A Brief History of Insulin and Type 1 Diabetes

March 25, 2025

Class Act Endocrine 8 min read

By Matthew Ross

Peer Reviewed

In 1910, Ezra Hayman was on top of the world. The 26-year-old Nebraska native was a young ear, nose, and throat doctor studying abroad in Vienna, then one of the most prominent scientific and intellectual hubs in Europe. One can imagine his heady enthusiasm as he strolled down the same sidewalks as Sigmund Freud and imbibed the culture of this cosmopolitan metropolis.

Eight years later, Ezra Hayman would be dead. His killer: type 1 diabetes.

As a physician, Ezra may have been the first to grasp the significance of his symptoms. He tired more easily and experienced constant thirst. Most ominously, his body produced copious amounts of urine with a sickly sweet odor. Ezra would have known that his symptoms were consistent with diabetes. He would have also known that such a diagnosis was a death sentence.

Type 1 diabetes is an autoimmune condition in which the body’s immune system attacks insulin-producing beta cells in the pancreas. Insulin is a hormone that regulates a person’s blood sugar. Without insulin, blood sugar skyrockets after a meal, potentially leading to fatal complications like diabetic ketoacidosis.

Diabetes has been a scourge of humankind for millennia. A papyrus from 1500 BC allegedly written by the Egyptian physician Hesy-Ra described a “sugar disease” that caused patients to produce excessive amounts of urine.1 Centuries later, the Greek physician Aretaeus described the symptoms of diabetes more vividly as “a melting down of the flesh and bones into urine as though the aqueducts were opened wide …thirst is extreme, mouth parched, body dry, and wasting progressive.”2 The name diabetes (Greek for siphon) describes how this disease causes patients to lose sugar in their urine, thus draining their bodies of the energy they need to survive.1

The scientific understanding of diabetes advanced little from ancient Greece to the early 1800s. In 1869, a German medical student named Paul Langerhans discovered tiny islands of cells in the pancreas.2 Langerhans did not realize it, but these pancreatic islets contained the beta cells that produce insulin. Two decades later, German researchers Joseph von Mering and Oskar Minkowski discovered that removing the pancreas from a dog caused the dog to develop diabetes.2 They hypothesized that the pancreas secretes a substance that controls the level of blood sugar. American physician Moses Barron connected the pieces when he performed an autopsy on a patient with diabetes and discovered that Langerhans islands were obliterated. He proposed that these pancreatic islets must produce a substance that prevents diabetes. In 1910, English physician Sir Edward Albert Sharpey-Shafer named this substance insulin after the Latin word for “island.”1

Despite these advances, there was still no effective treatment for diabetes. Physicians in Europe had discovered that starvation diets allowed diabetes patients to survive longer. These diets recommended low-calorie options ranging from “thrice boiled vegetables” to “skimmed milk.”1,2 We now know that starvation diets prevent the large spikes in blood sugar that can cause diabetic ketoacidosis. However, these diets do not contain enough calories to support a healthy human body. Thus, when Ezra Hayman was diagnosed with diabetes, he was prescribed a life of hunger and misery. A picture of him taken around 1915, the year of his wedding, reveals a gaunt man with dark circles under his eyes, appearing far older than his 32 years. He passed away three years later, just before a series of discoveries revolutionized the treatment of his ancient ailment.

On October 31, 1920, Frederick Banting, a researcher at the University of Toronto, awoke in the middle of the night with a radical idea about how to extract insulin from the pancreas of a dog. He would tie shut the pancreatic duct, causing the pancreas to digest itself and leaving behind the insulin-producing cells.2 Banting collaborated with fellow scientists J.J.R. Macleod, Charles Best, and James Collip to perfect the purification technique. On January 11, 1922, they injected their solution into Leonard Thompson, a 14-year-old boy with type 1 diabetes who had withered away to 64 pounds.1 Although the initial injections caused allergic reactions, the treatments saved Thompson’s life. Banting and Macleod shared a Nobel Prize in 1923 for the discovery of insulin as a treatment for diabetes, just five years after Ezra Hayman’s death.

The Toronto researchers realized that they needed to create insulin at scale. The University of Toronto entered a partnership with Eli Lilly and Company, a pharmaceutical manufacturer in Indianapolis, who would produce insulin commercially. Eli Lilly took advantage of the fact that insulin from other mammals, such as pigs and cows, has a very similar structure to human insulin. Pig insulin differs from human insulin by one amino acid, cow insulin by three. Thus, the human body responds to pig or cow insulin similarly to human insulin, with the unfortunate caveat that these foreign insulin proteins can cause allergic reactions.3 Eli Lilly obtained mountains of livestock pancreases, which were waste products of the meatpacking industry, and began extracting insulin from them.2,3 Soon, insulin became available across much of the world.2

In the following decades, researchers developed new formulations of insulin that were less likely to produce allergic reactions and that acted more like the human body’s own insulin response.3 Because insulin was one of the first proteins to be purified in large quantities and was medically significant, it became fertile ground for biochemistry research. In 1958, Fred Sanger won a Nobel prize for discovering the amino acid sequence of cow insulin. It became the first protein ever to be sequenced.4

