EPO the molecule

EPO – Erythropoietin – Edgar Allan Poe

EPO is a glycoprotein hormone that controls red blood cell production. It was discovered by Eugene Goldwasser in a long drawn out process.
The history is pretty interesting.

Goldwasser spent two years in the US Biological Weapon Laboratory after being drafted in 1944, where he worked on the army’s anthrax vaccination program. After the war he complete a PhD in biochemistry at the University of Chicago, and spent the rest of his career there. He first worked on a cold war project aimed at finding a cure for radiation sickness. This led him, in 1955, to begin research to find the signal that regulates the production of new red blood cells. The quest became his life’s work.

The initial discovery in 1957 was that EPO was produced in the kidneys. (People with kidney failure are anemic.) He then guessed that anemic patients would produce excess EPO. This lead to years of making sheep anemic and then harvesting their blood. This turn out to be a dead end and he was on the point of giving up when another group discovered that more of the excess EPO is in the urine. (The easiest drug test for EPO is a urine test, not a blood test.) He was then gifted a package of dried concentrate made from 2500 litres of urine from anemic patients by a Japanese researcher Takaji Mijake. It then took Goldwasser and his team another 15 years before they were able to isolate eight milligrams of EPO. They published in 1977.

Goldwasser had difficulty in convincing pharmaceutical companies to commercialise the discovery due to the complexity of isolating the compound. In 1980 gave his entire stock of purified EPO to a small californian company: called Applied Molecular Genetics. This company was able to clone the human gene for EPO. The gene was then spliced into hamster cells, which churned out enough EPO to sell as a drug. The rest is history.

Epogen was approved for human use by the FDA in 1989 and Epogen and Neupogen were the company’s first products on the market. By 1996, annual sales in the US exceeded $1 billion. This company is now known as Amgen, and is the biggest bio-tech company in the world, employing ~ 17,000 people. In 2006, Amgen began sponsoring the Tour of California (ToC) the biggest cycling race in the US. The last stage of the Amgen Tour of California this year ended in Thousand Oaks, Amgen’s headquarters.

In a bizarre coincidence, many of the recent drug related cycling controversies occur during the Amgen ToC. In 2009, the Armstrong comeback 2.0 was unveiled; and Kimmage announce that “…the sport has been in remission for two years, but the cancer is back.” During the 2010 race the Floyd Landis revelations appeared. In 2011 we had the Tyler Hamilton interviews. Pro-cycling is all about entertainment on so many levels.

EPO is fantastic drug that has saved many lives. Recombinant DNA technology made it possible to produce EPO economically on a large scale. In 1986 the first clinical studies had confirmed that the drug could correct anemia in patients with kidney failure. Patients who started treatment with the EPO drug were spared multiple blood transfusions and able to lead longer lives.

It is easily injected under the skin, pharmaceutical EPO can boost hematocrit for 6-24 weeks, or longer. If too much is used, then the red blood cell count can be raised so much that the blood becomes more viscous, putting a strain on the heart. The 1990’s saw many cyclists at grand tours each with their own thermos. At the hotels there would be a rush for ice to replace in the thermos. It also came common to see cyclists suddenly jumping on exercise bikes in the middle of the night to get their sluggish blood flowing.

In 2000 a test was developed by scientists at the French national anti-doping laboratory (LNDD) to detect pharmaceutical EPO by distinguishing it from the nearly identical natural hormone normally present in an athlete’s urine. The inherent problem is that pharmaceutical EPO can only be detected in the circulation for a few days after administration, while its benefit to the cyclist persists long after. It requires testing before, rather than during competition. Hence pro cyclists must make their whereabouts known out of competition.

Among other many good deeds, Amgen sponsors Tony Abbot’s Pollie Pedal charity ride.

Some other reading: here and here

Crystal structure:
Nature, (1998), 395, 511-516.

This entry was posted in Armstrong, doping. Bookmark the permalink.

1 Response to EPO the molecule

  1. 888riley says:

    Great story. Hilarious that Amgen sponsors the ToC

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