Better Insulin: Nothing Better Than Insulin

During anniversaries of the discovery of insulin, Grant Maltman, the curator of Banting House in London, Ont., likes to point out that while we have better insulin today, there is still nothing better than insulin. “[W]e have to get beyond that.” Banting House, known as “The Birthplace of Insulin,” is where Dr. Frederick Banting, early in the morning on October 31, 1920, was struck by the novel idea that led to the discovery. The historical significance to diabetics, and to Canadians, has yet to be eclipsed by the discovery of a cure. While we wait for such a development, the seminal story of Banting’s discovery and the development of insulin by Banting, Best, Collip and Macleod remains uniquely compelling.

Insulin has certainly gotten better over the past century. Much of the research and innovation behind the further development, particularly from the early 1920s through the late 1960s, was led by Canadian researchers based at the University of Toronto and Connaught Laboratories, which supplied all of Canada’s insulin until the early 1980s. There were also important collaborations, most notably between Connaught and Nordisk Laboratories, that led to the first major improvements in insulin, especially the preparation of longer acting forms of insulin.

By late November, 1923, Connaught was producing some 250,000 units of insulin weekly in the former Y.M.C.A. Building on the University of Toronto campus under the direction of Charles Best, assisted by Dr. David A. Scott and a staff of 26 working day and night shifts. Connaught was able to supply Canadian diabetics and also ship its surplus to Ireland, South Africa, Central America, New Zealand, and Australia, among other countries without their own production facilities.

The former YMCA Building on the U of T campus after it was renovated into the Connaught Laboratories insulin production facility in 1923, which supplied all of Canada’s insulin and from which considerable amounts were exported until 1927. Sanofi Pasteur Canada Archives, Connaught Laboratories & The Making of Insulin, The University of Toronto.

In early 1924, as insulin production was also being established in different parts of the world, price sensitivity remained high, especially for Eli Lilly and Connaught as insulin’s pioneering producers. Yet Lilly and Connaught were not in direct competition, as Lilly’s insulin wasn’t available in Canada and Connaught’s would not be sent to the U.S., except to treat one notable diabetic case: Elizabeth Hughes, daughter of U.S. Secretary of State Charles Hughes. She had come to Toronto in August 1922, as Banting’s private patient. When she returned home in November 1922, a special arrangement was made to have Connaught’s insulin sent to her.

During this period, Connaught was the world’s primary driver of research and innovation in insulin production. As a self-supporting, public service-based part of the University of Toronto and intimately connected to the Insulin Committee, Connaught was ideally placed to freely experiment, innovate, test, apply and share its results. This work was led by Peter Moloney, David Scott, and Charles Best, as reflected in their many scientific publications.

Toronto Star article from January 1924 titled “Discover the New System for Purifying Insulin”.

Moloney’s research was of particular interest to the press. A Toronto Star article in early January 1924, heralded the discovery of a “New System for Purifying Insulin,” describing how Moloney’s year of research was “Of Immense Value” and would yield a “Much purer, Much cheaper Extract.” Although he remained characteristically “diffident about discussing the new method,” Moloney presented his work to the American Association for the Advancement of Science. His research, in collaboration with D.M. Finlay, was focused on a new charcoal purification method that built upon their earlier work with insulin adsorption and purification using benzoic acid.

Connaught’s insulin production facility was able to meet Canadian insulin needs and to also export, but it was clear to the Labs’ director, Dr. John G. FitzGerald, that a larger space was needed. Connaught also required new facilities for vaccine research, development and production work and for the university’s public health education and research programs, the latter ideally integrated into a School of Hygiene. For FitzGerald, these integrated needs fit with the Rockefeller Foundation plans to help establish a third school of public health in North America, in addition to those opened at Johns Hopkins University in 1918 and Harvard University in 1921. In 1920, the Rockefeller Foundation had provided $1 million to the University of Toronto’s Faculty of Medicine, and, in 1923, offered another $10,000 to support Banting’s clinical studies of insulin. Members of the Rockefeller International Health Board had also expressed their admiration of the innovative public health services that had developed in Toronto between the University of Toronto, especially through Connaught, and the City’s Department of Public Health, the Provincial Board of Health, and local hospitals. The university’s fundamental role in the insulin discovery and development solidified it as the obvious choice as home of a third school of public health on the continent.

