Discovery of Insulin – Standing on the shoulders of others

Scientific ‘discovery’ is rarely easy and almost always has an historical context, the relevance and impact of which are often not recognized until well after the fact.
–David Sadleir, Ph.D. P.Eng., SFBLF

The insulin discovery ‘timeline’ reflects a 55 year journey starting in 1869: 51 years of exploration, a ‘Eureka Moment’ leading to a remarkable 9 months of research and 2 more years to achieve mass production of ‘Toronto’ insulin by 1924.

1869
1870 – 1888
1889
1901
1906
1911-1912
1915
1916
1920

1869

Finding a basic relationship

Medical student Paul Langerhans is the first to observe mysterious islands of cells in the pancreas not connected to the gland secreting digestive juice. These would later Become known as the “Islets of Langerhans”.

1870 – 1888

Searching for a substitute

In the following decades, scientists speculate that the Islets of Langerhans secrete a hormone responsible for the body’s utilization of sugar. Although some come close, none have success isolating the hormone or producing an extract of the pancreas capable of treating diabetes.

1889

Searching for a substitute

Minkowski and vonMering establish a relationship between the pancreas and diabetes.

1901

Opie demonstrates diabetes is caused by the destruction of the “islets” noted by Langerhans.

1906

Zuelzer has some success treating dogs with pancreatic extract but is unable to continue his work.

1911-1912

Scott uses aqueous pancreatic extract with some success but is unable to convince his director and the work is shut down.

1915

Kremer demonstrates similar effects but his work is interrupted by WW1 and he does not return to it.

1916

Paulescu develops an aqueous pancreatic extract that ‘works’ when injected in diabetic dogs but cannot be used on humans and WW1 also interrupts his work.

1920

October 30, 1920 – Eureka Moment

The young surgeon Dr. Frederick Banting is working as an assistant in Physiology at the University of Western Ontario. While preparing for a lecture, Banting reads an article by Moses Barron and is fascinated by Barron’s theories on the Islets of Langerhans in relation to diabetes. That evening, Banting concludes the internal secretions of the pancreas might hold the key to the treatment of diabetes, and jots down an idea for an experiment that he thinks might solve the diabetes puzzle.


Discovery of Insulin – Research at the University of Toronto

A remarkable research effort achieved over just 9 months by a team of 4, of whom, 3 were age 30 or younger.

Nov. 6, 1920
May 17, 1921
July 27, 1921
July 30, 1921
Nov. 18, 1921
Fall 1921
Dec. 1921
Dec. 20, 1921
Jan. 11, 1922
Jan. 23, 1922
Jan. 25, 1922

Nov. 6, 1920

Banting presents his idea to Dr. J.J.R. Macleod, Professor of Physiology at the University of Toronto, and leading expert on diabetes. Skeptical but won over by Banting’s proposal, Macleod agrees to supply a small lab for the upcoming summer session. Macleod also assigns Charles Best, a recent graduate in Physiology and Biochemistry, to assist Banting in the lab.

May 17, 1921

Frederick Banting and Charles Best begin experiments which lead to the discovery of insulin at the University of Toronto.

July 27, 1921

Banting and Best isolate an extract from the pancreas of dogs naming it “isletin”, and begin testing it on dogs with no pancreas.

July 30, 1921

A diabetic dog receives regular injections of the extract, this causes the dog’s blood sugar to fall dramatically.

Nov. 18, 1921

A successful longevity experiment of isletin begins on Dog 33 “Marjorie”. She lives for 33 days on the extract.

Fall 1921

Isletin takes six weeks to extract. Banting suggests using fetal calf pancreas and it works well.

Dec. 1921

Macleod recruits Dr J.B. Collip from the University of Alberta to apply his biochemical expertise to purifying the extract.

Dec. 20, 1921

The team administers the pancreatic extract to the first human subject – Dr. Joseph Gilchrist. This oral form of Banting and Best’s original extract produces no beneficial results.

Jan. 11, 1922

Leonard Thompson, a 14-year-old diabetic lies dying at the Toronto General Hospital, is given the first injection of insulin. However, the extract is so impure, Thompson suffers a severe allergic reaction, and further injections are canceled.

Jan. 23, 1922

Collip works day and night for 12 days to improve the extract, and Leonard is given a second dose that is completely successful, with no obvious side-effects and completely eliminates the glycosuria sign of diabetes.

Jan. 25, 1922

Dr John G. FitzGerald, Director of Connaught Antoxin Laboratories, offers Banting, Best and Collip the use of Connaught’s lab facilities. Work begins to develop methods to produce a purified extract for clinical trials.


Discovery of Insulin – From ‘idea’ to mass production 1922 – 1980s

Moving an ‘idea’ to a practical use is often a tortuous journey. Such is
the case for insulin (from the Latin “insula’ meaning islet/island).

January 25, 1922
March 1922

January 25, 1922

Dr John G. FitzGerald, Director of Connaught Antoxin Laboratories, offers Banting, Best and Collip the use of Connaught’s lab facilities. Work begins to develop methods to produce a purified extract for clinical trials.

March 1922

The production of the extract fails; no potent extract is made for two months. Collip, Best and others frantically work to regain the formula. Best finally succeeds in May.


