During the summer of 1921, two floors below Banting and Best’s Medical Building laboratory, Dr. John G. FitzGerald, director of Connaught Antitoxin Laboratories, heard the sound of dogs barking and wondered why. He soon connected the barking with some interesting research going on upstairs when he later ran into Banting in the Medical Building. FitzGerald’s office was next to a small laboratory and adjoining room for the filling and storage of various antitoxins and vaccines. Prepared by Connaught, these biological health products were primarily provided to provincial health departments across the country at cost, for free distribution to local health departments, hospitals and physicians. Connaught’s products were also distributed outside Canada, particularly to fellow members of the British Commonwealth, which, coincidentally, reached its geographic peak in 1921.
The existence of Connaught as a unique public service and self-supporting part of the University of Toronto proved vital to the development and production of insulin. The Labs’ main facilities, in the Medical Building, were close to where Banting and Best worked, and fostered the important personal relationship that formed between Banting and FitzGerald.
Connaught Laboratories originated within a uniquely Canadian public health context that evolved between the 1890s and the 1910s, defined by increasingly proactive local and provincial public health efforts to control infectious diseases, especially diphtheria. However, the treatment of diphtheria depended on the import of the recently discovered diphtheria antitoxin from the U.S., but its price, especially after import taxes, was often beyond the means of middle-class families threated by this deadly disease. Indeed, diphtheria 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.
Known as “the strangler,” diphtheria is a bacterial infection transmitted through close contact with an infected individual, usually via airborne droplets. Corynebacterium diphtheria produces a toxin that spreads throughout the body. The infection produces a thick, sticky film in the throat that makes breathing increasingly difficult. The diphtheria bacterium was first identified by Edwin Klebs in 1883 and cultured by Freidrich Loeffler in 1885, both scientists based in Germany. In 1888, Emile Roux and Alexandre Yersin in France isolated diphtheria toxin, and in 1890, Emil von Behring and Shibasaburo Kitasato, working in Germany, developed diphtheria antitoxin by injecting guinea pigs, goats, and particularly horses, with a series of small but increasingly large doses of diphtheria toxin, which harmlessly stimulated immunity. Some blood was later drawn from the horse, with the antitoxin refined from the white blood cells and used to treat people infected with diphtheria. When administered early enough, and in sufficiently large doses, the antitoxin could save lives.
The discovery of diphtheria antitoxin followed the discovery of the Pasteur rabies treatment vaccine by Louis Pasteur in 1885. The rabies treatment countered what were almost universally fatal bites by rabid animals. Both discoveries of such dramatically life-saving biological treatments fuelled the establishment and growth of new institutions in Europe to further their development and production, most notably the Pasteur Institute in France (other Pasteur Institutes were later established elsewhere) and the Lister Institute in England. Such public health institutions also focused on scientific research and teaching, and also facilitated the public distribution of biological health products, sales of which financially supported the work of the institutions. Private endowments and some government funds were also important to the creation and financial health of such institutes. Several European governments played a larger role in establishing what became known as state serum institutes to facilitate production, distribution and further research into biological health products, sometimes in collaboration with pharmaceutical companies.
In North America, the European developments inspired several cities, most notably New York City, and several state governments, to establish labs to produce and distribute antitoxins and vaccines; a number of large pharmaceutical companies did the same on a commercial basis. In Canada, other than several small public and private operations to produce smallpox vaccine, there was no public or private production of biological health products; doctors, hospitals and local and provincial health departments imported them from U.S. companies and some public health labs. The price of such imported products in Canada became a growing concern, prompting lobbying, especially by members of the medical profession, for governments, provincial and federal, to take a more direct role in producing and providing such essential public health products. Dr. John G. FitzGerald was one such member of the medical profession.