In 1976, partly due to concerns about the livestock pancreas supply chain, Eli Lilly called a meeting to discuss the need for new techniques to produce insulin.2,3 Four teams of researchers left the meeting determined to clone human insulin. Within three years, the team from Genentech won the race. They had created a human insulin gene from scratch and inserted it into E coli bacteria. The bacteria then produced human insulin. This was the first successful example of genetic engineering, and it helped spawn the modern biotechnology industry.2

The production of human insulin by bacteria had many advantages over the use of animal insulin. Besides the logistical and ethical considerations of using animal insulin, human insulin was also less likely to produce allergic reactions in patients.3 Furthermore, once it was possible for researchers to produce insulin genes from scratch, they were able to make subtle changes to the DNA sequence to produce insulin proteins with new qualities. So-called “designer insulins” could work faster or last longer than human insulin, making them more convenient and potentially safer for patients.2

The delivery mechanisms for insulin have also advanced greatly. Insulin pumps allow users to enter their precise dose and self-administer insulin without the use of a syringe. Continuous glucose monitors allow patients to obtain real-time feedback about their blood sugar levels. However, these technologies still require a large amount of human input and require numerous decisions per day on the part of the patient. The artificial pancreas is a new technology that combines continuous glucose monitors and insulin pumps to provide an appropriate dose of insulin without requiring user input.5 This technology can greatly reduce the cognitive burden of managing one’s insulin dosing.

Another emerging therapy in type 1 diabetes is pancreatic islet transplantation. This technique involves harvesting the insulin-producing cells from an organ donor’s pancreas and infusing them into a patient with diabetes. In 2023, the US Food and Drug Administration approved islet transplantation for patients with diabetes who suffer from chronically low blood sugar.6 This technology remains limited by logistical hurdles, including the availability of donor organs.7 However, researchers are working to create insulin-producing stem cells that could obviate the need for donor tissue.8 This technology has the potential to cure type 1 diabetes, meaning that patients would never have to inject insulin again.

Now that insulin has been commercially available for over 100 years, one might assume that this life-saving treatment is universally available. Sadly, this is still not the case. Three companies (Eli Lilly, Novo Nordisk, and Sanofi) produce 96 percent of the world’s insulin.9 Although these companies export insulin to countries around the world, insulin remains unaffordable to many people living in lower- and middle-income countries. One estimate found that the median patient with diabetes spends $9 per vial of insulin.9 Since patients often use multiple vials per month, this cost is prohibitive to many people who must purchase insulin out of pocket.9,10 Insulin manufacturers have created nonprofit organizations that distribute insulin to patients with diabetes; however, these efforts are currently insufficient to meet the total global demand for insulin.9

Historically, access to insulin has also been a struggle for many patients in the US. The cost of insulin skyrocketed here in the early 21st century.11 Many patients, particularly those without health insurance, were forced to ration their insulin to make it last longer. One such individual was Alec Smith-Holt, a 26-year-old man who died of diabetic ketoacidosis within a month of losing access to his parents’ health insurance.10 According to his family, Alec’s medications cost $1300 per month out of pocket, with most of the cost coming from insulin.10 For context, the cost of manufacturing one month’s supply of insulin for a typical patient with diabetes has been estimated in the range of $5-10.9,10 Alec died 100 years after Ezra Hayman. Ezra’s death just before the discovery of insulin was a tragedy; Alec’s death a century later is unconscionable. Stories like Alec’s placed pressure on the pharmaceutical industry to make insulin more affordable. Through a combination of public policy and new incentives for pharmaceutical companies, insulin is now available for $35 per month to most patients regardless of their health insurance status.12

Nevertheless, health disparities persist. Even though insulin is now more affordable, many patients still lack access to pumps, glucose monitors, and other technology that make insulin delivery more seamless. For instance, only 18 percent of non-Hispanic black patients and 40 percent of Hispanic patients in the US have access to an insulin pump, versus 72 percent of non-Hispanic white patients.13 The struggle for equitable insulin access in this country is still far from over.

I would like to return for a moment to the story of Ezra Hayman. Of all the millions of lives shattered by type 1 diabetes, the reader may wonder why I chose to focus on Ezra. The answer is that Ezra Hayman is my great-great-grandfather. When Ezra died, he left behind a grieving widow and two young sons. Their lives were forever transformed by Ezra’s death. Now, over a century later, type 1 diabetes is no longer a death sentence. It is a chronic condition that can be managed with insulin. There are 8.4 million people living with type 1 diabetes today, and that number is expected to nearly double between now and 2040.14 Until we cure type 1 diabetes globally, we must ensure that all these patients can obtain the life-saving treatment we call insulin.

Matthew Ross is a Class of 2027 medical student at NYU Grossman School of Medicine

Reviewed by Michael Tanner, MD, Executive Editor, Clinical Correlations

Image: Ezra Hayman (right) appears gaunt and aged in this photo taken around 1915. Next to him, looking off into the distance, stands his wife, Martina. Photo and biographical information courtesy of Hayman family archives, compiled by Roger Hayman.

References

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