Mass spectrometry exposes Landis

[Rach3]

Amazing what some criminals think they can get away with! This guy should have taken more chemistry courses in college.

New Finding Challenges Tour Champ’s Claim

Tests performed on the cyclist Floyd Landis’s initial urine sample showed that some of the testosterone in his body had come from an external source and was not produced by his system, according to a person at the International Cycling Union with knowledge of the results.
...
The French national antidoping laboratory in Châtenay-Malabry performed a carbon isotope ratio test on the first of Landis’s two urine samples provided after Stage 17, the person, who is in the cycling union’s antidoping department, said in an interview yesterday.

http://www.nytimes.com/2006/08/01/s...&en=3f51b3d7def2bbea&ei=5094&partner=homepage

 

[Chi Meson]

I am sick. I tell you I am so ******* SICK about this! I can't tell you how p****d off I am at the whole thing. Tyler Hamilton doped, and lied about it. Now Landis! And Lance isn't in the clear either especially with Frankie Andreu's statement.

I tell you, George Hincapie is looking better than ever now simply bcause he DID sag after a valiant start.

Well anyway, three cheers for Oscar Perriro (assuming he's clean). I hope thay make a special ceremony for him.

G! D! I!

 

[BobG]

I am sick. I tell you I am so ******* SICK about this! I can't tell you how p****d off I am at the whole thing. Tyler Hamilton doped, and lied about it. Now Landis! And Lance isn't in the clear either especially with Frankie Andreu's statement.

I tell you, George Hincapie is looking better than ever now simply bcause he DID sag after a valiant start.

Well anyway, three cheers for Oscar Perriro (assuming he's clean). I hope thay make a special ceremony for him.

G! D! I!

OLN has to be even sicker. With Lance gone, I think they really needed Hamilton, Landis, or Hincapie to come through in order to keep Americans interested. As it is, just about every star in cycling has been wiped out by drug testing, including the two best Americans.

Cycling looks even dirtier than track and field and baseball. It's starting to look as cheap as weightlifting.

 

[JasonRox]

OLN has to be even sicker. With Lance gone, I think they really needed Hamilton, Landis, or Hincapie to come through in order to keep Americans interested. As it is, just about every star in cycling has been wiped out by drug testing, including the two best Americans.

Cycling looks even dirtier than track and field and baseball. It's starting to look as cheap as weightlifting.

It makes me laugh so much.

This is what happens when you try to push the limits of your athletes. They just can't keep up after awhile.

Note: They tested every single guy on the NHL Draft this year and they were all clean. I'm talking everyone and not just random testing. Cheers to the NHL!

 

[Astronuc]

“I’ve seen bodybuilders with numbers 100 to 1,” Kay said. “Although Floyd’s was elevated, it’s not off the chart or anything.”

I wonder what Landis's doctor was thinking when he referenced 'bodybuilders'. This is not helping his case.

 

[Rach3]

Is this his doctor or his lawyer?

Experts Say Case Against Landis Is Tough to Beat
...
Landis said last week that he was expecting the worst because backup samples, or B samples, almost always confirm the initial result. But Kay said the B sample could come back negative.

“The carbon isotope was only mildly elevated,” he said. “We know, from a statistical standpoint, that the first result could have been a false positive.”

http://www.nytimes.com/2006/08/02/s...&en=2fc43a3b867cc26d&ei=5094&partner=homepage

Yes, there's a big uncertainty here, because we all know the sample size of atoms in mass spectrometry is rather small. (*insert sarcastic smilie here*) And of course "only mildly elevated" is a very meaningful, non-deceptive phrase to use, when talking about C13/C12 isotope ratios. (*and here*)

 

[Moonbear]

I still find it strange that he only had a positive result in one urine sample out of all the tests conducted during the Tour. If he was doping, you'd expect to see a consistently elevated ratio in all his samples.

The isotope test, according to the literature I scanned a few days ago when I first saw this story, seems to be a bit controversial still.

None of this rules out the first sample being contaminated. If a technician forgot to change the pipet tip after running a reference sample or the high concentration standards, then dipped it into the urine sample, it doesn't matter how many times you re-run it, it's going to keep showing the odd result.