On October 19, 1923, six days before the announcement of the Nobel Prize to Banting and Macleod, Wickcliffe Rose, of the Rockefeller International Health Board, arrived in Toronto and met with FitzGerald, who was not shy about describing what was required. 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 dedicated to the construction of a new building that would include a new insulin production facility. A further $250,000 gift would endow two departments in the School and provide fellowships in public health. The new building would also enable an expansion of Connaught’s vaccine production activities, the proceeds from which were directed to the Connaught Research Fund, which soon provided a further $250,000 endowment to the School. The School of Hygiene building, at 150 College Street on the University of Toronto campus, opened on June 9, 1927, with a ceremony followed by a tour of the building led by Banting and Best.

Brass plate for the University of Toronto School of Hygiene and Connaught Laboratories, installed at the main entrance of the School of Hygiene Building, c. 1927. Image courtesy of Sanofi Pasteur Canada (Connaught Campus) Archives.

In the School of Hygiene Building, Connaught’s insulin plant was significantly expanded and upgraded across two basement floors in one of the wings. The close proximity of the new insulin plant with the Lab’s other research and public health production facilities, and the various departments of the School of Hygiene, were quite significant to FitzGerald, as he stressed in Connaught’s 1927 Annual Report. “It may not be out of place to point out again that in no other institution of higher learning in the world is a serum institute an integral part of a School of Hygiene within such an institution, as is the case in the University of Toronto, where the School of Hygiene and the Connaught Laboratories serve a three-fold purpose: research, teaching and medical public service.” A key focus of this three-fold purpose was the production of insulin, its constant improvement, and its distribution as a public service to Canadian diabetics at the lowest possible price.

In addition to a new and larger plant, Connaught’s insulin productivity was expanded due to important advances in extraction technology and in the development of “insulin crystallization,” which precipitates insulin into a pure dry crystalline form. Small quantities of insulin crystals had been produced at Johns Hopkins University in 1926. After studying crystallization in 1929 at the University of London, Scott returned to Connaught, ready to develop a new and more efficient method of insulin crystallization. Scott’s research revealed how zinc, cobalt and nickel were important components of pancreatic tissue; indeed, he discovered that zinc was an essential element in the crystallization process. He found that if a trace amount of zinc was removed from insulin, it remained non-crystalline when dried to a powder, but still retained its anti-diabetic power. Crystalline-based insulin was purer, but not as long lasting as the original form; more daily injections would be needed. This work became critical to the international standardization of insulin, which would be based on the defined amount of insulin crystals first established at Connaught in 1932. This work was also critical to the development of a new and longer-acting type of insulin in 1936.

The first steps toward longer-acting insulin were taken in Denmark. Dr. H.C. Hagedorn, at Nordisk Insulin Laboratories, discovered that a small molecule extracted from fish sperm, known as protamine, when combined with insulin, significantly slowed its action. A diabetic who had required four injections per day, or five injections of the purified type, could make do with two daily injections of the new Protamine Insulin (first introduced in 1935 by Nordisk). Within a year, the Connaught research team of Scott and Dr. Albert M. Fisher further discovered that adding a trace amount of zinc to Protamine Insulin produced a more stable combination that prolonged the action of insulin from seven hours and up to three days. Introduced in 1936, Connaught’s Protamine Zinc Insulin represented a major advance that was quickly adopted globally. It soon became the most widely used form of insulin in Canada.

While the price of Connaught’s insulin preparations remained stable in Canada between the 1940s and the 1960s, maintaining such levels was difficult. The Labs faced a variety of external pressures through this period, especially the rising costs of beef and pork pancreas, and all other aspects of production. This was happening at the same time as new developments in insulin production technology afforded opportunities to further improve insulin yields, while increasing international demand for insulin brought new opportunities for export.

