In 1957, McCulloch joined the Ontario Cancer Institute, incorporating the Princess Margaret Hospital, where he soon began collaborative research with James Till. His experience in hematology, when combined with Till's experience in biophysics, yielded a novel and productive combination of skills and interests.
In the early 1960s, McCulloch and Till started a series of experiments that involved injecting bone marrow cells into irradiated mice. Visible nodules were observed in the spleens of the mice, in proportion to the number of bone marrow cells injected. Till and McCulloch called the nodules 'spleen colonies', and speculated that each nodule arose from a single marrow cell: perhaps a stem cell.
In later work, Till and McCulloch were joined by graduate student Andy Becker, and demonstrated that each nodule did indeed arise from a single cell. They published their results in Nature in 1963. In the same year, in collaboration with Lou Siminovitch, a trailblazing Canadian molecular biologist, they obtained evidence that these cells were capable
of self-renewal, a crucial aspect of the functional definition of stem cells that they had formulated.
A major focus of McCulloch's more recent research has been on cellular and molecular mechanisms affecting the growth of malignant blast stem cells obtained from the blood of patients with Acute Myeloblastic Leukemia.
In 1974, McCulloch became a Fellow of the Royal Society of Canada. In 1988, he became an Officer of the Order of Canada and was made a member of the Order of Ontario in 2006. On 1999, he was made a Fellow of the Royal Society of London. In 2004 McCulloch was inducted into the Canadian Medical Hall of Fame. He holds the distinguished title of University Professor Emeritus at the University of Toronto.
In 2005, he and James Till were awarded the Albert Lasker Award for Basic Medical Research.
- McCulloch, E.A., Till, J.E. (1960) The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantaiton into irradiated mice. Radiation Research 13:115-25.
- Till, J.E., McCulloch, E.A. (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiation Research 14:213-22.
- Becker, A.J., McCulloch, E.A., Till, J.E. (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452-4.
- Siminovitch, L., McCulloch, E.A., Till, J.E. (1963) The distribution of colony-forming cells among spleen colonies. Journal of Cellular and Comparative Physiology 62:327-36.
- McCulloch, E.A. (2003) Stem cells and diversity. Leukemia 17:1042-48.
- McCulloch, E.A. (2003) Normal and leukemic hematopoietic stem cells and lineages. In: Stem Cells Handbook, Ed. Stewart Sell, Humana Press, Totowa N.J., pp. 119-31.
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