In his third in a series on Toronto pandemics past, Richard Longley explores diphtheria, “the strangler,” the fight against which would lead to the development of the University of Toronto’s world-famous laboratory for vaccines.
When diphtheria was epidemic it was called “the strangler.” In severe cases, it was a horrible disease. A leathery, greyish “pseudomembrane” grew over the throat and nasal passages, blocking the airways, causing whistling, stertorous breathing, a barking cough, and, eventually, asphyxiation and death. In the past, there were two options for opening the airways, both of them brutal: tracheotomy, severing the windpipe 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 had existed since 1894. It was produced in many countries but not in Canada, where it had to be imported from the U.S. at a price so high that one in every 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 needed, at a price that would be affordable for all.
In 1913 this challenge was taken up in Toronto by 31-year old John Gerald FitzGerald. Driven by his determination, a diphtheria antitoxin would eventually be free and the foundations of vaccine research, development and production would be built in Canada, with consequences that would be felt worldwide. But this pioneer’s almost forgotten brilliant life and work would end tragically.
Stable-laboratory on Barton
In December 1907, four years after he graduated from the University of Toronto Medical School, John Gerald FitzGerald’s 51-year old mother died of heart failure. Nine months later, shaken that the medicine of her day could not save her, FitzGerald resigned his position as pathologist and clinical director at what was then the Toronto Asylum for the Insane (it’s now CAMH) to pursue a new career in public health and preventative medicine. In 1910 he married Edna Leonard, who’d inherited a fortune from her grandfather, a London, Ontario iron founder. After a year as an associate professor at the University of California, Berkeley, FitzGerald took Edna to Europe, where he spent much of his “working honeymoon” at the Pasteur Institute in Brussels, learning how to make vaccines and antitoxins.
In 1913, FitzGerald returned with Edna to Toronto where he had been appointed to the University’s Department of Hygiene. In the Provincial Laboratory at 5 Queen’s Park Crescent he set to the preparation of this country’s first rabies treatment, with his assistant William “Billy” Fenton, who bravely tested it on himself.
But FitzGerald was more concerned with the greater threat of diphtheria. He insisted that a laboratory patterned after the Pasteur Institute should be established by the University of Toronto for the manufacture of antitoxin. But the university’s governors demurred, so FitzGerald proceeded on his own.
With a $3,000 gift from his wife (who would complain: “I’m married to an idea, not a man”). FitzGerald built a stable-laboratory in the backyard of Billy Fenton’s home at 145 Barton Avenue, just east of Christie Pits. It was here that he kept Crestfallen, Surprise, Fireman, Goliath and J.H.C., five aged horses FitzGerald had bought for $5 each. They had been destined for slaughter and sale to a glue factory, instead, they were recruited into FitzGerald’s great enterprise.
The horses were injected with progressively increased quantities of diphtheria toxin to levels sufficient to kill several men but none of those horses died. They built up immunity instead. Then, from their blood serum, FitzGerald made diphtheria antitoxin.
John Gerald FitzGerald’s stable-laboratory at 145 Barton Avenue, in the backyard of the home of his assistant William “Billy” Fenton, who stands at the door.
Connaught Laboratories is born
FitzGerald’s success reinforced his determination that the University of Toronto should establish its version of a Pasteur Institute. This time he had other supporters. They included Ontario’s Chief Medical Officer of Health, Charles McCullough, who had long complained about the high price of imported antitoxin in Canada.
On May 1, 1914, the university’s Board of Governors established the Antitoxin Laboratory in the Department of Hygiene in the basement of the Medical Building. The timing – three months prior to the outbreak of the First World War – was prescient.
Demand for tetanus antitoxin, meningitis serum, and smallpox vaccine would be enormous. The scaling up of the lab was enabled by the head of the Red Cross in Ontario, Albert Gooderham of the distillery family, with a donation of 56 acres of farmland at Dufferin and Steeles and funding for the construction of new stables and laboratories.
In 1917, at Gooderham’s urging, the University of Toronto labs were renamed the Connaught Antitoxin Laboratories and University Farm, after Queen Victoria’s youngest son, Arthur, Duke of Connaught. The departing Governor General of Canada and father of Canada’s royal sweetheart, the beloved Princess Pat, who would become Colonel-in-Chief of Princess Patricia’s Canadian Light Infantry.
The original building of Connaught Antitoxin Laboratories and University Farm, circa 1917. Over 100 years later, it still stands at Sanofi Pasteur Canada and accommodates the laboratories’ Heritage Room.
Meeting at the Pasteur Institute
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 architects Mathers & Haldenby, began in 1924. It was completed in 1927.
In 1975, the School of Hygiene closed and elements of it were integrated into U of T’s Faculty of Medicine Division of Community Medicine. In 2008, thanks to a donation by Paul and Alessandra Dalla Lana, these elements and others were integrated into the new Dalla Lana School of Public Health and relocated to the former Toronto School Board building at 155 College Street.
