He died in a plane crash on a secret military mission to England in 1941 as part of a study on aviation medicine.

We think of Frederick Banting in the following context. Images of diabetic patients in Toronto prior to the introduction of insulin still have the power to shock, as current patients receive treatment before they reach such a wretched and emaciated state. The resurrection of Teddy Ryder and Elizabeth Hughes, among the first diabetic patients successfully treated with insulin, is a testament to its life-saving effects. No patient in 1922, their families, or the embattled doctors treating them would argue that insulin therapy was anything other than a miracle.

(Dr Amit Saraf MD FRCP (London, Edinburgh, Glasgow) FACP (Phily) FICP FCPS

Director Internal Medicine Jupiter Hospital)