And, every so often, when running hormone assays, you just get an inexplicably odd result that you know is impossibly high...you just don't get a huge spike in concentrations without a subsequent metabolic decay curve. So, when something goes from baseline, to extremely high, and back to baseline with no intermediate samples between, I'm more suspicious of sample contamination than an actual elevated hormone concentration, either produced naturally or injected.

On the other hand, if he has been doping, it's not like he's going to just admit it and hand over the title, and it must have been an awfully short-acting form of testosterone, which doesn't really make a lot of sense in an endurance competition.

I'm also concerned that the biosynthetic pathway of epitestosterone is not known. To use something as a reference value without fully understanding what regulates its synthesis or metabolism is risky.

 

[Rach3]

The isotope test, according to the literature I scanned a few days ago when I first saw this story, seems to be a bit controversial still.

What's the controversy about? Is any of this literature publically available?

 

[Moonbear]

What's the controversy about? Is any of this literature publically available?

It hasn't been tested in a lot of subjects where it's known they were doping or not. As you read through the literature, you'll see results that are outside the normal range in what are supposed to be control subjects dismissed as an athlete who has been doping rather than considering that maybe these occassional odd results are of physiological or pathological origin. I'm having difficulty actually finding studies where they took volunteers who would have no reason to dope (non-athletes) and monitored them pre and post administration of testosterone to validate these tests. Instead, they're taking populations of athletes and using the fact that they find values several standard deviations from the average as evidence that those subjects are doping, even if they deny it.

There also seem to be a few articles that suggest diet can shift the carbon isotope ratio, especially an abrupt change in diet (such as when one might go to a foreign country and carbo-load before a big competition ).

Here's one review article that's freely accessible and the bit they have to say on the isotope testing.

Another noninvasive test is the determination of the carbon isotope ratio (CIR). Most carbon atoms are 12C, and a very few are 13C and 14C. Becchi et al. (44) explored the hypothesis that the 13C/12C of synthetic T differs from the 13C/12C in endogenous T. Using a specialized GC-MS that measures this CIR, they found support for the hypothesis by showing that, after T administration, the 13C 0/00 values for T were <-27, whereas samples from normal controls had values that were less negative than -27. In a subsequent study, the 13C 0/00 values for T, cholesterol, and metabolites of T were determined for 25 samples from 8 apparently healthy volunteers before and after T administration (45). The 13C 0/00 values of T and metabolites were lower after T administration, and discriminant analysis correctly identified the samples collected after T administration (45). More recently, we have measured the 13C 0/00 values of T in 14 urines from three individuals whom we expected to have physiological increases of T/E. The 13C 0/00 values of T in all 14 was between -24 and -27. At this juncture, the CIR studies consistently show that after T administration the 13C 0/00 values of T are -30 to -36 if the T/E is >10; however, the studies to this point have not included enough samples from T users with T/E ratios in the critical range of 4:1 to 10:1, so the sensitivity of the CIR test is not known. Although it was encouraging to find high T 13C 0/00 values in three subjects presumed to have physiologically increased T/E, more data are needed. Further on-going studies are anticipated to improve on the measurement of CIR and on the premeasurement analytical techniques.

http://www.clinchem.org/cgi/content/full/43/7/1280

There seems to be a gray area between -27 and -30 as to whether it would be a naturally occurring variation in isotope ratios or due to doping. That may be what they meant by it being only mildly elevated, that it's suspicious, but in the gray area.

 

[LeBrad]

Note: They tested every single guy on the NHL Draft this year and they were all clean. I'm talking everyone and not just random testing. Cheers to the NHL!

That just means they can't yet detect what the players are taking these days.

 

[Rach3]

http://www.clinchem.org/cgi/content/full/43/7/1280

There seems to be a gray area between -27 and -30 as to whether it would be a naturally occurring variation in isotope ratios or due to doping. That may be what they meant by it being only mildly elevated, that it's suspicious, but in the gray area.

