How it began
James Till, a physicist who studied how radiation affects cells, and Ernest McCulloch, a physician who studied blood diseases, joined the Ontario Cancer Institute in Toronto in 1957. In 1961 they joined forces to study mice given a lethal dose of radiation and then a bone marrow transplant. The mice that survived had enlarged spleens covered in bumps. Till wondered whether each bump was a colony grown from one cell. They published a first paper that year.
How it works
McCulloch cut sections through the bumps and found a mix of immature and mature blood cells. Till counted the bumps and found their number rose in a straight line with the number of marrow cells injected, as expected if each came from one cell. The student Andrew Becker marked marrow cells with radiation-induced chromosome changes and showed that all dividing cells in a bump carried the same marker. Each colony was a clone.
What changed first
By 1963 it was clear that the spleen colonies each came from one cell and held several types of blood cell. Louis Siminovitch suggested a test for self-renewal: cells from a colony were transplanted into a second mouse and formed new colonies, and again in a third. In 1964 the group agreed to call the colony-forming cells stem cells. That year Till, McCulloch and Siminovitch published a model in which chance decides whether a stem cell renews itself or specializes.
What lasted
The work fixed the defining properties of a stem cell: extensive division, self-renewal and differentiation into one or more cell types. It set the textbook picture of multipotent stem cells that give rise to more restricted progenitor cells. Later marker studies by Alan Wu suggested that the immune system comes from the same stem cell as the blood. The 1964 model became a basis for later work on cancer treatment and regenerative medicine.
