On March 31^st of this year, the House passed The Affordable Insulin Now Act by a margin of 232-193. The bill, which is now being reviewed by the Senate and which would take effect in 2023, seeks to cap the monthly cost of insulin at $35 for the more than 10 million Americans with diabetes who rely on the medication (that is almost one third of all people with diabetes). What better time to look at how this important drug came to be in the first place?

Just over 100 years ago on January 11, 1922, a 14-year-old boy named Leonard Thompson was given an injection of insulin at Toronto General Hospital.  He had been diagnosed the previous year with type 1 diabetes.  Prior to the advent of insulin therapy, people with type 1 diabetes lived for a few months and the only treatment available to them was a diet that excluded carbohydrates. It was more akin to a starvation diet.

The first injection contained too many impurities and failed.  Leonard developed an abscess at the injection site and the extract given to him did not lower his blood glucose.  Twelve days later he received a 2^nd injection—a more purified extract of insulin—and there was a dramatic reduction in his blood glucose level.  He continued to receive insulin injections and lived for an unprecedented 13 more years before succumbing to a lung infection. 

Today, millions of individuals worldwide with both type 1 and type 2 diabetes receive insulin injections, which are truly lifesaving.  Diabetes, however, is not a new disease.    It has afflicted humans for thousands of years.  A disease resembling diabetes was described by the Egyptians as far back as 1550 BC.    Sushruta (600–500 BC), a phyisician in India, wrote about a disease he termed “Madhumeha” which translates to the sweetness of urine.  The physicians in ancient times would often diagnose diabetes by noting that an individual’s urine attracted ants. They also commented on the extreme thirst and occasional foul breath in people afflicted with this condition.  This was likely due to the presence of ketones in the blood and breath because of a deficiency of insulin and inability to metabolize carbohydrates.

Greek physicians coined the term “diabetes” in 250 BC. The term emanates from the Greek word meaning “siphon,” as people with the disease appeared to pass urine like a siphon.

In 1675 AD, a British doctor Thomas Willis coined the term “diabetes mellitus,” the latter a Latin term meaning sweet like honey. It took almost a century and a half for the chemist Michel Eugene Chevreul in Paris to prove that the sweetness was due to glucose.   In 1848, a German chemist, Hermann von Fehling, developed a method for quantifying the amount of glucose in the urine.

Claude Bernard (1813–1878) was a prolific scientist and physiologist, reportedly referred to by the legendary Louis Pasteur as “physiology itself.” He performed an experiment in which he tied off the pancreatic ducts of dogs and noted that this led to atrophy of the gland. This set the stage for future studies.  In 1889, Oskar Minkowski and Joseph von Mering were the first two investigators to discover that removal of the pancreas in dogs led to excessive urination and that the urine contained large amounts of glucose.  Minkowski pursued additional experiments in which he implanted a small portion of the removed pancreas underneath the dog’s skin and observed that doing this prevented high blood glucose levels in the dog.  When the implant was removed or once it had spontaneously degenerated, the diabetes returned. This was proof that the pancreas was key to regulating blood glucose.

In 1921, Frederick Banting, an orthopedic surgeon, approached John MacLeod, a Professor of Physiology at the University of Toronto, requesting laboratory space to do some novel experiments in a small number of dogs.  He requested an assistant to perform these experiments over an 8-week period in the summer.  Macleod sent Banting two of his

students who had just graduated from the physiology and biochemistry course at the University of Toronto – Charles Best and E. Clark Noble. Banting desired to have only one assistant, so Best and Noble flipped a coin to see who would start first in the lab.  Best won the toss and with great enthusiasm joined Banting.  According to some accounts, Noble went on a vacation to Europe.  So did Macleod, who left for Scotland.

Beginning the experiments in May 1921, Banting and Best removed pancreatic tissue from dogs, ground it up in a mortar and injected it as an extract into dogs whose pancreases had

been removed to render them diabetic. Although the initial results were not promising, by the end of July they observed success - injection of the pancreatic extract into one of the dogs lowered the blood glucose and the dog’s condition improved!  Repeat experiments yielded similar results and they presented their groundbreaking findings in the fall of 1921. 

In late 1921, a biochemist named James Collip joined the team at Macleod’s laboratory, and they continued to work on the production of a pure pancreatic extract for administration to humans.  All of the above culminated in the historic experiment on Leonard Thompson.

Banting and MacLeod received the Nobel Prize in Physiology or Medicine in 1923. Banting was incensed that Best was not a fellow awardee and shared his monetary winnings with him. Macleod subsequently shared his prize money with Collip.

On January 23, 1923, Banting, Best and Collip were awarded the American patents for insulin.  Banting refused to put his name on the patent as he felt it was unethical for a physician to profit from a discovery that would save lives.  He said “Insulin does not belong to me, it belongs to the world.”  Best and Collip promptly sold the patent to the University of Toronto for a mere $1.00.

So many advances have been made in the development and production of insulin during the past century – the manufacturing of human insulin using recombinant DNA technology, and modifications of human insulin to affect how rapidly or slowly it exerts it effects (to more closely mimic normal insulin physiology) to name a few.  How wonderful it would be to honor the legacy of Banting, Best, and Collip by ensuring that insulin really does “belong to the world” and that everyone who requires this life saving treatment can afford it.