HAEMOPOIETIC GROWTH FACTORS NOW CLONED

The progressive development, beginning in thc mid-1 9 60s, of semisolid culture techniques able to support the clonal proliferation of various haemopoietic populations, led to recognition that the proliferation, maturation and some functional activities of haemopoietic cells are controlled by a series of specific regulatory glycoproteins or haemopoietic growth factors. Most of the haeinopoietic regulators were discovered because of their mandatory role in stimulating the clonal proliferation of various haemopoietic cells in vitro and the most commonly used group name for these regulators is the colony stimulating factors (CSFs). With the assistance of bioassays based on in vitro colony formation, it has been possible to purify and characterize a number of these CSFs, the most extensively studied being those controlling granulocyte and macrophage proliferation. In the past decade. four murine and three human granulocyte-macrophagc CSFs have been purificd to homogeneity and much information established on their actions in vitru (sec review: Metcalf, 198 5). Although the CSFs are highly active and exert their effects in the 10-”-10-13 M concentration range, two disturbing facts emerging from this work were that the CSFs are produced in only minute amounts by even the richest tissue sources and that the in vivo halflives of injected CSFs are very short, being a matter of minutes or hours. This made it clear that if the CSFs were ever to be tested in vivo and possibly used in the treatment of patients, the genes coding for the CSFs would need to be isolated and the mass-production of recombinant material successfully accomplished.