The number of red blood cells, or erythrocytes, in our body is controlled by a feedback loop between an oxygen sensor in our kidneys and our bone marrow—the factory that produces blood cells. Erythrocytes don’t have a nucleus and can’t repair themselves. After about 120 days of service, they are shot, and the spleen shuffles these red blood cells out of circulation at a rate of 2 to 3 million erythrocytes per second. Like a manager calling down to the production line when a new order for widgets comes across his desk, when the kidneys sense that our red-blood-cell count is getting low (our hematocrit level), EPO signals the bone marrow to crank up blood cell production. Stem cells start a chain of sequential divisions that eventually results in fresh new erythrocytes eager to cart oxygen to our muscles for four months. A hormone, erythropoietin, works as the middleman in this process; it binds with blood-cell receptors and triggers the creation of erythrocytes.
Like a second temporary factory manager who suddenly appears on the floor with a megaphone and starts barking out orders for more product, when a doctor injects synthetic EPO into your body, the artificial hormone tricks the stem cells in the bone marrow into creating more red blood cells. It can be a life-saving event when natural erythropoietin levels wane due to pathologies like bone marrow cancer or kidney failure.
This process also works in healthy people, only instead of fooling an ailing body into boosting its flagging red-blood-cell count back up to normal, injecting EPO into a healthy human causes the bone marrow to produce more red blood cells than are normally needed. The resulting surplus of these oxygen-carrying cells can increase endurance by as much as 10 percent. The ideal adult hematocrit percentage varies between individuals and genders, but it is generally in the 40 to 54 percent range at sea level, and about 5 percent higher than that for people who live at altitude. When athletes figured out that exogenous EPO could juice their red-blood-cell count, they got the same performance-enhancing benefit as living at altitude or sleeping in a hypoxic chamber. Describing the effect of EPO on his performance, cyclist Tyler Hamilton said in his 2012 book, The Secret Race, “That holy place at the edge of your limits gets edged out—and not just a little.”
Although endurance athletes probably began experimenting with this new synthetic hormone during the drug’s clinical trials in 1986, its use as a potential performance enhancer was first recognized in the early 1950s. Beginning in 1953, a University of Chicago biochemist named Eugene Goldwasser set about understanding how the human body created and regulated red blood cells. Solving this problem had tremendous life-saving potential. Inventing a way to artificially replace the body’s EPO would be a boon for millions of patients affected by kidney failure. After three decades of research, Goldwasser isolated the erythropoietin gene, thereby opening the door to its synthesis.
In his autobiography, A Bloody Long Journey, Goldwasser recalls that not long after he began his 1953 investigations, a man with racehorses to sell came looking for equine EPO. Horses that ran faster and longer commanded premium prices, and the horseman wanted to inject his stock with EPO to increase their performance in claiming races—events where horses are sold based on their placings. As Goldwasser recalls, “He had done his homework and knew that for short races, increasing red cells was no help . . . but in longer races, having a bigger erythron [red-blood-cell count] was an advantage.”
Buckets of horse blood soon began showing up on Goldwasser’s doorstep. Although Goldwasser never extracted enough pure EPO from the blood to test its sporting efficacy, he, like the racing entrepreneur, saw the performance-enhancing potential in the blood-regulating hormone in the early 1950s.8 When Goldwasser’s lab finally isolated the EPO gene in the early 1980s, an infant biotech startup called Applied Molecular Genetics approached him, and Goldwasser began sharing his three decades of knowledge with the company that would later rename itself Amgen. The company was funded by Montgomery Securities, an investment bank founded by Lance Armstrong’s U.S. Postal Service team backer Thomas Weisel.9
Amgen finally cloned EPO in November 1983, opening the door to industrial scale production of a synthetic version of the hormone under the name Epogen. It also licensed the patent to Johnson & Johnson, which sold its EPO as Procrit. The startup exploded into a pharmaceutical giant worth over $100 billion today. By 2006, annual EPO sales were $13 billion worldwide.10 After Amgen went public in 1983, the company generated a stock-market windfall that seed investor and dedicated cyclist Weisel would later use to fund pro bike racing teams and pay for his own personalized coaching by Eddie Borysewicz.
The spectacular rise of Amgen and its miracle drug coincided with what appeared to be a rash of mysterious deaths among endurance athletes. Echoing claims made in other general news and cycling-specific publications, a May 1991 New York Times article concluded that EPO’s development came too close to a glut of pro cyclist funerals to be mere coincidence. The piece described the mysterious death of Dutch pro Johannes Draaijer, who passed away in his sleep in 1990 at the age of 27. A caption beneath a photo of Draaijer read, “Mr. Draaijer’s widow believes that the drug recombinant erythropoietin was involved with his death.” A pull quote declared, “You just don’t get 18 deaths in 4 years, mysteriously.” The story left the impression that the new life-saving anemia drug played double duty as an indiscriminate athlete killer.