Thursday, February 3, 2011

The Discovery of Insulin

Great Advances in Science

No one has ever had an idea in a dress suit.
Frederick G. Banting

Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates, so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life.
Frederick G. Banting, Nobel Prize Lecture (1923)

No single event the history of medicine had changed the lives of so many people, so suddenly.
Stephen Hume, biographer of Banting
Frederick Banting [1891-1941]: Taken, circa 1920–1925 in Toronto, Ontario
Photo Credit: Arthur S. Goss (1881–1940)
Source: Library and Archives of Canada - PA-123481
The discovery of insulin is one of the monumental discoveries of the 20th century, bettering and extending the lives of countless people around the world who suffer from various types of  diabetes, a metabolic disorder that impairs the body's production  and use of insulin, a natural hormone.

Persons with diabetes either don't produce any insulin or not enough to regulate their metabolism. Before the discovery of insulin, a diagnosis of diabetes meant eventual coma and certain death, often as soon a month and no later than two years after diagnosis.

One of the prime movers behind the discovery is Frederick Banting, a Canadian medical doctor. (Charles Best, another Canadian, is the other chief co-discoverer, along with John  James Rickard Macleod and James Collip, to a lesser but still essential degree. Best, although a Canadian citizen, was American-born in the state of Maine.)

The discovery, like many if not all scientific and medical discoveries, was a product of hard work, perseverance toward a promising goal, intuitive insights that build on the knowledge of previous work, and teamwork that looks at the common good, and not personal aggrandizement. For his medical breakthrough, Banting received the highest honors, including the Nobel Prize in Medicine a year later (1923), a British knighthood (1934), a number of honorary degrees, and worldwide acclaim. His team members received similar honours, yet Banting is the one remembered most.

Twenty years after his monumental discovery, Banting was dead. He died in 1941, during the Second World War in a non-combat accident, when the military plane he was traveling in had engine failure and crashed onto a frozen pond in Newfoundland.

Even so, he received more recognition. In 1994, more than 50 years after his death, Banting was inducted into the Canadian Medical Hall of Fame. In 2004, he was nominated as one of the top 10 "Greatest Canadians" by viewers of the Canadian Broadcasting Corporation. Banting placed fourth behind Tommy Douglas, Terry Fox and Prime Minister Pierre Elliott Trudeau.

Persevered When Young

Frederick Banting was born to William Thompson Banting and Margaret (née Grant), on November 14, 1891, in a farmhouse in the town of Alliston, 60 km north of Toronto. He was the youngest of five children. Although he was not an exceptionally strong student, he persevered and finished high school.

As a rule, perseverance in the face of obstacles is a common trait among scientists who have made outstanding contributions to the betterment of humanity. Banting is no exception to the rule. It is no guarantee of success, of course, but lack of hard work applied in a directed fashion is often a guarantee of failure.

At first Banting entered University of Toronto's divinity school. But this was not his destiny or calling. He dreamt of becoming a doctor and so he persevered through university until finally, in September 1912, he was admitted to the University of Toronto's Faculty of Medicine. One of his classmates was Norman Bethune, who would later achieve both fame and success as a surgeon. Banting graduated from medical school in 1916, during the height of the First World War, a savage affair.

Even so, Banting wanted to take part in some helpful capacity. He tried to enlist twice and was twice rejected due to poor eyesight. He was eventually accepted into the Canadian Army Medical Corps. In late September 1918, just weeks before Armistice, he was wounded in the right arm by an exploding German shell at the Battle of Cambrai. Despite haven been wounded, he continued treating other wounded soldiers. In 1919 he was awarded the Military Cross for heroism under fire.

Banting returned to Canada in February 1919, where he completed his medical training, Archives Canada notes:
He completed his training as an orthopedic surgeon and, in July 1920, he began to practise medicine and surgery in London, Ontario. It was a struggle for this unknown doctor. He had only a few patients and was burdened with serious financial problems and a girlfriend who threatened to leave him. To earn extra cash, he took a part-time job lecturing in surgery and anatomy at the University of Western Ontario's medical school. His wage was two dollars an hour.
Banting became deeply interested in diabetes after reading an article in a medical paper on the pancreas during a sleepless night on October 31, 1920. The work of Bernhard Naunyn, Oskar Minkowski, Eugene Opie, Edward Albert Sharpey Schafer, and others had indicated that diabetes was caused by lack of a protein hormone secreted by the Islets of Langerhans in the pancreas. Schafer named the hormone that is used today, insulin, from the Latin word, insula, for island.

