The discovery of insulin was one of the most dramatic and important milestones in medicine - a Nobel Prize-winning moment in science.
Witnesses to the first people ever to be treated with insulin saw "one of the genuine miracles of modern medicine," says the author of a book charting its discovery.1
Starved and sometimes comatose patients with diabetes would return to life after receiving insulin.
But how and when was the discovery made, and who made it?
How and when was insulin discovered?
The discovery of insulin did not come out of the blue; it was made on the back of a growing understanding of diabetes mellitus during the nineteenth century.
Experiments involving the pancreas were key to the discovery of insulin. The beta cells of the pancreas that produce insulin were discovered in 1869.
Diabetes itself had been understood by its symptoms as far back as the 1600s - when it was described as the "pissing evile" - and the urination and thirst associated with it had been recognized thousands of years before.
A feared and usually deadly disease, doctors in the nineteenth century knew that sugar worsened diabetes and that limited help could be given by dietary restriction of sugar. But if that helped, it also caused death from starvation.
Scientists observed the damaged pancreases of people who died with diabetes. In 1869, a German medical student found clusters of cells in the pancreas that would go on to be named after him.
Paul Langerhans had discovered the beta cells that produce insulin.
Other work in animals then showed that carbohydrate metabolism was impossible once the pancreas was removed - the amount of sugar in the blood and urine rose sharply, and death from diabetes soon followed.
In 1889, Oscar Minkowski and Joseph von Mering removed a dog's pancreas to study its effects on digestion. They found sugar in the dog's urine after flies were noticed feeding off it. In humans, doctors would once have diagnosed the condition by tasting the urine.
But as for the discovery of the "active ingredient" of the pancreas, numerous scientists followed the work of Minkowski and von Mering in their attempts to extract it.
Between 1914 and 1916, it was the Romanian physiologist Nicolas C. Paulescu who first extracted a pancreatic antidiabetic agent that treated dogs - but his experiments would be overlooked in favor of work by other scientists.
Banting, Best, Collip and Macleod
It was in 1921 that Canadian physician Frederick Banting and medical student Charles H. Best would be credited with discovering the hormone insulin in the pancreatic extracts of dogs.
Banting and Best injected the hormone into a dog and found that it lowered high blood glucose levels to normal. They then perfected their experiments to the point of grinding up and filtering a dog's surgically tied pancreas, isolating a substance called "isletin."
The pair then developed insulin for human treatment with the help of Canadian chemist James B. Collip and Scottish physiologist J.J.R. Macleod.
Macleod had been impressed with Banting and Best's work but wanted a retrial of the evidence. He provided pancreases from cows to make the extract which was named "insulin," and the procedures were repeated. Collip's role was to help with purifying the insulin to be used for testing on humans.
Ultimately, the first medical success was with a boy with type 1 diabetes - 14-year-old Leonard Thompson - who was successfully treated in 1922. Close to death before treatment, Leonard bounced back to life with the insulin.
The news rapidly spread beyond Canada, and in 1923 the Nobel Committee decided to award Banting and Macleod the Nobel Prize in Physiology or Medicine.