To Catch a Cheat: Testing in the Steroid Era
OK, stop me if you’ve heard this one before. There’s no doubt that steroids are the worst thing to ever happen to sports, disrupting the sanctity of athletics for generations to come and (probably) leading to the inevitable fall of mankind. While we might all agree about this, even the fate of the world may not be enough to sway the potential doping athlete to stay clean. Instead, a simpler maxim may win out: “It ain’t cheating if you don’t get caught.”
In the case of performance-enhancing drugs, however, getting nailed is not as simple as just getting caught with your pants down – though usually that’s how the process starts. The decrees of sports organizations are only as strong as the scientific technology that’s available to enforce the rules, and athletes looking to get a substance-induced edge are in a continuous battle with the testers trying to catch them in the act.
This is a battle with high stakes – the most coveted athletic titles in the world – and one organization, the World Anti-Doping Agency (WADA), has positioned itself as the international authority on accurate and state-of-the art testing. The Olympic Games and le Tour de France are the biggest events that specifically subscribe to WADA’s guidelines, sanctimoniously referred to as the Code. In the U.S., Major League Baseball (MLB), the National Football League (NFL) and the National Basketball Association (NBA) don’t specifically follow WADA guidelines, but all have started to ramp up their rules to combat a perceived tidal wave of doping athletes. As a result of the apparent urgency of this problem, in recent years athletes worldwide have been subject to a set of increasingly complex procedures and sophisticated analyses to determine if they’re clean.
Your Pee, Please
The easiest way to avoid a positive detection is to provide clean urine. While this would typically be done by, well, not using steroids, athletes in the past have also used false bladders like the whizzinator to provide unblemished pee. Let’s see the requirements in place to avoid the old switcheroo:
WADA: “Once in the toilet facility the Athlete must remove all clothing between the waist and mid-thigh, in order that the Witness has an unobstructed view of sample provision. Sleeves should be rolled up so that the Athlete’s arms and hands are also clearly visible…The Witness shall directly observe the Athlete provide the urine sample, adjusting his/her position so as to have a clear view of the sample leaving the Athlete’s body.”
If you want to be thorough, you have to provide detail. Graphic detail.
MLB: “As you accompany the player to and from the restroom facility, be sure to walk BESIDE him, not in front or behind him. This way, you always have a view of the collection cup…You must have a clear and unobstructed view of the passing of the specimen. [No observing from behind.]”
I’m guessing the bracketed sentence did not appear in the job description.
NFL: “Dress Code: The player’s dress code for NFL drug testing is BARE ABOVE THE KNEES. No shirts or other upper body garments are to be worn for a test and all lower body garments are to be lowered to the knees.”
That is actually the exact opposite dress code of my grade school.
NBA: “Under direct observation of the collector.”
Open to interpretation, just like the Framers intended.
The athlete’s sample is immediately separated into the “A” and “B” containers, the second of which is only used to confirm a positive result from A. Otherwise, the B jar remains untested. A small remainder of the sample may be tested to ensure the integrity of the sample, such as measuring specific gravity and pH before any drug testing. The samples are identified only by an ID number, and a strict “chain of custody” process is followed to diffuse the possibility of framing, as if scientists would ever be so dishonest. Samples are then sent to designated testing centers – here the supremely commercialized NFL even manages to get in a plug for official sponsor Federal Express in their testing protocol.
There are currently only two WADA-accredited labs in the U.S., one in Los Angeles and another in Salt Lake City. The pro sports leagues, however, are less stringent, requiring that facilities only be approved by the federal Substance Abuse and Mental Health Services Administration (SAMHSA), which number around fifty nationwide.
The requirements for constituting a positive test result vary depending on the nature of the prohibited substance. Essentially, there are three distinct manners in which illicit use of a substance can be determined: (1) Detection, in any amount, of a prohibited substance or its metabolites; (2) Detection of a naturally occurring substance in a quantity greater than the allowable limit; and (3) Detection of secondary markers of doping.
The majority of this testing involves using gas chromatography/mass spectrometry (GC/MS) and the technique so nice they named it twice, liquid chromatography tandem mass spectrometry (LC-MS/MS). These techniques uniquely identify molecular compounds based on retention times in a gas or liquid stream and the mass-to-charge ratio of its characteristic ions. When these attributes precisely match those of a prohibited substance, a positive detection has been made.
Urine Trouble with Steroids
Anabolic-androgenic steroids exist in exogenous (not typically present in human body) and endogenous (naturally present) forms. For known exogenous steroids, testing is a pretty straightforward process. If the compound is detected in the urine sample, then it is marked as a positive. For those endogenous compounds that are found naturally in the body, however, it is important to set a threshold for determining a positive. For instance, compounds such as clenbuterol and methandienone must be present at a quantity of 2 ng/mL or higher to be considered a violation.
