Search for the Vaccine

More than one month in, we’re all living the “new normal”. The COVID-19 pandemic has not only threatened public health and stretched the medical profession, but it has also closed national borders, changed personal lifestyles, and damaged Canada’s economy.

A previously unknown virus, COVID-19’s genetic sequence was quickly identified by Chinese scientists in January. Still, many of its behaviours and characteristics remained unclear as worldwide public health authorities rushed to minimize its impacts. We now know that the virus is highly contagious.

The funding announced by Prime Minister Justin Trudeau is sizable by any account, but is amplified by contributions from other countries in a worldwide race to find a vaccine. Public authorities have targeted an ambitious 12 to 18 month time frame. If achieved, it will be the fastest vaccine developed in human history, superseding the mumps vaccine which took four years to get to market.

On the way to setting this record, many questions remain. How effective would a COVID-19 vaccine be? How would it be administered? Will it be mandatory?

For some insight, we look back at Toronto’s history with preventive medicine, and its successes in the development and refinement of several vaccines in the 20th century.

The Vaccination Act of 1914 gave municipal health officers across Ontario the power to order general immunization during outbreaks. During a 1919 smallpox outbreak in Toronto, medical officer of health Charles Hastings ordered the vaccination of all schoolchildren; those who did not receive the vaccine within a prescribed period of time would be banned from schools.

A public outcry resulted, fueled by misinformation, including the claim that vaccines were made from dead bodies, and concerns about physical complications. Smallpox vaccinations required scratching a patch of skin raw, and this could cause unsightly and painful sores.

The Anti-Vaccination League, formed in 1900, organized a campaign across the city protesting against mandatory vaccination.

Faced with this vocal uproar, the city ended compulsory vaccination. When the outbreak ended a few months later, there had been 2,864 cases, 11 deaths, and 200,000 vaccinations.

In the early 20th century, smallpox outbreaks continued in Toronto, and throughout the country. 30 to 50% of non-vaccinated people who contracted smallpox died. Through public health measures, like the inoculation of schoolchildren, incidences were under control by the 1940s.

Then, on August 17, 1962, 14-year-old James Orr became the first confirmed case of smallpox in Canada in 20 years. He had travelled with his family from Brazil, where the disease remained a significant threat, through New York to his home in Toronto. Orr’s case, though mild, attracted wide public attention, and given his travel history and delay in diagnosis, led to thousands of people in the United States and Canada being vaccinated, all through contact tracing.

The case highlighted the potential worldwide threat posed by the virus, still prevalent in developing countries, with increased international travel. The result was galvanized international action led by the US and the World Health Organization, including increased funding and resources for smallpox research and vaccine production.

A lead player in the effort was Toronto’s Connaught Laboratories. It had led the production of the modern smallpox vaccine for Canada since 1916. During World War I, it provided smallpox vaccines to the Canadian war effort. Now, it teamed with the WHO, providing research, training and direction for local labs in Latin America. Connaught also continued its own smallpox vaccine and testing improvements, supplying vaccines for the Canadian market, and eventually 35,000,000 doses for several African countries, and Bangladesh, India, Iran, and Pakistan.

This internationally recognized research facility had humble, if inspired, beginnings. It began on May 1, 1914, as the Antitoxin Laboratory in the University of Toronto’s Department of Hygiene. The vision of public health pioneer Dr. John Gerald FitzGerald, the laboratory’s initial work focused on treatment for diphtheria.

Well into the 20th century, diphtheria was the leading cause of death in Canadian children. An airborne bacteria transmitted through close contact, it caused respiratory disease. The antitoxin treatment developed in Germany was expensive to import. FitzGerald, a professor in the Department of Hygiene at the University of Toronto, negotiated a personal agreement with Ontario’s Chief Medical Officer that the Provincial Board of Health would buy any diphtheria antitoxin he could produce at cost and distribute it for free.

He began the preliminary work in a barn on Barton Avenue using horses saved from the glue factory. There, he injected the animals with a diphtheria toxin, and used the antibodies they produced to create Canada’s first antitoxin for the disease.

