Hunting Down a Mystery Chemical
In the fall of 1920, a young Canadian surgeon named Frederick Banting was preparing a lecture on the physiology of the pancreas, the carrot-shaped organ that sits next to the stomach. At the time, the pancreas was known to be important for the digestion of food molecules: digestive juices secreted from the pancreas into the small intestine contain enzymes that help break down carbohydrates, proteins, and fats. But scientists were learning that the pancreas has other functions as well. Experiments in 1890 had shown that surgical removal of the pancreas in dogs led quickly and inevitably to all the symptoms of severe diabetes: high blood-sugar levels, sugar in the urine, coma, and death. This finding suggested that the pancreas plays a critical role in the regulation of blood sugar.
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Until 1921, there was no effective treatment for diabetes, and a diagnosis was in essence a death sentence.
Scientists were beginning to suspect that the pancreas was essentially two organs in one: one part of the pancreas released digestive enzymes into the intestines through ducts, while another part, made up of discrete islands of cells, released an unidentified substance into the blood that regulated blood-sugar levels. A number of researchers had tried, unsuccessfully, to isolate this mystery chemical from these groups of cells (called islets of Langerhans after Paul Langerhans, who first noticed them under a microscope in 1869). So convinced were researchers that the substance existed that they gave it a name: “insuline”–from the Latin insula, meaning “island” (INFOGRAPHIC M7.1).
The notion that certain ‘internal secretions’ produced by glands in the body and released into the bloodstream could influence physiology was a relatively new idea at the beginning of the 20th century. Before that time, conventional wisdom held that physiological processes, like the regulation of blood sugar, were controlled primarily by the brain through nerves. But evidence was accumulating that blood-borne chemicals called hormones controlled a number of different physiological processes, including blood-sugar regulation. The study of hormones and the glands that produce them would come to be known as endocrinology.
Today we know that the body has numerous hormone-secreting glands, which together coordinate many physiological processes. The adrenal glands, located above the kidneys, for example, secrete the hormone adrenaline, which controls the “fight or flight” response; the ovaries and testes produce steroid hormones that control reproductive physiology; the thyroid gland, located in the neck, produces thyroid hormones, which regulate metabolism; and the pituitary gland in the brain produces several hormones that control glands and tissues throughout the body. All these hormones work in a similar fashion: they are released by glands into the circulation and carried in the blood to their target cells.
Banting knew about previous attempts to isolate a pancreatic hormone. While preparing his lecture on the physiology of the pancreas, he read an article in a medical journal describing how surgically tying off the main duct leading from the pancreas to the intestine led to the death of the enzyme-secreting cells of the organ, but left the “islands” unharmed. That’s when an idea came to him: perhaps other researchers had been unable to isolate insulin because, when they ground up the pancreas to perform the isolation procedure, the digestive enzymes that the pancreas produces destroyed the insulin. Perhaps he could avoid that problem by first performing surgery on an animal to tie off the pancreatic duct and then waiting for the enzyme-secreting part of the organ to die. He jotted down some hasty notes, then went to bed, but was so excited he was unable to sleep.
A few days later, Banting presented his idea to John Macleod, the head of the physiology department at the University of Toronto. Macleod listened patiently to Banting but was skeptical of his ideas, finding them not very well thought out and poorly researched. Macleod was aware that other researchers had tried and failed to isolate insulin and was doubtful about the new approach. But Banting was enthusiastic and persistent; eventually, he convinced Macleod to provide him with some lab space and 10 dogs on which to test his hypothesis. Macleod also agreed to appoint a graduate student, Charles Best, to assist him.
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