Celebrating the centenary of insulin – how a life-saving medicine gave rise to 100 years of groundbreaking achievement

Before the 1920s, children with type 1 diabetes had a short life expectancy. The situation for those with adult onset wasn’t much better. Traditionally, the condition was often managed through harsh diets that avoided carbohydrates, leaving patients exhausted, with little muscle or body fat, and a poor quality of life.

Medical experts were aware of the links between diabetes and changes in the pancreas, but attempts to prepare pancreatic extracts to lower blood sugar levels were generally unsuccessful. Then, in 1920, a surgeon called Frederick Banting began developing his idea to isolate a little-known substance – insulin – that seemed to control metabolism.

Knowing he needed specific expertise, he turned to Prof John Macleod, chair of physiology at the University of Toronto, in Canada, for help. Macleod recommended the services of a research assistant, Charles Best, as well as providing access to a laboratory and equipment. By 1921, Banting, Best and Macleod had figured out how to isolate insulin, and believed they knew how to use it.

Boy survivor
With the help of the biochemist James Bertram Collip, the researchers produced more insulin, which they used on the first human patient in 1922. Fourteen-year-old Leonard Thompson had been drifting in and out of a diabetic coma in Toronto general hospital, but he quickly rallied after being injected with insulin. Although he would be dependent on injections for the rest of his life, he was able to go home within a matter of weeks, something that was previously unthinkable.

“One of the most dramatic moments in the history of medicine happened right here,” says Dr Kevin Smith, president and CEO of University Health Network, Canada’s largest research hospital network, which includes the Toronto general hospital. “Diabetes was once a death sentence. But the story of Leonard Thompson changed everything and gave hope to families the world over. We are extremely proud of this legacy.”

The success of this treatment earned Banting and Macleod a Nobel prize in 1923, and the discovery has benefited millions of people with diabetes ever since.

The work of the researchers at the University of Toronto was a gamechanger for medical science, but the story doesn’t end there as the institution has continued to make groundbreaking medical discoveries and innovations ever since. “Insulin focused the eyes of the world on Toronto,” says Meric Gertler, president of the University of Toronto. “And marked a culture of discovery, innovation and collaboration that has transformed healthcare and continues to generate beneficial ripples worldwide.”

After the development of insulin, the University of Toronto’s Connaught Medical Research Laboratory, established in 1914, started to manufacture and distribute the substance around the world. By 1923, the lab was producing more than 250,000 units of insulin a week. This success meant the lab could expand its remit, which allowed it to make exceptional progress in developing antitoxins and vaccines over the following decades.

Then, in the 1970s, the university sold the laboratory for $29m, a payment that became the foundation for the Connaught Fund, now worth $135m (£72m), an internal funding programme designed to spur on the next generation of discoveries by researchers, both emerging and established. According to its website, “more than $174.8m” has been awarded to researchers since its inception, and much of this work has strongly emphasised interdisciplinary approaches and innovations, especially those addressing global challenges.

Other discoveries have included a range of effective drugs, such as those that tackle type 2 diabetes. These drugs, broadly referred to as insulin mimetics, have revolutionised the treatment of the condition and grew out of research conducted at the university since the 1980s.

Lucky break
The institution has also played a pioneering role in the field of regenerative medicine, a blanket term used to describe the study of molecular, cellular, and developmental processes that control the growth of new, healthy tissue. In 1961, at Princess Margaret hospital in Toronto, the haematologist Ernest McCulloch and biophysicist James Till conducted experiments on irradiated mice that proved the existence of stem cells, which can become any type of blood cell. This discovery not only proved the existence of stem cells – cells that self-renew for various purposes – it also served as the foundation for bone marrow transplantation.

Later findings at the university include identifying stem cells in the pancreas and retina, as well as cancer stem cells associated with brain tumours, colorectal cancer and leukaemia.

The University of Toronto has also been a key player in developing precision medicine, a burgeoning field that treats and prevents disease using a patient’s genetic information, environmental data, lifestyle, and other factors. Among its notable contributions was the isolation of the genes responsible for Fanconi anaemia in 1978, a rare blood disease that prevents bone marrow from producing enough new blood cells.

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In 1989, a team of scientists headed by Lap-Chee Tsui identified the gene that causes cystic fibrosis – the cystic fibrosis transmembrane conductance regulator (CFTR) – which shone light on the underlying disease mechanism. The discovery was considered the most significant advancement in human genetics at the time. By 1995, scientists at the university’s Centre for Research in Neurodegenerative Diseases had identified two defective genes that caused early-onset forms of Alzheimer’s (presenilin 1 and presenilin 2). In 2007, they discovered another gene (SORL1) that is associated with the degenerative disease. The University of Toronto launched the Precision Medicine initiative (PRiME) in 2019, aiming to unite the cutting-edge work being conducted on precision medicine at the institute and give it a central focus for future challenges.

“Insulin is a story of pursuit and perseverance, but also of measured observation and collaboration at many steps along the way,” says Trevor Young, acting provost of the University of Toronto and dean of the Temerty Faculty of Medicine. “Its discovery, and the many other gamechanging advances in human health that have happened at the university over the past century, speak to our belief in curiosity-driven research and our commitment to powering the drive for the ‘next insulin’.”

With these developments and their future ambitions, there is every reason to believe that the next century for this prestigious university will be just as innovative.

Dr Russell Moul holds a PhD in the history of colonial science and medicine and medical ethics