The history of insulin is a nice illustration of the role of serendipity in research, and also of how credit is not always distributed in accordance with the rules of fair play. Back in the mid 19th Century, diabetes was a very serious and uniformly fatal disease. Oskar Minkowski (left) a German physiologist, was studying the problem in Strasbourg. He was working with dogs and had a colony of animals, some of whom were diabetic. One of Minkowski's gofers, whose job included cleaning the kennels, noticed that flies were attracted to the urine of the diabetic dogs in great numbers, but not to that of normal dogs. Analysis of the urine showed it had a very high content of sugar.

He pointed this out to Minkowski, who promptly decided it was a phenomenon worth examination. By experiments with ligation and extirpation of the pancreas, and insertion of pieces of the excised material under the skin, he succeeded in demonstrating that 1) the pancreas was needed to prevent diabetes from occurring; 2) the removal of the pancreas caused diabetes; 3) whatever it was the pancreas made, it could be transferred to the animal without the ductwork, because explants prevented diabetes even in pancreatectomized animals. A dog with diabetes could be temporarily "cured" by subcutaneous implants of pancreatic tissue, and remained non-diabetic until the implant was removed or rejected.

It was an obvious step to determine what might be the source of the pancreatic anti-diabetes factor. The islets Langerhans had discovered many years before were a candidate for the source of this material. here. Later work by Minkowski and others demonstrated this to be the case: some chemicals (e.g., alloxan) specifically destroy islet cells. When treated with alloxan, animals become diabetic. Extracts of material from pancreas tissue could be shown to prevent diabetes from occurring in full form. These discoveries paved the way for treatment, if not a cure, for the disease: administration of exogenous insulin.

In the 1950's insulin, which was by then established as a major therapeutic agent, was the first peptide to be fully sequenced by Sanger and his coworkers. They won a Nobel Prize for this achievement. In the modern era of genetic engineering, insulin also happens to be the first artificially synthesized peptide to be licensed by the FDA for therapeutic use.

This long saga, the heroic achievements it involved, and the prizes and honor won by the participants came about because of a kennel keeper's offhand remark to his boss about flies and dog pee. Although most of the credit goes to the scientists who carried out the work, it was this man's curiosity and observations that set the process in motion. Today nobody even knows what his name was.

Lab Exercise List