The Connaught Medical Research Laboratories was a non-commercial public health entity established by Dr. John G. FitzGerald in 1914 in Toronto to produce the diphtheria antitoxin. Contemporaneously, the institution was likened to the Pasteur Institutes in France and Belgium and the Lister Institute in London. It expanded significantly after the discovery of insulin at the University of Toronto in 1921, manufacturing and distributing insulin at cost in Canada and overseas. Its non-commercial mandate mediated commercial interests and kept the medication accessible. In the 1930s, methodological advances at Connaught set a new international standard for insulin production.
Efforts at Connaught to purify heparin for human clinical trials laid the foundation for various critical surgeries, including vascular surgery, organ transplantation, and cardiac surgery. During the First and Second World Wars, the Labs produced various antitoxins that became crucial due to increased risks of injury, infection, and exposure to diseases in other parts of the world, including the typhus vaccine and penicillin. Connaught's production technologies also enabled the mass-scale field trial of Jonas Salk's polio vaccine and its subsequent expansion. The institution played a particularly important role in restoring the U.S. public faith in the polio vaccine after a production mishap at California-based Cutter Laboratories.
In 1972, the University of Toronto sold Connaught Laboratories to the Canada Development Corporation (CDC), a federally-controlled corporation charged with developing and maintaining Canadian-controlled companies in the private sector through a mixture of public and private investment. The sale continued to stir controversy in the following years as the labs increased prices on its products and came under allegations of mismanagement and deteriorated manufacturing standards. In 1986, the labs were transferred to private ownership as the CDC was dismantled as part of the Mulroney government's program of privatization. Connaught was merged with Institut Mérieux in 1989, and in 1999, it was transformed into the Canadian component of "Pasteur Mérieux Connaught," owned by Rhône-Poulenc. A series of acquisitions since then have transferred ownership of what used to be the Connaught Laboratories to the global vaccine business of Sanofi.
History
Early history At the turn of the 20th century, Canadian public health was defined by increasing local and provincial efforts to control the spread of infectious diseases which worsened with urbanization. In particular, diphtheria (known as "The Strangler" for its infection of the respiratory system) was the leading cause of death among Canadian children under 14 until the mid-1920s. In Ontario alone, 36,000 children died from diphtheria between 1880 and 1929. Research at the end of the 19th century, notably involving Pierre Paul Émile Roux and Alexandre Yersin of the Pasteur Institute as well as Emil von Behring and Kitasato Shibasaburō, had paved the way for diphtheria antitoxin production using horses. The antitoxin could save lives when given early enough in the course of the disease, and in large enough doses. Despite the developments, treatment was often too costly for middle-class families since Canadian public health efforts to counter the spread of diphtheria were largely dependent upon expensive imports from commercial U.S. firms.
In 1913, John G. FitzGerald took up a new role as a part-time Associate Professor of Hygiene at the University of Toronto. After becoming one of the youngest graduates of the University of Toronto Medical School in 1903, he spent a decade pursuing further study across North America and Europe, learning how to make antitoxins and observing novel approaches to public health education, research, and biological manufacture. Around that time, calls had mounted for a "Pasteur Institute" in Toronto following a rabies outbreak in southwestern Ontario, since the only closest-available source of life-saving treatment was in New York. FitzGerald worked with William Fenton to prepare the rabies vaccine. Following the success, they soon moved to tackle the lack of access to the diphtheria antitoxin with a commitment from Ontario's Chief Medical Officer that the Ontario Board of Health would buy the antitoxin at cost and ultimately distribute it for free. The initial work done with a stable of horses in Fenton's backyard proved successful, and in 1914 FitzGerald presented a plan to the Board of Governors of the University of Toronto which included dedicating any proceeds to the improvement of public health and education.
On May 1, 1914, the Antitoxin Laboratory was formally established in the Department of Hygiene. It was to be self-supporting and received no funds from the University. $500 in donations from Edmund Boyd Osler (Ontario politician), brother of the famous Canadian physician William Osler, helped establish the space which contained a general laboratory, a sterilising facility, and a small bacteriological lab. The lab soon began to produce the diphtheria antitoxin and Pasteur rabies treatment that would eventually be made available to all Canadians, regardless of class or income.
