In his third in a series on pandemics in Toronto, Richard Longley explores diphtheria, the “strangler”, the struggle of which would lead to the development of the world’s renowned vaccine laboratory at the University of Toronto.
When diphtheria was epidemic, it was called “the strangler.” In severe cases, it was a horrible disease. A leathery, grayish “pseudomembrane” developed above the throat and nasal passages, blocking the airways, causing wheezing, stertorous breathing, barking cough, and possibly asphyxia and death. In the past, there were two options for opening the airways, both of which were brutal: tracheostomy, section of the trachea or intubation, insertion of a breathing tube through the membrane.
In 1924, the worst year for diphtheria in this country, there were 9,000 cases and 2,000 deaths.
A diphtheria antitoxin has been around since 1894. It has been produced in many countries but not in Canada, where it had to be imported from the United States at such a high price that one in three children infected with the disease died.
What Canada needed was a public health laboratory capable of producing and distributing diphtheria antitoxin in the quantities it needed, at an affordable price for everyone.
In 1913, this challenge was met in Toronto by John Gerald FitzGerald, 31. Driven by his determination, a diphtheria antitoxin would eventually be free and the bases for research, development and production of vaccines would be built in Canada, with consequences that would be felt worldwide. But the almost forgotten brilliant life and work of this pioneer would end tragically.
Laboratory stable on Barton
In December 1907, four years after graduating from the University of Toronto medical school, the mother of John Gerald FitzGerald, 51, died of heart failure. Nine months later, shaken by the fact that the drugs of his day could not save her, FitzGerald resigned from his position as pathologist and clinical director at what was then the Toronto Asylum for the Insane (now CAMH) for pursue a new career in public health and prevention. drug. In 1910 he married Edna Leonard, who had inherited a fortune from his grandfather, an iron founder from London, Ontario. After a year as an associate professor at the University of California at Berkeley, FitzGerald took Edna to Europe, where he spent much of his “working honeymoon” at the Institut Pasteur in Brussels, where he learned how to make vaccines and anti-toxins.
In 1913 FitzGerald returned with Edna to Toronto where he had been appointed to the University’s Department of Hygiene. At the Provincial Laboratory at 5, Queen’s Park Crescent, he began preparing the country’s first rabies treatment, with his assistant William “Billy” Fenton, who courageously tested it.
But FitzGerald was more concerned about the greater threat of diphtheria. He insisted that a laboratory on the model of the Institut Pasteur be created by the University of Toronto for the manufacture of anti-toxin. But the governors of the university hesitated, so FitzGerald proceeded on his own.
With a gift of $ 3,000 from his wife (who complains: “I am married to an idea, not to a man”). FitzGerald has built a stable laboratory in the backyard of Billy Fenton’s home at 145 Barton Avenue, just east of Christie Pits. This is where he kept Crestfallen, Surprise, Fireman, Goliath and J.H.C., five older horses that FitzGerald bought for $ 5 each. They were intended to be slaughtered and sold to a glue factory, but they were recruited from the large FitzGerald company.
The horses were injected with progressively increased amounts of diphtheria toxin at levels sufficient to kill several men, but none of these horses died. Rather, they have developed immunity. Then FitzGerald made diphtheria toxoid from their blood serum.
Birth of Connaught Laboratories
FitzGerald’s success has strengthened his determination to have the University of Toronto establish its version of a Pasteur Institute. This time he had other supporters. They included Ontario’s chief medical officer of health, Charles Hastings, who had long complained about the high price of the anti-toxin imported into Canada.
On May 1, 1914, the university’s board of governors established the hygiene department’s toxoid lab in the basement of the medical building. The timing – three months before the start of the First World War – was premonitory.
The demand for tetanus toxoid, meningitis serum and smallpox vaccine would be enormous. The laboratory expansion was made possible by the Ontario Red Cross chief, Albert Gooderham, of the distilleries, with a donation of 56 acres of farmland to Dufferin and Steeles and funding for construction new stables and laboratories.
In 1917, at Gooder’s instigation, the laboratories at the University of Toronto were renamed Connaught Antitoxin Laboratories and University Farm, named after the youngest son of Queen Victoria, Arthur, Duke of Connaught. The outgoing Governor General of Canada and father of the Royal Canadian sweetheart, the beloved Princess Pat, who will become Colonel-in-Chief of the Princess Patricia’s Canadian Light Infantry.
Meeting at the Institut Pasteur
In 1923, the Rockefeller Foundation invested $ 1.25 million to establish a school of hygiene at the University of Toronto. It would be the third funded by the foundation in North America, after its schools at Harvard and Johns Hopkins universities. Construction of the building, designed by the architects Mathers and Haldenby, began in 1924. It was completed in 1927. in 2008, the School of Hygiene became the School of Public Health Dalla Lana and moved to the former Toronto School Board building at 155 College Street. The FitzGerald building is currently being revitalized as a new university administrative building.