During the early post-WWII period, there was wider awareness among Canadians of the growing numbers of diabetics across the country and elsewhere, particularly in the U.S., and what this situation meant for the future security of the insulin supply. As pointed out in press reports in early May, 1948, there did not seem to be any immediate concerns about the Canadian insulin supply, but the numbers highlighted in the article and its headline, “Vital Need For Insulin Spurs U. of T. Campaign,” underscored the need for more research in Toronto, given that some 2300 kg of beef and pork pancreas yielded just 225 grams of purified insulin. For beef pancreas, the average weight of each is 5 kg, meaning 460 cows would be needed to produce 225 grams of purified insulin. There were about three million people around the world reliant on insulin, one million of whom lived in the U.S. “What of the future?” the article asked. It was expected that another four million people “will need insulin in their lifetimes. How will demand for insulin be met?”

From 10 lbs of frozen pancreas to 1/50 ounce of insulin crystals, c. 1940s. Image courtesy of Sanofi Pasteur Canada (Connaught Campus) Archives.

As of October, 1948, Connaught was operating its insulin plant 24 hours a day, five days a week, and had built up a reserve insulin supply of 750 million units. Connaught had an arrangement with the Canadian meat packing industry that supplied the Labs with all of the frozen beef and pork pancreas produced across the country. It was clear the current insulin plant in the School of Hygiene Building (also known as the College Division) would soon be insufficient to meet the demand, despite several expansions and equipment upgrades. Connaught’s executive committee began considering its options in 1948, debating between building a new production facility at the “Farm” site (also called the Dufferin Division), adding to the existing plant, or building a new facility elsewhere on campus. By early 1949, construction began on an additional insulin plant accommodated in an extension to the Spadina Building (Spadina Division), which Connaught had acquired in 1943 on Spadina Circle, further west on the University of Toronto campus, for penicillin and dried blood serum production for the Canadian military.

Vacuum stills for the concentration of insulin, Connaught Laboratories, 1932. Image courtesy of Sanofi Pasteur Canada (Connaught Campus) Archives.

The additional space and upgraded equipment were put to use for research into new and more efficient insulin production methods. A new approach, developed in 1949-50 by Dr. Gordon Romans and known as the “salt-alcohol” method, proved particularly successful in raising insulin extraction efficiency.

The increased capacity put Connaught in a better position to respond favorably to growing inquiries from laboratories, pharmaceutical firms, and governments in a variety of countries. Prompted by a request from Burroughs Wellcome in the U.K. for 10 million units of insulin in bulk crystals, in mid-February, 1949, Connaught’s Prices Committee developed an insulin export policy. In April, 1949, after Brazil inquired about buying finished insulin, it was clear international demand would grow. For Connaught, as pointed out at the Prices Committee meeting on April 6th, it was “essential that we sell insulin preparations in foreign markets for the Labs are now producing insulin at 3 times the rate at which the product can be used in Canada.” However, there were concerns about the impact such exports would have on the price of pancreas in Canada, as well as questions about what prices to charge for exported insulin.

By early 1950, however, the mounting insulin surplus prompted Connaught to start taking a more pro-active approach by sending letters to other insulin manufacturers and “any responsible lab,” in such countries as Denmark, Great Britain, Australia and the U.S., asking if they needed additional bulk supplies of zinc insulin crystals to meet their needs. However, it was sometimes a difficult sell as a large global surplus of insulin were building through the early 1950s. Some countries were interested, but they faced difficulties with foreign exchange. In the meantime, Connaught’s insulin surplus continued to build; in May 1952, there was 1.2 billion units in stock of insulin crystals, and the Labs only sold about 600 million units in Canada per year.

By October, 1950, it was clear that Canadian pancreas prices would rise. Nevertheless, Connaught’s Prices Committee voted to maintain the existing prices for Insulin-Toronto and for Protamine Zinc Insulin. However, the introduction of a new type of insulin, known as NPH Insulin, which was intermediate in its action between regular insulin and Protamine Zinc Insulin, slower in absorption than the former, but not as slow as the latter, provided an opportunity to offset the rising costs with a new product. NPH Insulin was originally developed at the Nordisk Laboratories in 1946, but not licensed in Canada until 1950.

