Ernest Armstrong McCulloch was a medical researcher who studied the biology of blood cells and blood cancer in Toronto, Ontario, in the second half of the twentieth century, and who, with James Till, demonstrated the existence of stem cells in the blood, called hematopoietic stem cells. Stem cells are cells that can develop into more specialized cells in the body. Hematopoietic stem cells, or HSCs, are a type of stem cell that, when present in blood and bone marrow, can develop into specialized blood cells, such as red blood cells, white blood cells, and platelets. Since the start of the twentieth century, researchers hypothesized the existence of something with the self-renewal properties of what were later called stem cells but lacked evidence identifying those stem cells. McCulloch’s work provided the necessary evidence, which laid the foundation for identifying the function of stem cells in other tissues. Through his work leading to the identification of blood stem cells, McCulloch aided the development of treatments for blood cancers, which affect roughly 1.6 million people in the United States.

Irving Lerner Weissman is a researcher and professor in developmental biology at the Stanford University School of Medicine in Stanford, California. Weissman is also a professor of pathology and Virginia & D. K. Ludwig professor of clinical investigation in cancer at the Stanford University School of Medicine. Weissman studies the biology of stem cells and immune cells and has conducted research in those fields during the late twentieth and early twenty-first centuries. In the late 1980s, Weissman’s team developed methods to identify hematopoietic stem cells, or HSCs, which give rise to the body’s blood and immune cells. Also, in the early 2000s, Weissman also co-authored California’s Proposition 71, which secured three billion dollars in state funding for stem cell research after the federal government restricted human embryonic stem cell work. Weissman’s efforts have demonstrated the therapeutic potential of stem cell transplantation in the treatment of diseases, including blood cancer.

In the 1990s, John E. Dick and Dominique Bonnet, researchers at the University of Toronto, in Toronto, Ontario, investigated how a blood cancer called acute myeloid leukemia, or AML, arises from blood-forming cells. Researchers in the field at the time did not know which cells initiate and maintain AML in the body, and there were conflicting hypotheses about which cells were responsible. Scientists hypothesized that AML might be mainly composed of more specialized and differentiated blood cells. Dick and Bonnet conducted experiments in which they grew human AML cells in mice and investigated which cells initiated and maintained the cancer to explore that hypothesis. Their study was one of the first to use sensitive mouse models to characterize and uncover which cells initiated and comprised AML, which contributed to the understanding of its cellular origin and aided in the development of targeted therapies for leukemia treatment.

In 2006, Shideng Bao and colleagues published “Glioma Stem Cells Promote Radioresistance by Preferential Activation of the DNA Damage Response,” hereafter “Glioma Stem Cells,” in Nature. The study describes how cells within a glioblastoma, a type of fast-growing brain tumor, have a high expression of a protein called CD133, which is associated with neural stem cells. Among those cells with high expression of CD133, there exist many stem cells called glioma stem cells. In the paper, Bao and colleagues demonstrate that glioma stem cells are more resistant to radiation compared to other cells within a glioblastoma tumor, and that their resistance has to do with their ability to repair DNA. “Glioma Stem Cells” was one of the first studies to identify the role of glioma stem cells in resistance to radiation and laid the framework for future studies that investigated their role in tumor progression and recurrence as well as novel treatments targeting those cells.

In 2003, Sheila Singh and colleagues published “Identification of a Cancer Stem Cell in Human Brain Tumors” in the journal Cancer Research. The study examines a small population of cells within brain cancers that have abilities similar to those of neural stem cells and can maintain the growth of a brain tumor. The researchers identified the brain cancer stem cells by looking at the expression of proteins CD133 and nestin, which are usually present in neural stem cells. In addition, they characterized brain cancer stem cells as having the ability to quickly proliferate and self-renew, form tumor spheres, as well as differentiate in a manner that resembles characteristics of the original brain tumor from which those cells originated. “Identification of a Cancer Stem Cell in Human Brain Tumors” was one of the first studies to identify cancer stem cells in brain cancer and laid the framework for future research investigating the role of brain cancer stem cells in response to treatment, as well as the recurrence of a tumor after treatment.