Serotta PETE
08-11-2006, 06:22 AM
FYI......from WSJ ONLINE today. PETE
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More on the Landis Controversy
August 11, 2006 (WSJ ONLINE)
Last week, I wrote about Tour de France winner Floyd Landis's positive doping test and the possibility -- raised by his doctor -- that an alcohol binge the night before had caused him to flunk. Since then, Mr. Landis's outlook has grown bleaker: A more sophisticated test showed synthetic testosterone, not made by Mr. Landis's own body, was in his urine.
Mr. Landis continues to maintain he didn't use any banned substances, but media coverage has become brutal. Much of the criticism centers on the variety of explanations offered by Mr. Landis and his doctor, lawyer and spokesman. "Landis's excuses like 1,000 monkeys with typewriters," read a headline on a SportsLine column. "Landis's excuses sound familiar: Earthquake, flood, locusts!" was the headline on a Richard Roeper column in the Chicago Sun-Times.
Inevitably, Mr. Landis has also become a punch line: David Letterman drafted a Top 10 list of Landis excuses -- No. 4: "Wanted to give 'New York Post' excuse to run hilarious 'Fink Floyd' headline." The Onion imagined a Lance Armstrong-inspired "Cheat to Win" Landis bracelet.
Judging from my mailbox, Numbers Guy readers have been a bit more cautious. In the past week, they've asked a number of questions about the numbers and science behind Mr. Landis's case. Many of these questions can't be answered because of the opacity of the drug-testing process, but with the help of doctors and drug-testing experts, I've attempted to answer as many of these as I can.
First, a bit of background: A sample of Mr. Landis's urine collected after the 17th stage of the race showed a testosterone-to-epitestosterone ratio (T/E ratio) of 11-to-1. Testosterone and epitestosterone are related hormones, usually found in roughly equal amounts in urine. The International Cycling Union considers any ratio above 4-to-1 to be a positive test, suggesting steroid use. A follow-up test examining the atomic structure of Mr. Landis's testosterone found that some of it wasn't produced by his body. Now Mr. Landis's case will be turned over to the United States Anti-Doping Agency. Pending the agency's decision, and results of possible arbitration hearings, Mr. Landis could be stripped of his title.
Here are my adaptations of readers' questions, and my best attempt at answering them:
Q: It has been reported that Mr. Landis's testosterone level was within the normal range, but his epitestosterone was very low. Do low levels of epitestosterone confer any advantage to an athlete?
A: No, nor do high levels. Epitestosterone doesn't have any known purpose in the body, several doctors told me. Ingemar Bjorkhem, a professor of clinical chemistry at Karolinska University Hospital in Stockholm who has studied testosterone, said epitestosterone's function is "controversial," but added, "Most probably, it's not very important."
"It's an accident in metabolism," said Richard Hellman, president-elect of the American Association of Clinical Endocrinologists. "For each molecule of testosterone made, there is a nonfunctional molecule [of epitestosterone] made." Hence the usual 1-to-1 T/E ratio.
Production of epitestosterone can be suppressed by adding synthetic testosterone to the body, so a high T/E ratio can be a marker for doping.
Landis spokesman Michael Henson confirmed to me that the high ratio was the result of very low epitestosterone. The cycling union has been more tight-lipped, and no one has specified the exact hormonal levels. Howard Jacobs, Mr. Landis's lawyer, told me he wouldn't release numbers yet because he hasn't yet received full documentation of the tests from the cycling union. "I want to see the documentation of how they calculate the numbers," he said. "I don't want to put out numbers that are flat wrong."
Q: Was Mr. Landis tested at other times during the race? Were any of those tests positive?
A: Mr. Henson, the Landis spokesman, told me Mr. Landis was tested eight times during the Tour, including the positive test on July 20, a test two days before, and a test two days after. Mr. Landis's positive test was the only positive test during the Tour, cycling union doctor Mario Zorzoli told me last week.
That raises the next question, also posed by several readers:
Q: How quickly does synthetic testosterone clear out of one's system?
A: Testosterone typically is injected straight into muscle, and, depending on the dosage, it generally creates an elevated T/E ratio for a week to 10 days, according to researchers I spoke with.