John FitzGerald’s ability to enable mass production of affordable diphtheria antitoxin in Canada has been a triumph, but as a treatment it has not always been successful, especially when administered late after ‘infection. It also had a short shelf life. This could be particularly problematic when diphtheria struck remote places, as it did, dramatically, in Alaska in 1925 and Fort Vermillion, Alberta in 1929. What was needed was a vaccine that would immunize children without having to undergo the test. infection.
In 1924, FitzGerald went to the Institut Pasteur in Paris to meet Gaston Ramon who discovered that by heating the diphtheria toxin and treating it with formaldehyde, it could be made into toxoid safe for vaccination. But as with anti-toxin, the challenge was to produce at low cost and in bulk. Confident that Connaught could do both, FitzGerald wired Ramon’s methods to the colleague he had recruited in 1919, Peter Moloney, with the order to drop everything and immediately start preparing and improving the toxoid.
23 years did it that year. In 1921, Moloney invented the “Moloney electrode” which accelerated the manufacture of diphtheria toxoid. It only took a year to produce enough for a trial.
Between September 1925 and February 1927, 120,000 children in nine provinces were vaccinated to test Connaught’s diphtheria toxoid. In Toronto, the most sophisticated nationwide field trial between 1926 and 1929 – one involving 46,000 children – has shown a 90% reduction in diphtheria cases after three injections. The results in Hamilton were particularly spectacular.
By 1940, the year FitzGerald died, Toronto and Hamilton had become the first diphtheria-free cities in the world. In the past 20 years, fewer than five cases of diphtheria have been reported in Canada each year.
From diphtheria to diabetes
In addition to being a superb biochemist and physiologist, FitzGerald was a brilliant promoter and manager of the sometimes thorny individuals who were pioneers of medical research in Canada. In January 1922, Frederick Banting and Charles Best successfully treated the diabetes of Leonard Thompson, 14, with insulin. Their previous attempt had failed. The problem was solved by the unsung hero of the saga, James Collip, who was able to prepare a more purified insulin that helped control the boy’s diabetes.
To speed up and expand their work, FitzGerald awarded the insulin discovery team $ 5,000 and facilities in the Connaught Medical Building.
He also facilitated an agreement between the team members who ensured the development of insulin for Connaught and the University of Toronto. In October 1923, Banting and Macleod received the Nobel Prize in physiology and medicine. Recognizing their partners in the discovery of insulin, Banting shared half the price with Best, while Macleod shared half with Collip.
But as with diphtheria, there was the production challenge. This challenge would be taken up by Moloney’s electrode and another FitzGerald recruit, David Scott, who discovered that replacing acetone with alcohol in the Collip purification process could increase production and significantly reduce the cost of insulin. Connaught’s production increased while the price of insulin fell.
In 1933 Scott further increased insulin production by using small amounts of zinc chloride to cause his first crystallization. With his colleague Albert Fisher, he made this success the goal of prolonging the effect of insulin injections and thus reducing their frequency.
On October 1, 1955, June Callwood described insulin production in an article she wrote for Maclean’s magazine, The Miracle Factory, which started in a stable.
A dreadful end
Much more than the enhancement of insulin by Scott and Fisher was made at Connaught Labs in the 1930s, most without the supervision of FitzGerald. Throughout this very productive decade, he delegated much of the management of the labs to the man who would eventually be his successor, Robert Defries, but that did nothing to slow the hectic pace of his professional life .
In 1931 FitzGerald became the first Canadian Scientific Director of the International Health Division of the Rockefeller Foundation. In 1936, after four years as dean of medicine at the University of Toronto, he spent a year traveling to 24 countries in Europe and North America, evaluating medical schools and hospitals for the Society of Nations. It was a rhythm that no one could keep up with, not even FitzGerald. In February 1939, suffering from migraines, a hemorrhagic ulcer, deep depression and paranoia, he attempted suicide. During the rest of the year, he received 57 insulin shock treatments that caused sweating, seizures and a diabetic coma. When his treatment ended, he was assured that “all your difficulties are now definitely behind you”.
In April 1940 FitzGerald attempted suicide again with sleeping pills, but again failed. While recovering at Toronto General Hospital, he made a third, final and successful attempt, this time with a knife with which he severed his femoral artery. It was a horrible end for a brilliant career. On the day of his death, FitzGerald was only 57 years old.
Pioneering role in vaccine research
Connaught scientists continued to play a pioneering role in the production of vaccines that immunize against multiple diseases at once. In the 1940s, they helped produce a typhus vaccine. And they combined the diphtheria and tetanus vaccines with another killer of children, whooping cough (whooping cough), which was produced in bulk at Connaught in the 1920s and 1930s. The result was DPT, a vaccine combined against diphtheria, whooping cough and tetanus.
In 1959, Connaught researchers combined the polio vaccine with DPT to make DPTP. It was not the first of Connaught’s many contributions to the polio campaign, nor the last.
If a vaccine for COVID-19 is discovered and produced in the quantities that will be needed, it will surely be by a team – probably international – which will include genius players and managers who share the strengths of FitzGerald in abundance.
To learn more about the Connaught saga, visit Christopher J. Rutty, A History of Connaught Laboratories.