Prior to the discovery of insulin treatment, type 1 diabetes, with severe insulin deficiency, was a fatal disease with many debilitating symptoms. This article will discuss how this life-saving medication was discovered.
Medical Past
History of Diabetes Mellitus
Diabetes was first documented in an ancient Egyptian papyrus, as well as later in ancient Chinese and Indian medical textbooks. The word diabetes was thought to have originated by an ancient Greek physician from a Greek word meaning passing through. The term diabetes mellitus was introduced in 1647 by the British physician Thomas Willis and referred to both the excessive sweetness of the urine (mellitus-Latin for sweet like honey) and the excessive urination (diabetes-passing through) seen in this disease. In 1776 Matthew Dobson, a British physiologist first documented that a diabetic’s urine sweetness was from an excess of sugar. In the distant past some physicians actually used to taste a patient’s urine to make the diagnosis. In 1889 German researchers, Oscar Minkowski and Joseph von Mering, discovered that when a dog's pancreas was removed it immediately became severely diabetic.
In the pre-insulin era also known as the “era of frustration,” physicians tried generally unsuccessfully to control the disease by use of opiates, as well as having their patients eat more calories. However, some physicians started recommending calorie restriction with some success, although some were so low in calories it caused patients to die of starvation. Calorie restriction was more successful in late onset diabetes (type 2 diabetes) where the person still produces some insulin although the amount is not adequate to maintain normal blood glucose levels.
Insulin
Insulin is a hormone secreted by beta cells located in the pancreas in the Islets of Langerhans (named after their discoverer Paul Langerhans in 1869). The word insulin comes from the Latin “insula” meaning island in reference to the Islets of Langerhans. The word insulin was coined by Sir Edward Albert Sharpey-Shafer who in 1910 suggested that only one chemical from the pancreas was lacking in people with diabetes.
Insulin is released from the pancreas when blood glucose levels increase after eating and causes the glucose to be moved into cells where it can be used as an energy source. Extra glucose is stored in the liver as glycogen which can be reconverted back to glucose when insulin levels are low, such as when fasting or overnight, to maintain relatively constant glucose levels in the body. Lack of insulin for any length of time causes ingested glucose to be mostly excreted in the urine, and glycogen stores in the liver to become depleted. The low insulin levels act as a stimulus for the body to produce more glucose and without available glycogen, muscle and fat are then broken down to produce more glucose (even though blood glucose levels may already be very high). This can lead to muscle wasting, potentially a severe acidosis from ketones produced in the breakdown of fats, and severe dehydration from the increased urination produced by the high glucose levels.
The Development of Insulin
By 1912 it was fairly common knowledge that destroying the pancreatic Islets of Langerhans could cause animals to develop diabetes. A number of researchers had taken pancreatic extracts from animals and found they could reduce blood sugar somewhat, but no one was able to get pure extracts solely from the Islets of Langerhans.
In 1921, working at Connaught Laboratories at the University of Toronto, a Canadian surgeon, Frederick Banting, and his assistant Charles Best figured out how to remove insulin from a dog’s pancreatic Islets of Langerhans, which had not been possible before. Colleagues said the material looked like “thick brown muck,” and they called it iletin (later renamed insulin although Eli Lilly initially used Iletin as a brand name for the drug). With iletin, Banting and Best kept a dog with severe diabetes alive for 70 days, the dog dying only when they ran out of Iletin extract. Banting and Best along with colleagues J.B. Collip and John Macleod, later produced a more refined and purer form of insulin from the pancreases of cattle.
In January 1922, a 14-year-old boy named Leonard Thompson was dying from diabetes in a Toronto hospital and became the first person in the world to receive an injection of insulin. The first dose was not curative, and the patient developed a sterile abscess at the site of the injection, thought to be due to some contaminants in the solution. Eight days later Collip, using higher concentrations of alcohol in the mixture, found a way to remove much of the extraneous proteins found in the iletin. Four days later Thompson received the new, more purified extract and it was an unqualified success. Within 24 hours his blood glucose levels had dropped to near-normal and his ketoacidosis, which is seen in severe diabetes, had reversed. The news of this advance spread quickly worldwide and in 1923 Banting and Macleod received the Nobel Prize in Medicine for their work.
Soon after, Eli Lilly and other companies around the world started manufacturing large-scale amounts of insulin. In 1936, slow-releasing versions of insulin were developed with longer half-lives. Initially, insulin was made from the pancreases of cattle and pigs, but in 1978, “human” genetically engineered insulin produced from E.coli bacteria was developed and is still used today.
Conclusion
In 2017, there were an estimated nine million type 1 diabetics in the world, who due to a lack of pancreatic insulin, require daily insulin injections or infusions. The work of the medical pioneers who helped isolate and manufacture insulin has improved both the quality of life for diabetics and saved countless lives since the 1920s.
References
The History of a Wonderful Thing We Call Insulin the American Diabetic Association. Updated July 1, 2019. Retrieved from: https://diabetes.org/blog/history-wonderful-thing-we-call-insulin
Vecchio I, Tornali C, Bragazzi NL, Martini M. The Discovery of Insulin: An Important Milestone in the History of Medicine. Front Endocrinol (Lausanne). 2018 Oct 23;9:613. Retrieved from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6205949/
Rutty CJ. The Making of Insulin. Connaught Fund/University of Toronto. Retrieved from: https://connaught.research.utoronto.ca/about/history/article3
Diabetes. World Health Organization. 14 November 2024. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/diabetes#:~:text=Key%20facts,%2D%20and%20middle%2Dincome%20countries.
Photo images reference- University of Toronto, Insulin Digital Library. Retrieved from: https://connaught.research.utoronto.ca/about/history/article3
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