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Dr. McCulloch was born in Toronto on April 21, 1926, and died there at the age of 84. After graduation from the Faculty of Medicine at the University of Toronto in 1948, he undertook further training in hematology and basic research at the Lister Institute in London, United Kingdom, and at the Sunnybrook and Toronto General Hospitals in Toronto. In 1957, he was appointed to the Ontario Cancer Institute (OCI) and initiated a research program that initially focused on the role of viruses in cancer, but soon diverged to studies on normal and malignant blood cells. Paired with James Till, a young radiation physicist, he undertook studies to measure the radiation sensitivity of normal bone marrow. Along the way, they made the seminal discovery of spleen colony forming units (CFU-S) containing mature red cells and white cells. With colleagues and inspired students at the OCI, they went on to demonstrate that the CFU-S were derived from a single cell capable of differentiation to multiple lineages and had the capacity to self-renew. Through their work with mutant animals, Steel and W mice, they also demonstrated the important interplay between stem cells and their environment. Their work defined the critical properties of a stem cell, which persist to this day, and established the importance of genetics and cell separation in the investigation of stem cells. This founding work provided the background for the development of successful allergenic bone marrow transplantation in the early 1970s.
Having established the biological properties of normal stem cells and recognizing the importance of clonal analysis in the study of rare cells, Dr. McCulloch turned his focus to the problem of acute myeloid leukemia (AML). With similar precision and passion he developed assays to study these cells and established—for the first time—human AML as a growth factor-dependent disease that, like its normal counterpart, was organized as a hierarchy, maintained by a rare cell with self-renewal capacity. A young Ron Buick, who was responsible for this early work in leukemia, went on to similarly show the hierarchical nature of cancers in solid tumors, thus laying the groundwork for today's emphasis on stem cells as crucial targets in cancer. Over the decades in which Dr. McCulloch worked and influenced science, he published over 275 articles.
Dr. McCulloch was the recipient of several prestigious awards (shared with James Till), including the Gairdner Foundation International Award, the Thomas W. Eadie Medal, the Albert Lasker Award, and the National Cancer Institute of Canada Diamond Jubilee Award. He was an elected member of prestigious societies, including the Royal Society of London; recipient of numerous honors, including the Order of Ontario; inducted to the Canadian Medical Hall of Fame; and named an Officer of the Order of Canada.
A modest man full of integrity, passion, innate insight, and wisdom, Ernest McCulloch will be missed by the scientific community, to whom he provided novel insights and leadership.