The Identification of Stem Cells

History

The following description is excerpted with permission of the Toronto Star and author Joe Sornberger. Copyright, the Toronto Star 2005.

They have always been a scientific odd couple. Dr. Ernest McCulloch, a short, stocky man given to wearing academic tweeds and his Order of Canada pin, is affectionately referred to by friends by his childhood nickname, "Bun." He comes from Old Toronto Scottish stock but is anything but dour. He reads widely (from Jane Austen to Mordecai Richler), is a keen observer of the world around him (he appreciates baseball but thinks hockey is "just people running around on skates"), and believes the best thing that ever happened to Toronto was the post-war influx of immigrants that brought style and culture - and better restaurants - to what had been a "nasty, narrow-minded" city.

Dr. James Till, at least a head taller than his former research partner, is as neat as Dr. McCulloch is rumpled. The son of Alberta homesteaders, he went from studying science at the University of Saskatchewan to a doctorate in biophysics at Yale "because they just kept giving me scholarships." He never worried about taking on difficult challenges with his research because, "I knew I could always go back to the farm." He prefers curling to golf, retains a self-deprecating prairie boy charm, and laughs easily and loudly.

The two were brought together by Dr. Harold Johns, who ran the physics division at OCI when it began operations in 1957. Dr. Johns thought Dr. Till's hard-headed, check-everything-twice, physics-based style of science and his experience with measuring radiation would be a good counterweight to Dr. McCulloch's big-picture, what-if conceptual approach. To this day, Dr. Till defers to Dr. McCulloch as the big thinker, saying he "rode Ernest's coattails," although he will agree to instilling a degree of rigour in their work.

How they discovered stem cells is a research legend.

"We were in the salt mines," said Dr. McCulloch, who recently published a book about the early days at the OCI. "The centre of the world was the Toronto General Hospital, and we had been exiled to Sherbourne Street. It was the best thing that ever happened to us. There was no one looking over our shoulders."

Back then, in a Cold War world eager for information on how to survive nuclear war, they were brash, young men studying the effects of radiation on mice.

"One has to consider the context of the time," said Dr. Till. "This was the late-1950s, early 1960s. The memories of Hiroshima and Nagasaki were still fresh. There was much concern about the threat of nuclear weapons, that we might have to fight an atomic war. So, being able to ameliorate the effects of total-body irradiation by having a bank of marrow was a big deal. Some of our very early funds came from the Defence Research Board of Canada. They were very interested in this when other agencies were less excited. I still feel a debt of gratitude to that agency."

One Sunday afternoon in 1960, Dr. McCulloch stopped into the lab to check an experiment he was conducting injecting mice with cells from bone marrow. He noticed bumps growing on the spleens of the mice, and observed a "linear" match with the number of marrow cell doses. Dr. Till agreed they might be on to something: colony-forming units originating from single cells.

Said Dr. Till: "Of course, being able to find what were the active cells in that bone marrow - well, you can imagine being able to purify that and bank those. Whoa! That was the underlying area of applied rationale."

Their 1961 paper in the little known journal Radiation Research went largely unnoticed. Their 1963 follow-up in Nature, however - made possible by the brilliant work of a young researcher named Dr. Andrew Becker - showed that the colonies originated from single "multipotent" cells. It changed everything. Essentially, stem cell science had begun.

 

In recognition of their historic discovery, both Till and McCulloch have received numerous Canadian and international awards, including the Canada Gairdner International Award and the Albert Lasker Basic Medical Research Award. Both are also Fellows of the Royal Society in the United Kingdom and in Canada, Officers of the Order of Canada, and both have been inducted into the Canadian Medical Hall of Fame and the Canadian Science and Engineering Hall of Fame. And every year, the Stem Cell Network recognizes the Canadian researcher who has published findings with the most impact in the field of stem cells by awarding them the Till & McCulloch Lecture.

Selected resources