Ernest McCulloch received his MD in 1948 from the University of Toronto. Upon graduation, he began his education in research at the Lister InstituteinLondon, England.
In 1957 he joined the newly formed Ontario Cancer Institute, where the majority of his research focused on normal blood-formation and leukaemia. Together with his colleague, Dr. J.E. Till, McCulloch created the first quantitative, clonal method to identify stem cells and used this technique for pioneering studies on stem cells. 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 & 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.[citation needed]
McCulloch's later research was on cellular and molecular mechanisms affecting the growth of malignant blast stem cells obtained from the blood of patients with Acute Myeloblastic Leukemia.
In 1969, McCulloch won the Canada Gairdner International Award with James E. Till in recognition of their development of the spleen colony technique for measuring the capacity of primitive normal and neoplastic cells to multiply and differentiate in the body.[6] This technique has been applied by them and their colleagues, and by many others, to gain important knowledge of the normal formation of blood cells, the behavior of leukemic cells and methods of treating leukemia, and other aspects of cell biology.[7]
Till, J.E., McCulloch, E.A. (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiation Research14:213-22. [Link to article]
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. Nature197:452-4. [Link to article]
Siminovitch, L., McCulloch, E.A., Till, J.E. (1963) The distribution of colony-forming cells among spleen colonies. Journal of Cellular and Comparative Physiology62:327-36. [Link to article]
Till, J.E., McCulloch, E.A., Siminovitch, L. (1964) A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proceedings of the National Academy of Sciences (USA)51(1):29–36. [Link to article]
McCulloch, E.A., Siminovitch, L., Till, J.E. (1964) Spleen-colony formation in anaemic mice of genotype WWv. Science144(1620):844–846. [Link to article]
McCulloch, E.A., Siminovitch, L., Till, J.E., Russell, E.S., Bernstein, S.E. (1965) The cellular basis of the genetically determined hemopoietic defect in anaemic mice of genotype Sl/Sld. Blood26(4):399–410. [Link to article]
Wu, A.M., Till, J.E., Siminovitch, L., McCulloch, E.A. (1968) Cytological evidence for a relationship between normal hematopoietic colony-forming cells and cells of the lymphoid system. J Exp Med127(3):455–464. [Link to article]
Worton, R.G., McCulloch, E.A., Till, J.E. (1969) Physical separation of hemopoietic stem cells differing in their capacity for self-renewal. J Exp Med130(1):91–103. [Link to article]
McCulloch, E.A. (2003) Stem cells and diversity. Leukemia17:1042–48.
McCulloch, E.A. (2003) Normal, and leukaemic hematopoietic stem cells and lineages. In: Stem Cells Handbook, Ed. Stewart Sell, Humana Press, Totowa N.J., pp. 119–31.
