Inside the Story: The Discovery of Insulin

The Intrigue Behind the Discovery and Early Use of Insulin!

By Dace Trence, MD, FACE

So much of what we are told about discoveries is a simplified version of what really happens in the scientific world. Scientists are human, just like the rest of us, and the path to discovery can be a very interesting story that shows just how human scientists are.

Such a story lies behind the discovery of insulin and its’ travels to market—a drug that we all tend to take for granted in the world of diabetes!

Elizabeth Hughes was a cheerful, pretty little girl who grew up in the early 1900s. She had straight brown hair and a large interest in birds. She was diagnosed with diabetes when she was 11. Doctors started her on the Dr. Frederick Allen diet, the only treatment for diabetes mellitus type 1 at that time. The diet was basically a starvation diet. She started to lose weight and got to 65 pounds, then to 52 pounds, then to only 45 pounds after a dangerous episode of diarrhea. And she was 5 feet tall! She had survived on the diet for three years—far longer than her doctors had predicted—but she was getting sicker. Then her desperate mother heard some incredible news: insulin was tested in Canadian dogs with diabetes and they recovered from near death!

Who was the scientist who tested insulin in the dogs? It was Frederick Banting, a very awkward Ontario farm boy. He graduated from medical school as an average student and began working in a laboratory at the University of Toronto. During a very hot summer in 1921, Banting and his assistant Charles Best experimented on diabetic dogs, with dismal results. But when they got to dog number 92, a yellow collie, she jumped off the table after an injection of pancreas extract and began to wag her tail.

Dr. Banting’s mentor and lab director, Dr. John J.R. Macleod, had spent the summer in Scotland. Macleod returned to Toronto in the fall of 1921, rested and refreshed from his vacation, and reviewed the exciting research from Banting. A strain in their relationship began and resentment developed between student and mentor. This hostility lasted years, even after the Nobel Prize ceremony in 1923, which Dr. Banting refused to attend because he would not share the stage with Macleod.

Another researcher of insulin was James Collip, a professor of physiology and biochemistry. He offered to help Banting and Best to identify and purify whatever in the pancreas was the active treatment agent. As time progressed, Collip and Macleod became closer, mostly in discussions but then in actual lab work. When Banting and Macleod were awarded the Nobel Prize, Banting insisted on sharing his prize with Best, and Macleod shared his with Collip.

Elizabeth Hughes had a significant advantage. She was the daughter of Charles Evans Hughes, a member of the US Supreme Court. When Elizabeth’s mother pleaded for insulin for her daughter, Dr. Banting replied initially that no insulin was available. His team was having trouble making enough for patients who needed it in Canada.

But Banting changed his mind. So, Elizabeth received her first insulin injection in Toronto. Was it due to Justice Hughes, her father, who was nicknamed “the bearded iceberg”? Or did others intervene? We can only guess!

The Miracle of Insulin
By Donald A. Bergman, MD, MACE

Few discoveries of the last century had as dramatic an impact on the lives of suffering children and adults as the discovery of insulin. The discovery of insulin, and the techniques required to mass produce it, stopped the slow painful death that was unavoidable in Type 1 Diabetes and allowed patients with this previously dread disease to lead long productive lives. An exhibit at the New York Historical Society highlights those involved in the discovery and production of this life saving drug and the patients whose lives were saved in those early years. Elizabeth Mudge was one of the few adults treated. She was a nurse who was described by her physician Dr Joslin as ‘....just about the weight of her bones and a human soul”. After starting insulin she underwent a dramatic recovery and went on to a long career working with diabetic patients, helping to restore them to good health and teaching them about healthy living. Elizabeth Hughes, the daughter of Secretary of State Hughes, was one of the first from the US to be treated. She lived into her seventies. She said “I don’t recognize myself when I look in the mirror.”

And rather than being an advocate for the treatment of diabetes mellitus, Elizabeth Hughes shied away from the headlines that made her the most famous diabetic child in the United States. Before she died in 1981 at the age of 74, she destroyed material documenting her illness, removed all references to her diabetes from her father’s papers, and occasionally was known to even deny she had been ill as a child. She did not even share her medical information with her fiancé until a week after their engagement. But without mass production of insulin, little could be accomplished. The tedious process of initially purifying insulin from animal pancreases could not possibly supply the large need for ongoing available insulin. Eli J. Lilly and Company, the Indianapolis drug firm, won the right to mass produce insulin in the United States. It was the first partnership negotiated among university circles, individual physicians, and the drug industry, facilitated by a research chemist George Clowes who worked at Lilly. August Krogh wanted to produce insulin in Denmark. In1920 he won the Nobel Prize in physiology and medicine and he was motivated by his wife Marie’s battle with late-onset of diabetes. He traveled to Toronto to obtain permission to produce insulin in Europe. In 1923 he joined forces with Dr. Hans Christian Hagedorn, a specialist in regulating blood sugar, and pharmacist August Kongsted. They founded the not-for-profit company Nordisk Insulinlaboratorium. Because Denmark had abundant bacon factories, pork pancreases were easy to obtain and “insulin-Leo” came on the market. In 1925, two brothers who had both worked at Nordisk Insulinlaboratorium founded Novo Terapeutisk Laboratorium. Novo Nordisk was formed in 1989 when the two companies came together. Although animal insulin is similar to human insulin, they are slightly different. To produce human insulin researchers have been using recombinant DNA technology for more than 25 years. This method is more reliable and sustainable. Today, different types of insulins with different durations of action are available. As a result, individuals with diabetes are able to control their blood sugars much better and live a healthier life!

Dr. Dace Trence is Director of the Diabetes Care Center and Associate Professor of Medicine at the University of Washington Medical Center in Seattle. She is also the University of Washington Endocrine Fellowship Program Director and Director of Endocrine Days, a medical education program for endocrinologists practicing in the Pacific Northwest. She is on the Board of Trustees for the American College of Endocrinology, chairs the AACE CME committee and is co-editor of EmPower Magazine.