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The Discovery of Insulin & 100 Years of History

Written by: Kathryn Levesque
The Discovery of Insulin & 100 Years of History

Insulin therapy is one of many options available today for the treatment of diabetes. Its discovery 100 years ago marks a historic turning point for people with type 1 diabetes who rely on insulin injections to live.

The discovery of insulin has made it possible for people with diabetes to live longer and healthier lives. Over the years, new insulin types and injection methods have emerged, making safer and more customizable treatment plans possible. Read on to learn more about this pivotal development in medical history, including:

Diabetes Treatment Before Insulin

Researchers and healthcare providers recognized the symptoms and severity of diabetes long before the discovery of insulin. However, they had difficulty finding a suitable treatment in the absence of knowing the root cause.

People affected by diabetes — particularly type 1 diabetes — didn’t have long to live. The most effective treatment at the time was restricting calorie intake and fasting. According to the American Diabetes Association (ADA), these diets could be limited to as few as 450 calories per day. Unfortunately, this was not effective for patients long-term, and at best it gave those with severe diabetes a few more months or years to live.

Our understanding of insulin began to change in 1889 when German researchers Oskar Minkowski and Joseph von Mering found a link between the pancreas and diabetes. The breakthrough occurred when they removed the pancreas from dogs and observed symptoms of diabetes. A new theory emerged: the pancreas was the source of a substance — now known as insulin — that was vital to preventing diabetes.

The Discovery of Insulin

The laboratory at the University of Toronto where insulin was discovered [Source: Thomas Fisher Rare Book Library, University of Toronto]

Researchers knew by the beginning on the 20th century that the substance (insulin) that helped regulate blood glucose levels originated in the pancreas, within a specific group of cells. This group of cells was first described by Paul Langerhans in 1869 and later named the “islets of Langerhans.”

Sir Edward Albert Sharpey-Shafer believed that just one chemical in the islets of Langerhans was missing in people with diabetes. As stated by the ADA, “he decided to call this chemical insulin, which comes for the Latin word insula, meaning ‘island.’” Insulin got its name about a decade before it was successfully extracted from the pancreas.

Who Discovered Insulin?

F. G. Banting and C. H. Best, August 1921 [Source: Thomas Fisher Rare Book Library, University of Toronto]

Leading up to the discovery of insulin in 1921, many attempts were made to extract insulin from the pancreas, yet none were consistently effective at treating diabetes. In 1920, Sir Frederick G. Banting came up with a new theory to isolate the pancreatic extract. He would spend the next year at the University of Toronto, alongside Charles Best and under the guidance of John J.R. Macleod, testing his theory.

Banting and Best eventually succeeded at extracting insulin and using it to lower blood glucose levels in dogs — they even treated a dog with severe diabetes, keeping it alive for 70 days until no more extract was left. This was a huge milestone in their research, though they still had some work to do to make the extract suitable for human use.

The liquid was brown and murky, so Banting and Best brought James B. Collip onto their team in late 1921 to refine and purify the extract. It took him roughly two months to land on a version of the extract that would be safe for human trials. This version came from the pancreases of cattle and became the first insulin to treat hyperglycemia — high blood glucose — in a person, successfully and consistently.

Banting and Macleod were awarded the 1923 Nobel Prize in Physiology and Medicine for the discovery of insulin. They shared the prize money with their colleagues Best and Collip.

Controversy Around Who Discovered Insulin

Credit for the discovery of insulin soon became a topic of discussion. Banting and others felt the Nobel Prize recognition should have gone to Best rather than Macleod. The viewpoint amongst the public quickly changed to a belief that Banting and Best had discovered insulin — Macleod and Collip were not equally honored. Efforts have been made, in more recent years, to recognize this as a collective achievement of all four men.

There were also claims that credit for the discovery of insulin should go to earlier researchers who had experimented with pancreatic extracts for the treatment of diabetes. Those trials were unsuccessful at achieving consistent results without severe side-effects. The reason Banting, Best, Macleod, and Collip were successful is the refining and purifying efforts that Collip contributed, making it safe and effective for human use.

Discovery of Insulin Timeline

First Therapeutic Use of Insulin in Humans

Leonard Thompson, the first person to receive insulin treatment [Source: Thomas Fisher Rare Book Library, University of Toronto]

The first dose of insulin given to a human was administered in January of 1922, shortly after the extract was refined and purified. Leonard Thompson, a 14-year-old boy hospitalized with type 1 diabetes, was the recipient. He showed quick signs of improvement after receiving the initial dose and significant lowering of sugar and ketones in the urine after a week of treatment. This was a historic accomplishment.

The Connaught Antitoxin Laboratories at the University of Toronto began to ramp up insulin production. In the following year, large-scale manufacturing of insulin provided access to people across the globe.

