Ernest McCulloch
Encyclopedia
Ernest Armstrong McCulloch, OC
, O.Ont
, FRSC
(27 April 1926 – 20 January 2011) was a University of Toronto
cellular biologist, best known for demonstrating – with James Till
– the existence of stem cell
s.
, Canada on 21 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 leukemia. 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 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. In 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
.
The death of McCulloch is greatly mourned by stem cell scientists throughout Canada and the world, many of whom have, with bated breath, been anticipating a Nobel Prize for Till and McCulloch.
McCulloch's work revolutionized cell biology and cancer therapy with the discovery of stem cells in the hematopoietic system.
Their seminal research has been touted as the incipient event that led to revolutionary therapy and survival of leukemia patients worldwide.
Order of Canada
The Order of Canada is a Canadian national order, admission into which is, within the system of orders, decorations, and medals of Canada, the second highest honour for merit...
, O.Ont
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 is administered by the Governor-in-Council and is intended to...
, FRSC
Royal Society of Canada
The Royal Society of Canada , may also operate under the more descriptive name RSC: The Academies of Arts, Humanities and Sciences of Canada , is the oldest association of scientists and scholars in Canada...
(27 April 1926 – 20 January 2011) was a University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
cellular biologist, best known for demonstrating – with James Till
James Till
James Edgar Till, OC, O.Ont, FRSC is a University of Toronto biophysicist, best known for demonstrating – with Ernest McCulloch – the existence of stem cells.-Early work:...
– the existence of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s.
Biography
McCulloch was born in TorontoToronto
Toronto is the provincial capital of Ontario and the largest city in Canada. It is located in Southern Ontario on the northwestern shore of Lake Ontario. A relatively modern city, Toronto's history dates back to the late-18th century, when its land was first purchased by the British monarchy from...
, Canada on 21 April 1926, and was educated at Upper Canada College
Upper Canada College
Upper Canada College , located in midtown Toronto, Ontario, Canada, is an independent elementary and secondary school for boys between Senior Kindergarten and Grade Twelve, operating under the International Baccalaureate program. The secondary school segment is divided into ten houses; eight are...
and the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
.
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
Ontario Cancer Institute
The Ontario Cancer Institute is the research division of Princess Margaret Hospital, part of the University Health Network of the University of Toronto Faculty of Medicine. As Canada's first dedicated cancer hospital, it opened officially and began to receive patients in 1958, although its...
where the majority of his research focused on normal blood-formation and leukemia. 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
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
, when combined with Till's experience in biophysics
Biophysics
Biophysics is an interdisciplinary science that uses the methods of physical science to study biological systems. Studies included under the branches of biophysics span all levels of biological organization, from the molecular scale to whole organisms and ecosystems...
, 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
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
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
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
in 1963. In the same year, in collaboration with Lou Siminovitch
Louis Siminovitch
Louis Siminovitch, CC is a Canadian molecular biologist. He was a pioneer in human genetics, researcher into the genetic basis of muscular dystrophy and cystic fibrosis, and helped establish Ontario programs exploring genetic roots of cancer.Born in Montreal, Quebec to parents who had emigrated...
, 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
Royal Society of Canada
The Royal Society of Canada , may also operate under the more descriptive name RSC: The Academies of Arts, Humanities and Sciences of Canada , is the oldest association of scientists and scholars in Canada...
. In 1988, he became an Officer of the Order of Canada
Order of Canada
The Order of Canada is a Canadian national order, admission into which is, within the system of orders, decorations, and medals of Canada, the second highest honour for merit...
and was made a member of the Order of Ontario
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 is administered by the Governor-in-Council and is intended to...
in 2006. In 1999, he was made a Fellow of the Royal Society of London. In 2004 McCulloch was inducted into the Canadian Medical Hall of Fame
Canadian Medical Hall of Fame
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 a museum in London, Ontario, and has an annual induction ceremony.-2012:*Terry Fox*John...
. He holds the distinguished title of University Professor Emeritus at the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
.
In 2005, he and James Till were awarded the Albert Lasker Award for Basic Medical Research
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 the understanding, diagnosis, prevention, treatment, and cure of disease...
.
The death of McCulloch is greatly mourned by stem cell scientists throughout Canada and the world, many of whom have, with bated breath, been anticipating a Nobel Prize for Till and McCulloch.
McCulloch's work revolutionized cell biology and cancer therapy with the discovery of stem cells in the hematopoietic system.
Their seminal research has been touted as the incipient event that led to revolutionary therapy and survival of leukemia patients worldwide.
Selected publications
- McCulloch, E.A., Till, J.E. (1960) The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiation Research 13(1):115-125. [Link to article]
- 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 anemic 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 anemic 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 leukemic hematopoietic stem cells and lineages. In: Stem Cells Handbook, Ed. Stewart Sell, Humana Press, Totowa N.J., pp. 119-31.
External links
- Canadian Medical Hall of Fame entry
- University Health Network entry
- Joint publications by McCulloch and Till, 1961-1969; full text courtesy University of TorontoUniversity of TorontoThe University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...