An interesting case is the steroid nandrolone, a commonly abused compound that is detected in an average of 0.23% of all WADA urine samples each year. Recently, San Diego Charger Shawn Merriman tested positive for the substance, resulting in a four-game ban. A nandrolone positive actually indicates the presence of its urinary metabolites, usually 19-norandrosterone (19-NA) at a level greater than 2 ng/mL. Although nandrolone is an exogenous steroid, 19-NA can be naturally produced as part of the pathway from androgens to estrogen. Several studies have examined how natural levels of 19-NA can vary following exercise or throughout the menstrual cycle, but controlled study has yet to find natural levels above the positive cutoff. However, exceedingly high levels are present in pregnant women, so such a scenario must be ruled out before reporting an adverse event. Don’t worry, guys, a far more plausible excuse is available: high urinary concentrations of 19-NA could, in theory, result from eating large amounts of uncastrated boar, particularly the liver, kidney and testes (need a recipe?) within a day of testing.
The major problem with these current testing techniques is the necessity that a compound must be characterized by its ionic properties before a lab can look for it. If a lab does not know of a newly-developed performance enhancer, the steroid will escape detection. This loophole is a major battleground in the fight between dopers and testing scientists. “Designer steroids” are developed and circulated among athletic circles unbeknownst to labs and sport officials, and until the labs get their hands on the substance, athletes have free reign. Such was the case with the BALCO designer steroid tetrahydrogestrinone (THG; “the clear”), which was analytically invisible until a syringe containing the steroid was anonymously mailed to L.A.’s Olympic Analytical Laboratory in 2003 (the sender was later revealed to be U.S. track coach Trevor Graham). But BALCO chief Victor Conte (himself no bedrock of credibility) has claimed that he was dispensing THG since at least 2000.
So the two sides are essentially pitted in an arms race (or legs, as the case may be). The deep pockets behind the athletes give them a leg up (or…never mind) in the clash, and they are probably always a step ahead of testers. The federally-funded U.S. Anti-Doping Agency (USADA) tries to compete by committing $2 million per year towards research. That’s not to say the USADA budget should be too much higher. Despite the hype, sports doping falls well below childhood obesity on the list of serious medical issues facing the country, though still somewhere above shark attacks. There is some hope, though. Recent research is making advances towards a method that does not require previous characterization of anabolic substances for detection, which would be a huge chink in the armor for the designer steroid market.
The T Factor
GC/MS and LC-MS/MS techniques are also not foolproof when it comes to testosterone, because the endogenous and pharmaceutical variants look identical in these tests. Due to this inconvenience, the approach is instead to monitor the ratio of testosterone to epitestosterone (T/E). A normal T/E ratio is approximately 1:1, and use of any compound that artificially raises testosterone levels will do so without increasing epitestosterone; most organizations consider 4:1 the level for indication of possible foul play. So why not just take epitestosterone, too? This is in fact was the idea behind BALCO’s “the cream,” a topical ointment that contained both compounds in order to maintain a relatively even T/E ratio (this is not to be confused with Falco’s Rock Me Amadeus, which is pure testosterone). But organizations have caught on – epitestosterone, which has no direct benefits, is now a prohibited substance as well.
Due to some natural variability of T/E ratio, it is not typically considered an absolute marker of doping. Instead, a second test can be performed to detect the carbon isotope ratio (13C/12C) in the urine, which can differentiate between endogenous and exogenous testosterone. WADA states that this test should be performed for anyone with a ratio over 4:1. The NFL policy is similar, but if the ratio is above 10:1 they don’t even bother: the athlete is “conclusively positive.” The carbon isotope ratio – well, it’s complicated – let’s just say it changes with your diet, and the 13C/12C value of testosterone or its metabolites should match that of the reference compounds that are altered with diet.
The complexity of testosterone testing is well-illustrated by the curious case of Floyd Landis, who overcame a degenerating hip and a wispy mustache to finish first at last year’s Tour de France. Landis was suspected of doping, and though the case has yet to be fully resolved, many Americans immediately came to the defense of Landis since he’s from the U.S. and he doesn’t play baseball. After a high T/E ratio was found in both the “A” and “B” samples, though, WADA reported that the carbon isotope test found that Landis had used synthetic testosterone. Landis has disputed the results on a variety of levels, primarily blaming failures to follow WADA’s own scientific protocol.
Note: A Landis defense can be seen here; I don’t recommend it unless you want to see a man with a lot of pins on his vest speak to a bunch of cyclists who have no idea what he’s talking about. Actually, scratch that – I recommend it for those same reasons. The woman who introduces him…well, just watch it. But don’t watch the whole thing.
