hat is Biology Good For?
Boosting Red Blood Cell Production: Epogen

(This assignment is optional. Read this essay and answer the questions at the bottom for 3 extra credit points. You may only turn in one per six weeks. The assignment is due one week before the end of the six weeks. It is not necessary to visit the links in the text unless you are interested in more information.)

On June 1, 1989, a genetically engineered protein -- EPOGEN -- was .introduced by the Biotechnology company Amgen , providing patients with kidney failure the ability to lead more productive lives. Prior to the availability of EPOGEN, many individuals receiving dialysis treatments were affected by debilitating anemia (low red blood cell count) found in approximately 90% of all kidney dialysis patients.

Anemia: Many symptoms associated with kidney failure -- despite excellent dialysis care -- are frequently due to anemia. This anemia is caused by insufficient production of erythropoietin, a protein naturally produced in the functioning kidneys, which circulates through the bloodstream to the bone marrow, stimulating production of red blood cells (RBCs). Without adequate erythropoietin, there are too few RBCs to deliver oxygen to tissues. Anemia develops, leaving dialysis patients tired, sometimes unable to work or perform even routine tasks. A person with anemia may feel tired and weak and may lack energy. Even mild exercise may bring on fatigue, difficulty in breathing and chest pain. Blood transfusions can be performed to relieve the anemia, but they can be potentially dangerous to the patient. [Image]

EPOGEN: Recombinant Erythropoetin EPOGEN (Epoetin alfa, or "EPO") is a recombinant DNA version of the human erythropoetin protein that stimulates the production of RBCs. EPO is identical to natural erythropoetin, works in the same way, and has the same beneficial effects as the erythropoietin naturally produced by healthy kidneys. Erythropoetin is a fairly small protein of 165 amino acids. However, EPO, unlike Insulin, is a complicated human protein, too complicated to be made correctly in bacteria. It must be made is small batches in animal tissue culture cells called Chinese Hamster Ovary cells (CHO cells). Once isolated and purified, however, EPO supplements the dialysis patient's supply of erythropoietin and provides the boost needed to stimulate the production of anadequate supply of red blood cells.

Effects and Usage of EPO: Since its approval in 1989, EPO has eliminated the need for blood transfusions and helps correct anemia in dialysis patients. Today, most dialysis patients receive EPO by injection as part of their treatment. More than 150,000 dialysis patients take EPO on a regular basis.

Studies have demonstrated that an increased hematocrit (%RBCs in blood volume) resulting from EPO therapy has significant impact on the dialysis patients' lives.The target hematocrit range for dialysis patients using EPO therapy is 30-36%. Healthy persons have a hematocrit range of 38-46%. Studies have showed no consistently observed side effects as a result of treatment with EPO other than mild hypertension and flu-like symptoms. EPO is an expensive drug, costing Medicare over $1 billion a year and boasts annual sales of over $4 billion a year.

The Dark Side of EPO: Blood Doping
(note: original links and quotes from the Denver Post, have expired)

Unfortunately, some of the features that have made EPO a blockbuster drug for kidney dialysis patients has also led to its becoming a highly abused performance-enhancing drugs. "EPO Doping" has been practiced by athletes to illegally enhance their performance in everything from the Tour de France to the 2000 Sydney Olympics.

Once EPO was on the market, it was discovered by some athletes as a performance-enhancing drug. Middle distance runners, swimmers, and cyclists knew that a high concentration of RBCs would allow the blood to carry more oxygen - and thus improve endurance. A 15%-20% increase in RBCs results in a large increase in oxygen-carrying capacity, and about a 6%-8% increase in maximum aerobic capacity (Birkland et al. 2000). Before EPO, athletes used to extract their own blood and freeze it so they could inject themselves with extra blood just before a competition. This process of ``blood doping'' was banned by the Olympic Committee in the mid-1980s. [Source]

EPO doping provided an easy way around the ban, although it came with a risk. High concentrations of RBCs can cause the blood to thicken, leading to the possibility of heart attacks and strokes, particularly during hard exercise, and possibly death. The potential risks have not stopped athletes from using the drug. Its use became widespread in some sports. Additionally, because EPO is so similar to natural erythropoetin, it was an extremely difficult drug to test for, making it hugely popular. [Source]

The most sordid examples came in the Tour de France, the grueling three-week bicycle race that is considered the most trying endurance competition in the world. In 1996, world champion Jerome Chiotti of France admitted to using EPO and was subsequently stripped of his title. in 1998, the top-rated Festina team from France was disqualified after French customs agents discovered hundreds of vials of EPO and other performance-boosting drugs in a team car. Seven out of the 20 teams entered in the Tour eventually dropped out of the race. [Source]

New Test for Epo Doping at the Tour de France 2000.

Erik Zabel at the Tour De France 2000: The rewards of NOT becoming involved in EPO doping!

The UCI (International Cycling Union) has begun using a new urine test for EPO in the 2000 Tour de France, and this test was also endorsed by the Sydney Olympices 2000 (IOC) International Olympic Committee . The test was developed by a French national labaratory with the strong encouragement of the French Ministry of Sport.

Before the urine test for EPO, it was difficult to test for EPO directly. Instead, blood drawn from cyclists before the start of a race was used to test their hematocrit levels (% RBCs in blood by volume). An average hemotocrit for a healthy athletic person is 43. EPO raises hematocrit levels. The UCI does not allow riders to have a hematocrit above 50. Since checking hematocrit levels is only an indirect test, the UCI punishment was a two week "health" suspension - high hematocrit is actually a medical risk, and can lead to cardiovascular disease or death. However, with the new urine test that will be able to detect the actual use of EPO, there are now much stiffer penalties for riders, team physicians, and anybody else involved in EPO doping. [Source]

Sydney Olympics put EPO under scrutiny (note: original link from the Denver Post, has expired)

In 2000, the International Olympic Committee (IOC) introduced new testing procedures for use at the Sydney Olympics. Somewhere between 300 and 700 athletes -- were tested during the Sydney Olympics for EPO. Charles Yesalis, a professor at Penn State University and an expert on the International Olympic Committee anti-doping efforts, was qouted as saying ``EPO can give a 5 percent to 15 percent enhancement. Athletes feel they can't afford not to do this.''

2/24/02: Salt Lake City Olympics Doping: New Drug Darbepoetin Behind Olympic Scandal "Three cross-country skiers, including Spain's triple gold medallist Johan Muehlegg and record-equalling Russian Larisa Lazutina, were expelled from the Salt Lake City Olympic games on Sunday after testing positive in out-of-competition tests."

Material for this Good For was modified from sources listed in the text, especially:
Epogen Backgrounder
EpoDoping - The Why Files

The text of this "What is Biology Good For" exercise is copyrighted under the name of Dr. Kathleen A. Marrs, 1999, 2000, 2001, 2003. There are no restrictions on its use by educators or by non-profit institutions as long as its content not modified, proper copyright acknowledgement is retained, and this statement is not removed.


Lance Armstrong: "I don't do EPO doping, and neither should you! Now, let's toast to my 4th Tour de France win!!!"

Extra Credit Questions: Please answer the following questions on a piece of paper and turn it into me.
1. Why is EPO used for kidney dialysis patients?
2. What are some of the risks associated with EPO doping by athletes?
3. What does Lance Armstrong have to do with
Indiana University Medical Center right across the street?
[PS. Summer reading: Lance's new Book:
"It's Not About the Bike"]