A quest for erythropoietin over nine decades.

The major research accomplishments of the author are described from the time of his PhD thesis work on the mechanism of cobalt polycythemia to the present day. His early work on the quest for the cell that produces erythropoietin (Epo) to his current work on oxygen sensing and signal transduction pathways involved in erythropoietin gene expression are reported. He describes his main research interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his research on how hormones such as the glucocorticoids function in the regulation of erythropoiesis (1956-1962). His major findings during this period were the discovery that hydrocortisone and corticosterone stimulated erythropoiesis (1958) and that cobalt increased erythropoietin production in the isolated perfused dog kidney (1961). He describes how he was led astray in some of his early studies on the cells in the kidney that produce erythropoietin, because of the less-developed technology available to him at that time; and how in situ hybridization and other molecular biology techniques enabled him to confirm some of the earlier work in mice by other investigators that interstitial cells in the kidney were the site of production of erythropoietin in the primate. His work in the controversial area of the mechanism of the anemia of end-stage renal disease is described in detail, as it pertains to Epo deficiency and suppressed erythroid progenitor cell response to Epo. He also discusses his recent work on signal transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen sensing and Epo gene expression.