That makes this form of testosterone usage an unlikely candidate to explain Mr. Landis's positive test, since -- assuming the tests were conducted properly -- his elevated ratio would have shown up in one of his other tests.
Using testosterone in this form also wouldn't be much help, as it "takes at least a week to have a physiological effect," said Simon Davis, technical director for Mass Spec Solutions Ltd., a Wythenshawe, U.K., maker of mass-spectrometry devices. He has helped athletes defend allegations of doping.
Testosterone can also be taken orally or applied to the skin with a gel, cream or patch. These forms have several advantages: They can provide more short-term boost than injected steroids, and can also clear out of the system more quickly. Mario Thevis, professor for preventive doping research at German Sport University, said in an email that, depending on the dosage, T/E ratios could return to normal after several hours.
But the athletic benefit of such doping is unproven, said Dr. Davis. "These provide a very small amount of testosterone, and certainly would not improve performance at any significant level," he said.
Q: Which lab conducted the tests? Is it reputable?
A: The tests were done at Laboratoire National de Depistage du Dopage (known by its French acronym, LNDD) in Chatenay-Malabry, outside Paris. It is accredited by the World Anti-Doping Agency, the international body that coordinates global drug-testing measures. Several readers have suggested that a French lab could be biased against an American cyclist, particularly a former teammate of Lance Armstrong, who has many vocal critics in France. But doctors spoke highly of LNDD's reputation.
"The lab in Chatenay-Malabry has an excellent reputation and has fulfilled the accreditation requirements for sports drug testing for more than 15 years," Dr. Thevis at German Sport University told me. Others I talked with also praised the lab.
However, the lab had some stumbles in the 1990s. Reader Rudy Lim pointed out that, in 1998, cyclist Paola Pezzo was cleared of a positive drug test by LNDD, in part because of flaws in the lab's testing procedures.
More recently, tests by LNDD on a sample of Lance Armstrong's urine turned up the presence of synthetic erythropoietin (known as EPO), which can be used to enhance performance. But earlier this year, an investigator appointed by the cycling union cleared Mr. Armstrong of the charges, finding among other things, that LNDD "did not follow a single one" of the required technical procedures for handling urine samples. (See the full report here.)
No one answered the phone at LNDD's general number Wednesday, and an email I sent to the lab got not response.
Q: How conclusive are the results of the test? Could there have been an error by the lab?
A: The numbers don't bode well for Mr. Landis.
A difference of more than three parts per thousand in the examination known as isotope ratio mass spectrometry is considered a positive test (the test is explained in more detail here; see the paragraph starting with "stable isotope abundances"). Mr. Henson, the Landis spokesman, told me that Mr. Landis's difference was 3.99 parts per thousand, calling it a "mild bump." But Dr. Thevis's interpretation differed: "The difference (3.99 to three) is a big number and not related to uncertainties. …The established value of three parts per thousand covers all possibly occurring uncertainties. Hence, a difference of almost four is perfectly positive."
However, there are difficulties in conducting the test. "It's a very complex test that requires very skilled people and is easy to mess up," said Dr. Hellman of the American Association of Clinical Endocrinologists.
Q: How are the urine samples transported? Could they have been tampered with or damaged?
A: Here's how the process should work: "Once the samples have been collected they are delivered by accredited persons to the laboratories, where the sample is stored at four degrees Celsius [39.2 degrees Fahrenheit] until analysis," said German Sport University's Dr. Thevis. "They are locked in a cooling chamber and taken out only for sample preparation."
However, samples have been mishandled, causing degradation. In 1995, U.K. middle-distance runner Diane Modahl was cleared of drug allegations when a panel found that bacteria in the sample could have caused an elevated T/E ratio.
Still, mishandling alone wouldn't explain the presence of synthetic testosterone in Mr. Landis's sample. Some commentators have gone so far as to suggest foul play, though there has been no evidence of tampering with the sample. Dr. Davis of Mass Spec Solutions told me that if someone did want to spike an athlete's sample, testosterone would be a good choice. "If you did an analysis on testosterone, you wouldn't be able to distinguish between testosterone injected straight into the sample, or coming out through urine," he said.
