Insulin Research & Innovation Legacies: Institution Building

By Christopher J. Rutty, Ph.D

Lead Historian, Defining Moments Canada, “Insulin 100”.

The discovery of insulin was a transformative event on many levels, starting with its impact on the lives of millions of diabetics around the world. In Canada, more than any other country, the discovery of insulin was transformational in its influence on the creation of new medical research institutions and infrastructures; the rapid development of medical research investment, activity and discovery; and the biotechnological innovations involving insulin and applied to the development and production of new health products.

The seeds of potential growth in these areas had already been planted, particularly at the University of Toronto, before Dr. Frederick Banting brought his novel idea to Toronto in November 1920. Physiology professor J.J.R. Macleod was aware of these early developments, particularly in the Medical Building, which was designed for supporting scientific research. Some were dormant during and soon after World War I, while others, such as the medical, public health, and biotechnology work of the university’s Connaught Antitoxin Laboratories, based in the Medical Building’s basement, were germinating. Connaught’s growth since its founding as the Antitoxin Laboratory in May, 1914, and its expansion during World War I, was fuelled by its public service to provincial governments as well as the Canadian and British military in response to serious public health challenges, especially diphtheria, rabies, smallpox and tetanus.

Though comparatively modest in its operations before the discovery of insulin, Connaught had a predictable and steadily growing income stream, some of which was directed into a Connaught Laboratories Research Fund, worth more than $110,000 as of the end of 1921. In late January, 1922, $5,000 from this Fund,[i] along with the Lab’s facilities in the Medical Building, were provided to Banting, Best, Collip and Macleod, to develop methods to produce the pancreatic extract that would soon be known as “insulin.”

More broadly, the original insulin patent, held in trust by the University of Toronto on behalf of Banting, Best and Collip, fertilized and sustained the growth of Canada’s medical research infrastructure and the funding of laboratory research, discovery and innovation. The patents and licensing of insulin were managed in Canada and the U.S. by the University of Toronto Insulin Committee. Patent royalties provided predictable and growing funds for medical research in Canada from the 1920s and into the 1960s. These were bolstered by additional insulin patents that the University of Toronto held and administered on behalf of insulin innovations made by scientists at Eli Lilly and Connaught. From 1923 to 1967, royalties from insulin sales totaled to $8 million, as was reported to the Insulin Committee at the time. During the 1930s, insulin royalties averaged over $180,000 per year, which could go a long way during the Depression.[ii]

Insulin patent royalties were paid by producers licensed by the Insulin Committee, primarily U.S. firms, at a rate of 5% of the retail sales price. Paying royalties on insulin was a point of contention for some, but it proved to be a reasonable and reliable source of funding for Canadian medical research. Banting and Macleod were among those who had early concerns about charging royalties on insulin sales. There was also resistance in Britain and Europe to the idea of an insulin patent and paying royalties to the University of Toronto. Soon, the Insulin Committee gave up trying to collect royalties from insulin producers outside North America. The royalties’ original purpose was to pay for the laboratory testing of insulin samples provided by producers, and to meet the administrative and legal expenses of the Insulin Committee. Such costs, however, were never very high, except initially, and the Committee never had to defend the patents in court.

Any surplus funds collected from patent royalties were directed to an Insulin Committee Trust Fund. Half the proceeds supported general research in the Banting and Best Department of Medical Research at the University of Toronto. The other half underwrote the medical research work of Banting and Best, as well as Collip’s research at the University of Alberta (1923-27), McGill University in Montreal (1928-47), and at the University of Western Ontario in London (1947-61). In 1925, Collip’s share of the insulin royalties totalled $8,000, rising to $13,648 in 1927. From 1930 to 1935, his share ranged from $20,000 to $30,000 per year.[iii] In fact, Collip’s share of insulin royalties were a significant factor in the establishment of the Research Institute of Endocrinology at McGill University in 1941. Prior to the start of World War II, as Michael Bliss has noted in The Discovery of Insulin, Banting, Best and Collip shared what was “probably the largest pool of Canadian capital supporting medical research.”