Connaught’s insulin production steadily increased from the mid-1950s and into the 1960s, driven by the need to process the frozen beef and pancreas it bought at controlled prices, which was the entire Canadian supply; provide all available insulin preparations to Canadian diabetics at the lowest possible price; and maintain a substantial stock and secure emergency reserve. In 1954, the Labs processed more than 635,000 kg of pancreas in the production of insulin. Such a large insulin production operation, with production that had doubled every seven years and totalled 1.3 billion units in 1955, operated “around the clock” with close co-operation of Canadian pharmacists and the meat packing industry, as well as continuous research in the Laboratories. By 1957, Connaught’s insulin exports accounted to about 23% of domestic distribution.

Through this period, Connaught’s insulin sold at lower prices than in the U.S. and at about the same price as in Great Britain. European insulin prices, however, were generally cheaper. As Connaught produced more insulin than it could sell in Canada, the export market became increasingly important, particularly in Japan, South America and parts of Europe, as well as countries behind the Iron Curtain. As noted by Connaught’s Executive Committee in September, 1955, “While such distribution will return only a small margin to the Labs, it would further our objective of reducing our inventory by about 500,000,000 units.” Such export sales helped, but they did not ease the financial pressures building at Connaught, leading to another suggestion at a late November, 1955, meeting of the Prices Committee to raise insulin prices. However, after considerable discussion, the Committee “agreed that from the standpoint of the Labs and from the standpoint of patients, it was desirable that there be no increase in price at this time.”

One factor that may have influenced the decision against an insulin price increase was the pending addition of another type of insulin, known as Lente Insulin. Developed at Novo Laboratories in Denmark in the late 1940s, Lente Insulin was another variation of insulin combined with zinc, but without any other protein added that slowed the action of insulin. There were actually two additional special types of Lente insulins known as Semilente and Ultralente. Semilente was soluble in blood and acted nearly as fast as unmodified Insulin (such as Insulin-Toronto). Ultralente was insoluble in blood and acted very slowly, much like Protamine Zinc Insulin.

After arranging approvals from Novo in late in 1955, Connaught applied for a Canadian license for Lente Insulin. While awaiting the license, Fisher worked out the production methods and, on an experimental basis, distributed Lente Insulin to Canadian physicians for free. The license was granted in December, 1956, and Connaught sold Lente Insulin in 10 cc vials of 40 and 80 units per cc concentrations at prices slightly higher that NPH Insulin. By early 1963, Connaught had also introduced the Semilente and Ultralente Insulin preparations, which sold at the same price as Lente Insulin.

Research into the development of further insulin refinements were taking place in Toronto as well. During the late 1950s and early 1960s, a small team at Connaught, led by Peter Moloney, undertook studies into the immunochemistry of insulin, and specifically the problem of insulin resistance. As he first described in 1955, Moloney was convinced that “insulin can exercise a true antigenic effect,” prompting an allergic reaction, “as manifested by anaphylaxis and by the production of neutralizing antibodies.” However, many had been skeptical about this idea since the early days of insulin in the 1920s, suggesting that other factors were at play, in particular, the rare development of immunity to insulin among diabetics.

In 1957, Moloney detailed how insulin was actually a “weak antigen,” at least in comparison with other antigens such as diphtheria or tetanus toxoids. Yet, since insulin was a foreign protein prepared from beef or pork pancreas, administered to diabetics daily over long periods of time, its role as an antigen could have a significant impact. As he emphasized at an international symposium in 1958, Moloney believed that certain diabetics could develop antibodies “which neutralize the physiological action of insulin.” Although rare, these antibodies, he said, are “responsible in these [cases] for the ineffectiveness of insulin to control the disease.”

Moloney’s research had shown that insulin prepared from guinea pig or cod-fish pancreas was much less antigenic and therefore could be of potential value in treating diabetics resistant to regular insulin. However, the effectiveness of such alternate insulin sources was temporary. Taking another approach, Moloney modified regular beef or pork insulin by trying various chemical treatments that might reduce its neutralizability, or ability to stimulate an immune response. He soon discovered that treating insulin with sulphuric acid looked promising. The insulin molecule reacted with the sulphuric acid and altered its chemistry in several specific ways that left the treated insulin much less neutralizable by anti-insulin antibodies, which were present in insulin-resistant diabetics.