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__________________________________________________ _______
More on the Landis Controversy
August 11, 2006 (WSJ ONLINE)
Last week, I wrote about Tour de France winner Floyd Landis's positive doping test and the possibility -- raised by his doctor -- that an alcohol binge the night before had caused him to flunk. Since then, Mr. Landis's outlook has grown bleaker: A more sophisticated test showed synthetic testosterone, not made by Mr. Landis's own body, was in his urine.
Mr. Landis continues to maintain he didn't use any banned substances, but media coverage has become brutal. Much of the criticism centers on the variety of explanations offered by Mr. Landis and his doctor, lawyer and spokesman. "Landis's excuses like 1,000 monkeys with typewriters," read a headline on a SportsLine column. "Landis's excuses sound familiar: Earthquake, flood, locusts!" was the headline on a Richard Roeper column in the Chicago Sun-Times.
Inevitably, Mr. Landis has also become a punch line: David Letterman drafted a Top 10 list of Landis excuses -- No. 4: "Wanted to give 'New York Post' excuse to run hilarious 'Fink Floyd' headline." The Onion imagined a Lance Armstrong-inspired "Cheat to Win" Landis bracelet.
Judging from my mailbox, Numbers Guy readers have been a bit more cautious. In the past week, they've asked a number of questions about the numbers and science behind Mr. Landis's case. Many of these questions can't be answered because of the opacity of the drug-testing process, but with the help of doctors and drug-testing experts, I've attempted to answer as many of these as I can.
First, a bit of background: A sample of Mr. Landis's urine collected after the 17th stage of the race showed a testosterone-to-epitestosterone ratio (T/E ratio) of 11-to-1. Testosterone and epitestosterone are related hormones, usually found in roughly equal amounts in urine. The International Cycling Union considers any ratio above 4-to-1 to be a positive test, suggesting steroid use. A follow-up test examining the atomic structure of Mr. Landis's testosterone found that some of it wasn't produced by his body. Now Mr. Landis's case will be turned over to the United States Anti-Doping Agency. Pending the agency's decision, and results of possible arbitration hearings, Mr. Landis could be stripped of his title.
Here are my adaptations of readers' questions, and my best attempt at answering them:
Q: It has been reported that Mr. Landis's testosterone level was within the normal range, but his epitestosterone was very low. Do low levels of epitestosterone confer any advantage to an athlete?
A: No, nor do high levels. Epitestosterone doesn't have any known purpose in the body, several doctors told me. Ingemar Bjorkhem, a professor of clinical chemistry at Karolinska University Hospital in Stockholm who has studied testosterone, said epitestosterone's function is "controversial," but added, "Most probably, it's not very important."
"It's an accident in metabolism," said Richard Hellman, president-elect of the American Association of Clinical Endocrinologists. "For each molecule of testosterone made, there is a nonfunctional molecule [of epitestosterone] made." Hence the usual 1-to-1 T/E ratio.
Production of epitestosterone can be suppressed by adding synthetic testosterone to the body, so a high T/E ratio can be a marker for doping.
Landis spokesman Michael Henson confirmed to me that the high ratio was the result of very low epitestosterone. The cycling union has been more tight-lipped, and no one has specified the exact hormonal levels. Howard Jacobs, Mr. Landis's lawyer, told me he wouldn't release numbers yet because he hasn't yet received full documentation of the tests from the cycling union. "I want to see the documentation of how they calculate the numbers," he said. "I don't want to put out numbers that are flat wrong."
Q: Was Mr. Landis tested at other times during the race? Were any of those tests positive?
A: Mr. Henson, the Landis spokesman, told me Mr. Landis was tested eight times during the Tour, including the positive test on July 20, a test two days before, and a test two days after. Mr. Landis's positive test was the only positive test during the Tour, cycling union doctor Mario Zorzoli told me last week.
That raises the next question, also posed by several readers:
Q: How quickly does synthetic testosterone clear out of one's system?
A: Testosterone typically is injected straight into muscle, and, depending on the dosage, it generally creates an elevated T/E ratio for a week to 10 days, according to researchers I spoke with.
