Milestones in Erythropoietin
An article on the story of erythropoeitin by John W. Adamson, MD, and these accompanying milestones were published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.
|Richard Bright describes anemia as a complication of renal (kidney) failure.
|Denis Jourdanet describes an association between an overproduction of red blood cells, called polycythemia, and people living in the low-oxygen environment of high elevations.
|Paul Carnot and C. Deflandre describe the existence of a hormone responsible for erythropoiesis: "We have observed, with Mlle. Deflandre, that regeneration of blood after bloodletting is under the influence of a humoral process [a process controlled by a substance in the blood]…we give this substance the generic name Hemopoietine."
|C.L. Krumdieck and other investigators report evidence that a factor in anemic or hypoxic (low oxygen) plasma could increase the release of young red blood cells (reticulocytes).
|K.R. Reissman provides evidence of the presence of a humoral mechanism by experiments in surgically-connected rats in which he demonstrates that when one partner is made hypoxic, marrow erythropoiesis is increased in the partner rat with normal oxygenation.
|Allan J. Erslev confirms an erythropoietic-stimulating activity in the plasma of anemic rabbits, which he theorizes would be of potential therapeutic value if isolated.
|Leon O. Jacobson, Eugene Goldwasser, Walter Fried, and Louis F. Plzak establish that the kidney produces erythropoietin.
|Takaji Miyake, Charles Kung, and Eugene Goldwasser purify human erythropoietin from the urine of patients with aplastic anemia.
|Two groups of scientists, one under the leadership of Fu-Kuen Lin and the other under Kenneth Jacobs, clone and express the human erythropoietin gene.
|Joseph W. Eschbach, John W. Adamson, and colleagues in the U.S., and Christopher G. Winearls and colleagues in England, establish that recombinant human erythropoietin can correct the anemia of chronic renal disease.
|Mark J. Koury and colleagues, as well as Catherine LaCombe and colleagues, demonstrate the presence of erythropoietin RNA in kidney and liver cells and large white blood cells called macrophages.
|The first recombinant human erythropoietin is approved by the FDA for the treatment of renal anemia.
|Epo is approved for use in treating anemia in some patients with marrow disorders who fail to respond to naturally generated levels of erythropoietin, but who respond to the higher levels achieved with the pharmacologic product.