Alleged blood doping and Lance Armstrong: Blood Doping and False Negatives

My apologies to my occasional readers, as I've been on hiatus for a few months now. Between travel to a conference in Japan, sporadic progress in my research, and a dearth of other things that have come up, I've had little time or inclination to update this blog.

Now that things have settled down, I aim to both put up some more interesting posts in the coming weeks and months, and to also go through the backlog of updates that I'd planned and penned, but had not yet posted.

The New York Times has released an interesting article regarding Lance Armstrong and his alleged doping, and follows a release by the CEO of the United States Anti-Doping Agency (USADA) discussing the findings of their recent investigation. Though I am only vaguely aware of the recent scandal surrounding Armstrong, I thought it a worthwhile piece to share, and to offer some comments along the way.

Firstly, a quick look through the NYT article indicates that new tests on blood samples obtained for the purposes of drug testing were anomalous, and were consistent with blood doping. In my work and research, the main method of concealing the use of illicit, recreational or performance enhancing drugs is through urine adulteration. Indeed, this method is arguably rather simple, and can be extremely effective if one uses the correct chemicals in the correct volumes and concentrations, and is able to adulterate the urine unnoticed.

Blood ≠ Urine

Such a method of concealing alleged drug use does not translate well to a biological matrix such as blood, and for a range of reasons:

1. Addition of adulterants to blood is likely to have a significant effect on the chemical composition of the blood, and will potentially affect the settling of red blood cells. Consequently, it would potentially have a visible effect on the blood sample.
2. For obvious reasons, it would be difficult and quite dangerous to attempt to adulterate the blood prior to sampling. 
3. More importantly, it would be unlikely that a person attempting to adulterate their blood would be able to do so during sampling. Indeed, it would be more likely for a co-conspirator working in a drug testing laboratory to accomplish this.

However, has not claimed that this type of adulteration has occurred. Rather, it has been alleged that a doctor associated with Armstrong administered saline solution to the athlete, thereby restoring normal blood levels. I'm aware of two main methods of blood doping where such a strategy would be effective:

1. Instances where blood is collected and stored, and prior to an event, the stored blood is infused into the athlete's bloodstream, thereby increasing the number of red blood cells. This in turn improves the oxygen-carrying capacity of the blood, and ultimately improves an athlete's performance and endurance. Injecting saline prior to a blood test will reduce the concentration/count of red blood cells to a normal value, and will potentially provide a false negative for blood doping.
2. Injection of performance-enhancing substances like erythropoietin (EPO) will potentially be detectable in blood. Similar to the point above, transfusing "normal" (unadulterated) blood, will "hide" traces of performance enhancing compounds.

It would appear that USADA alleges that Armstrong and his cycling colleagues used EPO, testosterone and other drugs to enhance his performance, and that transfusion of stored, "normal" blood was used to mask this. This technique was helped by the fact that previous methods used for testing EPO levels were not necessarily sensitive or specific, and as such, could be fooled. On this point, the press release from USADA indicates that:

"The evidence shows beyond any doubt that the US Postal Service Pro Cycling Team ran the most sophisticated, professionalized and successful doping program that sport has ever seen."

Again, though I am only partially aware of this case, its ramifications, and have only read part-way through USADA's document "Reasoned Decision of the United States Anti-Doping Agency on Disqualification and Ineligibility; United States Anti-Doping Agency v. Lance Armstrong", this entire debacle raises some interesting questions regarding the use of performance enhancing drugs, and the methods that are currently used to detect doping.

Certainly, it is unfair that some athletes will use, or attempt to use, performance enhancing substances, and that it is a sad example of poor sportsmanship, and should not be condoned in any way, shape or form. Indeed, significant advances in detecting blood doping and urine adulteration have been made in recent years, and improvements, refinements and new techniques are continually being explored. It therefore raises the questions: "Will testing agencies be able to keep up with designer drugs and the people who use them?" and "Will there come a point where it is no longer possible or practical to engage in doping?".

I cannot definitively answer either question, but I have found it interesting talking with colleagues about such matters. Opinion appears to be firmly split. On one hand, many of my peers feel that it is only a matter of time before the flow of novel designer drugs slows, and that testing agencies will gain the upper hand. Others are more cynical, and feel that toxicologists and testing agencies will always be playing a game of "catch-up", never truly able to be in a position where all novel drugs can be detected in a safe, effective, sensitive and specific manner.

I guess only time will tell...