John “Gerry” FitzGerald was born in the village of Drayton, Ont., on December 9, 1882, the eldest son of a pharmacist. In 1903, the tall, slim, fiery redhead graduated from the University of Toronto Medical School. Frustrated by the challenges of private practice, FitzGerald soon yielded to a characteristic restlessness, enthusiasm and ambition, and signed up as ship surgeon on the S.S. Philadelphia in 1904. He then developed an interest in the study of mental diseases and their prevention and interned at hospitals in Buffalo and Baltimore. In 1906, he returned to Toronto to become clinical director at the Toronto Hospital for the Insane, later the Clarke Institute and then CAMH. Swept up in the revolutionary bacteriological discoveries of the time, he thought that perhaps the cause of mental disturbances like schizophrenia could be discovered through a microscope. However, he soon realized that progress in preventing mental illness would be painfully slow. In 1907-08, he switched his focus to the more promising advances being made in the field of bacteriology when applied to the treatment and prevention of infectious diseases. Diphtheria antitoxin was of particular interest.
By the summer of 1910, following additional bacteriological studies at U of T and Harvard, FitzGerald went to study at the Pasteur Institute in Brussels. Over the next two years, he held a professorship in bacteriology at the University of California, and then conducted more studies in Germany, the Lister Institute in London, and the New York City Department of Health. During this period of extensive international travel and network building, FitzGerald soaked up unique knowledge and experience in bacteriology and public health. He learned how to make antitoxins as well as the Pasteur Rabies Treatment. FitzGerald also observed novel approaches to public health education, research and the production of biological products that he was eager to apply when he returned to Toronto in the spring of 1913 to take on the role of part-time associate professor of hygiene in the medical school.
FitzGerald’s initial task was to prepare Canada’s first rabies vaccine treatment supply for the Ontario Provincial Laboratory. A rabies outbreak in early 1910 among dogs in southwestern Ontario resulted in the death of a young boy, as well as calls for the establishment of a Pasteur Institute in Toronto. With no local supply available, people bitten by rabid animals had to travel to the New York Bacteriological and Pasteur Institute to receive the life-saving rabies vaccine treatment.
FitzGerald worked with William “Billy” Fenton, technician at the Provincial Laboratory, to prepare the rabies vaccine, with Fenton offering himself up as human guinea pig to test it. Yet besides rabies, the two scientists also spent time discussing diphtheria antitoxin and why an inexpensive supply was not available in Canada. FitzGerald knew how to make it and he had a network of experts available for advice, particularly at the New York City Health Department Laboratory, which was preparing antitoxins and vaccine for the city as a free public service. He also had a commitment from Ontario’s Chief Medical Officer that the Provincial Board of Health would buy the antitoxin at cost and ultimately distribute it for free. On his own initiative, FitzGerald thus decided to produce diphtheria antitoxin. All he needed were some horses, a place to accommodate them, and a small lab to process the antitoxin.
Fenton offered his backyard, at 145 Barton Avenue, near Christie Pits in west Toronto, to build a modest stable with a small lab. FitzGerald’s wife offered her dowry and a portion of an inheritance to pay for the project. In December 1913, they acquired five horses that would be needed to prepare the antitoxin for $5 each. (Otherwise, the animals would have been sent to a glue factory.) The aged horses passed the required tests, and dubbed Crestfallen, J.H.C., Fireman, Goliath, and Surprise, were given their first small injections of diphtheria toxin.
FitzGerald had hoped U of T would establish a Pasteur Institute and in early 1914 he made a presentation to the university’s Board of Governors. FitzGerald’s vision, included dedicating any proceeds earned on sales to research into new and improved products, and to supporting public health education. Impressed by his efforts, the University of Toronto on May 1, 1914, formally established the Antitoxin Laboratory in the Department of Hygiene. To get started, the department’s Museum of Hygiene — a collection of sanitation and plumbing exhibits designed to illustrate the pollution of wells and the transmission of communicable diseases — was sacrificed to provide space for the new Lab.