By 1961, Moloney’s progress with preparing “sulphated insulin” led to a clinical trial involving an initial group of seven insulin-resistant diabetics. As was reported in 1964, the trial’s results proved very encouraging. The clinical trial group grew to 11 patients, five of whom had successfully relied on sulphated insulin for two years. There was no evidence of the modified insulin acting as an antigen, since the dosage did not increase. Also, in two cases where sulphated insulin treatment was interrupted, the patients were able to re-establish control of their diabetes when sulphated insulin therapy resumed.

Vial and package of Sulphated Insulin, Connaught Medical Research Laboratories, 1969-70. Image courtesy of Sanofi Pasteur Canada (Connaught Campus) Archives.

Connaught’s “Sulphated Insulin” was approved for use in Canada in 1964 and then in the U.S. as an investigational drug in 1968. Although a highly specialized compound, sulphated insulin played an essential role for insulin-resistant diabetics until 1996. At this point, it was found that newer generation of human and synthetic insulins were much less antigenic and that all diabetics could safely take regular insulin. The production of sulphated insulin thus ended.

During the mid-1960s, it was becoming increasingly clear at Connaught that a frequently delayed insulin price increase was unavoidable. In April, 1967, the price of 40-unit strength 10 cc vials of Insulin-Toronto rose by 8.4%; 80-unit strength rose by 9.3%; and 100-unit strength by 10%. The price of Protamine Zinc Insulin rose by 19.8% for 40-unit strength vials, and 21.6% for 80-unit strength vials. The prices for the other more specialized types of insulin also rose by similar amounts. After holding the prices on these key types of insulin for 25 years in the face of the economic pressures highlighted earlier, Connaught’s increases were not unreasonable. As Dr. A.M. Fisher noted in a 1972 article, entitled “The Cost of Insulin” and published in the Newsletter of Canadian Diabetes Association, the effect of the 1967 price increase for average diabetics reliant on 40-unit strength Insulin-Toronto meant a rise from about 8.3¢ per day to 9.0¢ per day, while users of 40-unit strength NPH Insulin paid not more than 12¢ per day.

On November 20, 1970, the official opening the new Defries Building at the Dufferin Division, named after Connaught’s Director from 1940 through 1955, marked the beginning of a new era of insulin production for the Labs, completing its consolidation and modernization just as 50th anniversary celebrations of insulin’s discovery began. However, with inflationary pressures accelerated during the early 1970s, it was more difficult for Connaught to prevent further insulin price increases during the next several years.

An important factor that made it more difficult for Connaught to absorb rising insulin production and other costs during the 1960s and 1970s was the loss of royalty income that had been generated by various insulin patents. In particular, there were four U.S. patents managed by the University of Toronto Insulin Committee, all of which generated substantial revenues. For example, the original Banting, Best and Collip patents, which expired in 1940 (prior to October, 1989, patent protection in Canada lasted 17 years, whereas today it lasts for 20 years), generated net royalties of $2,400,304 for University of Toronto, half of which were assigned to the Insulin Committee Trust Fund to support research in Banting’s and Best’s research laboratories. The other half was split three ways to support the research work of Banting, Best and Collip in their respective institutions.

Of more direct significance to Connaught was Scott’s patent for the crystallization of insulin, which expired in January, 1956, as well as Scott and Fisher’s patent for Protamine Zinc Insulin (PZI), which expired in November, 1956. From 1937 through 1957, the PZI patent yielded $4,492,373; after paying the expenses of the Insulin Committee, the royalties netted more than $3.5 million, half of which went to the Insulin Committee Trust Fund and divided similarly as the Banting, Best and Collip patent. Connaught received the other half, with over $970,000 then granted to the School of Hygiene between 1929 and 1972 out of a total of more than $2,400,000 in royalties. For Connaught, this steady stream of predictable income from insulin royalties and sales allowed a development of staff and research which had been the envy of similar institutes of public service in England and elsewhere. Indeed, it was clear that Connaught was lucky to have insulin.

