About the Cover
Hematopoietic populations are organized in a hierarchical manner. The cover image shows the family tree of granulocytes and macrophages. A limited number (1 per 10⁵ marrow cells) of self-renewing multipotential hematopoietic stem cells serve as the origin of all blood cells. These stem cells can produce 100-fold higher numbers of blast colony-forming cells (BL-CFC), which are likely the progenitors that sustain the daily requirements for new blood cells. Each BL-CFC can self-renew and generate up to several thousand committed, lineage-restricted progenitor cells (only the granulocyte-macrophage and dendritic lineages are shown). In turn, each progenitor cell can generate up to 10⁴ maturing progeny. The ability of one stem cell to produce 10⁹ progeny is rarely required. The cytokines that control each differentiation/proliferation step are listed: DC, dendritic cell lineage; FL, Flt3 ligand; G, granulocytic lineage; G-CSF, granulocyte colony-stimulating factor; GM, granulocyte-macrophage lineage; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-3, interleukin 3; IL-6, interleukin-6; M, macrophage lineage; M-CSF, macrophage colony-stimulating factor; SCF, stem cell factor; TPO, thrombopoietin.

About the Master
Donald Metcalf completed a BSc(Med) in virology and an MD at Sydney University (Sydney, Australia). After an internship at the Royal Prince Alfred Hospital in Sydney, he joined The Walter and Eliza Hall Institute (WEHI) of Medical Research in Melbourne as the Carden Fellow in Cancer Research, a position he has continued to hold since 1954. His work at the WEHI has been interspersed with periods of 1 to 2 years as a visiting scientist at Harvard Medical School (Boston, MA), Roswell Park Memorial Institute (Buffalo, NY), the Swiss Institute for Experimental Cancer Research (Lausanne, Switzerland), the Radiobiological Institute (Rijswijk, the Netherlands), and the University of Cambridge (United Kingdom).
Dr. Metcalf is distinguished for his work on the control of blood cell formation. He discovered the function of the thymus in directing lymphocyte development and, beginning in 1965, developed a series of specialized culture techniques permitting the growth of the various types of blood cells. These cultures led to the discovery of the colony-stimulating factors (CSF), hormones that control the formation of immune cells and the defense against infections. Dr. Metcalf's team purified all four CSFs and characterized their complex functions. His work, along with that of others, led to the cloning of both mouse and human genes encoding the four CSFs and the mass production of these hormones in culture. They showed that the CSFs, when injected into animals, stimulated the formation and activity of immune cells. Metcalf and his colleagues demonstrated the effectiveness of granulocytemacrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in humans. These CSFs have been used in 10 to 20 million patients around the world as reagents in accelerating the regrowth of blood cells following anticancer treatment, in permitting improved methods for blood cell transplantation, and for increasing resistance to infections.
Dr. Metcalf has published more than 730 scientific papers and nine books on his research, received the highest honors and awards from every industrial nation, and is recognized internationally as the leader in his field. Just to name a few of these accomplishments, Dr. Metcalf is a Fellow of the Australian Academy of Science, a Fellow of the Royal Society London, a Foreign Associate of the U.S. National Academy of Sciences, and a Companion of the Order of Australia. Yet, at the age of 84, Dr. Metcalf continues to work at the bench 8 hours each day. His recent work analyzes the mechanisms by which lineage commitment occurs in hematopoietic populations and the cellular events in oncogene-induced myeloid leukemogenesis.