The establishment of the Antitoxin Laboratory took place within the context of significant public health developments in Canada, particularly after 1910. Nationally, the Canadian Public Health Association was established that year, while bold new public health acts were implemented in Saskatchewan and Ontario, the latter under the leadership of Ontario’s new Chief Medical Officer of Health, Dr. J.W.S. McCullough. The Ontario public health act mandated a new education standard for local medical officers of health that would be implemented through Dr. FitzGerald’s position as professor of hygiene at U of T. At the city level, Toronto appointed a new Medical Officer of Health, Dr. Charles O. Hastings, in 1910, who, nearing retirement as an obstetrician, was inspired to take on a new mission in public health reform after his baby daughter died because of contaminated milk traced to a dairy farmer with typhoid fever. Hastings transformed the city’s health departments and focused especially on ensuring the safety of the water and milk supply, modernizing the sewage system and enforcing the chlorination of water and the pasteurization of milk.
Located in the Medical Building basement, the Antitoxin Laboratory was to be self-supporting and received no funds from the University. Indeed, Sir Edmund Osler, brother of the famous Dr. William Osler and a U of T governor, donated $500 to convert the Museum of Hygiene into three rooms: a general laboratory, a room for washing and sterilizing glassware, and a small bacteriological lab. Space in the sub-basement would be utilized for processing blood plasma into antitoxin and for the packaging and storage of products.
During the summer of 1914, FitzGerald focused on expanding the Antitoxin Laboratory’s modest facilities as well as increasing its output and range of products. In addition to diphtheria antitoxin and Pasteur Rabies Treatment, the Labs began preparing typhoid vaccine, anti-meningitis serum and tetanus antitoxin to also meet demands from outside of Ontario. FitzGerald also found space for research and enlarged facilities for teaching.
However, after a productive spring and summer, Canada’s sudden entry into the First World War, on August 4, 1914, threatened to end FitzGerald’s ambitious plans prematurely, although the conflict soon provided new opportunities for the fledgling lab. In November, surprised at the unexpected impact of wound infections, the British Expeditionary Force ordered that all wounded soldiers be given prophylactic doses of tetanus antitoxin. With both sides in the war ramping up the use of this antitoxin, a severe global shortage soon developed, despite the efforts of serum labs in the U.K., France, Germany, and the U.S.
Tetanus is an insidious bacterial disease that can cause prolonged, and deadly, contraction of muscle fibres, with “lock jaw” among its most dangerous symptoms. Many animals harbour Clostridium tetani which generally passes through their system and into the soil, where it can persist and release spores. Tetanus disease develops in humans when the bacterium enters the body through deep cuts or puncture wounds and take root in anaerobic conditions found in dead or damaged cells. As the bacterium reproduces, tetanus toxin is released and spreads through the nervous system, interfering with muscle control and leading to progressive muscle spasms; if left untreated about 10 percent of cases prove fatal.
As with diphtheria antitoxin, small doses of tetanus toxin can stimulate an immune response in horses. Some blood is then collected and the white blood cells containing antibodies are processed into antitoxin. Demand for tetanus antitoxin was quite limited until the outbreak of the war, but the fetid trenches that crisscrossed battlefields in France provided ideal conditions for wounded soldiers to be exposed to the tetanus bacterium.
At the end of January, 1915, Dr. Robert D. Defries, who had just joined the Antitoxin Lab, described the tetanus antitoxin situation to the University’s Board of Governors. “[N]ot a fraction of the necessary amount was available” since the entire output was spoken for in advance by the Allied nations, he said.
Defries had received his M.D. from U of T in 1913, followed by a Diploma in Public Health (DPH) in 1914. He was the first to take the DPH course and served as FitzGerald’s lab demonstrator. Defries had considered becoming a medical missionary but FitzGerald persuaded him to focus on the more pressing mission of public health. Defries outlined a plan whereby, over the next five to six months, the Antitoxin Lab could prepare enough of the serum for every Canadian soldier for 65¢ a dose, compared to $1.25, which was the lowest price the Canadian Red Cross could negotiate with the New York City Health Department Laboratory. The proviso was that expanded stables and laboratories were needed as quickly as possible.