Innovations in Insulin Types

Banting, Best, and Collip were awarded an American patent for the insulin, which they sold to the University of Toronto for one dollar. This allowed the university to partner with drug manufacturers for large-scale production, making insulin accessible to many. Overtime, manufacturers would continue researching, and develop new insulins with different characteristics such as peak time, onset, and duration. These advances offered more options in treatment plans.

The First Long-Actioning Insulins

The insulin that Banting, Best, and their team created was considered a rapid-acting insulin, according to an article published by the ADA. This meant patients with type 1 diabetes needed several injections each day to manage their blood glucose levels. Long-acting insulins — that lower glucose levels more gradually over a longer period — were greatly needed.

A discovery in 1936 made long-acting insulins possible. Hans Christian Hagedorn and Norman Jensen — founders of Novo Nordisk — discovered a substance that could extend the effect of insulin. This substance was added to insulin to make protamine zinc insulin (PZI), the first commercially available long-acting insulin.

The variety of insulins continued to increase over the years with an intermediate-acting insulin (NPH) becoming available in 1946 and a series of insulins (the lente series) with varying characteristics a decade later.

The Development of Human Insulins

Up until the 1980s, all available insulins were made from animal pancreas extracts (mainly from cattle and pigs). These insulins helped millions of people live longer, healthier lives, however they weren’t perfect. They were complex to produce and triggered allergic reactions in some patients.

A new biotechnology developed in the early 1970s paved the way for the next generation of insulins. Scientists working at the insulin manufacturer Eli Lilly began experimenting with genetic engineering. Before long, they successfully created an insulin identical to the kind produced in the human body. In late 1982, the company received FDA approval for their new ‘human insulin,’ Humulin. This milestone in the history of insulin made the therapy safer and even more accessible.

Animal insulins began to phase out and were discontinued in the U.S. for human use by 2006, according to the Food and Drug Administration (FDA).

The Newest Insulins: Insulin Analogs

Scientists continued looking for ways to make injected insulin act more like insulin generated within the human body. This is how insulin analogs emerged.

The JDRF states, insulin analogs are an altered form of human insulin that more closely mimics how insulin acts naturally in the body. They also have more predictable absorption patterns, making it easier for people to dose and reducing the risk of hypoglycemia — low blood glucose.

The first human insulin analog was approved in 1996. Today, these are available in rapid-acting, short-acting, intermediate-acting, and long-acting (basal) insulins.

The History of Insulin Delivery Methods

Insulin injection methods have also evolved overtime. There are several options available today including syringes, pens, pumps, and inhaler. Advances in insulin delivery have improved the safety, dosing accuracy, and quality of life for people with diabetes.

Syringes

The original method for insulin injection was a reusable glass or metal syringe. These needed to be boiled after each use for sterilization, a not-so-practical process. By the mid 1950s, commercially available disposable syringes were developed, to eliminate cleaning after use and help reduce needle associated infections. Disposable syringes are still a common method for administering insulin today.

Insulin Pens

To improve the convenience and accuracy of insulin dosing, the insulin pen was designed. Insulin pens are small, discreet, and portable making them a popular option for all ages. Novo Nordisk made the first insulin pen available in 1985, improving the quality of life for people with diabetes. Meanwhile, another insulin device was on the rise: the insulin pump.

Insulin Pumps

Insulin pumps provide a continuous delivery of rapid-acting insulin through a small, flexible tube inserted below the skin. It may be surprising to learn that insulin pumps were available as early as the mid 1970s. However, it wasn’t until the early 2000s that they rose in popularity, according to an article published by the ADA. The insulin pump was a significant development in insulin therapy, and it would later become a key part in the most advanced insulin delivery method: the Automated Insulin Delivery (AID) system.

Some insulin pumps have been designed to receive glucose readings directly from a continuous glucose monitor (CGM) and automatically calculate and administer the appropriate insulin dose with little to no input from the patient. That’s exactly what an AID system — also known as an Artificial Pancreas or closed loop system — is designed to do. The first of its kind was approved by the FDA in 2016.

Inhalers

Lastly, a novel method for administering insulin is through inhalation. The main advantage that makes it unique among insulin therapies is that an inhaler is non-invasive, meaning there is no needle. The FDA has currently approved two types of rapid-acting, inhaled insulin – Exubera in 2006 and Afrezza in 2014. Despite being less invasive than injectable insulin, inhaled insulin is not commonly used.

The Future of Insulin

The previous 100 years have brought drastic improvements to life expectancy and quality of life for people with diabetes. As we look to the future, researchers are continuing to advance new developments in insulin and insulin delivery systems, including: longer-acting insulins — lasting several days to a week, ‘smart’ insulins, and AID systems utilizing the latest insulins and CGM technology. Additionally, non-invasive methods for delivering insulin continue to be studied, as researchers seek more comfortable, patient-friendly solutions for the growing number of people with diabetes across the world.

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Written by: Kathryn Levesque

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