There's more confusion - this study looks at C13/C12 ratios in T. Another study, four years later, looks at C13/C12 ratios in three metabolic byproducts (I think that's what they are), which all have isotope ratios different from each other, and from T:

http://www.clinchem.org/cgi/content/full/47/2/292

Methods: Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) was used to determine the {delta}13C values for 5{beta}-androstane-3{alpha},17{beta}-diyl diacetate (5{beta}A), 5{alpha}-androstane-3{alpha},17{beta}-diyl diacetate (5{alpha}A), and 5{beta}-pregnane-3{alpha},20{alpha}-diyl diacetate (5{beta}P) in a control group of 73 healthy males and 6 athletes with testosterone/epitestosterone ratios (T/E) >6.

So it's quite different depending on which carbon atoms they choose to test. I'm not sure what the French lab did, or what numbers it came up with. Is there a standard?

One clarifcation - the "mildly elevated" quote came from Landis' personal doctor, not from an official source. Just to prevent possible confusion.

 

[Mickey]

High levels of testosterone? So we figured out he might be male. :/

Maybe we should test that guy who recently lifted a car to save a girl and see if he doped.

 

[Moonbear]

There's more confusion - this study looks at C13/C12 ratios in T. Another study, four years later, looks at C13/C12 ratios in three metabolic byproducts (I think that's what they are), which all have isotope ratios different from each other, and from T:

Technically, everything measured is a metabolite of T (they don't measure testosterone itself in urine, but a metabolized form).

So it's quite different depending on which carbon atoms they choose to test. I'm not sure what the French lab did, or what numbers it came up with. Is there a standard?

That's my question too, and one I haven't found an answer for. I really don't find an amazing number of research papers on this, so it seems more like something with a couple semi-promising articles on it, but far from conclusive, has suddenly found its way into drug testing labs. As far as I'm concerned, these athletes are still part of a big experiment, because I'm just not finding the hard evidence that this is a test proven to be reliable under normal competition conditions.

One clarifcation - the "mildly elevated" quote came from Landis' personal doctor, not from an official source. Just to prevent possible confusion.

I realize that. It's probably the closest we're going to get to a report of the actual test result (I'm sure the media doesn't think anyone would know how to interpret an actual number if they reported it).

It's certainly all very suspicious, but I'm not ready to hang the guy and strip him of his title just yet. It'll only be a couple days before they have the B sample tested. That's still not foolproof, if the original sample was contaminated before they split it into the A and B sample, or if there is something going on that day to have altered his production or excretion of either testosterone or epitestosterone.

 

[Chi Meson]

Mildly elvated? 11 to 1? A HIGH natural elevation is 2 to 1! The Cycling Federation allows up to 4 to 1.

I watched Floyd on that 17th stage. He appeared to be greater than Eddie Merckx, Indurain, AND Armstrong that day. The only thing I can say in his defense is:

If he did KNOWINGLY take testosterone, he should have known that he MUST NOT win that stage sice that would ensure he'd be tested, and ensure he'd be caught. And Floyd is a smart guy, and he had hours to think about it as he soloed over four mountains. That part doesn't make sense to me.

 

[Moonbear]

Mildly elvated? 11 to 1? A HIGH natural elevation is 2 to 1! The Cycling Federation allows up to 4 to 1.

I watched Floyd on that 17th stage. He appeared to be greater than Eddie Merckx, Indurain, AND Armstrong that day. The only thing I can say in his defense is:

If he did KNOWINGLY take testosterone, he should have known that he MUST NOT win that stage sice that would ensure he'd be tested, and ensure he'd be caught. And Floyd is a smart guy, and he had hours to think about it as he soloed over four mountains. That part doesn't make sense to me.

There are documented cases of people with natural levels as high as 13:1. If he was doping, why wasn't this showing up in all his tests? The whole point of using the elevated ratio is that it's supposed to last longer than the drug itself, so the day after he used, it still should have been somewhat elevated. (And, you'd think someone who is at that level of competition would have the sophistication to know to take T and E together to keep the ratio in check.) But, again, my problem is that they're using as a reference value something that is itself an unknown (epitestosterone). Without knowing the biosynthetic pathway of epitestosterone, there is no way to know if there are conditions (such as extreme exertion over several days of competition) when the natural ratio shifts, perhaps favoring the synthesis of testosterone rather than epitestosterone from the common pre-cursor pregnenolone (that's about all that's known about epitestosterone is that it is synthesized from the precursor pregnenolone, but other steroids can be synthesized in more than one way, so just knowing one precursor doesn't mean you know all there is to know).

