“To study the phenomena of disease without books is to sail an uncharted sea; while to study books without patients is not to go to sea at all.”
– Sir William Osler –
Aetiology concerns what causes a disease. You know this bit – it’s the sieve!
Fred Banting (pictured above) had grown up on a farm in Canada. Directly after medical school, he went to serve in World War I and was awarded the Military Cross after selflessly treating injured soldiers under conditions of personal injury and great danger. Banting later specialised in orthopaedic surgery. Business was slow, however, and he was forced to take a job demonstrating at a medical school where one day he was required to give a lecture on the pancreas. Not knowing much at all about the pancreas, Banting went to the library to do some reading. There he found a recent article noting that when the ducts of the pancreas were blocked, the whole organ would shrivel apart from the Islets of Langerhans. What is more, diabetes would not develop unless these cells were also destroyed. This mysterious observation kept Banting awake that night, until at 2am, he leapt out of bed and scribbled the following words in his notebook: “Diabetus; Ligate pancreatic ducts of dogs. Keep dogs alive till acini degenerate leaving Islets; try to isolate the internal secretion of these to relieve glycosurea.” (The spelling errors are his.)
Banting took the idea to MacLeod, a Professor of Physiology in Toronto, who gave him use of an aging unused laboratory and an assistant. This assistant was decided, by the toss of a coin, to be the young biochemistry and physiology graduate, Charles Best. After much hard work (with no salary) the two proved Banting’s late-night insight. First, they made dogs diabetic by removing their pancreases, then painstakingly kept them alive by extracting fluid from the Islets of Langerhans of healthy dogs and injecting it into the diabetic dogs. One favourite dog of the researchers, Marjorie, was kept alive for 70 days. Recognising the importance of the discovery, MacLeod enlisted the help of the expert chemist, James Collip, who helped extract a reasonably pure form of insulin from slaughterhouse cattle – an idea that Banting got from his boyhood on the farm. The extract was tested on a diabetic teenager in hospital who underwent such a dramatic improvement that word spread like wildfire and just one year later, insulin was widely available and saving many lives. The Nobel Prize was awarded to Banting and MacLeod in 1923, however Banting was furious that MacLeod had received so much credit, and declared he was sharing his Prize with Best. A few days later, MacLeod declared he was sharing his with Collip.
Many years later, type I diabetes was distinguished, and it was further clarified that the aetiology of pancreatic cell destruction was immune-mediated.
Before the discovery of insulin, diabetes mellitus was a merciless disease. The diagnosis meant an agonising death sentence for the unfortunate patient, who wasted away while suffering a voracious thirst and appetite. For many years, the cause of diabetes defied all explanation. A breakthrough came in 1889, when the German Paul Langerhans associated the disease with damage of specific cells found only in the pancreas. Other scientists found that when the pancreas was removed, diabetes resulted. However, the discovery of insulin had to wait until 1921, and the work of Banting and Best.
The Cause of Diabetes and the Discovery of Insulin