Pioneer of hematopoietic colony-stimulating factors: Leo Sachs (1924-2013).

It is with great sorrow that we write about the demise of Leo Sachs, the Otto Meyerhof Professor of Molecular Biology, friend, colleague and brilliant scientist. Leo was born in Leipzig, Germany in 1924, emigrated with his family from Nazi Germany to England in 1933, and reached Israel in 1952. He began studying agricultural botany at the University of Wales, became fascinated by genetics and development, and ended up completing a doctorate in genetics in 1951 at Cambridge University. Upon arrival in Israel, he joined the Weizmann Institute of Science as a geneticist. One of us (M.S.) was already at the Institute and remembers well the arrival of this impressive gentleman with a huge height, deep conviction, and a blessed capacity to express himself clearly on the subject of his deep scientific interests. The questions that would anchor Leo’s research throughout: What controls normal development and what happens when development goes wrong? Why does the machinery in cancer cells run amok, causing abnormal proliferation? Focusing on blood stem cells, a small group of bone marrow cells that produce some 200 billion new blood cells every day, Leo initiated research that revolutionized understanding of stem cell biology, molecular and cellular hematology, and leukemia. In his initial experiments, Leo used normal feeder layer cells as a possible source of the factors that are required for growth and differentiation of the hematopoietic stem cells, and in 1961 described the culture of leukemic cells on these feeder layers (1, 2). Leo also conducted experiments with normal hematopoietic cells (3–5) and in 1963 discovered the first cell culture system for cloning and clonal differentiation of normal hematopoietic stem cells (3). With this method, Leo then discovered the first protein regulators of this clonal growth and differentiation (5–7). He found that these regulators, later named colonystimulating factors (CSFs) and IL-3, induce viability, growth, and differentiation of specific cell lineages, such as macrophages and granulocytes (5–8), and are secreted by the cells that produce them (5–7); he also determined that there is a continued requirement for these proteins for cell viability, growth, and differentiation (9–12). Leo then showed that CSFs and IL-6 can induce granulocyte differentiation and that myeloid leukemic cells can be induced to differentiate to mature nondividing cells that are no more malignant (13–17). These findings showed that cancer cells, which are genetically abnormal, can be epigenetically reprogrammed, and thereby created the basis for the clinical use of differentiation therapy (18–21). Indeed, one of these CSF proteins, G-CSF, is now used worldwide in a variety of clinical procedures, including boosting the production of infection-fighting white blood cells in cancer patients undergoing chemotherapy or radiation, and improving the success of bone marrow and peripheral blood cell transplants. Leo’s findings on the control of hematopoiesis have pioneered new approaches and insights into stem cell biology that have led to new therapies. At the Weizmann Institute, Leo initiated and fostered research in genetics and in 1960 established the Department of Genetics, which he headed for 27 years. The Institute’s Department of Molecular Genetics, which was Leo’s home until his last day, emerged from the historical Department of Genetics. In the laboratory, Leo was quite rigorous and preferred to follow his own intuition: this aspect could be described as “a lone wolf,” but he chose well. Leo educated many gifted students who became well-recognized researchers, including Ernest Winocour, the late Yosi Aloni, Eliezer Huberman, Eitan Fibach, Israel Vlodavsky, and Joseph Lotem, to mention a few. Leo received many honors reflecting his most important contributions to the progress of science in the field of stem cell biology and cancer. The prizes he received include the Israel Prize in 1972, the Rothschild Prize in 1977, the Wolf Prize in Medicine in 1980— which he shared with Cesar Milstein and James Gowans, being the first Israeli to receive this prize—the Bristol-Myers Award for Distinguished Achievement in Cancer Research in 1983, the Royal Society Wellcome Foundation Prize in 1986, the Alfred P. Sloan Prize of General Motors Cancer Research Foundation in 1989, and the E.M. T Prize for Life Sciences, Medicine and Genetics, in Jerusalem in 2002. In 1965 Leo became a founding member of the European Molecular Biology Organization. In 1975 he was elected Member of the Israel Academy of Sciences and Humanities. Later, Leo became a Foreign Associate of the US National Academy of Science and a Fellow of the Royal Society, as well as a Foreign Member of Academia Europaea. In 1985 Leo become aDoctor Honoris Causa at Bordeaux University in France, sharing the honor with one of us (M.S.). In 1997 he became a Doctor of Medicine Honoris Causa at the University of Lund Leo Sachs (1924–2013). Image courtesy of the Weizmann Institute Department of Photography.