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 university, public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park (Toronto), Queen's Park. It was founded by royal charter in 1827 ...
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 the ...
– the existence of
stem cells.
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 anch ...
, 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 university, public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park (Toronto), Queen's Park. It was founded by royal charter in 1827 ...
.
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, u ...
in London, England.
In 1957 he joined the newly formed
Ontario Cancer Institute
The Ontario Cancer Institute (OCI) is the research division of Princess Margaret Cancer Centre, affiliated to the University Health Network of the University of Toronto Faculty of Medicine. As Canada's first dedicated cancer hospital, it opened of ...
, 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
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 ...
'' 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 p ...
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
The Order of Canada (french: Ordre du Canada; abbreviated as OC) is a Canadian state order and the second-highest honour for merit in the system of orders, decorations, and medals of Canada, after the Order of Merit.
To coincide with the cen ...
and was made a member of the
Order of Ontario
The Order of Ontario () is the most prestigious official Award, honour in the Provinces and territories of Canada, Canadian province of Ontario. Instituted in 1986 by Lieutenant Governor of Ontario, Lieutenant Governor Lincoln Alexander, on the A ...
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 mathemat ...
.
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
The University of Toronto (UToronto or U of T) is a public university, public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park (Toronto), Queen's Park. It was founded by royal charter in 1827 ...
.
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
The University of Toronto (UToronto or U of T) is a public university, public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park (Toronto), Queen's Park. It was founded by royal charter in 1827 ...
Ernest Armstrong McCulloch archival papersheld 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