John FitzGerald’s enabling the mass production of affordable diphtheria antitoxin in Canada was a triumph but as a treatment, it was not always successful, especially when it was given late after infection. It also had a short shelf life. That could be particularly problematic when diphtheria struck in remote places, as it did, dramatically, in Alaska in 1925, and in Fort Vermillion, Alberta in 1929. What was needed was a vaccine that would make children immune without having to go through the ordeal of infection.
In 1924, FitzGerald went to the Pasteur Institute in Paris to meet Gaston Ramon who had discovered that by heating diphtheria toxin and treating it with formaldehyde, it could be turned into a toxoid safe for vaccination. But as with the antitoxin, the challenge was producing cheaply and in bulk. Confident that Connaught could do both, FitzGerald cabled Ramon’s methods to the colleague he’d recruited in 1919, Peter Moloney, with an order that he drop everything and immediately begin preparing and improving the toxoid.
That year 23-year old did. In 1921, Moloney invented the “Moloney Electrode” which sped up the making of diphtheria antitoxin. It took him just 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 of the nation-wide field trials between 1926 and 1929 – one involving 46,000 children – showed a reduction of diphtheria cases by 90 per cent after three injections. The results in Hamilton were especially spectacular.
By 1940, the year of FitzGerald’s death, Toronto and Hamilton had become the world’s first diphtheria-free cities. In the last 20 years, fewer than five cases of diphtheria have been reported each year in Canada.
John Gerald FitzGerald, 1882-1940.
From diphtheria to diabetes
As well as a superb biochemist and physiologist, FitzGerald was a brilliant promoter and manager of the sometimes prickly individuals who were pioneering medical research in Canada. In January 1922, Frederick Banting and Charles Best successfully treated 14-year old Leonard Thompson’s diabetes 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 which brought the boy’s diabetes under control.
To expedite and expand their work, FitzGerald gave the insulin discovery team $5,000 and facilities in Connaught’s Medical Building.
He also facilitated an agreement between the members of the team that secured the development of insulin for Connaught and the University of Toronto. In October 1923, Banting and Macleod were awarded the Nobel Prize in Physiology and Medicine. Recognizing their partners in the discovery of insulin, Banting shared his half of the prize with Best, while Macleod shared his half with Collip.
But as with diphtheria, there was the challenge of production. That challenge would be met by Moloney’s Electrode and another of FitzGerald’s recruits, David Scott, who discovered that substituting acetone for alcohol in Collip’s purification process could increase production and reduce the cost of insulin considerably. Connaught’s production grew while the price of insulin fell.
In 1933, Scott enhanced insulin production yet again by using small amounts of zinc chloride to bring about its first crystallization. With his colleague Albert Fisher, he turned that success to the goal of prolonging the effect of insulin injections and thereby reducing their frequency.
On October 1, 1955, June Callwood described the manufacture of insulin in an article she wrote for Maclean’s magazine, The Miracle Factory that began in a Stable.
A ghastly end
Much more than the improvement of insulin by Scott and Fisher was achieved at Connaught Labs during the 1930s, most of it without the oversight of FitzGerald. Throughout that highly productive decade, he delegated much of the running of the labs to the man who would eventually be his successor, Robert Defries, but that did nothing to slow the frenetic pace of his professional life.
In 1931 FitzGerald became the first Canadian scientific director of the Rockefeller Foundation’s international health division. In 1936, after four years as dean of medicine at the University of Toronto, he spent a year travelling to 24 countries in Europe and North America, assessing medical schools and hospitals for the League of Nations. It was a pace nobody could sustain, not even FitzGerald. In February 1939, suffering from migraines, a bleeding ulcer, deep depression and paranoia, he attempted suicide. Through the remainder of that year, he was given 57 insulin shock treatments that caused sweating, convulsions and a diabetic coma. When his treatment concluded he was assured that “all your difficulties are now permanently behind you.”
In April 1940 FitzGerald tried to kill himself again with sleeping pills, but again he failed. While he was recovering in 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 ghastly end to a brilliant career. On the day of his death, FitzGerald was just 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 in a single shot. In the 1940s, they contributed to the production of a vaccine for typhus. They also combined the vaccine against diphtheria with a vaccine against another child-killer, pertussis (whooping cough). By the end of World War II, they had added tetanus toxoids to create DPT, a combined vaccine against Diphtheria, Pertussis and Tetanus.
In 1959 Connaught researchers combined the polio vaccine with DPT to make DPTP. This was not the first of Connaught’s many contributions to the campaign against polio nor would it be the last.
If a vaccine for COVID-19 is discovered and produced in the quantities that will be required, it will surely be by a team – probably international – that will include players of genius and managers who share the strengths of FitzGerald in abundance.
University of Toronto’s School of Hygiene FitzGerald Building was erected in 1927.
For more about the Connaught saga, visit Christopher J. Rutty’s, A History of Connaught Laboratories.
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