I don't want to come across sounding like I'm trying to defend doping, because I'm not. My concern is more that this test could be coming up with false positives on clean athletes due to lack of understanding of the full synthetic, metabolic and excretory rates of the hormones being tested under different types of competition stresses, while those who want to cheat can still circumvent it (by using both testosterone and epitestosterone to keep the ratio consistent).

 

[Chi Meson]

You're getting my hopes up, Moonb. I'm going to have to not listen for a while.

:smiley covering ears: "La la la la la la la la"

 

[Moonbear]

You're getting my hopes up, Moonb. I'm going to have to not listen for a while.

:smiley covering ears: "La la la la la la la la"

:rofl: Sorry. I'll try not to get your hopes up. Afterall, he hasn't offered to pay me gobs of money to be an expert witness in his defense yet. :tongue2:

 

[Rach3]

:rofl: Sorry. I'll try not to get your hopes up. Afterall, he hasn't offered to pay me gobs of money to be an expert witness in his defense yet. :tongue2:

He'll be doing lots of that soon enough. Maybe give him a call?

 

[Astronuc]

On Wikipedia today -

Spanish cyclist Oscar Pereiro Sio claims he is the true 2006 Tour de France winner after Floyd Landis fails a second drug test.

http://en.wikipedia.org/wiki/2006_Tour_de_France

http://en.wikipedia.org/wiki/Floyd_Landis

On Yahoo -
http://sports.yahoo.com/sc/news?slug=ap-landis-doping&prov=ap&type=lgns

PARIS (AP) -- The Tour de France no longer calls him champion. His cycling team cut him loose.

About the only chance Floyd Landis has of keeping his prized yellow jersey will now likely be decided by an appeals process that could drag on for months.

Landis was discredited and disowned in short order Saturday when elevated levels of testosterone showed up in his "B" or second doping sample -- as it did in the initial "A" sample released last week.

The samples also contained synthetic testosterone, indicating that it came from an outside source.

 

[Rach3]

His choice - he can simply admit he's just another shameless cheat and that he's been publically lying about it for weeks, or he can drag on an endless legal battle claiming he has no idea how he ingested synthetic steroids, until everyone forgets about him. My expectation is he'll choose the latter.

 

[Chi Meson]

His choice - he can simply admit he's just another shameless cheat and that he's been publically lying about it for weeks, or he can drag on an endless legal battle claiming he has no idea how he ingested synthetic steroids, until everyone forgets about him. My expectation is he'll choose the latter.

I bet $5000 that he returns to his Mennonite roots and disappears behind an "Abe Lincoln" beard! Who's taking me on?:Smiley with fingers crossed:

 

[stepperry]

Could lab techs have put the synthetic hormone in the samples to make Landis look as if he was a cheat? Since the French had always wanted get Armstorng in trouble for doing and never did. The only reason think this is a possibility is because it is the only test came up as dirty not only during the Tour but Landis' whole season.

 

[Gokul43201]

The only reason think this is a possibility is because it is the only test came up as dirty not only during the Tour but Landis' whole season.

Also ask yourself if you've seen a better performance in the rest of the Tour or any other time in Landis' career (or heck, even any other time this last decade) than Landis' in the 17th stage?

 

[Astronuc]

Also ask yourself if you've seen a better performance in the rest of the Tour or any other time in Landis' career (or heck, even any other time this last decade) than Landis' in the 17th stage?

Landis fell behind by about 8 minutes in Stage 16. In stage 17 he reduced most of the deficit! That was an unprecented comeback and impressed everyone - until the drug test.

While Floyd Landis was a leading favorite even before the Spanish doping scandal came to light, in an epic eight minute loss of performance in Stage 16, it appeared he had lost all hope to finish on the podium, much less win. But the following day, during Stage 17, Landis set such a high pace on the first climb of the day that no one chose to follow. He caught a breakaway group that had escaped earlier, passed them, and continued to the finish line, making up almost all of his deficit, ending up 30 seconds behind yellow jersey wearer Oscar Pereiro Sio, which he made up with an extra minute in the final Stage 19 time trial.

From the Wikipedia article cited in my previous post.

