Remembering Ernest McCulloch, James Till and the Discovery of Stem Cells in Toronto: February 4: Snapshots in History

February 9, 2017 | John P.

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Local history can and does intersect with many disciplines: business, medicine, science, politics, sports, and so on. As Canada and Ontario are both on track to celebrate their 150th anniversaries, that affords all of us an opportunity to look back, remember, and/or learn…

On February 4 and beyond, take a moment to celebrate the work of two Canadian academics at the University of Toronto (and their associated colleagues) whose groundbreaking discovery of  stem cells in the blood (that paved the way for further strides in medical research and treatment) was published in the journal Radiation Research, Volume 14, pages 213-222 on February 4, 1961 under the title A Direct Measurement of the Radiation Sensitivity of Normal Mouse Bone Marrow Cells, viz.: Lloydminster-born James E. Till, PhD (1931-  ) and Toronto-born Ernest A. McCulloch, MD (1926-2011). This paper showed that single cells taken from bone marrow could establish colony-making units containing those cells needed to make red blood cells, white blood cells, and platelets. Working with Till and McCulloch at the time was Dr. Till’s PhD student in medical biophysics, Andrew John Becker (1935?-2015) MD, who subsequently co-authored an article with Till and McCulloch entitled Cytological Demonstration of the Clonal Nature of Spleen Colonies Derived from Transplanted Mouse Marrow Cells that was published in Nature on February 2, 1963.

A third article entitled The distribution of colony-forming cells among spleen colonies (published in the Journal of Cellular and Comparative Physiology, December 1963, Volume 62(3), pages 327-336)  by Louis Siminovitch (1920-  ), PhD, as the lead author along with McCulloch and Till as co-authors,  proved that stem cells do not just differentiate themselves into new cells but also have the ability of self-renewal, thereby perpetuating the process throughout one’s lifetime. Taken together, these three academic papers explained the purpose of stem cells and provided the opportunity for regenerative medicine.

Much of this significant scientific and medical research took place not just within a Canadian but within a Toronto-based context at the University of Toronto and with the Ontario Cancer Institute. McCulloch and Till received numerous awards for their research, including the 2005 Albert Lasker Basic Medical Research Award, but missed out on winning the 2009 Nobel Prize in Medicine to Elizabeth Blackburn, Carol Greider, and Jack Szostak for discovering how chromosomes are protected during cell division by telomeres and the enzyme telomerase.

For a layperson lacking a scientific background, it is easy to become intimidated by a lot of terminology. However, the irony in McCulloch and Till’s stem cell story was that their discovery was accidental. After irradiating mice with X-rays at Princess Margaret Hospital in conjunction with the Ontario Cancer Institute, McCulloch and Till injected fresh, bone marrow cells at different amounts to find out how much would be necessary to keep the mice alive. 10 days after injecting the mice with new cells, Dr. McCulloch noticed new nodules on the spleens of the mice and surmised that blood cells were forming bacterial colonies from which new blood cells were emerging, thereby keeping the mice alive. The research from their 1961 paper published in Radiation Research languished in obscurity until the 1963 paper published in Nature concluded that single stem cells can produce red blood cells, white blood cells, and platelets. Dr. Michael Rudnicki of the Stem Cell Network emphasized that bone marrow transplants would have never happened without that pioneering work by Doctors McCulloch and Till in the late 1950s and early 1960s and acknowledged that McCulloch and Till were heroes to many and that those associated with stem cell research and treatment owe them thanks.

The names Banting and Best are known the world over for their discovery of insulin in Toronto and its impact on helping Type 1 diabetics around the world. Maybe we need to learn more about the significant discovery of stem cells in Toronto and those who helped make it happen, especially Dr. Ernest McCulloch and Dr. James Till. However, while the stem cell journal began with McCulloch and Till, other Canadians have played an important role along the way – take a look at the chronological list titled Canada’s Contribution on the Canadian Stem Cell Foundation’s website.


Consider the following title for borrowing from Toronto Public Library collections:


Dreams and due diligence Till and McCulloch's stem cell discovery and legacy




Dreams and due diligence Till and McCulloch's stem cell discovery and legacy