Extraction of insulin from islet of Langerhans

The term of “diabetes” was coined by the Greek Aretaeus in the second century AD. In 1776, the Liverpool physician, natural philosopher and experimental physiologist Matthew Dobson (1732 or 1735–1784) discovered that urine of diabetic patients is sweet because of excess in sugar.

In 1869, Paul Langerhans discovered with his doctoral thesis the existence of clusters of cells in the pancreas, despite their function was unknown. Islets of Langerhans are islands of endocrine cells scattered throughout the pancreas. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering.

In 1909, the Belgian Jean de Meyer coined the term “insuline” to refer to the “internal secretions” of the pancreas, from the Latin word for “island”. In 1910 and later in 1916, in London, Sir Edward Albert Sharpey-Schafer described in depth that the pancreatic islands are able to secrete a substance capable of controlling glucose metabolism.

There were many attempts to isolate the “internal secretions” of the pancreas during the first two decades of the twentieth century.

It was not until October 1920 that Fredrick G. Banting, a young orthopedic surgeon, got inspired while reading an article to prepare a lecture about the pancreatic islets of Langerhans and diabetes. He believed that earlier failures were attributable to the destructive action of trypsin.

Since November 1920, Banting began working in a laboratory led by John James Richard MacLeod. Banting's goal was to isolate the hormone secreted by the pancreatic islands.

He hypothesized that ligation of the pancreatic ducts before the extraction of the organ would destroy the acinar tissue, the enzyme-secreting compartment of the pancreas, while the islets of Langerhans would remain intact and able to produce the internal secretion regulating sugar metabolism.

In 1921 the Canadian scientists Banting, Charles H. Best, J. J. R. Macleod and James B. Collip discovered insulin, a peptide (small protein hormone) which lowers blood sugar. They extracted insulin from the islets of animal pancreases.

They closed the pancreatic ducts with a technique designed by Banting to get the degeneration of the pancreatic exocrine tissue and to obtain a pancreatic islet from the pure state. With this liquid extract, for the first time, in the history of medicine, Banting and Best found the way to control glucose in a diabetic animal.

Their experiments produced an extract of pancreas that reduced the hyperglycemia and glycosuria in dogs made diabetic by the removal of their pancreases. They next developed a procedure for extraction from the entire pancreas without the need for duct ligation.

The discovery of insulin, and the demonstration that it can lower blood glucose in dogs, by Frederick Banting and Charles Best in 1921, and its subsequent development for clinical use, in collaboration with John Macleod and James Collip, led to the award of the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923.
Extraction of insulin from islet of Langerhans

Discovery of Insulin

In the past Type 1 diabetes always resulted in death usually quite quickly.

In 1889 Oskar Minkowski in Germany formulated the hypothesis that a substance in the pancreas must regulate metabolism, somehow preventing the formation of diabetes.

In 1921 the Canadian scientists Frederick G. Banting, Charles H, Best, J. J. R Macleod and James B. Collip extracted insulin from the islets of animal pancreas.

It is remains one of the most dramatic achievements in the history of medicine.

In 1924 the first studies on insulin inhalation were published by Laqueur and Grevenstuk of their investigation on intratracheal administration.

James B. Collip, a biochemist later was able to purify the extract in his own laboratory.

Commercial production of insulin was under way in 1992.

The first human to be treated with insulin was a 14 year old boy, Leonard Thomson, in Canada in the year 1922. His recovery was remarkable and immediate.

In the 1930s, and 1940s, it was recognized that crystallization of insulin with zinc and combination with the cationic protein protamine resulted in prolongation of insulin action, leading to the commercial availability of intermediate acting insulin.
Discovery of Insulin

Frederick Banting

Frederick Banting
Frederick Banting received the Nobel Price for Medicine in 1923 for his discovery of insulin as a treatment for diabetes. He was only thirty two year old.

The Nobel Price had only been introduced and awarded since 1901, and Banting was the first Canadian to receive one. As a result of his Nobel Price, he went from obscurity to world fame, from small town doctor to world renowned scientist and he became a national hero overnight.

The discovery of insulin was not vague esoteric or of questionable value to society. Its impact was clear, practical and immediate. There were literally millions of people all over the world who suffered from diabetes and who could previously only look forward to a life with a progressive, debilitating illness that usually led to an early death.

Frederick Banting was born in November 19, 1891 on a farm near Alliston, Ontario. He attended school in Alliston, where he had an average but undistinguished academic career but he excel at athleticism was good at art and was a hard working determined student.

After graduating from high school, Banting entered Divinity College to satisfy his parent’s wishes. He soon realized the medicine was his real interest and he transferred into the medical program.

When he graduated as a doctor in 1916, World War I was at its peak, and he felt compelled to do his part for his country. He enlisted on the Royal Canadian Army medial corps and was sent to Europe to work as a military surgeon in a rear field hospital.

After the war he served for a year as resident surgeon at Toronto’s Hospital for Sick Children. But for a young doctor just out of the army, earning a decent living was practical necessity. So Banting opened a small practice in London, Ontario.

He also lectured at the Medical school of the University of Western Ontario, and conducted research in neurophysiology under Dr. F.R Miller.

One day while Banting was preparing a lecture in the pancreas he read a paper by Moses Barron in a medical journal. The article described changes that occurred in the pancreatic juice when the pancreatic duct was blocked by gallstone.

Banting was intrigued by the possibility that something that occurred in this process might hold the secret to diabetes – a disease that had distressed Banting since school days, when young classmate slowly wasted away from the disease before his eyes and finally died in her teens.

He had the idea but neither a lab nor funds for the necessary research. Banting arranged meeting with Dr. John MacLeod of the University of Toronto to use facilities in the university.

The first human patient treated with insulin was a fourteen year old boy with severe juvenile diabetes. His discovery was remarkable and immediate. Other patients followed with the same impressive results.
Frederick Banting