Charles Best & Frederick Banting: Chief co-discovers of insulin, circa 1924.
Source: University of Toronto
The Problem & The Experiment

The problem simply reduced, was how to extract insulin from the pancreas, without destroying it in such a procedure. While he was considering this problem, Banting read an article by Moses Baron, which pointed out that, when the pancreatic duct was experimentally closed by ligatures, the cells of the pancreas which secrete trypsin degenerate, but the Islets of Langerhans remain intact.

This provided a possible avenue, leading to a successful solution, both simple and elegant, to extract insulin from the pancreas. A ligation of the pancreatic duct would, by destroying the cells which secrete trypsin, avoid the destruction of the insulin. After enough time had elapsed for the degeneration of the trypsin-secreting cells, insulin would be able to be extracted from the intact islands of Langerhans

Determined to investigate this possibility, Banting discussed it with various people, including John J. Macleod, professor of physiology at the University of Toronto. Although Macleod didn't think much of his theory at first, he provided him with experimental facilities at the top floor of the university medical building, research animals and a young assistant, Charles Best, who started working the day after he graduated with honours in physiology and chemistry from the University of Toronto

Banting and Best started working on the pancreatic hormone on May 17, 1921. They started off with the pancreases from ten dogs and then moved on to cattle. The results were so promising that they were soon ready for human trials, seven months after they began. But they were having trouble refining the pancreatic hormone for usable form for a human trial.

In December 1921, James Collip, who held a doctorate in biochemistry, joined the team. Within a month, Collip achieved the goal of preparing a pancreatic extract pure enough to use in clinical trials. Now, they had to test the insulin on a human.

That day came on January 23, 1922, at the Toronto General Hospital, where a  14-year-old boy, Leonard Thompson, was chosen as the first person with diabetes to receive insulin, reports
The test was a success. Leonard, who before the insulin shots was near death, rapidly regained his strength and appetite. The team now expanded their testing to other volunteer diabetics, who reacted just as positively as Leonard to the insulin extract.
The discovery was first announced to the world on May 3, 1922. The discovery of insulin had an immediate effect.The Nobel Prize in Physiology or Medicine in 1923 was awarded jointly to Frederick Grant Banting and John James Richard Macleod, as the Nobel Committee put it,  "for the discovery of insulin." Banting became the most famous man in Canada, and received many letters from persons worldwide.

Humanity's Benefit

Left out of the Nobel laureate honours were Charles Best, the 22-year-old medical student, and James Collip, whose contributions to the discovery of insulin are not debatable. It was an unfortunate omission, according to many science historians. Banting was so incensed, that he shared half his prize money with Best. Macleod followed suit and gave a share to Collip. Such are the measures of both men. As is the fact that Banting, Best and Collip sold their patent to the University of Toronto for one dollar.

Fan Mail: Banting received many letters from people around the world after insulin became widely available. This is a letter from a young American girl named Betsy from Galveston, Texas.
Source: Collections Canada:
Banting married Marion Robertson in 1924, and they had one child, William, born in 1928. This marriage ended in a divorce in 1932. In 1937 Banting married Henrietta Ball.

Frederick Banting died on February 21, 1941, near Musgrave Harbour, Newfoundland. (Newfoundland was then not part of Canada, but under the dominion of Britain. It joined Canada on March 31, 1949.) He was 49.  Banting was on his way to England on a mission of, as Prime Minister Mackenzie King put it, "high national and scientific importance," reported the Ottawa Citizen on February 26, 1941.

Banting was serving officially as a liaison officer between the British and North American medical services, when the plane crashed in the wilds of Newfoundland, a report said:
Banting managed to dress the wounds of the pilot, Captain Joseph Mackey, but then began lapsing into and out of consciousness. Mackey snow-shoed out of the wilderness to find help, but by the time the rescuers arrived Frederick Banting was dead. The purpose of Banting's mission is unknown to this day.
It took some time to recover Banting's body. In March he had a full military funeral, consisting of his Great War medals on his chest, a 200-hundred man military escort of the carriage where Banting's casket lay, four trumpeters playing The Last Post and Reveille, and a final salute from the officers present. This is all in keeping with a major of the Canadian Armed Forces. Fredrick Banting was buried at Mount Pleasant Cemetery in Toronto.