Eero Mantryanta’s High EPO Gene

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eero mantyrantaEero Mantyranta was one of the greatest cross country skiers ever.  He competed in four Winter Olympics (1960–1972) and won seven medals.  In the 1964 Winter Olympics in Innsbruck, Austria, he won the 15 kilometer race by an incredible forty seconds and then won the 30 kilometer race by more than a minute.  When athletes are much better than everyone else, they are  always likely to be accused of cheating.  Although there were no drug restriction rules in the Olympics at that time, Mantyranta was found to have a red blood cell count that was much higher than normal. Normal healthy men have a hemoglobin of 14 to 16.  His hemoglobin was always above 20 and in his 70s, it was recorded at 23.6.
 
How fast you can move over distance is partly determined by how long it takes to get oxygen into your muscles.   More than 98 percent of the oxygen that reaches your muscles comes bound to hemoglobin in your red blood cells, while less than two percent of the oxygen can be carried in the blood fluid itself. The higher your hemoglobin, the more oxygen your blood can carry to your muscles and the faster you race over distance in all endurance sports: skiing, running, cycling, swimming and so forth. 
 
For more than 30 years after his great Olympic victories, Mantyranta lived with a cloud over his head, under suspicion of cheating even though he was never found to have taken blood transfusions or drugs to raise his hemoglobin.  
 
Prodigious Training
Mantyranta grew up in extreme poverty in rural Finland while the country was devastated with debt from World War II.  He learned how to ski soon after he learned to walk.  Skiing was the only way he could cross a frozen lake to get to school.  By age 15, he worked with people who needed to be able to ski to get jobs as forest workers.  Since he was faster than everyone else, he tried ski racing and found that he could always win.  He got a job working as a Finnish border patrol officer where he had to ski all day and in 1960, he made the Finnish Olympic team for the Games in Squaw Valley, California. He won a gold medal in the 4 × 10 kilometer relay team but did not medal in the 15 kilometer individual race. 
 

He came back from those games with his sole purpose in life to be an Olympic champion.  Six days a week his full time job allowed him to train for four to eight hours a day.   On Sundays, he left his house at the first signs of daylight with his lunch strapped to his leg and skied continuously until sundown.  At the 1964 Olympics in Innsbruck, Austria, he raced all by himself while winning both the 15 kilometer  and 30 kilometer races by wide margins.  He also was part of the Finnish 4 × 10 kilometer relay team that won a silver medal. In 1968 in Grenoble, France, he picked up a silver and 2 bronze medals. 
 
They Named a Syndrome After Him
He spent most of his life being accused of taking drugs to give him a high hemoglobin level, but it wasn't until 1993, almost 30 years after his greatest Olympic performance, that doctors proved that his high hemoglobin was due to his genes and had nothing to do with drugs or transfusions (Eur J Haematol, Mar 2007;78(3):183-205).  Mäntyranta was born with a condition called Primary Familial and Congenital Polycythemia (PFCP) that caused an increase in his red blood cells and hemoglobin due to a mutation in the erythropoietin receptor (EPOR) gene.
 
• In 1976, a dozen years after his incredible Olympic performance, scientists discovered erythropoietin (EPO) a chemical made by the kidneys that causes the bone marrow to make red blood cells (Eur J Haematol. Mar, 2007;78(3):183-205). 
 
• In 1985, scientists discovered the gene that codes for EPO (Blood, 1990 Jul 1;76(1):24–30).  
 
• In 1990, the structure of EPO was discovered (Blood, July 1, 1990;76(1):24–30).
 
• In 1993, scientists found that Mantyranta had the gene that increases EPO, the reason for his high hemoglobin levels (Proc Natl Acad Sci, May 15, 1993;90(10):4495–4499).  Hematologist Eeva Juvonen showed that Mantyranta's bone marrow cells had a genetic modification of special receptors on them that allowed the marrow to make new red blood cells with insignificant amounts of EPO.  Researchers then tested 97 of Mäntyranta's family members and found that 29 also had that same genetic mutation.  Two of these relatives were also skiing champions.  
 

How Athletes Try to Raise EPO
When Lance Armstrong and his cycling teammates cheated with EPO injections and blood transfusions, their hemoglobin levels were still far below those that Mantyranta's body produced naturally.  Now endurance athletes often work to raise hemoglobin legally by training at high altitudes in air with low oxygen levels.  Breathing air with sparse oxygen causes your body to produce extra EPO to raise your hemoglobin levels.  This is called "live high and train low", where they do more intense training when they breathe air with normal amounts of oxygen near sea level, and then they sleep in special chambers that have air with low levels of oxygen.   At one time Olympic officials debated whether to ban these high-altitude tents but decided there would be no way to enforce such a rule.  
 
The Rest of Mantyranta's Life
Having very high hemoglobin levels can kill you because it increases risk for clotting to cause heart attacks and strokes.  However, as far as I know, he was never reported to have had a clotting problem.  In 2013, he died at age 76, but I could not find a cause of death. However in his last years he was very strong with large muscles, a full head of hair, a barrel chest and full mental capacity and he still worked herding his reindeer.  One reporter said that his face was "bright red" from the extra red blood cells beneath his skin.
 
What is Fair and What is Unfair?
Virtually all of the very best athletes have some genetic advantage that makes them better than their competitors.  They may be exceptionally tall, be extremely flexible or have a genetic ability to build large muscles.  For example, humans have a hormone called myostatin that inhibits strength and muscle growth.  A child who is born with myostatin deficiency has very large and strong muscles right from birth (N Engl J Med,  2004;350: 2682–2688).  Athletes may also have environmental advantages such as living at a high altitude, and of course they may have social advantages that provide them with superior coaching and equipment and allow them the luxury of training instead of working.
 

In a world where sports are divided into men's and women's teams, a particularly difficult issue is deciding who is male and who is female.  This week we saw the South African runner Caster Semenya, win the 2016 Olympic 800 meter run for women, slowing down at the end so she wouldn't win by too much.  Her body naturally produces so much of the male hormone,  testosterone, that she has the muscles and strength of a man even though she has the genitals of a woman.  In 2009, at age 18, she dominated the ladies 800 meters at the world track and field championships and tests showed that she had very high levels of testosterone.  In 2011, the International Association of Athletic Federations (IAAF), the governing body of track and field, banned all women with high testosterone levels (>10 nmol/L), but the Court of Arbitration for Sport (CAS), the Swiss-based high court for international sport, suspended the policy and Semenya was able to win a silver medal at the 2012 London Olympics.  Nobody has ever shown that she takes drugs.  Her high testosterone is the result of the fact that she was born with a female body that produces lots of testosterone. At this time, women who are born with a disorder of sex development but have female genitalia are allowed to compete as women (The Journal of the American Medical Association, August 04, 2016).   Watch the video at the end of this report and see how she was abused by people who should have known better. It took great courage for her to continue training and competing against such brutal criticism and obstruction.

People who are born with the capacity to grow larger and stronger muscles will always have the potential to be better athletes, as will those who have the ability to deliver more oxygen to their muscles.  The debate on what is fair and what should be banned will continue.   
 
November 20, 1937 – December 29, 2013