The case does present an interesting point about the nature of testing and doping. The length of time over which a substance is detectable is typically related to the duration it actually benefits performance. For instance, stimulants assist the athlete for only a matter of hours, and can be discerned in the urine for only a few hours or days, so a positive result would most likely only be seen immediately after competition if an athlete is effectively cheating. Likewise, athletes may not appreciate the long-term effects of most anabolic steroids come testing time, as the compounds are detectable for several months following injection. (Sometimes, a specialized test is even necessary to ensure that an athlete has not injected again since a previous positive test.) In the Landis case, the high T/E ratio occurred between two days of testing with a T/E in the normal range. There would be no real advantage of taking testosterone for one day only; it is better suited for long-term muscle growth. So either Landis botched his masking technique (not inconceivable) or the French screwed up (no comment).
hGH: The Worst Form of Cheating?
Much recent firestorm have focused on the lack of testing for human growth hormone (hGH; the injected form is recombinant hGH, or rhGH) in the major American sports leagues. hGH is naturally released in pulses by the pituitary gland and, among other functions, promotes growth (particularly in childhood) and increases muscle mass. But here’s the funny thing about supplementing with rhGH (as I resist temptation to call this “the straight dope”): it might not even work. Controlled research of supraphysiologic use of hGH in normal adults has found that muscles may increase in size, but there is no change in strength (though it may help protect muscles or tendons from rupture).
So why might rhGH be attractive to athletes? Perhaps just the very fact that it is difficult to detect. It’s like cheating on your high school geometry test. When you copied your classmate’s acute answer, were you more concerned with its correctness or whether your wandering eyes would be spotted? If you didn’t get caught, at that point a right answer is a bonus. So it goes with rhGH: Other guys are doing it, and there aren’t any repercussions (professionally speaking), so why not?
Now, technically, we don’t really know how many athletes use rhGH. And, technically, it is possible to detect, via a blood test (urine concentrations are extremely low). At the 2004 Olympics in Athens and the 2006 Games in Torino, blood samples from athletes were tested for rhGH. Total positive tests: zero. You see, rhGH has a short half-life, so it can only be detected in the bloodstream within about 24-36 hours after injection. Such testing is thus better suited for randomly timed testing, but it would still be a logistical nightmare to implement testing that requires such immediate action.
Of course, another requirement is that the league actually tests for the hormone. No American professional leagues take blood samples, thus eliminating the possibility of detecting rhGH even though it is listed as a prohibited substance by MLB and the NFL. When NFL commissioner Roger Goodell recently explained, “There is no reliable test for hGH right now,” he wasn’t too far off. Reliable? Yes. Useful? Not really. Even if a better blood test is developed, it is unlikely to be implemented without a fight. NFL Player’s Association chief Gene Upshaw has stated that he is opposed to any type of blood testing for pro football players, who have a reputation for being squeamish.
In the end, this debate probably doesn’t matter too much. It is thought that rhGH is often taken in concert with steroidal compounds, which would do the real dirty work. Barry Bonds reportedly took rhGH with his supplements of THG (“the clear”) and testosterone (“the cream”). If reliable tests for these more potent compounds are in place, then the hGH problem is not so significant.
There are plenty of other doping techniques and new methods on the horizon, where new battle lines will be drawn. The next step may be gene doping, in which genetic alterations would be utilized to enhance muscle growth. WADA claims they will be able to test for gene doping. Now, if you read enough WADA press releases, you catch on that they don’t like to admit that they can be beat. It’s a good stance to have—they function best as a combination of impartial policing and fierce intimidation. And if its intimidation you want, having a chief named Dick Pound goes a long way.
So the quest continues, and the battle will likely never be truly and completely won. The never-ending struggle makes one long for the days before the steroid era, a time when sports were pure. Back then, you didn’t need a biochemistry degree to know whom to respect. Instead, the cheaters did it the right way: by stealing signs, sharpening spikes and corking bats. Now, that is how sports were meant to be played.
References
Sportsology
You probably didn’t learn about the scientific method in your junior high gym class, and not too many post-game interviews touch on quantum theory. But don’t be fooled: the athletic and scientific worlds are not such strange bedfellows. Boxing, for instance, is often called “the sweet science.” And no less an expert than Ted Williams, perhaps baseball’s greatest batter, described his craft in his book, The Science of Hitting. We turn our focus to this intriguing relationship here in Sportsology, where we endeavor to examine the world of sports with a scientific eye. Sportsology will explore athletic topics you never knew you cared about, from the physics of the curveball to Olympic abstinence. We hope to arm you with knowledge to, at the very least, make you the most annoying person at the sports bar.
Companion Piece - “The Chemical Drive to Do Better” by Robert Roose, MD MPH