Ernest McCulloch

Ernest Armstrong McCulloch (27 April 1926 – 20 January 2011) was a University of Toronto cellular biologist, best known for demonstrating – in a partnership with James Till – the existence of stem cells.

Biography

McCulloch was born in Toronto, Ontario, Canada on 27 April 1926, and was educated at Upper Canada College and the University of Toronto.

Ernest McCulloch received his MD in 1948 from the University of Toronto. Upon graduation, he began his education in research at the Lister Institute in London, 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.

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. 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.

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. In 1999, he was elected a Fellow of the Royal Society. 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.

Selected publications

*
*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
[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. ''Nature'' 197:452-4
[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 Physiology'' 62:327-36
[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. ''Science'' 144(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. ''Blood'' 26(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 Med'' 127(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 Med'' 130(1):91–103
[Link to article]
*McCulloch, E.A. (2003) Stem cells and diversity. ''Leukemia'' 17:1042–48.
*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.

References

External links

Canadian Medical Hall of Fame entryUniversity Health Network entryJoint publications by McCulloch and Till, 1961–1969
full text courtesy University of Toronto
Ernest Armstrong McCulloch archival papers
held at th
University of Toronto Archives and Records Management Services

{{DEFAULTSORT:McCulloch, Ernest
1926 births
2011 deaths
Canadian fellows of the Royal Society
Fellows of the Royal Society of Canada
Members of the Order of Ontario
Officers of the Order of Canada
Stem cell researchers
Academic staff of the University of Toronto
University of Toronto alumni
Upper Canada College alumni
Recipients of the Albert Lasker Award for Basic Medical Research
Scientists from Toronto
20th-century Canadian biologists
21st-century Canadian biologists