Hypotheses had been made in the early 20th century that there was a substance that triggered the body to produce more red blood cells, but no one had been able to identify a material that matched the description. In 1955, hematologist Leon O. Jacobson challenged Goldwasser to begin a search for the red blood cell-promoting substance, a task that Goldwasser assumed could be accomplished in a few months. His initial approach involved the step-by-step removal of different organs from laboratory rats, leading to the conclusion that anemia resulted from a substance produced in the kidneys. Though the discovery of where the material was produced was made in 1957, it took Goldwasser and his team another 15 years before they were able to isolate eight milligrams of EPO from material that had been precipitated from 2,500 litres (550 imp gal; 660 US gal) of urine from anemia patients by Japanese researcher Takaji Miyake. Results of Goldwasser's research, which had been funded by grants from the National Institutes of Health, were first published in 1977 in the Journal of Biological Chemistry.[1] University of Chicago biochemist Donald F. Steiner called the discovery "one of the great contributions to science or medicine of the 20th century, comparable to the discovery of insulin".[2] Goldwasser had submitted a patent disclosure form, though the University of Chicago never pursued a patent.[2]
After providing a sample of the purified EPO to researchers at Amgen, a team there led by Fu-Kuen Lin was able to identify and patent the gene that produced EPO and was able to generate useful quantities of human EPO by using genetic engineering techniques to insert the gene into hamster cells. After successful tests on patients undergoing dialysis, Epoetin alfa, marketed by Amgen under the trade name Epogen starting in 1989, became a financial success, generating a billion-dollar market for Amgen and other companies that had developed their own versions of EPO, though Goldwasser would say that "the enormous clinical success of Epo still astonishes me". Goldwasser didn't receive any royalties from Amgen and noted that having received "one percent of one percent of the drug's annual revenues would have funded my lab quite handsomely" before his retirement from the university in 2002.[1] Goldwasser faced criticism for turning over his government-funded research results to Amgen, though he wrote in 1996 that he had received permission from the NIH.[1]
In subsequent years EPO has faced controversy for its use as a performance-enhancing drug, particularly in long-distance bicycle racing, where participants have been found to have used EPO as a means to increase endurance.[1] Floyd Landis admitted to using EPO and other performance-enhancing substances during his professional career, and was stripped of his title as winner of the 2006 Tour de France.[3]
A resident of Hyde Park, Chicago, Goldwasser died at his home there at the age of 88 on December 17, 2010, due to renal failure that occurred as a complication of prostate cancer. He was survived by his second wife, Deone Jackman; three sons from his first marriage, Thomas, of San Francisco, Matthew, of Chicago, and James, of New York; and five grandchildren. His first wife, Florence Cohen, died in 1981.[1] His memoir, A Bloody Long Journey: Erythropoietin (Epo) and the Person Who Isolated It, (ISBN 978-1-4568-5736-3) was published in 2011
After providing a sample of the purified EPO to researchers at Amgen, a team there led by Fu-Kuen Lin was able to identify and patent the gene that produced EPO and was able to generate useful quantities of human EPO by using genetic engineering techniques to insert the gene into hamster cells. After successful tests on patients undergoing dialysis, Epoetin alfa, marketed by Amgen under the trade name Epogen starting in 1989, became a financial success, generating a billion-dollar market for Amgen and other companies that had developed their own versions of EPO, though Goldwasser would say that "the enormous clinical success of Epo still astonishes me". Goldwasser didn't receive any royalties from Amgen and noted that having received "one percent of one percent of the drug's annual revenues would have funded my lab quite handsomely" before his retirement from the university in 2002.[1] Goldwasser faced criticism for turning over his government-funded research results to Amgen, though he wrote in 1996 that he had received permission from the NIH.[1]
In subsequent years EPO has faced controversy for its use as a performance-enhancing drug, particularly in long-distance bicycle racing, where participants have been found to have used EPO as a means to increase endurance.[1] Floyd Landis admitted to using EPO and other performance-enhancing substances during his professional career, and was stripped of his title as winner of the 2006 Tour de France.[3]
A resident of Hyde Park, Chicago, Goldwasser died at his home there at the age of 88 on December 17, 2010, due to renal failure that occurred as a complication of prostate cancer. He was survived by his second wife, Deone Jackman; three sons from his first marriage, Thomas, of San Francisco, Matthew, of Chicago, and James, of New York; and five grandchildren. His first wife, Florence Cohen, died in 1981.[1] His memoir, A Bloody Long Journey: Erythropoietin (Epo) and the Person Who Isolated It, (ISBN 978-1-4568-5736-3) was published in 2011
Purification of human erythropoietin.
- T Miyake,
- C K Kung and
- E Goldwasser
Abstract
Human erythropoietin, derived from urine of patients with aplastic anemia, has been purified to apparent homogeneity. The seven-step procedure, which included ion exchange chromatography, ethanol precipitation, gel filtration, and adsorption chromatography, yielded a preparation with a potency of 70,400 units/mg of protein in 21% yield. This represents a purification factor of 930. The purified hormone has a single electrophoretic component in polyacrylamide gels at pH 9, in the presence of sodium dodecylsulfate at pH 7, and in the presence of Triton X-100 at pH 6. Two fractions of the same potency and molecular size, by sodium dodecyl sulfate gel electrophoresis, but differing slightly in mobility at pH 9, were obtained at the last step of fractionation. The nature of the difference between these two components is not yet understood.
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