A further significant factor in the role of insulin in Canadian medical research institution-building was the potent political and public desire to honor Banting personally and provide both him and Best with public funds to support further research. The first such pledge came from the Ontario government, which, on May 4, 1923, passed the “Banting and Best Medical Research Act,” and provided an annual provincial grant of $10,000 to the University of Toronto to promote medical research.[iv] The grant made possible the establishment of the “Banting and Best Chair of Medical Research,” a special non-teaching professorship held by Banting. This provincial grant paid Banting a salary, supported his research expenses, and also provided funds to Best for his research. This Chair, however, was not part of an established university department. The provincial government also appropriated a special payment of $10,000, to be given to the discoverers of insulin as a reimbursement for their work during the discovery period. From Ontario’s perspective, this payment went to Banting alone, although he promptly gave Best $2,500.

A little over a month after the act was passed, on June 27th, the federal government approved an annuity of $7,500 per year to Banting, sufficient, it was thought, to permit him to devote the rest of his life to medical research.[v] Despite objections from some, including, Dr. J.G. FitzGerald, director of Connaught Labs, Best was excluded, as a federal annuity could only go to one person. However, on October 26, 1923, the day after Banting learned that he and Macleod had been awarded the Nobel Prize in Physiology or Medicine, he pledged to split his half of the prize money with Best, which left them with $10,000 each. Soon after, Macleod split his half of the prize with Collip, which also left them with $10,000 each.

To Banting, the accolades and the money for medical research were somewhat embarrassing and would become a burden. In his own mind, he saw himself more as a physician and surgeon than a medical researcher. He felt that Best or Collip were more likely to make the next great discovery. Indeed, Banting’s first instinct after winning the Nobel Prize was to dedicate his prize money to supporting the medical research of other promising scientists with interesting ideas but no money to explore them. Thus, on November 1, 1923, Banting announced that his $10,000 Nobel Prize share would kick-start the establishment of a “Banting Medical Research Foundation.” By early March, 1924, this initiative was formalized as the “Banting Research Foundation.” Initial fundraising and organization efforts continued until the launch of a major public initiative in June, 1925, to secure a $500,000 endowment. By 1931, this endowment had grown to $600,000 and was yielding about $30,000 per year to support research projects.[vi] Although the Banting Research Foundation was a separate corporate entity from the University of Toronto, the Board of Governors served as trustees and sent earnings to the Foundation for disbursement to applicants. A portion, however, was committed to the support of the Banting and Best Chair of Medical Research. The only other similar organization in Canada at the time was the Research Council of Canada (later known as the National Research Council), which was primarily focused on industrial rather than medical problems. As of 2021, the Banting Research Foundation had an endowment fund of over $4 million.

A key figure in the original leadership of the Banting Research Foundation was Dr. J.G. FitzGerald, director of Connaught Laboratories. In 1924, the Connaught Laboratories Research Fund had provided support to Banting Research Foundation’s original organization. FitzGerald was also driven to see the discovery of insulin yield brick and mortar benefits at the University of Toronto that would support insulin’s expanded production at Connaught, and also consolidate the university’s public health teaching and research mission. Indeed, in 1923, FitzGerald envisioned accomplishing both goals in a new building that would combine a new and larger insulin production facility for Connaught, with the creation of a School of Hygiene. Such a new building would also serve as Connaught’s primary facility for its vaccine research and production work. To make this possible, FitzGerald approached the Rockefeller Foundation, which was based in New York City, and had plans to establish a third school of public health in North America, in addition to faculties opened at Johns Hopkins University in 1918 and Harvard University in 1921. In 1920, the Rockefeller Foundation had provided funds to Canadian medical schools, and in 1923 offered $10,000 to support Banting’s clinical studies of insulin. The University of Toronto’s fundamental role in the insulin discovery and Connaught’s role in its development solidified Toronto as the obvious choice as home for a third school of public health in North America.

On October 19, 1923, Wickcliffe Rose, of the Rockefeller International Health Board, arrived in Toronto and met with FitzGerald. The initial proposal for the establishment of a School of Hygiene at the University of Toronto was made in 1924 with a $400,000 commitment from the Rockefeller Foundation. The funds would go to the construction of a new building that included a new insulin production facility. A further $250,000 gift would endow two departments in the School. The new building would also enable an expansion of Connaught’s vaccine research and production activities, the proceeds of which were directed to the Connaught Research Fund, which, in turn, provided a further $250,000 endowment to the School. The School of Hygiene formally opened on June 9, 1927, with the ceremony followed by a tour of the building led by FitzGerald, Banting and Best. During the tour, Best showed the new insulin production plant, as well as his new office, which he now occupied as head of the Department of Physiological Hygiene, endowed with the Rockefeller Foundation funds.

