Blood doping — the illicit process of increasing the amount of oxygen in the bloodstream to enhance athletic performance — has a decades-long history in the athletic world but the methods for using it to cheat have changed over the years.
The issue is in the news once again this week, with Lance Armstrong admitting to Oprah Winfrey that he used different blood doping methods during his cycling career.
His interview with Winfrey follows the United States Anti-Doping Agency (USADA) banning Armstrong for life last August and then being stripped of his seven Tour de France titles. The USADA's decision came after Armstrong dropped his challenges to their allegations that he took performance-enhancing drugs and engaged in blood doping.
The science about blood doping is pretty straight-forward. The body uses more oxygen during exercise, perhaps 20 times the rate, during intense exercise compared to when at rest.
Blood moves oxygen from the lungs to the muscles. Since oxygen doesn't dissolve readily in blood, it is carried by a protein called hemoglobin inside red blood cells.
The purpose of blood doping is to increase the quantity of hemoglobin, which carries the energy-fueling oxygen, into the athlete's bloodstream.
Blood doping began in the 1970s
A takeaway from the 1968 Summer Olympics in Mexico City, 2,240 metres above sea level, was that increasing the number of red blood cells would enhance athletic performance. Training at higher altitudes will boost the red blood cell count but hardly by Olympian amounts.
A few years after the Mexico Games, and through the 1970s and 1980s athletes used transfusions to blood dope.
That method wasn't banned until 1986, after the 1984 Los Angeles Olympics, where the U.S. cycling team boasted about their use of transfusions.
There are two methods of using transfusions for blood doping, plus other methods that use substitutes and hormones.
For transfusions, there's the standard method, using blood from someone of the same blood type. The hemoglobin in the transfused blood increases the amount of hemoglobin in the recipient's bloodstream. That's called homologous transfusion.
Another method used by athletes is transfusing their own blood, which is called autologous transfusion. Hospital patients awaiting elective surgery sometimes choose this method to avoid infections and blood type match errors.
Difficulties in detection
Athletes have their own blood withdrawn, preferably when their hemoglobin level is high, stored and then re-infused before a competition. The athlete's blood could also be run through a centrifuge to isolate red blood cells from blood plasma.
In 2006, Spanish police raided a cycling team doctor's office in Madrid and discovered 99 bags of athletes' blood allegedly being stored for later transfusion.
American cyclist Tyler Hamilton, an Armstrong teammate, was investigated by the IOC during the 2004 Athens Games, after his initial sample indicated he had tested positive for a blood transfusion but the case was dropped after his backup "B" sample was mistakenly frozen and couldn't be properly tested.
The IOC stripped him of the medal in August.
It took 20 years until a successful test was developed in 2004 for homologous transfusions, which involves using another person's blood, but experts are still confounded by the use of an athlete's own blood.
"No test exists to detect when an athlete has used autologous blood transfusion," according to Dr. Michael Ashenden, one of the world's top blood doping experts who played a key role in the Armstrong blood doping case.
EPO becomes favored method
In the 1990s blood transfusions took a back seat as cheating athletes turned to a new method of blood doping. A genetically-engineered hormone that could stimulate bone marrow to produce more red blood cells was for sale.
The kidneys naturally produce a hormone called erythropoietin (EPO) to do that. In the 1980s, scientists figured out how to engineer the hormone. By 2002, according to a New York Times story, EPO had become "the best-selling genetically engineered drug ever, and one of the largest-selling drugs of any kind in the world."
EPO's primary medical use is for patients with anemia. It's standard for patients on dialysis to take EPO.
"Athletes quickly realized that EPO injections were a quicker, neater and more convenient means to blood dope than either homologous or autologous transfusions," wrote Ashenden, who heads the Australia-based research consortium Science and Industry Against Blood Doping.
"EPO tipped the sporting world upside down so that cynical doctors and drug gurus, rather than talent and training, came to dominate results," Ashenden added.
Not until the Sydney Olympics in 2000 did officials have a method to detect athletes using the engineered hormone EPO to cheat.
Italy's Alex Schwazer, a race walking gold medalist in 2008, was kicked off the team at the 2012 Olympics after testing positive for EPO.
Another method of blood doping is using blood substitutes, called hemoglobin-based oxygen carriers (HBOC) and Perfluorocarbons.
HBOCs were developed for use in emergencies or on the battlefield when blood is not available for transfusion, or testing for blood type is not an option.
The World Anti-Doping Agency implemented a test for synthetic oxygen in 2004.