Thursday, April 17, 2008

Project Believe: Be Very Afraid

The Associated Press has reported that the United States Anti-Doping Agency (USADA) has announced a new pilot longitudinal testing program which will measure blood and urine values of twelve participating athletes. This program was patterned after the UCI biological passport and may become a requirement to participate in the upcoming Beijing Olympics. In theory changes in an athletes' biological profile may indicate performance enhancing drug use.

Participate with enthusiasm or else

At present, in the adversarial nature of the anti-doping crusade athletic contests are presumed to be filled with athletes who resort to any method to succeed, including doping. In an attempt to reverse the doping scourge, USADA now measures virtuous athletes by demanding overt vocal enthusiasm of chances to participate in new anti-doping strategies. Athletes are cowed into a state of fear and loathing by WADA labs and USADA prosecutions where athletes never win. As a result of this unfair system of arbitration, athletic paranoia has become manifest. Bryan Clay a selected subject of the new USADA longitudinal pilot program "Project Believe" says, "I'm anxious to let people know hey look I'm clean." Allyson Felix echoes the fear, "Whatever I can do to prove I'm clean, I'll do it, no matter what time I have to wake up, where I have to drive. I'll do whatever possible to prove I am a clean athlete." And former director of WADA accredited lab UCLA, Don Catlin, cheer leads "It's no surprise that good athletes, clean athletes, will jump up and down for this thing."

Be very afraid

So, if ghoulish vampires appear to collect your blood and urine at a crematorium where you are attempting to inter your infants' remains, like they did to Kevin van Impe, you had better cloak your grief and submit a sample with elan. Otherwise, you will be regarded with suspicion of attempting to subvert the anti-doping process.

Project Believe: Any change in physiology could constitute a failed test

The Associate Press article states the rational of the new longitudinal testing pilot program thus, "These tests wouldn't necessarily look for specific substances, but could detect changes in body chemistry that would indicate use [of performance enhancing substances.]" This is a very dangerous departure from current criteria needed to establish an Adverse Analytical Finding. At present an Adverse Analytical Finding can only result from a positive test of a performance enhancing substance. Changes in biological parameters do not constitute a failed test. However, the anti-doping crusade is attempting to negate clear evidence of doping by positive tests. They are attempting to file Adverse Analytical Findings based upon changes in biological parameters. Danilo DeLuca can attest to this new policy. DeLuca was measured after Stage 17 of the Giro de Italia with hormone levels "of a child." The Italian Olympic Committee (CONI) dismissed the allegations against DeLuca because he did not test positive for a prohibited substance. But as is always the case, WADA and the UCI can appeal to the Court of Arbitration of Sport (CAS). If the CAS were to imply that an medical method was used to evade detection of performance enhancing drugs by DeLuca or his doctor based on low hormone levels, then any "abnormal" change in an athlete's profile, no matter how small, could be used in future cases as a rational to file an Adverse Analytical Finding. In these cases there would be no defense since the locus of the change in a biological parameter could never be determined.

Down the slippery slope

How many more promising athletic careers will be destroyed? How many more lives? Changes in biological parameters of urine and blood without a locus cannot substitute for a positive test for exogenous performance enhancing substances. Think. A "biological passport" scheme to detect doping in absence of a "positive test" is useless. Longitudinal tests should only be used when a WADA lab result is inconclusive, or in cases where a valid concern exists that the Adverse Analytical Finding was caused by a departure in International Standards by a WADA accredited lab.

USADA, WADA, and the UCI should never water down the criteria needed to establish an Adverse Analytical Finding by intimidation of athletes. USADA abandon the "Project Believe" pilot program now.

Thursday, April 3, 2008

Genotype Variations in Enzyme UGT2B17: Implications

Dr. Jenny Jakobsson Schultz et.al, of the Karolinska Institute in Sweden, have published a study examining inherited variations of enzyme UGT2B17 and their effect on testosterone/epitestosterone ratio testing. Variations in UGT2B17 genotype may cause a false positive in the absence of doping or a false negative even after exogenous testosterone use.

Well, at least someone has found that individual differences in genotype does cause different testosterone/epitestosterone ratio results. WADA would have never conceded this: the golden standard of 4:1 is written in stone and "bullet proof." Yes. WADA is stubborn as an ox with these standards of what constitutes a doping violation and are very resistant to change. Even though most peer reviewed papers that deal with testosterone doping warn of subjects who have been found with natural testosterone/epitestosterone levels greater than 4:1.

One day scientific papers may warn of people who have one testosterone metabolite(s) above a 3 delta per mil threshold on an IRMS test is due to variations in genotype. They may warn of people who have variations in genotype expression of hepatic enzymes, or in first, second, or third messengers, or in G-proteins. WADA will have to alter their testing methods to accommodate this new information.

WADA Remains Resistant to Change.

WADA refuses to worry about trivial genetic factors. WADA is loath to do longitudinal tests of athletes. WADA might find a variable that might refute their laboratory findings or challenge their presumption of laboratory perfection. WADA would never invest time and money doing pedigree studies to determine if a single metabolite above threshold for exogenous testosterone is a trait common in a family, or among a group of people found in a geographical region. But idiosyncratic individual differences in medicine have been documented in many pedigree studies. For example, hematocrit levels above 50% have been found in fathers and sons of elite cyclists. These hematocirt levels are inherited tendencies, not based on EPO doping. The same is true for testosterone/epitestosterone ratio(s) and may be true for Carbon Isotope metabolite delta/delta scores.

No matter. WADA world can't even agree among the laboratories as to what criteria constitutes a positive IRMS result. The WADA Technical Documents are vague. Testosterone metabolites measured are selected at random. Uncertainty in measurement(s) are ignored. Laboratory personnel are unqualified in testing sequences, inexperienced, prone to make errors. But WADA will never invest the money needed to correct these problems. Why? Because WADA would rather budget to pay for prosecutions against athletes who appeal their bad lab results. WADA would rather defend idiots like Dick Pound from lawsuits. WADA would rather waste time with nonsense than to invest in hard science.

WADA abandoned the UCI biological passport system. Astana has more commitment and money invested in the UCI biological passport than WADA. Yet WADA maintains a myth of total commitment to anti-doping in sport.

Conclusion: The IRMS is an instrument that requires very precise controls of operation. The results of an IRMS is only as good as the laboratory performing the tests. Inexperienced laboratory personnel who cannot follow sequential steps in testing cannot be expected to arrive at the correct results. A valid IRMS is also only as good as the science behind the tests. A valid IRMS is only as good as the criteria required in WADA technical documents, by international standards, and by standardized criteria as to what constitutes a positive result. WADA has failed in all these areas.

One hundred years from now will the scientists of the future shake their heads in amazement at our ignorance. Will they abhor the stupidity and mistakes of the anti-doping crusade? Will they be forced to restore the honor to "fallen" athletes?

An appalling prospect, indeed.