A small but growing supply of insulin allows clinical trials to be conducted in Toronto and at several diabetes clinics in other Canadian and US cities. Press coverage of insulin’s first trials leads to a wave of requests for this diabetes ‘cure’ (widely misunderstood initially) from all over the world. However, the limited supply means that very few critically ill patients, mostly children, can be treated.

Soon after insulin’s discovery, the University of Toronto Insulin Committee is set up to safeguard the integrity of the life-saving extract, while making sure its benefits are widely available. Large-scale production would be crucial to expedite insulin’s availability to meet the ever-increasing demand.

Through the summer and fall of 1922 Connaught Antitoxin Laboratories and Eli Lilly & Co. of Indianapolis share in the immense task of standardizing and expanding the production of insulin. Eli Lilly is able to supplement Connaught`s output, which was being directed largely to diabetic clinics in Toronto, including at Toronto General Hospital under Banting`s direction, at no cost to patients.

While Connaught produces insulin in Canada, Eli Lilly is granted exclusive rights for production in the United States until 1924. Internationally, firms in the United Kingdom, Australia and Denmark are also granted licenses.

1923 – 1927: Production in Canada

Initially the cost of insulin was beyond the reach of most Canadians. On March 1, 1923, during a visit to Alliston with Best, Banting emphasizes that insulin is not a cure for diabetes – but rather, a vital treatment – and that much remains to be done to ensure enough is produced in Canada at an affordable price. It is Banting’s wish that every cent earned from the sale of insulin is put back into its manufacture, with a view to increasing production and lowering the cost.

However, the modest facilities at the U of T’s Connaught Labs have reached their limit, with no one yet coming forward to help fund large-scale production in Canada.

Private donations and a grant from the Ontario government provide much-needed capital to expand Connaught’s insulin production capacity.

To accommodate this, Connaught takes over the former University YMCA building, vacant since 1918. Production begins on June 1, 1923, and within just one month, Connaught is producing enough insulin for all of Canada.

Under the direction of Charles Best and Connaught researcher David A. Scott, the insulin plant produces 250,000 units per week. Increased capacity and improved methods result in the price of insulin falling by more than 50% (from five cents to two cents per unit) in a matter of a few short months.

For the next 60 years Connaught Labs would go on to supply all of Canada’s insulin and play a major innovative role in its evolution.

1927 – 1970: Meeting the Demand

Insulin’s resounding success attracts the attention of the Rockefeller Foundation, which helps finance the establishment of the U of T School of Hygiene. The new building (known today as the FitzGerald Building) accommodates a much larger insulin production facility for Connaught, allowing for expanded activities. The plant is operational by the fall of 1926, although its official opening would not take place until June 9, 1927.

The building is expanded in the 1930s and would produce all of Canada’s insulin until 1970. Several notable improvements to the lifesaving extract would also take place during this era. In the late 1920s, a small-scale process is introduced to further purify insulin into a crystal form. By 1930, Dr. David A. Scott discovers a method to produce insulin crystals on a much larger scale by adding zinc to the process. Through these advances, Connaught establishes the first international insulin standard.

Other milestone discoveries:

  • Danish researchers add protamine to insulin, prolonging its effectiveness
  • Connaught researchers discover that adding zinc to protamine insulin makes it more stable and longer-acting
  • By 1936, Protamine Zinc Insulin is pioneered by Connaught and is soon produced internationally; only two injections per day are needed, instead of four to five
  • By the end of the 1940s, several new types of longer-acting insulin are introduced to benefit approximately 3,000,000 diabetics around the world

By 1950, increasing demand prompts further expansion of the Connaught insulin plant, as well as intense research into more efficient production methods. By 1955, the plant is operating 24/7 to produce 1.3 Billion units/vials of insulin per year.

During the 1960s, Connaught’s Dr. Peter Moloney develops Sulphated Insulin – a novel type of insulin for diabetics who are allergic to regular insulin. It is launched for sale in 1965.

1979s to 1980s: A Decade of Change

The global insulin industry transforms significantly during this decade, driven by new technologies and intensifying global competition. Fuelled by demands to lessen reliance on increasingly costly beef and pork pancreas, new types of human and synthetic insulin are developed based on recombinant DNA methods.

In 1972, soon after the world celebrates the 50th anniversary of insulin’s discovery, U of T sells Connaught Labs, beginning its transformation into a commercial biotech company.

In 1980, Eli Lilly enters the Canadian market, marking the end of Connaught’s insulin monopoly in Canada.

The 80s also usher in an intensifying global insulin war, fought primarily between Eli Lilly and two Danish producers, Novo and Nordisk.

In 1984, Connaught partners with Novo, creating a new joint-venture, Connaught Novo, which involves Novo operating Connaught’s insulin plant.

However, Novo and Nordisk merge in 1989, consolidating its North American insulin production in the United States. In the same year, Connaught begins a process of global mergers, which – progressively over the span of several decades – lead to its present identity as Sanofi Pasteur Canada, a major producer of human vaccines.

Today, Sanofi Pasteur’s parent company, Sanofi, produces a long-acting insulin product, thus re-establishing a link to insulin’s Canadian birthplace.