Insulin at 100: a century of life-saving developments

2021 marks the centenary of the discovery of insulin, an achievement that ranks among the greatest discoveries in the history of medicine. Millions of people have survived and thrived thanks to the research conducted in Toronto in 1921 and the subsequent innovations in diabetes care that have helped people with the condition to live full and healthy lives.

Dr Richard Beaser is Medical Director of Continuing Medical Education at Joslin Diabetes Centre. His personal interest in diabetes began in childhood, through his father, Dr Samuel Beaser, a diabetes specialist who had decided to devote his professional life to the condition after reading the dramatic patient chart description of the race against time to get life-saving insulin for one of the first people with diabetes to receive it in 1922.

We spoke to Dr Beaser about the events that unfolded in Toronto in 1921, the key players involved and the significant developments in diabetes care that have occurred over the last century.

How was diabetes treated before the discovery of insulin?

Prior to the discovery of insulin, the treatment of diabetes was quite challenging. People affected might only live a year or two and were put on very strict diets with limited carbohydrates during that time. The most well-known of these diets was developed by Dr Frederick Allen, a physician based in New Jersey. Essentially, the Allen Diets were glorified starvation diets, consisting of a series of regimens with slightly different ratios of carbohydrates. They would keep people with diabetes alive for just a little longer than if they had followed a free diet. Unfortunately, people on the diets withered away and would typically die of ketoacidosis, particularly during the winter. The outlook for people with type 1 diabetes was therefore very grim before insulin was discovered.

Talk us through the discovery of insulin

The story of the discovery of insulin is very interesting. In the autumn of 1920, Frederick Banting, a young surgeon from London, Ontario (Canada), had the idea of an experimental procedure to ligate the pancreatic ducts and isolate the internal secretions. He took this idea to Prof. JRR Macleod at the University of Toronto. MacLeod was sceptical, but gave Banting the opportunity to work in his lab during the summer of 1921, and also assigned a young medical student, Charles Best, to assist him. During the summer, Banting and Best experienced a number of challenges trying to get the ducts ligated and extract the secretion they were looking for. They were ultimately successful and managed to keep several dogs with diabetes alive with injections of the internal secretion.

They communicated their excitement and results to Macleod, who was impressed and assigned the biochemist JB Collip to the team, in order to develop the extract further. By January 1922, Banting and Best were comfortable that the pancreatic extract they had discovered – which they called insulin – could potentially treat diabetes in humans. On January 23, they successfully administered insulin to Leonard Thompson, a 13-year-old boy with type 1 diabetes, who went on to live several more years thanks to his ongoing insulin therapy.

In January 1923, Banting, Best and Collip were awarded the American Patent for insulin, which they sold to the University of Toronto for the price of just one dollar. When asked why the team in Toronto did not seek more financial gain from their important discovery, Banting reportedly said, “Insulin belongs to the world not me.”

By the end of 1923, insulin had become available more widely thanks to increased production in Toronto and the start of production from companies such as Eli Lilly and Hoechst.

How would you rank the discovery of insulin in the list of scientific breakthroughs?

Ranking it is a little challenging, since many medical discoveries do not make immediate headlines, but are building blocks for subsequent developments. However, I think insulin deserves to be counted among the top scientific breakthroughs, especially if you consider how common both type 1 and type 2 diabetes are, and if you take into consideration the life-saving and life-enhancing effect that insulin has had for so many people.

How has insulin developed over the last 100 years?

Different kinds of animal-based insulins were developed over the next few decades following the discovery in Toronto. In 1936, the Danish pharmacologist Hans Christian Hagedorn developed an insulin with extended duration to limit the number of injections that people with diabetes required in one day. NPH (neutral protamine Hagedorn) and Lente insulins were subsequently developed in the 1940s and 50s, becoming the main intermediate insulins used, along with regular insulin taken during meals. The standard insulin regimen at that time (regular + NPH or Lente) approached the basal and bolus patterns that are now the norm.

In the 1970s, there was growing acknowledgement of the deficiencies of animal insulins. Firstly, their supply was not sufficient to meet the demand of the growing population of people living with diabetes. Secondly, animal insulins had many impurities, which affected the immune system, resulted in very irregular action and caused injection-site issues. Purity and reliability significantly improved with the development of synthetic insulins in the 1980s, which mimicked the structure of natural human insulin.

A number of short and very long-acting analogue insulins were developed subsequently and today we are heading into an exciting era of evolving insulins and technology to support their use, with possible future developments such as smart insulins that sense blood glucose levels and vary their actions accordingly.

What have been other important developments in diabetes care over the last 100 years?

Diabetes care has seen a number of very significant developments over the last century. In my opinion, the next very important advance after insulin occurred in the 1950s, when the first oral medications – sulfonylureas – were introduced to treat type 2 diabetes. People with this type of diabetes were not as acutely ill as those with type 1, and could hide in the shadows and not go for treatment because they did not want to have to take insulin, which was difficult at the time. A treatment that did not involve injections and controlled blood glucose reasonably well resulted in people running to their doctors to get it.

Another important development has been blood glucose testing. A first leap forward was the introduction of finger prick testing, using strips with chemicals on the tips. Blood glucose meters came next and offered more accurate measurements. A major breakthrough has been the development of continuous glucose monitoring (CGM), which I liken to the evolution from still photography to video. Finger prick testing is like taking a number of photographs during the course of a day to get an overall picture of blood glucose levels over twenty-four hours. CGM is similar to having a video constantly playing, providing a much better impression of what blood glucose patterns are doing over time. This helps healthcare professionals develop treatment programmes and, more importantly, offers people with diabetes real-time feedback on how their decisions affect their condition, allowing them to be more skilled at self-adjusting their treatment.

Insulin delivery has also advanced significantly from the glass syringes that were used initially. These required boiling before each use and therefore restricted the movement of people with diabetes. The introduction of disposable syringes, followed by insulin pens, have made delivery much more convenient. Now we have smart pens with computer technology that allow people with diabetes to calculate doses and keep logs of the insulin they are taking.

We are also one step closer to mimicking natural pancreatic action thanks to insulin pumps and their integration with CGM devices.

So, as we look back over the first century of pharmaceutical insulin, we can appreciate the progress made. Over the course of my 40-year career in the field of diabetes, I have seen the evolution of insulins from mixed beef/pork to synthetic analogues with customized characteristics. I’ve witnessed glucose monitoring go from crude urine testing strips through glucose meters and now continuous glucose monitors. I’ve seen insulin delivery go from injection by syringe to the hybrid closed-loop pumps, along with many other advancements and improvements to care. On the near horizon, we can anticipate improved insulins and pumps to allow a fully closed-loop insulin delivery system, as well as customised insulins that can be more responsive to physiological needs.

It is tantalising to speculate, should any of my grandchildren choose to go into the medical care of people with diabetes, what treatment tools and care capabilities they will have at their disposal a few decades from now. We can appreciate the present by observing the impact of the care we provide. However, to fully understand just how far we’ve come requires an appreciation of where we started from. Only then can we feel truly hopeful and excited about where we are going next.