Cite

Leone Farrell

The discovery and development of a lifesaving drug can only be deemed successful if it can be mass produced to match the needs of the population suffering from the disease. Such was the dilemma faced by Dr. Frederick Banting immediately following his discovery of insulin. He was caught by surprise with the demands for insulin from diabetics across the country and abroad, when news of insulin’s discovery spread before the mass production method could be formulated. The insulin extraction method had not yet been made efficient enough for mass production and this is when Connaught Laboratory offered to collaborate with Dr. Banting and his team to mass produce their life-saving insulin. A few decades later, the same Connaught lab also became the mass producer of a different elixir to treat  ‘The Crippler’ disease: the Polio vaccine. Working tirelessly, Dr. Leone Farrell had formulated a method, famously dubbed the ‘Toronto Method’, that brought the rate of  polio infections among Canadian children from 50,000 in the 1950s to almost zero by 1965. Yet, the story of this little known science heroine became buried in the archives, and has only recently been unearthed in the face of the global COVID-19 pandemic and the race for a vaccination.

Born in 1904 in Monkland, Ontario and raised in Toronto, Leone Norwood Farrell was a bright student with a promising future, winning top school awards in English and History, and a science scholarship at her high school graduation from Parkdale C.I. Very little is known about her life prior to her time at the University of Toronto (UofT) where she completed her Bachelor of Arts in 1928, followed by a Masters degree in Chemistry in 1929, and  a Doctorate in biochemistry in 1933 – a level of academic achievement rare for women at the time. Before she began her PhD at UofT, Farrell had pursued further studies at the National Research Council and at the London School of Hygiene and Tropical Medicine in the United Kingdom, only to later return to Toronto. After earning her PhD, she was employed by the Connaught Research Lab in 1934, working on the development of a toxoid vaccine for dysentery, an intestinal infection caused by staphylococcus bacteria. During this work, Leone developed a rather simple, yet highly effective, “Toronto Method” of gently rocking cell cultures in specially designed machines. This “Toronto Method” accelerated the vaccine production by allowing Farrell’s team to efficiently produce large vaccine stocks in a very short amount of time.

The development and improvement of vaccines became Leone’s expertise. She became involved in the successful production of cholera and penicillin vaccines in the 1940s. The pertussis vaccine, which was originally developed in 1912 in Belgium for the “whooping cough” disease had killed 1 in every 200 infected children under the age of 5 years by the early 1900s. In the 1940s, however, Connaught Lab refined the vaccine development method and Dr. Farrell then used her invention of the ‘rocking bottle machine’ for large-scale production of the improved Connaught vaccine. Owing to the vaccine’s mass production via ‘rocking bottle’ method, deaths linked with pertussis were brought down to almost zero in Canada by the 1950s.

At the turn of the 20th Century, cases of Poliomyelitis, more famously known as polio or infantile paralysis, grew to epidemic levels, with children suffering in higher numbers and with more detrimental consequences than adults. After the 1916 epidemic in the United States where polio claimed 6000 lives of the nearly 27,000 infected, Canada closed the borders to the U.S. Additional polio epidemic waves continued to hit parts of Canada until the 1950s, reaching its highest peak in 1953 with nearly 9000 infections. The Polio Epidemic caused border closures and other socio-economic effects, especially school closures to control the virus’ spread, as children were the worst affected. Interestingly, a Nobel Prize had been awarded in 1949 to American researchers for their discovery of poliovirus’ ability to grow in cultures of various tissue types, and not solely on nervous tissues as had been the case. This allowed Dr. Jonas Salk, an epidemiologist and the Director of the Virus Research Laboratory at the University of Pittsburgh School of Medicine, who was among the pioneers of the ‘killed-virus’ vaccination method, to develop the poliovirus vaccine. This major breakthrough made him into a highly celebrated public health figure. He was able to demonstrate that killed-poliovirus strain injected into the body caused antibody production as an immune response, but the next big issue facing Dr. Salk after his breakthrough was similar to Dr. Banting’s dilemma – too many deserving recipients, but too little elixir. Just as Dr. J. G. Fitzgerald from Connaught had appeared to Dr. Banting as a saviour at such a crucial moment, it was Dr. Farrell at the Connaught Laboratory that provided the solution yet again to the problem of limited production availability of the polio vaccine. Dr. Salk could produce only a few grams of the killed-virus using tissue culture of monkey kidneys, which posed a threat of allergic reactions to the vaccine recipients. No facility in the United States existed at the time that could grow large quantities of killed-virus needed for both the clinical trials or mass public inoculations. Leone refined her methods for mass production of vaccines by using “Medium 199”, a synthetic growth culture which was originally developed for cancer research by Connaught scientists. Leone then decided to use this culture to grow poliovirus in large quantities by using the specially designed bottle-rocking machines. This method was an immediate and major success, and became known as the ‘Toronto Method’, a method later standardized for polio vaccine production for the next several decades.  

When Dr. Banting had developed the insulin extract, and confirmed its effectiveness in treating diabetes, he was able to make demands from his institutional employers, such as a better administrative team, steady supply of research dogs, and better collaboration with other researchers. Conversely, Dr. Farrell was forced to multitask, even after developing her successful ‘Toronto Method.’ She was responsible for not only creating the means to mass produce vaccinations, but also recruiting qualified technicians, securing better equipment, and arranging the supply of 200 monkeys weekly. These poliovirus stocks prepared at Connaught were then supplied to Dr. Salk in the U.S. and were abundant enough to carry out the largest known clinical trial that involved around 1.8 million children. The trial was later declared a great success and plentiful stocks were produced to inoculate all Canadian children. Dr. Leone Farrell had requested Connaught administrators not to patent the mass production process, presumably to ensure that other labs, whether Canadian or abroad, were able to produce enough to eradicate polio and other infectious diseases, a gesture similar to Dr. Banting’s hesitance in patenting the insulin extraction process.

While Dr. Salk became a medical celebrity, with his face appearing on the cover of Time Magazine in 1954, Dr. Farrell and her groundbreaking work went under-recognized. Nevertheless, the successful results of her research were a sufficient satisfaction and reward for Farrell. Unfortunately, when Dr. Salk made a trip to Toronto’s Connaught Laboratory with the intention of showing gratitude to ‘team Farrell’, Dr. Farrell and the other women involved in the production of the vaccinations were not invited as the ceremonial meeting was held at a men’s-only dining hall at the UofT’s School of Hygiene. They were instead offered to meet him outside the hall, but maintaining her dignity, Leone gracefully declined this offer with a “no thank you”^[1]. Neglect of Dr. Farrell continued for almost a century, only to be finally recognized when infectious diseases and roles of vaccinations have once more become an issue of global importance.

Although little is known about Farrell outside of her role at the Connaught Laboratory and her research publications, there is growing interest in her story that provide clues to her struggles as a woman in research and development. For example, Dr. Farrell had once revealed her deliberate intent to disguise herself as a man in order to survive the ‘man’s world’ when seeking to apply for work at Naval Intelligence in 1941. “My intention” she stated “has always been ‘to be a lady chemist’ – and not look like it […]I have been charged with being a chameleon”.^[2] Leone was not alone in facing gender discrimination in research and development at Canadian institutions, but the question today begs if women as a collective have had to maintain that same ‘chameleon’ attitude in order to utilize their talents and build careers.

Leone Farrell had developed Alzheimer’s Disease towards the latter part of her life and died of lung cancer in 1986 at the age of 82. Like most Canadian women in scientific research and development in the first half of the 20th Century, Farrell too did not marry, nor had children, and resided alone in a nursing home in old age. While never gently rocking a child of her own, Leone’s ‘Toronto Method’ of gently rocking the polio and other vaccines, saved the lives of millions of children in Canada and around the world from ‘the crippler’ polio, whooping cough and other infectious diseases.

Bibliography

Austen, Ian. “Canada’s Key Role in Creating a Once Awaited Vaccine.” The New York Times. The New York Times, August 1, 2020. https://www.nytimes.com/2020/07/31/world/canada/leone-farrell-chemist.html.

Black, Karen. “Making a Vaccine Is Not the Same as Mass-Producing It. This Canadian Scientist Solved the Problem for the Polio Vaccine – Then She Was Largely Forgotten.” thestar.com, November 29, 2020. https://www.thestar.com/news/gta/2020/11/29/making-a-vaccine-is-not-the-same-as-mass-producing-it-this-canadian-scientist-solved-the-problem-for-the-polio-vaccine-then-she-was-largely-forgotten.html.

“Early Women Scientists.” Early Women Scientists | University College U of T. Accessed March 7, 2021. https://www.uc.utoronto.ca/news/early-women-scientists.

“Jonas Salk and Albert Bruce Sabin.” Science History Institute, January 12, 2021. https://www.sciencehistory.org/historical-profile/jonas-salk-and-albert-bruce-sabin.

“Polio”. Accessed March 7, 2021. https://www.museumofhealthcare.ca/explore/exhibits/vaccinations/polio.html.

Racaniello, Vincent. “Vincent Racaniello.” virology blog, September 7, 2007. https://www.virology.ws/2007/09/07/polio-and-nobel-prizes/.

^[1] Karen Black, “Making a Vaccine Is Not the Same as Mass-Producing It. This Canadian Scientist Solved the Problem for the Polio Vaccine – Then She Was Largely Forgotten,” thestar.com, November 29, 2020, https://www.thestar.com/news/gta/2020/11/29/making-a-vaccine-is-not-the-same-as-mass-producing-it-this-canadian-scientist-solved-the-problem-for-the-polio-vaccine-then-she-was-largely-forgotten.html.

^[2] https://www.nytimes.com/2020/07/31/world/canada/leone-farrell-chemist.html