Armed with this success and the commitment from the province to buy his product, FitzGerald approached his employer with an idea for a self-supporting research laboratory focused on the development of high-quality, low-cost vaccines and preventive medicines.

With additional support and funding from leading Toronto businessmen and philanthropists, Sir. Edmond Osler and Albert E. Gooderham, the laboratory was soon working on tetanus and rabies treatments for soldiers and civilians.

It had also expanded its facilities, purchasing a large farm property north of the city at present day Steeles Street, east of Dufferin Street.

Following the sensational discovery of insulin at the university in 1921, Connaught offered lab space and funding to discoverers Frederick Banting and Charles Best.

Their Nobel-prize winning work, combined with the efforts of local public health authorities and hospitals, grew Toronto’s reputation for innovative public health services, and led to a substantial donation from the Rockefeller Foundation to support the establishment of a School of Hygiene.

Situated within the school, Connaught Labs continued its advances . “The Strangler,” as diphtheria was known, remained a leading public health threat to children under 14. Treatment with the diphtheria antitoxin minimized deaths, but a new preventive treatment developed in France seemed to stimulate active immunity. The new discovery found that treating a potent diphtheria toxin with formaldehyde and heat could make it non-toxic. The resulting “toxoid’ could then be safely injected.

Connaught launched field trials in several cites in September 1925. In Toronto, 36,000 children were vaccinated between December 1926 and June 1929. Findings showed a reduction of disease by 90%. The number of cases and deaths declined, and in 1940, Toronto reported no cases of diphtheria for the first time.

In 1943, Connaught Labs acquired the vacant building at One Spadina Crescent – formerly Knox College – with help from the Department of Defence. The facility provided additional space for the large-scale production and refinement of penicillin needed for the Canadian war effort.

Post-war efforts soon concentrated on polio, a devastating virus present in human waste that could cause paralysis of the muscles that control breathing. Waves of the disease began appearing in the 1910s, with worsening outbreaks culminating in 1953 when Canada saw 9000 cases and 494 deaths.

American Jonas Salk developed one of the first successful polio vaccines; it used formaldehyde to inactivate the virus while still triggering an immune response when injected. The ability to scale-up the vaccine for human trial relied on two Toronto-based developments – the world’s first purely synthetic nutrient medium for growing cells, Medium 199, developed at Connaught for use in cancer research, and The Toronto Method – a new process for cultivating viruses using bottles that are gently rocked on custom-designed racks.

These key advancements allowed for the vaccine’s 1954 mass field trial on 1,800,000 children – the majority in the US, with about 25,000 in Canada. Connaught supplied all 3,000 litres of the vaccination fluids needed for the trial, whose findings proved the vaccine to be 60 to 90% effective.

Licensed for use in the US and Canada, Connaught Labs supplied Canada with a safe polio vaccine. The cost of the vaccine was covered by the government and it was distributed for free to children.

Always in the pursuit of refinements and advances, Connaught soon tackled an oral polio vaccine developed by Albert Sabin. Using a live but weakened virus, the vaccine builds immunity in the digestive tract where polio replicates. Benefits included longer immunity and cheaper production of the vaccine, which however, carried a potential risk of active disease and paralysis.

Sold by the University of Toronto in 1972, Connaught Labs continues today as Sanofi Pasteur Canada. Their current work includes “leveraging previous development work for a SARS vaccine as part of our goal to unlock a fast path forward for developing a COVID-19 vaccine”.

Built on a legacy of success, they know well the struggle and frustrations of this work. 17 years after the outbreak, there is no SARS vaccine. 

Much further back, a rush to develop a vaccine for the 1919 Spanish Flu failed. Connaught Labs produced and distributed an experimental vaccine based on the incorrect assumption that the disease was caused by a bacteria. Ineffective, at least the vaccine caused no harm.

In tackling the COVID-19 vaccine, we’ll need to address the immunity question. The federal government’s funding announcement included the development of an immunity task force comprised of leading experts and scientists from across the country. This group will work to determine if exposure and recovery results in immunity, and if so, how long that immunity lasts.

One million Canadians will be tested as part of the study over the next two years.