Who Done It? The Discovery of Insulin

My friend Midge would have celebrated her 61st birthday on May 25, just a few weeks from now.  However, Midge passed away almost three years ago after a decades’ long fight against diabetes.  Despite her own struggles, Midge devoted herself to helping everyone else.  After my daughter was hit by a car, Midge walked miles to the hospital. She drove me back from the hospital when I flipped my mini-van.  Even with failing eyesight, Midge insisted upon not just attending my mother’s funeral but traveling to the burial thirty miles away.  As her eyesight deteriorated, so did Midge’s balance and mobility.  She suffered from diabetic neuropathy, nerve damage that affected her feet, and she had wounds that just would not heal. For years insulin had prolonged Midge’s life, until it didn’t.  There was no one who was a better friend.  She left a hole, and I miss her every day.

Had Midge been born even 35 years earlier, she would have survived only a year or two after her diabetes was diagnosed.  The prevailing treatment for diabetes in 1920 was a starvation diet.  Patients consumed as few as 750 calories a day and progressively weakened.  We owe thanks to the discoverers of insulin that we had Midge for so long.

Insulin was discovered in 1922. Its discovery was simultaneously stirring and ugly, stirring because the discovery immediately commuted death sentences of thousands of diabetes sufferers around the world, ugly because of the battle for credit launched by one of the team of scientists, Frederick Banting, who insisted that the discovery was all his, with a bit owed to  his student assistant, Charles Best.

The discovery of insulin illustrates how much scientific discovery is actually a cumulative process.  Before insulin could be discovered, scientists had to figure out that diabetes was caused by a malfunction in the pancreas.  Scientists needed to discern that the pancreas made two secretions: one a digestive enzyme and a second one thought to have a connection to diabetes.  They needed to locate the specialized cells in the pancreas known as the isles of Langerhans. Endocrinologists needed to devise a method for treating hormonal deficiency; just as a thyroid deficiency could be treated with thyroid, scientists began to theorize that diabetes could be treated with a pancreatic extract.  Blood tests needed to be developed that could accurately measure blood sugar and that would verify the efficacy of any proposed therapy for diabetes.  Insulin was discovered only after all this other work had first been completed.

After reading a journal article about diabetes, Banting had his eureka moment. Banting was not a scientist.  He was a surgeon and a war veteran; he had served with honor and been wounded.  After the war, Banting opened an unsuccessful medical practice.  He had no lab experience. Banting, nonetheless, thought that if the pancreatic ducts were tied off, the pancreas would degenerate, leaving only insulin-producing cells.  The atrophied pancreas could then either be grafted onto patients or an extract from the degenerated pancreas could be developed and injected.

Banting approached Dr. J.J.R. MacCleod, an internationally known expert in carbohydrate metabolism at the University of Toronto, about his hypothesis.   Although pessimistic, MacCleod provided Banting with a lab, some dogs, and Charles Best, a student research assistant with a background in biochemistry since Banting lacked the expertise to perform chemical tests himself.  After a few months of experimentation, Banting claimed that extracts of the degenerated pancreas successfully lowered the blood sugars of diabetic dogs (dogs whose pancreases had been surgically removed).  MacCleod added J.B. Collip, a biochemist, to the team and  provided his own expertise, making the key suggestion that alcohol be used to extract the insulin and demonstrating  a technique for evaporating it.    In truth, Banting’s hypothesis was neither valuable nor new.  Other researchers had previously come up with the concept of pancreatic extracts, although no one had been able to develop an extract that was not toxic to humans.  And the pancreas did not need to be degenerated to isolate the insulin.  Banting never developed an extract that controlled blood sugar in humans. With their science backgrounds and lab experience, MacCleod and Collip took the project to the next level, although not before Banting threw multiple temper tantrums accusing MacCleod and Collip of stealing his project, at times almost coming to blows with Collip.  Collip isolated the insulin and succeeded in removing many of the impurities. In apparent reference to Banting’s behavior, Collip later described the research process as a “disgusting business.” Clinical trials were successful, and insulin was lauded as a miracle drug.  Eli Lilly, the pharmaceutical company,  which had obtained a short-term exclusive license from the University, solved the problem of making insulin in large quantities and came up with a method of further purifying the extract.

Banting became the face of insulin since as a medical doctor he handled the majority of the clinical trials.  His was a feel-good, underdog story—failing medical practice, inexperience, eureka moment, wounded war veteran–and his refusal to cash in made him even more popular. Reporters don’t read the scientific records.  Banting was lionized in Canada.  The Nobel Committee was more discerning. It awarded the Nobel Prize for Medicine in 1923 to Banting and MacCleod.  Predictably Banting threw another hissy fit because of the recognition given to MacCleod and almost declined the prize before he was talked down.  Instead he shared his half with Best, and MacCleod shared his half with Collip.  Discoveries no matter how monumental are made by humans.  Human baggage comes with the turf.

Two other interesting facts about the discovery of insulin.  After insulin was tested on the first few patients, Collip lost for a few months the ability to create it.  Bad medical equipment, lack of knowledge about chemical composition and the influence of temperature and acidity caused the problem.  Also when you hear the term “rabbit test,” you think about pregnancy.   Collip used rabbit tests to test the potency of batches of insulin.  Too strong a dose would lead to hypoglycemia (too low blood sugar), convulsions and potentially death.  Collip learned that injecting a little glucose would restore the rabbits and, thus, removed a potential and real danger from insulin treatment.

For more, Michael Bliss, The Discovery of Insulin (1982).

 

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