In human physiology, the endocrine glands act by releasing chemical messengers called hormones. They are produced in extraordinarily small quantities, ranging from 10⁻⁹ to 10⁻¹² grams. They travel through the bloodstream to influence distant organs and tissues, guiding bodily functions. Nervous and endocrine systems carry out a common mandate: to transmit the brain’s instructions to peripheral organs and tissues. Unlike the nervous system, which operates through a network of neurons, the endocrine system executes the brain’s orders across the body without an anatomical network. 

The pancreas holds a unique position as both an endocrine and exocrine organ. It plays an important role in managing blood sugar levels through insulin. 

Type 1 diabetes mellitus (T1DM) is an autoimmune disease where the immune system attacks insulin-beta cells in the pancreas, leading to high blood sugar resulting from insulin deficiency. Unlike type 2 DM, which is common in adults, T1DM often affects children and young adults. Globally, around 9 million people have T1DM. The incidence in India is 4.9 per 1,00,000 annually, as per information from the PIB in 2022. The exact cause remains unknown, but genetic and environmental factors, including viral infections, are suspected.

The fight against type 1 diabetes

Humans were fighting this illness until the last century without a clue. Symptoms of diabetes like excessive thirst, frequent urination, and “sweet urine” associated with the disease were found in all major civilisations. It was not until the mid-19th century that meaningful progress began, to decrypt the mystery. In 1869, Paul Langerhans discovered specialised clusters of cells within the pancreas — later known as the “islets of Langerhans” — and discovered the endocrine role in this organ. 

In 1889, German physiologists Oskar Minkowski and Joseph von Merin experimented by surgically removing the pancreas from a healthy dog to investigate its role in digestion. Post-surgery, they observed that the dog developed symptoms characteristic of diabetes, notably, elevated blood sugar levels and the presence of sugar in the urine. This experiment established a direct link between the pancreas and blood sugar regulation. Despite these insights, between 1890 and 1920, several researchers tried, with many unsuccessful attempts, to discover the pancreas’s role in diabetes.

Breakthrough at University of Toronto

After serving as an orthopaedic surgeon in the First World War, Frederick Banting returned to Canada as a war veteran. Driven to pursue research, he approached John Macleod, head of the physiology department at the University of Toronto, in 1920, with the idea of identifying the pancreatic secretion responsible for carbohydrate metabolism. Macleod, though hesitant, provided laboratory space and assigned Charles Best, a medical student, to assist him. Together, Banting and Best conducted experiments on dogs, leading to the successful isolation of insulin from the islets of Langerhans. 

James Collip, a biochemist, played another important role in the practical application of insulin therapy. In 1921, he joined Banting and Best at the University. While Banting and Best had successfully extracted insulin, their preparations were impure and caused adverse reactions in patients. Collip developed a method for purifying insulin, removing toxic impurities, and ensuring its safety and efficacy, as the insulin was prepared mostly from dogs and cows. This was crucial as without Collip’s efforts, insulin could not have been administered to patients, and Banting’s discovery might have remained theoretical. 

The first injection of insulin

On January 11, 1922, Leonard Thompson, a 14-year-old boy with diabetes, became the first person to receive an injection of insulin. Unfortunately, the initial extract was impure, leading to an allergic reaction and minimal reduction in blood glucose levels. Recognising the need for improvement, Collip refined the purification process, producing a more potent and safer insulin extract. A second injection on January 23, 1922, resulted in a significant drop in blood glucose without adverse effects, marking a milestone for humanity.

In 1923, the Nobel Prize in Physiology or Medicine was awarded to Frederick Banting and John Macleod for discovering insulin, a rare instance of the prize being granted so soon after discovery. Macleod provided Banting with laboratory space and assigned an assistant. However, the award sparked controversy as Banting felt that Best, who had been instrumental in the research, deserved recognition instead of Macleod. Conversely, Macleod believed Collip, who refined the insulin extraction process, deserved credit. In response, Banting shared half of his Nobel Prize money with Best, and Macleod did the same with Collip. Decades later, the Nobel Committee acknowledged the oversight in not including Best, expressing regret for his exclusion from the original award.

Despite these conflicts, Banting, Best, Macleod, and Collip got to share their prize money among themselves. In a remarkable gesture, Banting sold the patent rights to the University of Toronto for just $1, ensuring that insulin could be produced widely and remain affordable.

Recombinant DNA Technology

Collip’s extraction techniques to purify insulin were viable for human use but not scalable for mass production. As diabetes cases increased since then, it became clear that a more efficient method was essential. Enter recombinant DNA technology in the 1980s: scientists developed a method to insert the human insulin gene into Escherichia coli bacteria using plasmids — small DNA molecules capable of self-replication. This approach enabled bacteria to produce large quantities of insulin identical to that made by human bodies. The recombinant process allowed for mass production to keep up with the demand. 

In 1989, Her Majesty Queen Elizabeth kindled the Flame of Hope in Sir Frederick G. Banting Square, London, Ontario, Canada, to honour Dr. Banting’s discovery of insulin. This eternal flame stands as a hope for millions affected by diabetes worldwide, representing the commitment to continue research until a definitive cure is found. 

The flame will remain lit until a cure is discovered. As we consider Banting’s legacy, we realise that insulin is not a cure but a treatment, allowing people with diabetes to live near-normal lives. His spirits might be happier when the flame of hope is extinguished after discovering a cure.

(Dr. C. Aravinda is an academic and public health physician. The views expressed are personal. aravindaaiimsjr10@hotmail.com)