Hikers and climbers who venture up to a mountain top can sense first-hand the physiological effects of the lower air pressure--and therefore, lower oxygen--at those high altitudes: shortness of breath and fatigue. What those climbers may not realize is that when their kidneys sense low oxygen levels, they release a chemical messenger that travels to the bone marrow, where it stimulates the growth of red blood cells, the conveyers of oxygen to our body's tissues and organs. Given time, a climber with healthy kidneys would acclimatize to the higher elevation as the bone marrow proceeded to churn out more red blood cells and increase the blood's oxygen-carrying capability.
That chemical messenger is erythropoietin, or EPO. Most patients with damaged kidneys don't produce enough EPO, and as a result they become anemic. Joseph W. Eschbach, clinical professor in the UW School of Medicine, and John Adamson, formerly of the UW faculty, conducted the first trial of genetically engineered EPO to correct anemia in kidney dialysis patients in conjunction with the Northwest Kidney Center in Seattle.
In the 1970s, Eschbach and colleagues proved they could correct anemia of renal failure in sheep using EPO. Those studies paved the way for treatment in humans when genetically engineered human EPO became available.
EPO and other blood growth factors can be manufactured by cloning the gene that codes for the growth factor and inserting that gene into a host organism, which, in turn, becomes a sort of living factory to manufacture the desired hormone. The factor is isolated and recovered and used to treat patients who are lacking it. Amgen, a biotechnology company in Thousand Oaks, California, discovered the gene for EPO in 1983, and produced material for the first clinical trial at the University of Washington by late 1985.
"Thousands of patients with anemia of renal failure in our region have been helped with EPO over the years," says Eschbach. "About 600 kidney dialysis patients are being treated today in the Seattle area with EPO at any given time. For these patients, it's been called the greatest advance since the kidney machine," he notes, explaining that EPO treatments improve patients' quality of life and allow them to avoid having to receive blood transfusions with the associated complications. Recently, anemias associated with other chronic diseases, chemotherapy, and AIDS have also been successfully treated with EPO.