Pioneer of Hematopoietic Colony-Stimulating Factors: Leo Sachs

RETROSPECTIVE Pioneer of hematopoietic colony-stimulating factors: Leo Sachs (1924–2013) Michael Selaa,1 and Yoram Gronerb,1 aDepartment of Immunology and bDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 76001, Israel Itiswithgreatsorrowthatwewriteaboutthe cells that produce them (5–7); he also de- demise of Leo Sachs, the Otto Meyerhof termined that there is a continued require- Professor of Molecular Biology, friend, col- ment for these proteins for cell viability, league and brilliant scientist. Leo was born in growth, and differentiation (9–12). Leo Leipzig, Germany in 1924, emigrated with his then showed that CSFs and IL-6 can induce familyfromNaziGermanytoEnglandin granulocyte differentiation and that mye- 1933, and reached Israel in 1952. He began loid leukemic cells can be induced to dif- studying agricultural botany at the University ferentiate to mature nondividing cells that of Wales, became fascinated by genetics and are no more malignant (13–17). These find- development, and ended up completing a ings showed that cancer cells, which are ge- doctorate in genetics in 1951 at Cambridge netically abnormal, can be epigenetically University. Upon arrival in Israel, he joined reprogrammed, and thereby created the the Weizmann Institute of Science as a genet- basis for the clinical use of differentiation icist. One of us (M.S.) was already at the therapy (18–21). Indeed, one of these CSF Institute and remembers well the arrival of proteins, G-CSF, is now used worldwide in this impressive gentleman with a huge height, a variety of clinical procedures, including deep conviction, and a blessed capacity to boosting the production of infection-fight- express himself clearly on the subject of his ing white blood cells in cancer patients un- deep scientific interests. The questions that dergoing chemotherapy or radiation, and Leo Sachs (1924–2013). Image courtesy of would anchor Leo’s research throughout: improving the success of bone marrow the Weizmann Institute Department of What controls normal development and what and peripheral blood cell transplants. Leo’s Photography. happens when development goes wrong? findings on the control of hematopoiesis Why does the machinery in cancer cells run have pioneered new approaches and insights James Gowans, being the first Israeli to amok, causing abnormal proliferation? into stem cell biology that have led to receive this prize—the Bristol-Myers Award Focusing on blood stem cells, a small new therapies. for Distinguished Achievement in Cancer group of bone marrow cells that produce At the Weizmann Institute, Leo initiated Research in 1983, the Royal Society Well- some 200 billion new blood cells every day, and fostered research in genetics and in 1960 Leo initiated research that revolutionized un- established the Department of Genetics, come Foundation Prize in 1986, the Alfred P. derstanding of stem cell biology, molecular which he headed for 27 years. The Institute’s Sloan Prize of General Motors Cancer Re- and cellular hematology, and leukemia. In his Department of Molecular Genetics, which search Foundation in 1989, and the E.M. initial experiments, Leo used normal feeder was Leo’shomeuntilhislastday,emerged T Prize for Life Sciences, Medicine and Ge- layer cells as a possible source of the factors from the historical Department of Genetics. netics, in Jerusalem in 2002. In 1965 Leo that are required for growth and differenti- In the laboratory, Leo was quite rigorous and became a founding member of the European ation of the hematopoietic stem cells, and in preferred to follow his own intuition: this Molecular Biology Organization. In 1975 he 1961 described the culture of leukemic cells aspect could be described as “a lone wolf,” was elected Member of the Israel Academy of on these feeder layers (1, 2). Leo also con- buthechosewell.Leoeducatedmanygifted Sciences and Humanities. Later, Leo became ducted experiments with normal hematopoi- students who became well-recognized re- a Foreign Associate of the US National Acad- etic cells (3–5) and in 1963 discovered the searchers, including Ernest Winocour, the emy of Science and a Fellow of the Royal first cell culture system for cloning and clonal late Yosi Aloni, Eliezer Huberman, Eitan Society, as well as a Foreign Member of Ac- differentiation of normal hematopoietic stem Fibach, Israel Vlodavsky, and Joseph Lotem, ademia Europaea. In 1985 Leo become a Doc- cells (3). With this method, Leo then discov- to mention a few. tor Honoris Causa at Bordeaux University in ered the first protein regulators of this clonal Leo received many honors reflecting his France, sharing the honor with one of us growth and differentiation (5–7). He found most important contributions to the progress (M.S.). In 1997 he became a Doctor of Medi- that these regulators, later named colony- of science in the field of stem cell biology and cine Honoris Causa at the University of Lund stimulating factors (CSFs) and IL-3, induce cancer. The prizes he received include the viability, growth, and differentiation of spe- Israel Prize in 1972, theRothschildPrizein Author contributions: M.S. and Y.G. wrote the paper. — cific cell lineages, such as macrophages and 1977, the Wolf Prize in Medicine in 1980 1To whom correspondence may be addressed. E-mail: michael. granulocytes (5–8), and are secreted by the whichhesharedwithCesarMilsteinand [email protected] or [email protected]. 