 

[Moonbear]

I heard from someone else that he dropped back near the end of one of the earlier stages, with some sort of excuse of trying not to overexert his teammates trying to keep that pace. Is that true? If so, it does start looking more like a smoking gun if he really dropped back to avoid being tested at that stage. I was under the impression he was tested daily during the race, but if he avoided earlier testing by dropping back, the single elevated sample makes more sense because there would have been a lot more time between samples. In that case, maybe he thought he had given an earlier dose enough time to get out of his system so didn't hold back on this stage thinking he'd come up clean in the test.

Can anyone fill in the gaps on that? At what stages (or days) were each of his tests done? Why isn't everyone tested daily or twice daily (before and after the race)? With such a large prize at stake, even if you don't run the test and just store the sample, you can go back later and better track the profile of hormones for the winners and/or anyone with a suspect test.

 

[Rach3]

I wonder, will he also be prosecuted for fraud, because of the large amount of money involved?

 

[JasonRox]

I heard from someone else that he dropped back near the end of one of the earlier stages, with some sort of excuse of trying not to overexert his teammates trying to keep that pace. Is that true? If so, it does start looking more like a smoking gun if he really dropped back to avoid being tested at that stage. I was under the impression he was tested daily during the race, but if he avoided earlier testing by dropping back, the single elevated sample makes more sense because there would have been a lot more time between samples. In that case, maybe he thought he had given an earlier dose enough time to get out of his system so didn't hold back on this stage thinking he'd come up clean in the test.

Can anyone fill in the gaps on that? At what stages (or days) were each of his tests done? Why isn't everyone tested daily or twice daily (before and after the race)? With such a large prize at stake, even if you don't run the test and just store the sample, you can go back later and better track the profile of hormones for the winners and/or anyone with a suspect test.

I believe the first sample was at Stage 17 and the second was after the end.

 

[Moonbear]

I believe the first sample was at Stage 17 and the second was after the end.

Okay, that changes things a bit. I was under the impression from earlier reports that he had been tested frequently during the race, and this was on oddball sample out of line with all the other clean tests before it, not that it was the first sample. I really hate trying to sort out information from news stories.

 

[Gokul43201]

I believe the first sample was at Stage 17 and the second was after the end.

No. Both samples came from the same day - after stage 17.

 

[Gokul43201]

Why isn't everyone tested daily or twice daily (before and after the race)? With such a large prize at stake, even if you don't run the test and just store the sample, you can go back later and better track the profile of hormones for the winners and/or anyone with a suspect test.

I don't get this either. I think dope tests are performed on all track athletes before every heat in an Olympic event. Why not here? This random sampling business is just weird.

 

[Moonbear]

I don't get this either. I think dope tests are performed on all track athletes before every heat in an Olympic event. Why not here? This random sampling business is just weird.

It's almost like an out, isn't it? If, hypothetically, everyone in the race was doping, and they're only testing the top 3 or so at each stage, plus a handful of randomly selected competitors, one could strategize and drop back to 4th place at every stage to avoid testing, and come out the winner while still doping.

Having only one or two samples during a race also more readily opens it up to challenge. You can argue almost any excuse you want to, and there's no evidence from earlier or later samples to prove otherwise.

From a scientific perspective, I'd also be really interested in seeing how the overall profiles look throughout the course of such a prolonged endurance challenge. With such physical and mental stress, I would predict you'd see quite a bit of changing hormone levels as the race progresses, or that you might see a change in the first few days that then levels off as the body compensates. If such changes weren't observed, it sure would toss a few hypotheses regarding stress/hormone interactions out the window. Having a good profile from a large cohort of athletes in a particular sport will also help validate the use of a single sampling procedure in the future if that's what they intend to use. But, before you can claim you know anything from a single sample, you really do need to know what happens over time in a series of samples.

 

[Chi Meson]

This makes me feel a little better. Colbert is the only one who's jokes on the matter made me laugh.
[MEDIA=youtube]O7n-BjM9Z1s[/MEDIA][/URL]

 

[Astronuc]

This makes me feel a little better. Colbert's jokes

:rofl: Of course he's got high levels of testosterone . . . He's an American. :rofl: :rofl: