James Till at the Princess Margaret Cancer Centre in Toronto on Dec. 14, 2017.Laura Pedersen/University Health Network
Canadian biophysicist James Till, who changed the future of medicine by proving the existence of stem cells with cell biologist Ernest McCulloch, was, by all accounts, a man of rare scientific rigour. If there’s any doubt, consider his pioneering research at the curling rink.
Dr. Till loved curling, or, as he liked to call it, “chess on ice.”
Just a few years after his co-discovery of stem cells in blood in 1963 – a feat that transformed human cell biology and opened the door to regenerative medicine and its potential to treat everything from sprains to spinal cord injuries – Dr. Till led an unusual physics experiment at a Toronto curling club to answer the burning question: “Does sweeping matter?”
He recruited two other scientists to join the study and two sweepers from the 1967 Ontario Championship curling team as they measured the distance travelled of curling rocks thrown with varying force, with and without sweeping. The result showed corn-broom-swept rocks could indeed travel up to two metres farther.
“It was the very first experiment to show how much sweeping can make a difference,” says retired geneticist Ronald Worton, a University of Toronto PhD student at the time who had Dr. Till as his thesis adviser. An earlier study by other researchers had relied on a special contraption to release the curling rocks and failed, but, Dr. Worton recalls, “Jim said, ‘I’ll throw the rocks myself.’”
Dr. James Till co-discovered stem cells in blood in 1963.University of Toronto Archive
Dr. Till died in Toronto on May 18 at age 94. In many ways, the curling study is emblematic of the methodical and determined approach he brought to virtually any question that stoked his curiosity. Yet initially, hunting for stem cells had not been among them.
James Edgar Till was born Aug. 25, 1931, in Lloydminster, Alta., to Will and Gertie Till, and grew up on the family farm north of the prairie city, which straddles the Saskatchewan border.
He received scholarships to study science at the University of Saskatchewan, and graduated from Yale with his PhD in 1957. A year later, Dr. Till arrived in Toronto at the newly founded Ontario Cancer Institute, then a research division of Princess Margaret Hospital, where he was eager to learn more about cell survival in response to radiation exposure. At that juncture, when atomic bombs haunted the world as a recent memory and a looming Cold War threat, interest surged in the health effects of radiation, especially at the OCI, since radiation was known to cause cancer and was also being used to treat it.
Dr. McCulloch, a clinician and cancer researcher everyone called “Bun,” had joined the OCI to investigate radiation as a treatment for leukemia, along with bone marrow transplants. Blasting patients with lethal doses of radiation to kill their cancers, then rescuing the patients with infusions of cancer-free donated bone marrow to replenish the blood supply was then still a novel and radical notion. The first successful bone marrow transplant, on a child with leukemia in New York, had only been performed in 1956.
Dr. McCulloch proposed studying the procedure in mice. But Harold Johns, a famous physicist and head of the OCI physics division, refused to let anyone use the radiation machines without a physicist present. As Dr. McCulloch told author Joe Sornberger in his 2011 book Dreams and Due Diligence, Dr. Johns ”wasn’t going to have any damn biologist ruining his reputation by misusing his machines.”
Dr. Till, then 26, volunteered to run the machines after Dr. McCulloch impressed him with his “unconventional way of thinking” in talks he had given. In 1960, Dr. Johns directed the unlikely pair to team up.
James Till was Professor Emeritus at the University of Toronto.University of Toronto Communications/University of Toronto
Dr. McCulloch, who died in 2011, came from a well-to-do Toronto family of doctors. He was educated at Upper Canada College and became an MD at 22, a short, stocky imaginative extrovert given to rumpled tweeds and quoting Shakespeare. In contrast, Dr. Till came from a modest farming background, lean, tall, tidy and reserved.
“The whole time I was there, [Dr. Till] never got angry, he never swore, or raised his voice,” says Dr. Worton, emeritus CEO and scientific director of the Ottawa Hospital Research Institute.
Alan Bernstein, the former head of the Canadian Institutes of Health Research and a student in Dr. Till’s lab from 1968 to 1972, remembers being “quite taken” with Dr. Till, who “had a way of speaking, directly, emphatically . . . always a sparkle in his voice. There was an energy that was hard not to admire. . . . It was a little bit hypnotic.”
Where Dr. Till economized words and insisted on rigorous testing, Dr. McCulloch was a talkative brainstormer and dreamer. “But they had a deep understanding of each other’s strengths and weaknesses,” says Dr. Bernstein, “. . . and the discovery of stem cells would not have happened by Bun working alone, or Jim working alone.”
The concept of stem cells had captivated scientists for more than a century before Dr. Till and Dr. McCulloch found them. Logic dictated that cells able to replicate and grow into the body’s various tissues and organs must exist, since we all start as nothing but a clump of cells. And as it turned out, it was a series of clumps that led the pair to their unexpected discovery.
James Till and Ernest McCulloch are credited as the fathers of stem cell science.University Health Network
They had been studying how bone marrow, the body’s chief blood-making system, recovers after radiation exposure. The work involved transplanting normal and irradiated bone marrow cells into mice, and in an e-mail to The Globe and Mail in 2011, Dr. Till wrote: “On a Sunday, 10 days after transplantation of cells, McCulloch noticed bumps on the spleens of the irradiated mice and counted them. He then found that irradiated mice that had received larger numbers of marrow cells also had larger numbers of bumps on their spleens. The next day, he told me, with some excitement, what he had found the previous day. We both had the same reaction. These lumps may be colonies of blood-forming cells.”
Their excitement grew as they discovered the lumps didn’t just contain one type of cell, but the various cell types that make up human blood – including red cells, white cells and platelets. Had all three types grown from a single bone-marrow cell? They published their first results to little fanfare in Radiation Research, a small, obscure journal, in 1961, and only speculated that that the lumps contained some kind of “precursor” cell that had given rise to different types of blood cells.
“I think they had it in their minds that this might be a stem cell,” although they never used the word, Dr. Worton says.
Finding out was no small task. Andy Becker, a graduate student in their lab, hunched for hours over a microscope figuring out how to tag the bone marrow cells so researchers could follow them and their progeny once they were transplanted. The effort provided the first visual confirmation that a single cell inside the lumps had in fact grown into the blood system’s various cell types.
Till & McColloch by Ruth Abernethy located at the MaRS Building in Toronto.David Lee/David Lee)
Subsequent studies with molecular geneticist Dr. Louis Siminovitch demonstrated these precursors also had the unique ability to self-renew – the other hallmark trait of a stem cell.
Years later, Dr. Till could not recall vivid details of the discovery, but said “I do remember the feeling – it was exhilaration.”
Published in Nature in 1963, the work ushered in a new understanding of how humans develop from the cell up, a new framework to study how things go wrong, and also raised the astonishing prospect of harnessing stem cells to repair and replace whatever ails us – damaged tissues, organs or malfunctioning cells.
“It’s almost impossible to enumerate how much they changed the world from a health and science perspective,” says neurobiologist Sam Weiss, who co-discovered stem cells in the adult mammalian brain (mouse) at the University of Calgary in 1992, upending century-old medical dogma that we’re born with all the brain cells we’ll ever have. “So much of what they started then still is foundational to a lot of the approaches of today, which has improved and saved millions of lives.”
Dr. Till’s pioneering work with Dr. McCulloch led to advances in bone-marrow transplants and treatments for various blood and immune-disorders. With the ability scientists now have to genetically modify stem cells and potentially fix the root cause of disease, the future looks bright.
“It should be an enormous source of pride for this country,” Dr. Weiss says.
Dr. Till and Dr. McCulloch received numerous honours, including the Gairdner Foundation International award, appointment as officers of the Order of Canada and induction into the Canadian Medical Hall of Fame. In 2005, they received an Albert Lasker Award, a top U.S. medical research prize that often precedes a Nobel Prize in Medicine. But the Nobel, never awarded posthumously, is now out of reach.
Neither fame nor accolades tainted Dr. Till’s humility.
“He never really wanted to be praised for anything,” says Dr. Bernstein, now director and visiting professor of global health at the University of Oxford. He fondly recalls the two-second thank you speech Dr. Till gave as he received his Lasker Award, an event where recipients usually spend several minutes describing their work.
That Dr. Till was more listener than talker was a gift to the generations of young scientists he inspired and mentored in Canada. Dr. Worton, for example, himself inducted into the Canadian Medical Hall of Fame said – “I learned more from him than from anyone else in my lifetime.”
In a YouTube video peers made to commemorate Dr. Till’s 90th birthday, Dr. Connie Eaves, a leading cancer and stem cell researcher at the University of British Columbia who died in 2024, described “how lucky I was that Bun decided a seven-months-pregnant 26-year-old was more than he wanted to supervise,” and took her straight to Dr. Till, who accepted her in his lab without hesitation – an unusually progressive move in 1970.
Janet Rossant, president and scientific director of the Gairdner Foundation, and world-renowned developmental biologist, says Dr. Till was her “scientific hero . . . and a gentleman.
“He was right there as an icon that we could all look up to, but someone who was so modest and quiet, everybody could connect with him.”
In the years after the stem-cell discovery, Dr. McCulloch left to apply what he had learned in the lab to treating leukemia patients.
“I think that left Jim wondering what he was going to do next, and he decided to go into the social sciences,” Dr. Worton says. “I was astounded that he did that.”
Dr. Worton soon realized, however, that his former adviser was applying the same scientific rigour to patient care and bioethics as he did to his lab research – and making a valuable difference in the process. Dr. Till, for example, conducted a survey to find out if cancer patients felt well supported followed their diagnosis. When too many respondents said they did not, Dr. Till spearheaded the creation of a “navigator” system at Princess Margaret Hospital “to help them co-ordinate all aspects of their treatment plan.” He was also an early adopter of web-based supports for patients and advocated fiercely for sharing scientific research online freely.
In his tribute to Dr. Till on behalf of Canada’s Stem Cell Network, which Dr. Worton helped launch in 2001, he wrote “There are few scientists in this world who can claim a prominent role in both basic science and social science.”
Also, he notes, in the annals of curling.
Dr. Till leaves his wife, Joyce, to whom he was married for more than 65 years, their three children, six grandchildren and one great-grandchild.
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