A Brief History of Insulin

How Was Insulin Discovered?

insulin(65836)Credit: Wikipedia

If Otto Folin of Harvard had solved his test for blood sugar in 1908 instead of 1913, insulin could have been in use 14 years earlier.  History, including medical history, is as full of bitter ironies as it is of happy accidents. Insulin, or something a lot like it, was drawn out from the pancreas in 1908 by a German scientist, Georg Zuelzer. This extract was injected into numerous dogs and the unlucky animals died. Zuelzer, unable to know exactly why the dogs died, determined that the substance was too dangerous.

A test would have exhibited that the insulin extract had induced so rapid a drop in blood-sugar that the dogs endured extreme insulin shock. Even without the blood-sugar test, had Zuelzer used diabetic rather than healthy dogs in the tests, his extract would have developed relief of symptoms instead of shock. And Zuelzer would today be among medicine's immortals, not an obscure scientist whose name is all but forgotten.

Still a different rendezvous with immortality ended in a close call when Israel S. Kleiner of New York and J. R. Murlin of Rochester, N. Y., Developed an insulin extract. As with Zuelzer, the blood test that would have shown the significance of the work wasn't yet available.

A lot of researchers had already helped pave the way when Frederick G. Banting came upon the scene.  Minkowski and von Mering had established in 1889 that the removal of the pancreas caused a diabetes-like disease in a dog.  In 1900, Opie of Johns Hopkins had described that in diabetics, there was degeneration in the islets of Langerhans, those inscrutable small cells in the pancreas.

Then, in 1916, Sir Edward Sharpey-Schafer contemplated that the islets of Langerhans produced a substance without which diabetes would build up. This was the mysterious "X" that scientists were debating about with great heat; some feeling that it existed and was involved in diabetes; other asserting that there was no such substance. Allen, of Allen diet fame, was prominent among those who opposed the possibility of "organ therapy" and felt that there was nothing inside the pancreas that can be used to treat diabetes.

Piece by piece, the evidence proceeded to mount. There had to be something in the pancreas, most probably in the islets of Langerhans, that somehow had a part in the onset of diabetes. Thus the stage was set for Frederick G. Banting of Canada. In 1920, he was a young orthopedic surgeon who found it so difficult to make a living at his profession that he took up part-time teaching at the Western Ontario Medical School.

One evening, while he was setting up a lecture to be given the next day, he got a copy of a medical journal and was drawn in by an article written by Moses Barron. What he read transformed him from a demoralized young doctor into an inspired researcher. Barron had written that when gallstones choked up the pancreatic ducts, the part of the pancreas that produced the digestive juices shrank—but the islets of Langerhans were unharmed. Moreover, wrote Barron, when dogs had their pancreatic ducts tied off the same thing occurred. The part of the pancreas that made the digestive juices degenerated, but the islet cells proceeded to function and the dogs lived.

Banting thought of Minkowski's work. If the whole pancreas were taken away the dog died of diabetes. Now Barron seemed to provide the final clue. Where the whole pancreas was destroyed except the islets of Langerhans, the dogs did not get diabetes and die. Therefore, there had to be something in the islets of Langerhans which, if removed, produced diabetes and death.

The next step was to access this mysterious substance. Barron had shown the way here too. By tying off the pancreatic ducts of dogs for six to eight weeks, the regular pancreatic tissue would degenerate. Then, taking out what was left and making an extract of the still-functioning islets, Banting should have the answer.

Banting won over Professor MacLeod of the University of Toronto Medical School that he had a promising approach to the diabetes problem. Having MacLeod's backing and blessing, as well as the facilities of his lab, Banting went to work. As an assistant, Banting had a second-year medical student, Charles H. Best, who had, literally, tossed a coin with another student for the job.

It was a gloomy, heartbreaking task. Failure followed failure. Then, one day in July, 1921, just as they were seesawing on the threshold of defeat, came the first gleam of possible success. Another in a long series of extracts was produced and injected into a diabetic dog —and this time the dog miraculously improved. Then it became sick once more and died.

Why should the animal die? The answer looked clear. One dose of insulin wasn't enough. The dog had to receive a steady supply of the mysterious substance its very own missing pancreas can no longer give.

Banting and Best(65837)Credit: Wikipedia

In January, 1922, after several more setbacks, Banting and Best accomplished what looked like an actual experimental success. They were treating a dog—part collie and part just dog—who was diabetic and should have been dead long since. But the dog, a female, was alive and frisky.  The extract worked.  Banting and Best were set for the really decisive test—on a human being. The human guinea pig was Joe Gilchrist, one of Banting's childhood friends. Gilchrist had life-threatening diabetes; and the Allen diet, though it kept him alive, had brought him down to a scant shadow of life.

And on February 11, 1922, Joe Gilchrist became the first diabetic human being to get an injection of insulin. He waited, waited—and then he felt a surge of new life pour all over him. The rest is medical history.