Ninety years ago, the hormone that has saved the lives of millions of people with diabetes was uncovered in a tiny laboratory just outside of Toronto, Canada. Liz Bestic reports on the discovery of insulin
Today, it is hard to believe that prior to the discovery of insulin, a diagnosis of Type 1 diabetes was a death sentence. But, previously, the only way to control diabetes had been through a diet extremely low in carbohydrates and sugar, and high in fat and protein – this only usually gave people a year to live, and many died of starvation before then.
It was established in the late 19th century that there was a connection between the pancreas and diabetes. In 1889, scientists Oskar Minkowski and Josef von Mering, while studying fat metabolism, discovered, by chance, that removing a dog’s pancreas caused diabetes in the animal.
Further research suggested that the pancreas must have at least two functions: to produce digestive juices and to secrete a substance that regulates blood glucose. Then, in 1869, medical student Paul Langerhans discovered that within the pancreatic tissue that produces digestive juices, there were clusters of cells whose function was unknown.
In 1893, Gustave Laguesse suggested that these cells, which he named the ‘islets of Langerhans’, produce the glucose-regulating substance later known as insulin. Over the following 30 years, scientists attempted to isolate and extract the substance which was to hold the key to treating diabetes, but failed.
Then, in October 1920, Canadian surgeon Frederick Banting approached John James Rickard Macleod, Professor of Physiology in Toronto, with a new research idea. He suggested that the pancreatic digestive juices were destroying the substance produced by the islets of Langerhans before it could be found.
Banting intended to stop the pancreas from working but keep the islets of Langerhans functioning in order to locate the elusive secretion. Macleod first scoffed at this idea, but eventually provided Banting with a sparsely equipped
laboratory, medical assistant Charles Best and 10 dogs on which to perform experiments.
The two scientists began their experiments in May 1921 and made quick progress. They surgically stopped the flow of nourishment to a dog’s pancreas so that it lost its ability to secrete digestive juices (in order to isolate the glucose regulating substance). They then removed the dog’s pancreas, chopped it up and froze it in a mixture of water and salts. When half-frozen, the pieces were ground, filtered and named ‘isletin’.
The next step was to inject isletin into the dog that had diabetes (due to having its pancreas removed). The canine’s blood glucose level dropped and it became healthier and stronger. The men continued giving the dog a few injections a day and reported that it remained free of symptoms.
Banting and Best repeated the experiment several times. The results were the same, but there were some problems due to the varying purity of the isletin. To solve this problem, Macleod enlisted biochemist James Collip to help with purification, and the team renamed the substance ‘insulin’, from the Latin word for island, ‘insula’.
Time to test
By late 1921, the team had conclusively proved that diabetes was a condition brought on by insulin deficiency – it was time to test the new substance, derived from a cow’s pancreas, on humans. Leonard Thompson, a 14-year-old diagnosed with Type 1
diabetes in 1919, was the first person to be successfully treated with the new wonder drug.
In 1923, Banting and Macleod were jointly awarded the Nobel prize for Medicine. Banting, however, felt that the prize should have been shared between himself and Best, so he gave credit to his assistant by sharing his cash reward with him. Macleod did the same with Collip.
Banting and his team patented their insulin extract, but gave away all rights to the University of Toronto, which later used the income to fund further research into insulin. Soon after, medical firm Eli Lilly began large-scale production of the extract.
In 1963, researchers managed to produce insulin chemically in a laboratory, but they could not make enough for it to be viable. At that time, insulin was extracted from pigs and cattle, and though animal insulin worked well, it was not an exact match with the human hormone and sometimes caused adverse reactions, such as skin rashes.
In 1977, researchers succeeded in manufacturing human insulin, by inserting the genes that code for human insulin into bacteria and yeast cells. This allowed its production on a much bigger scale.
The resulting commercial product, brand-named Humulin, revolutionised the treatment of diabetes as it caused fewer side effects. While Best continued to have a successful career, Banting’s life was cut tragically short when he died in a plane crash at the age of 41. But his legacy lives on, and millions of people with diabetes worldwide continue to live long and healthy lives as a result of his team’s discovery.
Read about Leonard Thompson