U of T’s Board of Governors quickly approved Defries’ plan, with President Robert Falconer telling Prime Minister Robert Borden that it was a “patriotic duty that we in Canada should manufacture tetanus antitoxin for our own expeditionary forces.” The Board, however, was unable to provide the needed $3,000 to $4,000, at least not immediately, suggesting that FitzGerald raise the money privately instead. Falconer had already approached a number of wealthy Toronto families for support, but they felt the Canadian government should foot this war-related cost.
Shortly after Falconer’s appeal to Ottawa, Colonel Albert E. Gooderham, manager of the Gooderham & Worts distillery in Toronto, met with Falconer and wrote a cheque for $3,000. A philanthropist, member of U of T’s Board of Governors and chairman of the Ontario Red Cross, Gooderham told Falconer that the funds had to be directed to providing facilities for the preparation of tetanus antitoxin so that a supply was available to the Canadian Red Cross. However, Falconer recognized he had a potential problem should the Canadian government grant funds, only to discover that the Lab had committed the entire output of antitoxin to the Red Cross. FitzGerald averted the conflict after arranging to immediately supply the Red Cross with 5,000 packages of antitoxin purchased, using the Labs’ reserves, from the New York City Health Department at a reduced price. In the meantime, Gooderham’s gift helped equip the Antitoxin Lab to produce enough Canadian supply of antitoxin by August.
By this time, Gooderham had also offered a much more valuable gift in support of FitzGerald’s enterprise. Falconer suggested that Gooderham visit FitzGerald to learn more about his plans. After a 90-minute discussion, FitzGerald showed Gooderham around the Lab’s Medical Building facilities, including the boiler room in the basement where he planned to stable a few tetanus antitoxin horses. Gooderham did not think much of that idea. He told FitzGerald, “I suppose for $12,000 to $16,000, it would be possible to purchase a few acres of land on Yonge Street and build a stable and some laboratories there.”
A few days later, Gooderham asked FitzGerald to meet at the offices of architects Stevens & Lee. Gooderham wanted to review preliminary sketches for the laboratory and stable building, and a superintendent’s residence, he had offered to build once a suitable site was found. Then, in early April, Gooderham took FitzGerald on a drive north into York Township. Gooderham’s real estate agent had heard about a possible site on the York-Vaughan town line at Dufferin Street, in the village of Fisherville. They found an abandoned 56-acre farm property that included a farmhouse, barn and unused mill. FitzGerald was impressed. Gooderham asked his agent to track down the owners and find out their price. But, he cautioned, “Don’t let them know that I am interested in it.”
While plans for the new buildings were finalized and construction proceeded, distribution of the Labs’ diphtheria antitoxin was expanding to most other provinces. In June 1915, FitzGerald highlighted the progress in his second Annual Report. “The support accorded the laboratory has greatly exceeded the most sanguine expectations, and its place in the scheme of public health activities is Canada made manifest.” 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.
In early 1916, the Antitoxin Lab also acquired the cattle stock and remaining smallpox vaccine supply from the Ontario Smallpox Vaccine Farm, which had been operating in the village of Palmerston in southwestern Ontario since 1885. Domestic and military demand for smallpox vaccine had grown beyond the capacity of the Vaccine Farm and similar small producers in Canada. The new lab facilities enabled a larger and higher quality vaccine supply for national distribution. By the fall of 1916, the Labs’ new farm property was largely occupied with its small staff focused on an expanded level of antitoxin and vaccine production for the war effort and the home front.
The new facility was not ready to be formally handed over to U of T until October 25, 1917, which coincided with Gooderham’s wedding anniversary. During the months leading up to the official opening of what was to be christened “Connaught Antitoxin Laboratories and University Farm” after the Duke of Connaught, Canada’s Governor General from 1911 to 1916, FitzGerald focused on securing more autonomy for the Labs. The director was given full authority over the Lab’s staff and over the “Connaught Laboratories Research Fund.” Under the arrangement with U of T, all surpluses from the sale of products were segregated from general university funds to support research in preventive medicine. Finally, so that Connaught might provide a truly national public health service, FitzGerald established an Honorary Advisory Committee of the Connaught Laboratories. Representatives of each provincial government health department and the federal government were appointed to this Committee to consult with FitzGerald in regard to scientific problems that Connaught could help address.
