History of Insulin

The Insulin Archive – a UNESCO World Memory Resource

For a definitive history of the discovery of insulin at the University of Toronto, supported by an in depth archive of pictures, manuscripts, images of artefacts and much more, please visit The Insulin Archive compiled by the Thomas Fisher Rare Book Library, University of Toronto.

Their site “documents the initial period of the discovery and development of insulin, 1921-1925, by presenting over six thousand page images reproducing original documents ranging from laboratory notebooks and charts, correspondence, writings, and published papers to photographs, awards, clippings, scrapbooks, printed ephemera and regalia. Drawing mainly on the Banting, Best and related collections housed at the Thomas Fisher Rare Book Library and the University Archives at the University of Toronto, it also includes significant holdings from the Aventis Pasteur (formerly Connaught) Archives.

This outstanding archive was recognized as a UNESCO World Resource in 2013


The following is an excerpt from the UNESCO ‘Memory of the World’ 2013 announcement

The Discovery of Insulin and its Worldwide Impact
Documentary heritage submitted by Canada and recommended for inclusion in the Memory of the World Register in 2013.

The collection contains the total archive pertaining to the discovery of insulin at the University of Toronto. This event was one of the most significant medical discoveries of the twentieth century and was of incalculable value to the world community. The discovery of insulin has meant the difference between life and death for those suffering from diabetes. The original, archival documents included in these collections contain the research which won the Nobel Prize for Medicine in 1923 for Dr. Banting and Dr. Macleod, both of whom shared credit and prize money with James Collip and Charles Best.

Year of submission: 2012
Year of inscription: 2013
Country: Canada


 From “Idea” to Mass Production – a tortuous trail

While the work of  the discovery team at the University of Toronto produced an outstanding result and in a very short period of time, like many major medical and scientific achievements, that work built on a context of prior knowledge created over decades.

Scientific ‘discovery’ is rarely easy and almost always has an historical context, the relevance and impact of which is often not recognized until well after the fact.”
– David Sadleir, PhD, PEng, President SFBLF

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). The ‘timeline’ reflects a 55 year journey starting in 1869: 51 years of exploration, an approximate 2 year period of ‘discovery’ and 2 more years to the mass production of ‘Toronto’ insulin by 1924.

The summary points provided below were compiled by David Sadleir and adapted from the Thomas Fisher Rare book Library, “Insulin Timeline” and augmented with excerpts from the Wikipedia “Insulin History” reference in 2013. These notes served as background for design of some of the original Exhibits placed in the historic Banting Farmhouse as part of the educational support for the SFBLF School Tours Program.

Many of the digital images used in those early exhibits were provided by the Thomas Fisher Rare Book Library and augmented with selections from the Banting Digital collection compiled by the New Tecumseth Public library.

Setting the stage: the scientific climate

1913   John James Rickard Macleod writes a monograph on Diabetes entitled Diabetes: Its Pathological Physiology (London: Edward Arnold, 1913).

1914   The Connaught Antitoxin Laboratory is founded in Toronto by Dr. John. G. FitzGerald.

1916   Frederick Grant Banting graduates in December 1916 with others from the Class of 1917 in a special session of the University of Toronto Faculty of Medicine.

James Bertram Collip is awarded a Ph. D. in Biochemistry from the University of Toronto.

Charles Herbert Best enters the University of Toronto, he enrolls in the general arts program at University College.

1918   J. J. R. Macleod invited to be chair of physiology department in Toronto.

  1. G. Banting awarded certificate from the Royal College of Physicians of London.

Initial work: the summer of 1921

1920   October 31. Banting reads “Relation of the Islets of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis” by Moses Barron in Surgery, Gynecology and Obstetrics, Nov. 1920. The article prompts him to jot down a note for an idea for experimentation.

1920   November 6. F. G. Banting meets J. J. R. Macleod in Toronto for the first time. Macleod later arranges for Banting to use the Physiology Labs at the University of Toronto to try out his idea.

1921   J. B. Collip wins a Rockefeller Travelling Fellowship and returns to the University of Toronto from the University of Alberta in Edmonton.

1921   April/May. F. G. Banting arrives in Toronto and begins, with Mr. Best on May 17, the experiments which lead to the discovery of insulin at the University of Toronto.

1921   July 30. Dog 410 is the first to receive extract.

1921   August 4. Dog 408 receives injection of extract. On August 4th the extract is called “Isletin” for the first time.

1921   August 11. Dog 92, depancreatized, receives regular injections of the extract. Lives for 20 days.

The work continues:

expanding the research and the first clinical trials

1921   September/October. J. J. R. Macleod returns from Scotland and asks that F. G. Banting and C. H. Best repeat their experiments to confirm their results.