Despite all the accolades and funds directed at the Banting and Best Chair of Medical Research, Banting still worked in makeshift space in the Medical Building and then in the Pathology Building at the Toronto General Hospital. At about the same time as the School of Hygiene was completed, the University of Toronto Board of Governors was developing plans for another new medical research building that would be constructed across the street from Toronto General Hospital, using funds from the hospital, the university, the provincial government, and the Banting Research Foundation. The University originally envisioned a grand institute in which all of the medical research would be concentrated, but existing departments objected. Building plans proceeded, nevertheless, as lab and office space was needed, most notably for Banting, and to accommodate the students and others he attracted as Chair of Medical Research.

In 1930, the top floor of the new building accommodated what would be called the “Banting and Best Department of Medical Research.” The new “institute” building, however, had yet to be named. The University of Toronto Board of Governors wanted to keep the idea of an “institute,” but were reluctant to name the building after a wealthy benefactor. Rather, the administration wanted to immortalize some of the university’s most illustrious graduates. Banting was at the top of that list, and based at the top of the new building. Thus, despite his objections, the new building was named the “Banting Institute.” He did not run the Institute, nor did he say much during the opulent official opening festivities on September 17, 1930. He was not feeling well that day and shortly after the opening was admitted to TGH across the street to have his appendix removed.

During the early 1930s, the School of Hygiene was at the centre of a remarkable growth industry, exemplified by the building’s expansion, its financing, the growth of its departments, and the scope of public health research. Proceeds from Connaught’s insulin sales and royalties were directed to the Connaught Research Fund, which in turn, provided funds to the operations of the School and, in particular, the expansion of the Hygiene Building and Connaught’s insulin plant. By the late 1930s, insulin sales and patent royalties were boosted significantly with the development of methods, led by Connaught researchers David Scott and Albert Fisher, to crystallize insulin on a large scale, and also to produce the first long-acting form of insulin, Protamine Zinc Insulin. Royalties from Scott and Fisher’s U.S. patent for Protamine Zinc Insulin, collected from U.S. insulin producers, were especially significant to Connaught. Indeed, into the 1960s, insulin royalties and the revenues generated for Connaught by Canadian insulin sales were a key source of funding for the Labs and the School of Hygiene. Such a steady and predictable source of funds allowed the development of staff and research that was the envy of similar institutes around the world.

After Banting’s tragic death in February, 1941, in a plane crash, Charles Best became the focus of the insulin and medical research and institution building legacy. Best became Director of the Banting and Best Department of Medical Research, and played a leading role in several wartime projects, most notably the preparation, with Connaught and the Red Cross, of dried blood serum for the Canadian military. After the war, Best refocused his attention on diabetes research and education, and played a leading role in the establishment of the Diabetes Association of Ontario through the late 1940s. In 1953, provincial diabetes associations amalgamated to form the Canadian Diabetes Association, later known as Diabetes Canada.

In 1942, in response to a need for expanded physiology research facilities, particularly to relieve the crowded Banting Institute building, the University of Toronto Board of Governors initiated plans for a new Physiology School of Research facility under the direction of Best. Wartime constraints limited progress, although movement began in 1946 when the provincial government freed up land immediately to the west of the Banting Institute for a new Physiological Institute. In 1949, the university Board of Governors committed $1.5 million to the construction of this new Institute building that — as had happened with the Banting Institute — it wanted to name after Best, despite his initial discomfort with the idea.

By May, 1950, $75,000 had been raised for the new “Charles H. Best Institute,” although construction did not begin until the spring of 1952. The new building would have a physiological research and teaching focus, and be physically linked to the Banting Institute via tunnels and a bridge. A feature of the bridge would be an exhibit space to showcase artifacts and memorabilia about the discovery of insulin. Federal funding in 1952 capped off fundraising efforts for what was now simply called the “Best Institute.” Its research work focused on diabetes, growth hormones, the use of radioactive isotopes, and problems of physiology, histology and nutrition. When the first phase of the Best Institute finally opened in September, 1953, it could also accommodate the Banting and Best Department of Medical Research, which had hitherto been jammed into the Banting Institute. The full six-storey Best Institute, built for $2.5 million, was completed in March, 1955, by which time it also accommodated the Department of Physiology.

