Subscribe to the OSS Weekly Newsletter!

Erythropoietin: Ticket to the Olympics or Recipe for Disaster?

Some athletes have genetic mutations allowing them to deliver oxygen more efficiently. Is it ethical to level the playing field by leveling red blood cell counts?

What if I told you that a simple one letter change in your DNA could have landed you seven Olympic gold medals? You’re right, it’s probably a little more complicated than this. But winners of this genetic lottery, like Olympic cross-country skier Eero Manytrata, have a natural tendency to perform better in aerobic sports. What exactly was it that gave Eero Manytrata an unequivocal advantage? 

 A large part of our ability to carry out strenuous exercise is dependent on the ability of our blood to deliver oxygen efficiently to working tissues, particularly muscles. This task is carried out by the erythrocytes in our blood – otherwise known as red blood cells! As you may know, erythrocytes bind oxygen in the lungs and proceed to deliver this oxygen to cells throughout the body. Red blood cells have a lifespan of approximately 120 days. This means your body is constantly regenerating erythrocytes through a process termed erythropoiesis. However, we don’t always make the same amount- sometimes we need more and sometimes we need less. Normally, our body requires more red blood cells under low oxygen conditions known as hypoxia. This can be due to a series of factors such as, low hemoglobin levels, reduced oxygen affinity, lower atmospheric pressure or increased metabolic rate. Metabolic rate is the amount of energy that we use in a given time period and thus tends to be higher in cases of intense exercise. Hypoxic conditions are sensed by specialized cells in the kidney. In turn, they release a hormone known as erythropoietin (EPO) into the blood stream. The EPO then acts on the EPO receptor on the bone marrow – the primary site of red blood cell formation in adults – and acts as a switch signal to increase the rate of erythropoiesis. This will increase the number of erythrocytes in the blood, normally resulting in what is known as a higher hematocrit. The hematocrit is the proportion of our blood that is made up of red blood cells and is typically around 45%.  

In rare cases, people like Eero Manytrata have a genetic mutation that results in constantly active EPO signaling. This means that people with this mutation make red blood cells even when they don’t require the extra oxygen. As a result, their oxygen-carrying capacity is increased by 25–50% allowing them to deliver oxygen more efficiently to their working muscles. For Eero Manytrata, his higher blood oxygenation and thus increased aerobic capacity provided a huge natural advantage in sporting competitions.  

Once EPO was identified as the glycoprotein hormone that stimulates red blood cell production, researchers were able to generate a synthetic EPO using DNA recombinant technology that ultimately mimics the action of natural EPO. DNA recombination is a common method used in many laboratories to obtain protein products of specific gene sequences by first isolating the gene of interest, then expressing the gene in animal cells and finally isolating the protein product. The synthetic EPO was initially made as a clinical treatment for patients with reduced oxygenation, but elite athletes soon began to inject the synthetic EPO into their bloodstream in attempts to gain a leg up in the competition. The synthetic EPO increased their red blood cell production, their hematocrit and thus, their ability to carry oxygen to their tissues. Since then, this method of blood doping has been banned by sports federation- but this didn’t stop everyone. Once banned, several athletes continued to abuse the synthetic EPO which ultimately helped them win many competitions. This was the case for famous cyclist Lance Armstrong whose use of performance enhancing drugs helped him win seven Tour de France Championships. Several studies investigating the effect of synthetic EPO found an increase of 9% on maximal aerobic power and an increase in 54% in exercise performance. That’s quite the head start if you ask me.  

The use of synthetic EPO in sporting events resulted in a great series of health concerns in addition to a great many ethical controversies. One of the most prominent health concerns regarding blood doping with synthetic EPO is that it greatly increases the viscosity of blood. You can think of this as turning your blood from a more maple syrup like texture to a thick molasses. Okay, probably not as extreme as this, but you get the idea. This increased viscosity can impede blood flow and increase an athlete’s risk of developing health complications such as hypertension and blood clots. There is also an interesting ethical controversy regarding EPO, both synthetic and natural. On one hand, athletes with naturally high EPO have an unequivocal advantage that some argue should render them unable to compete. But this genetic advantage is through no fault of their own. Does this mean that they should not be able to compete in the sport they have trained for their whole life? Should they be placed in a separate category? Should other athletes have the option of genetic doping – that is changing their genes to obtain the same advantage? These are all open questions that no one has quite yet figured out.  

Since the first synthetic EPO was released, there have been a series of derivative drugs that also result in increased erythropoiesis. These drugs have significant clinical implications in the treatment of patients with anemia. However, it also means that it is harder for officials to detect new erythropoiesis stimulating agents (ESA). The World Anti-Doping Agency initial attempts to reduce blood doping was to implement an athlete biological passport that measures several hematological parameters related to red blood cell mass and synthesis such as hemoglobin and hematocrit. Deviances from expected values in these values can be indicative of foul play. Since the development of new ESA’s and micro dosing techniques, committees have opted to develop more direct testing methods that attempt to detect any non-natural ESA’s in the blood. However, these methods are still being optimized and some athletes are still choosing to take the easy way to the top with little regards for the consequences on their body and the integrity of the sporting community. While I am not close to being an Olympic athlete, I trust that my body knows when to make more red blood cells – like on those famous hikes up Mont Royal.


Daniela is a third-year Physiology student at McGill University.

Back to top