1921   November 14. F. G. Banting and C. H. Best deliver the first paper on the results of their research to the Journal Club of the University of Toronto Department of Physiology. This paper is later published as “The internal secretion of the pancreas” in the Journal of Laboratory and Clinical Medicine).

1921   November 18. Dog 33 “Marjorie” is depancreatized and a longevity experiment begins on December 6th.

1921   December. J. B. Collip joins Banting, Best, and Macleod and begins insulin experiments with rabbits.

1921   December 20. Dr. Joseph Gilchrist, a friend of F. G. Banting, is the first human to receive the pancreatic extract manufactured by Banting and Best. It is administered orally and has no beneficial results.

1921   December 22. J. B. Collip demonstrates that glycogen is formed in the liver of a diabetic dog given pancreatic extract and determines that the extract enables a diabetic liver to function normally.

1921   December 30. F. G. Banting, C. H. Best, J. B. Collip, and J. J. R. Macleod attend the annual conference of the American Physiological Society in New Haven. Banting delivers an address entitled: “The beneficial influences of certain pancreatic extracts on pancreatic diabetes”. The abstract was published as “The Internal Secretion of the Pancreas” in the American Journal of Physiology, 59 (Feb. 1922).

1922   January. J. J. R. Macleod assembles a team and directs work on the physiological action of insulin. The University of Toronto insulin team now includes: F. G. Banting, C. H. Best, J. B. Collip, J. Hepburn, J. K. Latchford, and E. Clark Noble, under Macleod’s direction.

1922   January 11. The first injection of Banting and Best’s extract is given to a hospitalized patient. The injection, given to fourteen year old Leonard Thompson at the Toronto General Hospital, is administered by Ed Jeffrey, the house physician under the supervision of Dr. Walter R. Campbell and Dr. Duncan Graham. The injection has little effect.

1922   January 14. Press coverage of the discovery begins in Toronto, in a brief article in the Toronto Star Weekly.

1922   January 23. J. B. Collip’s extract is successfully administered to Leonard Thompson at the Toronto General Hospital.

Beyond North America: clinical use expands

1922   August 17. First recorded meeting of the Insulin Committee at the University of Toronto. The Insulin Committee was established by the Board of Governors of the University of Toronto early in 1922 to control the licensing, patenting, and trademarking of insulin as a pharmaceutical product.

1922   September 16. Col. Albert Gooderham, Chairman of the Insulin Committee, writes to Banting, Best and Macleod soliciting their accounts of the discovery of insulin. They each respond with a written submission.

1922   October. Elsie Needham is brought back to consciousness from a state of coma with the use of insulin.

1922 October. August Krogh begins experimenting with and producing insulin in Denmark.

1922 November. Patent for the manufacture of insulin in Great Britain and Ireland assigned to the Medical Research Council.

1922 November 25. Prominent diabetic doctors assemble in Toronto to discuss the clinical use of insulin.

1922 December. Canadian patent granted for insulin and assigned, in Jan. 1923, to the Governors of the University of Toronto.

1923 January 23. United States Patent number 1,469,994 for the manufacture of insulin is awarded to J. B. Collip, C. H. Best and F. G. Banting.

1923 March 28. Ontario Medical Association sends out a circular about a course of instruction on the treatment of diabetes with insulin being made available to all interested Ontario doctors.

1923 May. A special issue of the Journal of Metabolic Research devoted to articles on the clinical use of insulin is published. This is the first publication of the results of the clinical trials of insulin conducted in diabetic clinics across North America.

The Nobel prize : insulin available world-wide

1922   May 16. Insulin made commercially available in Great Britain (the first country in which this is done).

1923   June. Exclusive agreement with Eli Lilly & Co. ends. Other pharmaceutical companies are now invited to apply for licenses to manufacture insulin for distribution in the United States and for foreign export licenses. The Insulin Committee begins to collect royalties from pharmaceutical companies on the sale of insulin.

1923   mid-October. Insulin is made commercially available in the United States and Canada.

1923   October 25. The Nobel Prize in Medicine is awarded to F. G. Banting and J. J. R. Macleod.

1924   Insulin is now widely available; marketed and distributed in countries all over the world by large British and American Pharmaceutical companies.

1925   September 14. League of Nations Health Committee agrees upon an international standard for determining the potency of insulin.

1926   Insulin is now patented or trademarked in countries 44 countries world-wide.

1926   J. J. R. Macleod publishes Carbohydrate Metabolism and Insulin. (London: Longmans Green & Co., 1926).

 

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