Connaught Laboratories

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.

[2] 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.

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.

After becoming one of the youngest graduates of the University of Toronto Medical School in 1903, he had 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.

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.

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.

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.

[6] 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.

[8] 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.

The authors registered the University of Toronto's commitment as a public institution "to ensure that, at the earliest possible date, adequate supplies of potent and non-toxic preparations of Insulin will be constantly and readily available at reasonable prices all over the world.

David Scott, whom FitzGerald had personally recruited for the task, successfully replaced Collip's alcohol-based method with acetone use to allow for consistent results during the three months prior to external collaboration.

Peter J. Moloney pioneered an adsorption method using benzoic acid that reduced the amount of necessary alcohol/acetone to a minimal dose and eliminated far more protein material than had been previously possible.

[12] Nonetheless, large-scale manufacture of insulin at Connaught reached its limits, prompting the researchers to contract with Eli Lilly and Company to increase production and accept patents in Canada, the United States, and Great Britain.

[12][31] To prevent related legal complications, Connaught's Assistant Director and Head of the Insulin Division Robert Defries worked to establish an "innovative patent pooling policy".

[32] Nobel prize-winning physiologist August Krogh was given permission to manufacture insulin in Denmark while visiting Toronto in 1922, and a Danish patent was granted in February 1924 via Løvens kemiske Fabrik [da] (now LEO Pharma).

A team at Connaught led by David Scott and assisted by Arthur Charles and Albert Fisher refined this process into 1933 to consistently produce highly pure insulin.

In 1936, Fisher and Scott built upon the work of Hans Christian Hagedorn, one of Banting and Best's original Danish collaborators (along with August Krogh), to formulate protamine zinc insulin.

[41] As co-discoverer of insulin Charles Best returned from his postgraduate studies in Europe to continue as Connaught's Assistant Director, he began a program in 1928 to purify heparin for clinical use.

[36] Initial clinical trials, begun in April 1937 or slightly earlier with cruder forms, involved hundreds of complex surgical cases "in which heparin played an essential and often dramatic life-saving role".

In 1927, Connaught had begun to build on recent advances by Gaston Ramon at Pasteur Institute to develop various toxoids (inactivated toxins used to vaccinate against future infections).

Typhus fever, spread by the body louse, had ravaged both the military and civilian populations of Eastern Europe throughout WWI and continued to plague the European populace.

Their efforts culminated in a much richer bacterial culture and an improved ether-based purification method which lay the foundations for a large-scale vaccine production program in August 1942, overseen by Drs.

Various techniques of variolation (protection against smallpox) have been documented globally, the most prominent records of established practice dating back to the Ming dynasty (present-day China) in the 15th century.

At the turn of the century into the 19th, a number of individuals including Benjamin Jesty and Edward Jenner began to demonstrate considerable success using a vaccine made from cowpox material.

[66] To meet demands for transportability and a longer shelf-life, Connaught began its efforts to produce a dried version of the vaccine under Cleeve R. Amies, previously of the Lister Institute.

Nonetheless, the sale continued to stir controversy in the following years as the Labs became profit-driven and became subject to governmental investigation under allegations of mismanagement and deteriorated manufacturing standards.

A more serious faux pas was noted in regard to an unannounced increase in the potency of a smallpox vaccine which caused strong reactions in patients and alarmed health authorities in Saskatchewan.

[78] In April 1988, Institut Mérieux of France tried to buy a controlling stake in Connaught, but was blocked by the Ontario and Quebec securities commissions because the acquisition favoured one group of shareholders over others.

"[31][77][93] Since the 1972 sale of the laboratories to the CDC stipulated that the drug firm could not be sold to a foreign-owned company, the University of Toronto opposed the merger "on the ground that a foreign takeover would mean a loss of research spending and jobs in Canada.

"[94][95] It took Connaught to court seeking an injunction to block the sale, but withdrew its objection following an agreement with Mérieux that medical research support would continue if the company's bid succeeded.