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Ernest Armstrong McCulloch (27 April 1926 – 20 January 2011) was a
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
cellular biologist, best known for demonstrating – with
James Till James Edgar Till (born August 25, 1931) is a University of Toronto biophysicist, best known for demonstrating – with Ernest McCulloch – the existence of stem cells. Early work Till was born in Lloydminster, which is located on th ...
– the existence of
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
s.


Biography

McCulloch was born in
Toronto Toronto ( ; or ) is the capital city of the Canadian province of Ontario. With a recorded population of 2,794,356 in 2021, it is the most populous city in Canada and the fourth most populous city in North America. The city is the anchor ...
, Ontario, Canada on 27 April 1926, and was educated at
Upper Canada College Upper Canada College (UCC) is an elite, all-boys, private school in Toronto, Ontario, operating under the International Baccalaureate program. The college is widely described as the country's most prestigious preparatory school, and has produce ...
and the
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
. Ernest McCulloch received his MD in 1948 from the University of Toronto. Upon graduation, he began his education in research at the
Lister Institute The Lister Institute of Preventive Medicine, informally known as the Lister Institute, was established as a research institute (the British Institute of Preventive Medicine) in 1891, with bacteriologist Marc Armand Ruffer as its first director, us ...
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 Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...
, when combined with Till's experience in
biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. ...
, 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 Till & McCulloch are James Till and Ernest McCulloch who, while studying the effect of radiation on the bone marrow of mice at the Ontario Cancer Institute, in Toronto, demonstrated the existence of multipotent stem cells in 1961. Collaboratio ...
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 Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are p ...
'' 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 The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a ...
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 The Royal Society of Canada (RSC; french: Société royale du Canada, SRC), also known as the Academies of Arts, Humanities and Sciences of Canada (French: ''Académies des arts, des lettres et des sciences du Canada''), is the senior national, bil ...
. In 1988, he became an Officer of the
Order of Canada The Order of Canada (french: Ordre du Canada; abbreviated as OC) is a Canadian state order and the second-highest Award, honour for merit in the system of orders, decorations, and medals of Canada, after the Order of Merit. To coincide with ...
and was made a member of the
Order of Ontario The Order of Ontario () is the most prestigious official honour in the Canadian province of Ontario. Instituted in 1986 by Lieutenant Governor Lincoln Alexander, on the advice of the Cabinet under Premier David Peterson, the civilian order i ...
in 2006. In 1999, he was elected a
Fellow of the Royal Society Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge, including mathemati ...
. In 2004, McCulloch was inducted into the
Canadian Medical Hall of Fame __NOTOC__ The Canadian Medical Hall of Fame is a Canadian charitable organization, founded in 1994, that honours Canadians who have contributed to the understanding of disease and improving the health of people. It has an exhibit hall in London, O ...
. He holds the distinguished title of University Professor Emeritus at the
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
. In 2005, he and James Till were awarded the
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
.


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 The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...

Ernest Armstrong McCulloch archival papers
held at th
University of Toronto Archives and Records Management Services
{{DEFAULTSORT:McCulloch, Ernest 1926 births 2011 deaths Canadian biologists 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 University of Toronto faculty University of Toronto alumni Upper Canada College alumni Recipients of the Albert Lasker Award for Basic Medical Research Scientists from Toronto 20th-century Canadian scientists 21st-century Canadian scientists