World War I: 1914-1918 Canada entered World War I on August 4, 1914, and soon the need for antitoxins against tetanus became an urgent wartime matter. Robert Defries who joined the Antitoxin Lab in 1915 proposed that its operations be expanded to treat Canadian soldiers fighting trench warfare, for "not a fraction of the necessary amount [of tetanus antitoxin] was available". The proposal was quickly approved by the University of Toronto Board of Governors despite the lack of immediate funds, with University President Robert Falconer making an appeal to Prime Minister Robert Borden and the Ottawa administration. Shortly after, whisky magnate Colonel Albert Gooderham, then Chairman of the Red Cross Society funded an operation to equip the Lab with the capacity to produce a Canadian supply by August 1915. Gooderham had seen a need for antitoxins against tetanus, which had become an urgent wartime matter for the Canadian Expeditionary Force. He was impressed by the fledgling laboratory's capacity to produce the tetanus antitoxin in controlled conditions and at a lower price than the American sources the Red Cross had initially contacted. He turned over a 58-acre farm on Dufferin Street north of Toronto for a new production plant on condition that it be named after the Duke of Connaught, then Governor-General of Canada (1911-1916). In February 1916, the Ontario Board of Health began to distribute the Antitoxin Laboratory's products for free across the province. Other provincial governments soon followed suit, starting in Saskatchewan.
On October 25, 1917, the expanded lab was inaugurated under its new title, Connaught Antitoxin Laboratories and University Farm. John G. FitzGerald, the Director, was given full authority over the Labs' staff and the Connaught Laboratories Research Fund, which remained autonomous of University finances and supported the development of preventive medicine research. An Honorary Advisory Committee was also established so that Connaught would provide a truly national public health service, appointing representatives of each provincial government health department and the federal government to an annual meeting with FitzGerald.
By the end of the war in 1918, the Labs' wounded soldier treatment practices had reduced the rate of tetanus infection to 0.1%, making its anti-tetanus program one of the most successful health campaigns in wartime medicine. That same year, the Spanish flu spread across North America, spread in part through infected soldiers returning from overseas. Connaught swiftly intervened with large quantities of what Robert Defries described as an "experimental" vaccine, freely supplying it to health services and hospitals across the country as well as to several U.S. states and to Great Britain. While no claims for the effectiveness of the vaccine were made, it did no apparent harm and helped cement Connaught as a national public health centre in the minds of Canadian public health authorities.
The Spanish flu crisis revealed the inadequacies of Canadian public health infrastructure at the time. As a direct result, the government of Canada created the Department of Health in 1919. The new department's Dominion Council of Health had FitzGerald as its key member and took over the work of Connaught Labs' Honorary Advisory Committee. In April 1920, Connaught was granted a U.S. license. In July of the same year, it became an independent unit within the University of Toronto governed by a separate "Connaught Committee" of the Board of Governors.
Discovery and early development of insulin: 1921-1936
Peacemaking
In 1921, the Ontario Royal Commission on University Finances reported that "the work of the Connaught Antitoxin Laboratories is analogous to that done in the Pasteur Institutes in France and Belgium and to that of the Lister Institute in London, with this advantage on the side of these Laboratories that the Connaught Antitoxin Laboratories are an organic part of the University, are self-supporting and provide funds and facilities for research in Preventive Medicine and also opportunity for graduate teaching in Public Health."
That same year in the physiology laboratory two floors above FitzGerald's Connaught Labs office, Frederick Banting and Charles Best (medical scientist) under the auspices of J.J.R. Macleod successfully extracted insulin from the pancreas of dogs, fetal calves, and adult cows. In particular, Banting's experimental work with calf pancreas tissue took place at Connaught's farm site, where calves were involved in smallpox vaccine production. FitzGerald had arranged access to Connaught's modest facilities, along with $5,000 from the Labs' reserves, to expedite the team's work. In the months that followed, the researchers worked to refine the extracts to a degree safe for human injection with the help of biochemist James Collip. Tensions mounted during this time between the four "co-discovers" of insulin, exacerbated greatly by Collip's suggestion that he could return anytime to Alberta with his purification work and patent it. FitzGerald therefore stepped in as peacemaker to prepare a seminal research and development agreement between the Connaught Laboratories and the researchers. It established two key conditions: 1) that the collaborators would sign a contract agreeing not to take out a patent with a commercial pharmaceutical firm during an initial working period with Connaught; and 2) that no changes in the research policy would be allowed unless first discussed among FitzGerald and the four collaborators.