Rocking machine stimulated virus growth
supply the world? And that’s what Leone Farrell did. That is a huge contribution.”
At the time, no lab in the U.S. had the experience to mass-produce the live polio virus needed to make the vaccine, says Christopher Rutty, professor at the Dalla Lana School of Public Health and a medical historian. But Connaught labs had developed an international reputation for making vaccines. And so, in July 1953, the U.S. March of Dimes asked Connaught to provide all the polio virus required for a field trial of Salk’s vaccine.
Enter Farrell, who led a team of scientists working in the bowels of the imposing University of Toronto Gothic building that housed the lab in the 1950s. There, she discovered that applying a simple rocking motion to bottles of the virus stimulated its growth, using monkey kidney cells and a synthetic nutrient base developed by Connaught in the 1940s.
In an incubation room, the bottles were placed in a custom-made rocking machine and gently rocked for several days to promote cell growth, explains Rutty. Her technique became known as the “Toronto Method” and would be the standard for polio vaccine production until the late 1970s.
Not only did Farrell develop the Toronto Method, but she also took on the mammoth task of scaling Connaught for mass production of the virus, recruiting technicians, obtaining space and equipment and sourcing a supply of nearly 200 monkeys per week, says Rutty. And it was dangerous work.
In later years, she described the risks in notes on file with Sanofi Pasteur Canada Archives. “The danger of the virus was known but physical protection was inadequate,” Farrell wrote. “That no infection occurred at that time seems miraculous in retrospect. I believe everyone thought at least once that they had contracted the disease.”
Once the virus was produced, it was packed in ice, loaded into the back of a station wagon and rushed to laboratories in the U.S. for final processing into vaccines. By June of 1956, Connaught had produced enough polio virus to make 2.3 million doses of vaccine, thanks to the work of Farrell and her team.
When the field trials were over and the vaccine declared a success in April 1955, Salk became a household name while Farrell became, at best, a footnote.
But Salk himself understood the enormity of Farrell’s contribution to the vaccine’s success, so much so that he decided to make a trip to Toronto to meet and thank her team in person.
Salk was “gobsmacked” by the work done by Farrell, says 82-year-old Grace Darling of Lindsay, who worked with her in the 1960s, and would later go on to become Connaught’s director of personnel. But there was a complication.
The now world-famous scientist was to be feted in the dining room of U of T’s School of Hygiene, a place where only men were allowed, Darling recalls. Salk was insistent on meeting the women on the team, so administrators came up with what they felt was a reasonable compromise: the female scientists could stand at the doorway of the dining room to shake the great man’s hand.
Farrell’s answer to this offer, says Darling, was firm: “No thank you.”
And although Farrell never considered herself a feminist, Darling says, “she realized that she didn’t get the recognition that she should have because she was a woman and not a man.”
In a lecture Farrell gave years later, she exhorted her students to work hard and added, “but all of this may not be enough, especially for a woman.”
Born in 1904 in Monkland Station, Ont., a small farming community near Ottawa, Farrell was raised in Toronto and graduated from Parkdale C.I. with a scholarship in science and the school’s top prizes in English and history. She received a PhD in biochemistry from U of T in 1933, when very few women had advanced degrees, especially in science.
She started at Connaught the next year and worked on production of a cholera vaccine, as well as a vaccine to prevent dysentery. In the 1940s, she worked to improve the production of penicillin.
Sixty-five years ago, when the world waited for the results of the massive field trial of Salk’s polio vaccine — involving 1.8 million children, the largest experiment in medical history, says Rutty — few people knew that it was Farrell’s work that made it possible.
Farrell acknowledged the significance of her role in that critical moment in a speech she gave a few months later: “It was at this point that I found myself in a little spot in the enormous field of endeavour,” she told the University Women’s Club in October 1955.
Van Exan, the consultant, says Farrell’s contribution to making a polio vaccine can be compared to the challenges faced by leading COVID-19 vaccine candidates today — Pfizer/BioNTech and Moderna. Both, says Van Exan, are using new technologies and both had to have someone who could scale up for mass production. (AstraZeneca has also announced successful trials.)
“That would have been the role that Leone Farrell played. And she would have been working with a technology that had never been done before,” he says. “The difference is that today there are 235 vaccine candidates. Back in 1955 there was only one.”
Rutty says the backdrop to Farrell’s work was Connaught’s seamless integration of scientific research and vaccine manufacturing — something Canada could desperately use today as it faces second-in-line status for a COVID vaccine behind nations that make their own.
He calls the creation of Connaught in 1914, as part of the University of Toronto, “a bold commitment to public health” that resulted in an international reputation for vaccine research and production capacity. The company was sold to the Canada Development Corp. in
1972. Canadian ownership ended in1989 when the Mulroney government approved a sale to French-owned Institut Merieux. Several mergers later, it became Sanofi Pasteur Canada, with head offices in Lyon, France, producing existing vaccines for Canadian and global markets.
After the success of the polio vaccine, Farrell continued to lead a team of technicians working to improve and expand the vaccine’s use in the 1960s. Darling paints a picture of a woman who loved fashion, abhorred housework and preferred Swiss Chalet to cooking. She also loved to host bridge parties at her Avenue Road apartment. But most important, Darling says, Farrell “was a great lady and a great mentor.”
Darling recalls the time she got a call that her father was dying in hospital in New Liskeard, Ont.
She says Farrell “got on the phone and got the head of Connaught’s chauffeur to pick me up and take me immediately to the airport. She had the tickets and she had cash for me. She said ‘Maybe you can get there before he dies.’ ”
Farrell lived alone and never married. She retired from Connaught in 1969, but continued to write and publish research papers. She developed Alzheimer’s disease and lived in a nursing home in the latter part of her life. In 1986, she died of lung cancer at the age of 82.
For years, her grave at Park Lawn Cemetery in Toronto would go unmarked. In 2008, relatives, after learning of her groundbreaking work, would correct that oversight with a detailed inscription on a family gravestone:
“… Her development of the ‘Toronto Method’ of polio virus production in 1953 was essential to the success of the first polio vaccine saving millions from the crippling impact of this disease.”