The new Connaught Laboratories farm site and buildings officially opened on a rainy October 25, 1917. With dignitaries assembled on a covered stage set up next to the new laboratory and stable building, Ontario premier, Sir William Hearst, announced that the Ontario government would contribute a $75,000 endowment to the Connaught Research Fund. Gooderham also announced a further gift of $25,000 for research at the Labs. When asked by reporters why the University was involved in such an unusual manufacturing enterprise, Sir Edmund Walker, chairman of U of T’s Board of Governors, explained, “Through the laboratories, the university would extend the work it is carrying on as a great instrument of good for the entire community apart from the educational purpose, by way of direct service for the betterment of general conditions throughout the country.”
Almost exactly a year later, on the eve of the armistice, a new public health crisis provided another opportunity for Connaught to be of national service. “Spanish Flu” first emerged in China in early 1918, but news of the rapidly spreading and especially deadly influenza pandemic was first reported in Spain’s uncensored press. By October 1918, as the pandemic’s second wave was spreading through North America, public health officials launched desperate efforts to prepare a vaccine based on the prevailing suspicion that new strains of Bacillus influenza were responsible (the influenza virus would not be isolated until 1933). The New York City Department of Health prepared an influenza vaccine and shared its bacterial cultures and production method with Connaught.
While FitzGerald was serving in France, attached to the Royal Army Medical Corps and in charge of a mobile laboratory, Defries led a small team in the Medical Building. They worked day and night over two months to prepare large quantities of what Defries described as an “experimental” vaccine. It was freely supplied to provincial health departments, hospitals, the military and various health services across the country, as well as to several U.S. states and even to Great Britain. Due to this unprecedented emergency, no claims for the effectiveness of the vaccine were made, but it did no apparent harm. The Lab’s efforts were widely appreciated and helped establish Connaught as a national public health centre in the minds of Canadian physicians and public health authorities.
In the wake of the Spanish Flu pandemic, much would change in Canadian public health, most notably the long-delayed creation of a federal department of health in May 1919. The new department’s Dominion Council of Health first met in the spring of 1920, with FitzGerald as a key member. The Council’s work succeeded that of the Honorary Advisory Committee set up at Connaught. In April 1920, Connaught was also granted a U.S. license. By July, the Labs became an independent unit within U of T, overseen by the “Connaught Committee” of the Board of Governors, with Gooderham its first chairman.
It’s at this point that Connaught’s story intersects with Banting’s. Early in the morning of October 31, 1920, in London, Ont., a young surgeon fresh from military service woke up in the middle of the night with a compelling idea for how to isolate the internal secretion of the pancreas and possibly treat diabetes. The impact of Dr. Frederick Banting’s idea would prove transformative, both for U of T and Connaught Laboratories.
Indeed, as noted elsewhere, Banting’s experimental work with calf pancreas tissue, initially on October 4, 1921, and again on November 19th, took place at Connaught’s farm site on Steeles Avenue West near Dufferin Street, where calves were involved in smallpox vaccine production.
Today, the legacy of the former farm site continues as the Connaught Campus of Sanofi Pasteur Limited, a key facility within Sanofi Pasteur’s global vaccine operations, and the wider Sanofi healthcare organization, which includes Sanofi Canada, based in Laval, Que. Currently, Lantus, Toujeo and Apidra are modern synthetic forms of Insulin that Sanofi supplies to Canadians living with diabetes.
In the early 1920s, Insulin was a new type of biological health product for Connaught Laboratories, one that prevented the debilitating and life-threatening effects of diabetes from developing. But it had to be administered, ultimately by the patient, at least once daily over a lifetime. Thus, Insulin was both like a biological vaccine and a pharmaceutical drug treatment. The efficient and ethical development of Insulin ultimately depended on scientific and practical skills, academic openness, and the distinctive public health/public service culture that had been fostered within U of T’s Connaught Labs.