The institutional legacy of the discovery of insulin continued into the 1960s with the establishment of the Dr. Charles H. Best Foundation in 1960. The Best Foundation was initiated after the W. Garfield Weston Foundation donated Weston shares in order to provide a research fund for the discretionary use of Charles Best. When Best retired in 1965, this fund was placed under the control of a Board of Members and Directors to support the general research undertaken in the Banting and Best Department of Research. In 2005, the Banting and Best Department of Medical Research was integrated, along with the Best Foundation’s funding for research, into the Donnelly Centre for Cellular and Biomedical Research (DCCBR) within the University of Toronto Faculty of Medicine. The Best Foundation’s funds were to thus be focused on supporting Charles H. Best Postdoctoral Fellows based in the DCCBR.

The 1970s began with celebrations to mark the 50th anniversary of the discovery of insulin and coincided with the opening of a new insulin production facility at Connaught Medical Research Laboratories’ Dufferin Division site on Steeles Ave. West near Dufferin Street. Today, the site continues the Connaught Laboratories legacy as Sanofi Pasteur Canada. All of Canada’s insulin had previously been produced in the School of Hygiene building, but the new facility, specially designed for insulin production, provided larger space and improved research and production facilities. Insulin was produced there into the early 1990s. To create a symbolic connection between the old and the new sites of insulin production, some bricks from the original Medical Building were preserved and incorporated into the wall of the front lobby of the new building, along with a display to showcase historical documents and vials of early insulin. The new facility was named the Robert D. Defries Building to honor the second Director of Connaught and the School of Hygiene, who played a critical role in establishing the production of insulin on a large scale at Connaught. On November 20, 1970, Defries attended the official opening of the building named in his honour, as did several other dignitaries, including Charles Best.

As this article is being written, Sanofi has announced that the Defries Building (also known as Building #86) will soon be supplanted by new vaccine production facility at the Sanofi Pasteur Toronto site. This major investment from Sanofi and the federal and provincial governments will enable new vaccine production facilities primarily for influenza vaccine, but with flexibility to produce others, including to prevent COVID-19.

The institutional legacy of the discovery of insulin at the University of Toronto, in terms of focused diabetes research, education and patient care, found its home with the establishment of the Banting and Best Diabetes Centre (BBDC) in 1978. The BBDC was set up as an extra-departmental unit of the Faculty of Medicine. The launch of the BBDC followed the death of Charles Best on March 31, 1978, and was soon followed by the endowment of the Charles Herbert Best Chair of Medical Research at the University of Toronto. This endowment was made possible by the donation of $1 million from Ontario lottery funds, with a portion of the earnings dedicated to supporting the patient care work of the Banting and Best Diabetes Centre.

Within the lifetime of the discoverers of insulin, many new institutions and organizations were built and nurtured based on the legacy that the development, production and distribution of insulin generated from the University of Toronto. This growth was fuelled by the presence of existing institutions, especially the university’s Connaught Laboratories, as well as the careful management of patent royalties, the public and political desire to honor and underwrite further research by the discoverers, and their personal commitment to supporting medical research in Canada more broadly.

[i] The Bank of Canada’s online inflation calculator is useful for relating historical dollar values to current values: The $110,000 Connaught Research Fund in 1921 would be worth about $1.6 million in 2020, while the $5,000 provided to insulin development work would be worth about $75,000.

[ii] The $8,000,000 figure in 1967 dollars would be worth about $60,000,000 in 2020. The $180,000 figure in 1935 would be worth about $3,300,000 in 2020.

[iii] The $8,000 figure in 1925 coverts to about $118,000 in 2020 dollars; $13.648 in 1927 to about $200,000; $20,000 in 1930 about $300,000; and $30,000 in 1935 to $550,000.

[iv] The $10,000 amount in 1923 would be worth about $150,000 in 2020.

[v] The $7,500 amount in 1923 would be worth about $112,000 in 2020.

[vi] The $500,000 amount in 1925 would be work about $7.4 million in 2020; the $600,000 amount in 1931 would be worth about $10.4 million in 2020, and the $30,000 amount in 1931 would be worth about $520,000 in 2020.