1664–1665 | PNAS | February 4, 2014 | vol. 111 | no. 5 www.pnas.org/cgi/doi/10.1073/pnas.1324228111 Downloaded by guest on September 26, 2021 (Sweden). All of these honors express the high years ago to ask advice about the areas re- biology at the Weizmann Institute of Science, RETROSPECTIVE esteem in which his scientific colleagues, as quiring development in the biological sciences. but mainly because of his crucial and durable well as the medical community, held Leo. Because of his height, Leo was always a most contribution to the understanding of colony- Inhiscapacityasaleadingscientist,Leo impressive figure on campus, and despite stimulating factors and to human health. Leo also took an active role in the development his recent health problems he used to come will be greatly missed by his four children, and progress of the Weizmann Institute. Well to his office several times a week to satisfy his wife Pnina, and their grandchildren, and known is his correspondence with Francis his scientific curiosity. We shall always re- by his many friends in Israel and around Crick, whom he approached more than 40 member Leo for his contribution in shaping the world. 1 Ginsburg H, Sachs L (1961) In vitro culture of a mammalian 8 Lagunoff D, Pluznick DH, Sachs L (1966) The cloning of differentiation-inducing protein. Proc Natl Acad Sci USA 79(14): leukemia virus. Virology 13(3):380–382. macrophages in agar: Identification of the cells by electron 4347–4351. 2 Ginsburg H, Sachs L (1961) Long-term cultivation in tissue culture microscopy. J Cell Physiol 68(3):385–388. 15 Lotem J, Sachs L (1983) Coupling of growth and differentiation of leukemic cells from mouse leukemia induced by Moloney virus or 9 Paran M, Sachs L (1968) The continued requirement for inducer in normal myeloid precursors and the breakdown of this coupling in by X rays. J Natl Cancer Inst 27(5):1153–1171. for the development of macrophage and granulocyte colonies. J Cell leukemia. Int J Cancer 32(1):127–134. 3 Ginsburg H, Sachs L (1963) Formation of pure suspensions Physiol 72(3):247–250. 16 Shabo Y, et al. (1988) The myeloid blood cell differentiation- of mast cells in tissue culture by differentiation of lymphoid 10 Paran M, Sachs L, Barak Y, Resnitzky P (1970) In vitro induction of inducing protein MGI-2A is interleukin-6. Blood 72(6):2070–2073. cells from the mouse thymus. JNatlCancerInst31(1): granulocyte differentiation in hematopoietic cells from leukemic and 17 Lotem J, Shabo Y, Sachs L (1991) The network of hemopoietic 1–39. non-leukemic patients. Proc Natl Acad Sci USA 67(3):1542–1549. regulatory proteins in myeloid cell differentiation. Cell Growth Differ 4 Sachs L (1964) The analysis of regulatory mechanisms in cell 11 Lotem J, Lipton JH, Sachs L (1980) Separation of different 2(9):421–427. differentiation. New Perspectives in Biology, ed Sela M (Elsevier, molecular forms of macrophage- and granulocyte-inducing proteins 18 Sachs L (1978) Control of normal cell differentiation and the Amsterdam), Vol 4, pp 246–260. for normal and leukemic myeloid cells. Int J Cancer 25(6):763–771. phenotypic reversion of malignancy in myeloid leukaemia. Nature 5 Pluznik DH, Sachs L (1965) The cloning of normal “mast” cells in 12 Sachs L (1990) The control of growth and differentiation in 274(5671):535–539. tissue culture. J Cell Physiol 66(3):319–324. normal and leukemic blood cells. Cancer 65(10):2196–2206. 19 Cohen L, Sachs L (1981) Constitutive gene expression in myeloid 6 Ichikawa Y, Pluznik DH, Sachs L (1966) In vitro control of the 13 Fibach E, Landau T, Sachs L (1972) Normal differentiation of leukemia and cell competence for induction of differentiation by the development of macrophage and granulocyte colonies. Proc Natl myeloid leukaemic cells induced by a differentiation-inducing protein. steroid dexamethasone. Proc Natl Acad Sci USA 78(1):353–357. Acad Sci USA 56(2):488–495. Nat New Biol 237(78):276–278. 20 Sachs L (1987) Cell differentiation and bypassing of genetic defects 7 Pluznik DH, Sachs L (1966) The induction of clones of normal mast 14 Lotem J, Sachs L (1982) Mechanisms that uncouple growth and in the suppression of malignancy. Cancer Res 47(8):1981–1986. cells by a substance from conditioned medium. Exp Cell Res 43(3): differentiation in myeloid leukemia cells: Restoration of requirement 21 Lotem J, Sachs L (2002) Epigenetics wins over genetics: Induction 553–563.

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