In 1972, despite Connaught’s successes with insulin and other prominent products, including polio vaccines, the University of Toronto decided to sell the operation to the newly established federal crown agency known as the Canada Development Corporation. By the end of 1972, Connaught had become a profit-oriented commercial company, a transformation that generated concerns on many levels, not the least of which came from the Canadian Diabetic Association (CDA), which worried about the potential impact on insulin prices and supplies. In petitioning the Ontario government to halt the sale of Connaught to the CDC, the CDA pointed out that Connaught sold its insulin to Canadians at prices that were 25 to 35% cheaper than U.S. companies did south of the border. However, the Ontario government did not interfere with the sale and Connaught Medical Research Laboratories became Connaught Laboratories Limited, with the CDC chairman assuring diabetics that “insulin prices would not rise in the foreseeable future.”

In 1974, dramatic spikes in the price of beef and pork pancreas made it impossible for Connaught to avoid insulin price increases that year. Meanwhile, in July, Eli Lilly was forced to implement its first insulin price increase in 28 years, pressured by pancreas price increases of 85% since 1973, and wage costs that had risen 50% since 1968. In October, facing similarly dramatic pancreas price increases, Connaught had no choice but to raise its insulin prices by about 10%.

Insulin production tanks, Defries Building, Connaught Medical Research Laboratories, c. 1970. Image courtesy of Sanofi Pasteur Canada (Connaught Campus) Archives.

Amidst the news of pancreas prices rising alarmingly, prospects of global pancreas shortages and further price instability in the future, it was reported that there had been a breakthrough in the chemistry of human insulin at the Swiss pharmaceutical firm, Ciba-Geigy AG. Its scientists had totally synthesized the vital hormone. This significant development pointed to the large-scale production of insulin based on a synthesized human form of the hormone, although several more years of research and development work were needed.

Following an 11% increase in July, 1976, Connaught’s largest insulin price increase to date was implemented in January, 1977 — a 20 to 24% increase. When the changes were announced, the CDA appealed to the federal and provincial governments for financial assistance for diabetics on fixed incomes. As stressed in press reports, the latest insulin price change resulted in Canadians paying more for their insulin than did Americans, although such reports did not mention the differences in production scales that tended to favour U.S. producers.

The start of the 1980s marked the symbolic end of an era for insulin in Canada and the start of a new reality for Connaught’s insulin production operation. In 1978, Eli Lilly applied to Department of National Health and Welfare regulators for approval to sell a new form of its American-made insulin in Canada. The license, awarded in December, 1979, applied only to a more purified single-peak “Iletin” insulin aimed at the six to seven percent of Canadian diabetics sensitive to ordinary insulin. As noted in a July, 1980, Toronto Star report, Lilly’s entry into the $7 to $8 million Canadian insulin market seemed quick and “surprisingly easily,” although the decision prompted some debate that highlighted sensitivities surrounding the Canadian insulin supply, and in broader Canada-U.S. trade relations, especially with respect to pharmaceuticals.

At that point, Eli Lilly controlled about 60% of the global insulin market and was very active in developing and testing a new recombinant-DNA based biosynthetic form of insulin. Most of the remaining 40% of the global insulin market was controlled by Novo Laboratories of Denmark, which was making faster progress than Eli Lilly in developing and marketing a new generation of human biosynthetic insulin products. Nordisk, Novo and Lilly embarked on a major market share war built around the new forms of human insulin. For Connaught, there was little it could do during the early 1980s except watch the battle from the sidelines as it did not have the resources to compete in the development of the new biosynthetic insulins, nor was the company able to keep down the price of its insulin products.

