One of the best articles I have ever read on the subject of performance enhancing drugs and competitive cycling:
Waiting for the day when 'I've never tested positive' may mean something
By Prentice Steffen, MD, FAAEM
This report filed September 29, 2004
"I've never tested positive."
We've all heard this statement (or some variation) from any number of athletes. A lot of athletes and their supporters seem to think this is a meaningful argument. Certainly many people seem to be persuaded by those four simple words. But it's sad to say that these days, the statement "I've never tested positive" is very nearly meaningless.
So far, that is.
There are signs of progress that may some day give real meaning to the claim of never having tested positive. Of course some athletes move from this falsely persuasive argument to outright lies of denial of doping. That I won't be able to explain, except to say quite simply that there is a lot of money and prestige on the line in these situations.
The key to understanding all of this is knowing the key doping substances used, how they work, how they are tested for (if they even can be), and how the testing is inadequate. What follows may appear to be an athlete's "how to dope" primer, but in fact this information is such common knowledge to sports insiders that there's little risk that it will corrupt anyone. None of this requires a Ph.D in anything to understand ... just a certain amount of thought, an open mind, and a willingness to understand this critical aspect of doping.
Three important doping substances to consider are erythropoietin (EPO), growth hormone (GH), and the anabolic steroid testosterone. I'll stick to these three as a good start. There are certainly many others, such as synthetic oxygen transporters, masking substances, and good old fashioned blood transfusions (much has been written on this relating to Tyler Hamilton's recent positive result in the Vuelta). For a truly frightening description of the future of doping, read the recent article on gene doping in Scientific American
Current testing for these substances is inadequate for one or all of three main reasons:
* No tests exist for the drug.
* The performance-enhancing effects of the drugs last well after the time it takes for the body to flush them out.
* The substances are identical to those produced naturally by the body, so thresholds must be set to levels that are clearly dangerous and/or unnatural.
Natural EPO, for example, is produced by the kidneys and stimulates the bone marrow to produce more red blood cells. Red blood cells carry oxygen to working muscles. More red blood cells equal increased endurance. Synthetic EPO is produced in Chinese hamster ovary (CHO) cells grown in culture, using recombinant DNA technology. For nearly 10 years after its introduction, there was no anti-doping test for synthetic EPO.
In 1997, a limit was put on how high an athlete's blood count could be as a replacement for a direct test of synthetic EPO use. This measurement is called the hematocrit, and the limit was set at 50 percent. The hematocrit is the percentage of volume in a sample of blood that is taken up by just the red blood cells; the rest is taken up by serum and other blood-cell types. More red blood cells equal a higher hematocrit, which equals increased endurance. The 50 percent cut-off was set somewhat arbitrarily.
The important point here is that the average hematocrit for a professional cyclist is 42-43 percent, which leaves a considerable margin for manipulation up to the 50 percent cut-off. Competing with a hematocrit of 50 percent instead of 42 percent can constitute a significant enhancement of one's performance.
In 2001, a urine test was introduced that could detect the very subtle structural difference between natural EPO and synthetic EPO. Scientists know that the electrical charge of synthetic EPO is slightly different from that naturally produced by the human body. The test, developed in France, measures the charge of those isoforms. If too many in a sample show up with the incorrect charge, it is flagged as a positive.
The problem is that the test is only reliable for two or three days after the synthetic EPO is injected, while the lifespan of a red blood cell is six to eight weeks. In other words, the effect of synthetic EPO persists long past our ability to test for it. Indeed, some, more sublte, methods would allow a well-informed athlete to clear traces within 12 to 24 hours, allowing someone to continue to using EPO and still not test positive, even in multi-day events like the Tour de France.
Growth hormone is produced by the pituitary gland and has many effects throughout the body. The primary benefit, at least as it relates to athletic performance, is its ability to increase muscle size and strength. Until very recently, there has been absolutely no way to detect the use of growth hormone. Reportedly, such a test was implemented during the recent Athens Olympics, but the anti-doping authorities are intentionally (and I believe quite appropriately) mysterious about the introduction of new tests, so very few know the particulars of this method.
Finally, testosterone is an anabolic steroid that increases muscle mass and strength. The synthetic anabolic steroids (stanazol, norandralone, etc.) are molecules that are distinctly different from anything the human body produces and are consequently fairly easy to test for.
Testosterone, on the other hand, is a quite simple molecule and is easily synthesized. Even the synthetic version is absolutely identical to the testosterone produced by a human male's testicles. Consequently, detection is difficult, and authorities have been forced to rely on an indirect - and quite ineffective -method to test for the use of synthetic testosterone.
Natural testosterone, like all substances in the body, is eventually metabolized and eliminated. The body breaks testosterone down into a substance called epitestosterone. Both testosterone and epitestosterone are eliminated by the kidneys into the urine. At any point in time, if these two substances are measured in the urine, a ratio of testosterone to epitestosterone can be calculated. This "T/E ratio" averages about 2.5:1.
The use of synthetic testosterone should change this ratio. Somewhat like the 50 percent hematocrit cut-off established to watch for synthetic EPO use, anti-doping authorities have set a cut-off level for the T:E ratio at 6:1. Again, that leaves an awful lot of latitude, giving a dishonest athlete an upper limit to aim for. Even within that 6:1 T/E ratio there are significant performance benefits to be gained.
So what's to be done? The World Anti-Doping Agency (WADA) was formed in 1999 as the international agency charged with setting anti-doping policy and implementing anti-doping testing. Up to that point, individual sports' governing bodies were expected to test their own athletes; this resulted in fairly obvious conflicts of interest in which positive test results were suppressed to avert bad publicity for the sport involved.
Some of this conflict of interest seems to survive among some sports governing bodies and national anti-doping agencies, but the formation of WADA is a huge step forward. WADA has shown itself to be aggressive in its mission - it serves as a neutral and objective agency to oversee anti-doping and is structured to be free of all conflicts of interest.
August 13, 2004, the opening day of the Athens Summer Olympics, was day one of WADA's control of anti-doping efforts. Embarrassingly enough, our sport's own Union Cycliste Internationale became the last international governing body to sign. It was only under threat of exclusion from the '04 Games that the UCI signed, and it did so only on the very last day possible. Talk about a reluctant participant.
The WADA Code adopts several fundamental changes in the approach to fighting doping in sports. For example, it emphasizes targeted out-of-competition testing rather than random testing during competition, when most athletes are obviously ready for the increased scrutiny. Under the new rules, an athlete's entourage (physician, coach, trainer, etc.) are held more responsible for their actions when an athlete tests positive. Of course, considerable effort and resources will be invested in research to improve current anti-doping testing.
The WADA Anti-Doping Code is a lengthy, complex document, but these are the types of changes WADA has incorporated in its code; changes that have begun to make a real difference. WADA president Dick Pound and everyone actively involved in the anti-doping effort are to be praised for their victories at the Athens Olympics. Never before has the effort been so obviously successful.
If WADA is allowed to honestly carry out its mission, there may come a day when an athlete states that he or she has "never tested positive," it actually means something."
Dr. Prentice Steffen, board-certified in both Emergency Medicine and Sports Medicine, served this year as team physician for the Heathnet/Maxxis and TIAA-CREF/5280 Magazine teams. He has served as team physician for several teams over the years including Prime Alliance, Mercury, Spago and U.S. Postal. Steffen has also served as medical director and event physician for major races, including the Tour Du Pont, New York City Marathon and the Tour de Trump. Steffen also serves as the sports-medicine section editor for the Journal of Emergency Medicine. His services are outlined in detail at
www.pdssportsmed.com