COLUMBIA UNIVERSITY RECORD January 21, 1994 Vol. 19 No. 14 TWO BIOLOGISTS WIN COLUMBIA'S HORWITZ PRIZE Two scientists who made fundamental discoveries of how cells in the body develop and differentiate have won Columbia's 1993 Louisa Gross Horwitz Prize. The two, both developmental biologists, are Nicole Le Douarin, professor at the College de France, and Donald Metcalf, Research Professor of Cancer Biology at the University of Melbourne, Australia. Since the Horwitz Prize was first presented in 1967, more than half its recipients--28 of 51--have gone on to win the Nobel Prize. Phillip A. Sharp, one of two winners of this year's Nobel Prize in Physiology or Medicine, received the Horwitz Prize in 1988. President Rupp presented the prize in formal ceremonies Dec. 16 in the Low Rotunda. The scientists share the $22,000 monetary award. The Horwitz Prize is given annually for outstanding research in biology or biochemistry. Their work has addressed a fundamental question in the biological sciences: How do distinct types of cells develop from common precursor cells? Their research demonstrates that cell differentiation results from exposure to growth factors and other hormonal influences and is not solely predetermined by genes. Le Douarin and Metcalf delivered the 1993 Louisa Gross Horwitz Prize Lectures. Le Doaurin spoke on "Embryonic Chimeras and the Development of the Neural Primordium in the Vertebrate Embryo," while Metcalf spoke on "The Molecular Control of Granulocytes and Macrophages." Le Douarin, 63, is also director of the Institut d'Embryologie cellulaire et moleculaire du Centre national de la recherche scientifique et du College de France, Nogent-sur-Marne, France. She has made major contributions to knowledge of development in both the immune and nervous systems. Early in her career, she developed a now classic technique for studying the fate of a developing cell. She noticed that nuclei from quail cells had a distinct appearance from chicken nuclei and she inserted quail cells into chick embryos. The quail cells became part of the chick embryo, but remained distinct, allowing researchers to track the cells' growth and differentiation. That discovery was published in France in 1969 and the hybrid embryos, called "chimeras," have become a widely used tool to study developing cells. Le Douarin also studied the central nervous system using quail-chick chimeras and found that she could give the quail's song to the chick by transplanting certain quail brain cells to the chick embryo. In early development, undifferentiated precursor cells are located in the neural crest, an embryonic structure. Cells migrate from the neural crest to different parts of the embryo, and become nerve cells, glial cells, which support nerve cells, pigment cells and cartilage. As cells migrate from the neural crest, Le Douarin discovered, they are influenced by two growth hormones secreted within the embryo: brain-derived neurotrophic factor, which cells require to become neurons, and basic fibroblast growth factor, which is required to develop other kinds of cells. In recent studies, Le Douarin and her colleagues have cloned cells from different points along their migratory route to discover at what point they no longer produce identical daughter cells but begin to differentiate. She received the diplome d'etudes superieures and the doctorat d'etat es sciences naturelles from the Universite de Paris. Her doctoral thesis, on the development of liver cells, was sponsored by Etienne Wolff, a well-known developmental biologist, at the Institut d'Embryologie. Le Douarin taught at the high-school level from 1954 to 1960 and was a researcher at the Centre national de la recherche scientifique (CNRS) from 1960 to 1965. She spent the next 10 years teaching and conducting research at the Universite de Clermont- Ferrand and the Universite de Nantes. In 1975, she was named director of the Institut d'Embrylogie, and the following year appointed director of research at CNRS. She has been a professor at the College de France since 1988. She was named to the French Academy of Sciences in 1982, to the American Academy of Arts and Sciences in 1984 and to the Royal Society in 1989. She was elected a foreign associate member of the National Academy of Sciences in 1989 and has received a number of scientific awards, among them the Kyoto Prize in Advanced Technology, 1986; the Medaille d'Or du CNRS, 1986, and the Prix de la Fondation Louis Jeantet de Medecine, Geneva, 1990. Among the awards bestowed by the French government have been Officier dans l'Ordre des Palmes Academiques, 1981; Commandeur de l'Ordre National du Merite, 1988, and Officier de la Legion d'Honneur, 1991. Columbia awarded Le Douarin an honorary doctorate in 1989. She has delivered lectures at universities around the globe and has published more than 300 articles in academic journals. In his research, Metcalf has addressed the problem of depressed immune system function in cancer patients, resulting from complicating disease or from chemotherapy. The eventual therapies that came from his work and the work of others required 20 years of advances in cell culture techniques, separative protein chemistry and molecular biology. Metcalf, 64, is also director of the Cancer Research Laboratory at the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. He developed an innovative technique for culturing blood cells that first made possible study of development in the hematopoietic system. The cancer researcher cloned cells derived from single precursor blood cells at different stages in their development, then studied the factors that caused the cells to differentiate. He identified, purified and most recently cloned the genes for colony stimulating factors, four different hormones that regulate the differentiation of blood cells into granulocytes and macrophages, infection-fighting white blood cells. In a series of experiments, he demonstrated that a single precursor blood cell could give rise to different mature blood cells through the influence of specific colony stimulating factors. After he showed that these hormones could be manufactured using recombinant gene technology, they have become widely used to stimulate white cell production in patients with leukemia and depressed immune system function. In his most recent work, Metcalf has isolated a new hormone active on macrophages, leukemia inhibitory factor. The hormone has been shown to have powerful effects on embryonic precursor cells and on adult liver and bone-forming tissue. He received the B.Sc., M.B., B.S. and M.D. degrees from the University of Sydney. In 1954, he was named a Carden Fellow in Cancer Research, sponsored by the Anti-Cancer Council of Victoria, at the Walter and Eliza Hall Institute of Medical Research. Metcalf was appointed head of the Institute's Cancer Research Unit and assistant director of the Institute, both in 1965. He was named Research Professor of Cancer Biology at the University of Melbourne in 1986. He has held a number of visiting positions in Australia, Britain, Canada, France, the Netherlands, New Zealand, Switzerland and the United States. He was elected to the Royal Society in 1983 and was named a foreign associate of the National Academy of Sciences in 1987 and an honorary foreign member of the Association of American Physicians in 1988. Among his scientific awards have been the Wellcome Prize of the Royal Society, 1986; the Armand Hammer Prize for Cancer Research, 1988, and the Sloan Prize of the General Motors Cancer Research Foundation. Metcalf has published more than 400 articles in academic journals. Horwitz Prize winners who subsequently won the Nobel Prize are Luis F. Leloir, Har Gobind Khorana, Marshall W. Nirenberg, Max Delbruck, Salvador Edward Luria, Albert Claude, George Emil Palade, Renato Dulbecco, Sune Bergstrom, Bengt Samuelsson, David H. Hubel, Torsten N. Wiesel, Walter Gilbert, Frederick Sanger, Cesar Milstein, Aaron Klug, Barbara McClintock, Susumu Tonegawa, Stanley Cohen, Rita Levi-Montalcini, Michael S. Brown, Joseph L. Goldstein, Erwin Neher, Bert Sakmann, Thomas R. Cech, Sharp, Edwin G. Krebs and Richard Ernst. The Louisa Gross Horwitz Prize was established under the will of the late S. Gross Horwitz, in memory of his mother, to honor outstanding contributions to knowledge in biology or biochemistry.