That makes this form of testosterone usage an unlikely candidate to explain Mr. Landis's positive test, since -- assuming the tests were conducted properly -- his elevated ratio would have shown up in one of his other tests.
Using testosterone in this form also wouldn't be much help, as it "takes at least a week to have a physiological effect," said Simon Davis, technical director for Mass Spec Solutions Ltd., a Wythenshawe, U.K., maker of mass-spectrometry devices. He has helped athletes defend allegations of doping.
Testosterone can also be taken orally or applied to the skin with a gel, cream or patch. These forms have several advantages: They can provide more short-term boost than injected steroids, and can also clear out of the system more quickly. Mario Thevis, professor for preventive doping research at German Sport University, said in an email that, depending on the dosage, T/E ratios could return to normal after several hours.
But the athletic benefit of such doping is unproven, said Dr. Davis. "These provide a very small amount of testosterone, and certainly would not improve performance at any significant level," he said.
Q: Which lab conducted the tests? Is it reputable?
A: The tests were done at Laboratoire National de Depistage du Dopage (known by its French acronym, LNDD) in Chatenay-Malabry, outside Paris. It is accredited by the World Anti-Doping Agency, the international body that coordinates global drug-testing measures. Several readers have suggested that a French lab could be biased against an American cyclist, particularly a former teammate of Lance Armstrong, who has many vocal critics in France. But doctors spoke highly of LNDD's reputation.
"The lab in Chatenay-Malabry has an excellent reputation and has fulfilled the accreditation requirements for sports drug testing for more than 15 years," Dr. Thevis at German Sport University told me. Others I talked with also praised the lab.
However, the lab had some stumbles in the 1990s. Reader Rudy Lim pointed out that, in 1998, cyclist Paola Pezzo was cleared of a positive drug test by LNDD, in part because of flaws in the lab's testing procedures.
More recently, tests by LNDD on a sample of Lance Armstrong's urine turned up the presence of synthetic erythropoietin (known as EPO), which can be used to enhance performance. But earlier this year, an investigator appointed by the cycling union cleared Mr. Armstrong of the charges, finding among other things, that LNDD "did not follow a single one" of the required technical procedures for handling urine samples. (See the full report here.)
No one answered the phone at LNDD's general number Wednesday, and an email I sent to the lab got not response.
Q: How conclusive are the results of the test? Could there have been an error by the lab?
A: The numbers don't bode well for Mr. Landis.
A difference of more than three parts per thousand in the examination known as isotope ratio mass spectrometry is considered a positive test (the test is explained in more detail here; see the paragraph starting with "stable isotope abundances"). Mr. Henson, the Landis spokesman, told me that Mr. Landis's difference was 3.99 parts per thousand, calling it a "mild bump." But Dr. Thevis's interpretation differed: "The difference (3.99 to three) is a big number and not related to uncertainties. …The established value of three parts per thousand covers all possibly occurring uncertainties. Hence, a difference of almost four is perfectly positive."
However, there are difficulties in conducting the test. "It's a very complex test that requires very skilled people and is easy to mess up," said Dr. Hellman of the American Association of Clinical Endocrinologists.
Q: How are the urine samples transported? Could they have been tampered with or damaged?
A: Here's how the process should work: "Once the samples have been collected they are delivered by accredited persons to the laboratories, where the sample is stored at four degrees Celsius [39.2 degrees Fahrenheit] until analysis," said German Sport University's Dr. Thevis. "They are locked in a cooling chamber and taken out only for sample preparation."
However, samples have been mishandled, causing degradation. In 1995, U.K. middle-distance runner Diane Modahl was cleared of drug allegations when a panel found that bacteria in the sample could have caused an elevated T/E ratio.
Still, mishandling alone wouldn't explain the presence of synthetic testosterone in Mr. Landis's sample. Some commentators have gone so far as to suggest foul play, though there has been no evidence of tampering with the sample. Dr. Davis of Mass Spec Solutions told me that if someone did want to spike an athlete's sample, testosterone would be a good choice. "If you did an analysis on testosterone, you wouldn't be able to distinguish between testosterone injected straight into the sample, or coming out through urine," he said.
*