In fact, as an October, 1983, Globe and Mail article noted, the growing international insulin competition had “forced Connaught up against a wall over the past 10 years.” Rather than face an uncertain future of rapid change in the global insulin market and risk loss of control of the Canadian market, Connaught, in the fall of 1983 agreed to join forces with Novo. Formally launched in January, 1984, under a 10-year agreement, Novo established a Canadian subsidiary, Novo Industries Ltd., which would lease Connaught’s existing insulin production facilities. Connaught and Novo established a new company, Connaught Novo Ltd, which would assume control of marketing, clinical research and medical services for Novo products made in Canada. It was expected this new joint venture would not affect jobs at Connaught or Canadian insulin pricing. By July, 1984, the first Connaught Novo human insulins were launched in Canada: Actrapid (similar to Insulin-Toronto in its action), Montotard (similar to Lente), and Protophane (similar to NPH Insulin).

In May, 1985, Health and Welfare Canada hosted a symposium entitled, “Status of Diabetes in Canada.” The final report from the event provides a useful snapshot of not only the incidence of the disease at the time – there were estimated to be 160,000 Type I diabetics in Canada dependent on insulin – but also the changed status of insulin in Canada. There were by then at least 15 insulin manufacturers in the western world, three of them supplying insulin in Canada. Connaught-Novo had 87% of the market, Lilly 12%, and Nordisk 1%. Together, they provided some 2.5 million vials of insulin annually in Canada, with this amount increasing two to four percent annually. The report estimated that the average annual cost of insulin in Canada was about $250 per patient. With a total population of 250,000 insulin-dependent diabetics, the annual retail expenditure for insulin in Canada was approximately $60 million, most spent on either regular or NPH types of insulin.

While Connaught Laboratories divested itself of a direct role in insulin production in 1984, it maintained an interest in Connaught Novo Ltd. for another decade, after which it shifted into a distribution-only role for the insulin products produced by the newly merged firm of Novo Nordisk. Connaught’s move away from insulin during the 1990s was driven by the corporate take-over by Institut Mérieux of Lyon France in 1989, which transformed Connaught into the Canadian division of “Pasteur Mérieux Connaught” (or PMC), the primary focus of which was the development and production of human vaccines. The sale to Institut Mérieux also included Connaught’s U.S. vaccine production facility in Swiftwater, Pennsylvania, which the Labs acquired in 1978.

The events that led to the sale of Connaught to Institut Mérieux stemmed from the Canadian government, in 1985, proceeding with a policy to privatize Connaught through its dismantling of the Canada Development Corporation. Although Canadian and U.S. investors showed limited interest in Connaught’s Canadian and U.S. facilities, Institut Mérieux did, and beginning in 1986, initiated a complex process to acquire a controlling interest in Connaught Laboratories, which was finally approved in 1989. A decade later, Rhône Poulenc, the France-based parent company of PMC, merged with Hoechst of Germany to create a new company known as “Aventis.” Hoechst was granted Germany’s first insulin licence by the German Insulin Committee in October 1923, and soon became the sole insulin producer in Germany. PMC was re-branded as “Aventis Pasteur” and its Canadian subsidiary designated as the “Connaught Campus.” In 2004, the acquisition of Aventis by Sanofi Synthélabo of France, resulted in the creation of Sanofi-Aventis and the transformation of Aventis Pasteur into Sanofi Pasteur, a global division that inherited the original Canadian insulin legacy, as well as the German one.

Through all these shifts in name, the identity of the Toronto site known today as the Sanofi Pasteur Canada “Connaught Campus” has remained remarkably consistent, reinforced by its deep Canadian roots dating back to its founding as a self-supporting division of the University of Toronto, dedicated to medical research, biologicals production and public service. Thus situated, Connaught was able to provide a unique service to diabetics in Canada and abroad, one based on innovation and a dedication to providing all types of insulin at the lowest possible price. While constantly innovating production technologies to make better insulin and expanding outputs in the face of substantial economic and other challenges, its mission was successfully accomplished.

Apart from the Sanofi Pasteur Toronto site’s insulin legacy, its 100-year-plus human vaccines legacy has flourished and continues to grow, providing a wide variety of essential vaccines for Canadian and global distribution. The Sanofi Pasteur Toronto site’s vaccine development and production capacity remains committed to existing vaccines, although globally, Sanofi Pasteur is among many vaccine companies, in collaboration with universities, and also with each other, focused on developing and producing COVID-19 vaccines.