Why doesn't anyone question the isotope test???
Thomas A. Fine
question this exogenous testosterone test. They quote experts
and use words like "irrefutable", "proof", "perfect", etc.
Even CNN's Sanjay Gupta, himself allegedly some kind of expert,
simply referenced some other expert and then proved himself an idiot,
claiming there's something in synthetic testosterone that's not
in natural testosterone.
It's frustrating, because like most tests, it's not at all clear
cut and there's a significant margin for error, as well as possible
natural explanations for the results.
In attempt to clear things up, I've written up a page with everything
I've learned about the test, and everything I'd still like to know
about it.
http://hea-www.harvard.edu/~fine/opinions/testosterone_d13C.html
To sum up, the ranges of normal and synthetic testosterone's carbon-13
ratios seem to overlap. A simple limit on the delta 13C is not a
reliable test, nor is this what is used. Instead, the d13C of
testosterone is compared to other natural steroids and expected to be
similar.
The d13C of testosterone is influenced by diet, to a very significant
degree. It's unclear from what I've found so far if this can happen
fast enough to show a change overnight, but if it is possible, then
such an effect ought to be significantly exaggerated by an athlete
bonking and then consuming 10,000 or so calories. If the food consumed
was different than the past few days' meals, and if there was the expected
natural surge of testosterone you get from a performance such as stage
17, then you would expect a significant disparity between the d13C of
the testosterone and the comparison compound.
There's some other ideas in there as well. Some less likely, some more
likely. It's entirely possible that with additional information the
test might be shown to be highly reliable, but with the information
I have so far, this is simply not clear.
Input is welcome, and the web page will be updated with new information
as I find it.
tom
Tere
How much does diet effect 13C? Would one have to be vegetarian or even
vegan to see a significant elevation of C13? I assume that other
animals have 13C level similar to humans, so eating meat or dairy
products may mitigate any effect diet has on !#c.
Wouldn't a dietary source of 13C would effect all or many of the
compounds in the body.? Therefore they might be able to test the
background level of 13C in the urine and compare that to the 13C in the
testosterone
Charles Beristain
Fine) wrote:
>Nobody in the media is extending the tiniest bit of effort to
>question this exogenous testosterone test. They quote experts
>and use words like "irrefutable", "proof", "perfect", etc.
Tom
the Science Section of the New York Times ... I think it was two weeks
ago ( just after the announcement of Landis's situation) ..
they said that the cholestrol from the athlete was used as the
baseline for the comparison.. ... then testosterone from the urine
sample was separated out and it was tested .... they used typical
numbers like "25" for the cholesterol baseline and "28" for the
testosterone...with a difference of "3" proving there was some level
of synthetic testosterone in the athlete's body.
they also said that synthetic testosterone was made from Soy ... and
for some reason, soy has a different c13 level than the usual veggies
that we eat that our bodies convert to testosterone. I remember
something about 1 tenth of one percent difference... seemed like a
very small number.
charlieb in ct.
Nobody
Excellent questions. I too have wondered about the rate of
testosterone production and metabolism. Your questions
about the source of carbon in testosterone production and
how quickly diet can change the c12/c13 ratios are important.
Dave
Salvelinus
This blog is done by a real chemist who works for a large pharma.
http://pipeline.corante.com/archives/2006/08/01/testosterone_carbon_isotopes_and_floyd_landis.php
Salvelinus
This blog is done by a real chemist who works for a large pharma.
http://pipeline.corante.com/archives/2006/08/01/testosterone_carbon_isotopes_and_floyd_landis.php
gds
I find most of your premises plain wrong. The test being run is an
accepeted test that has been well researched for validity, reliability
and sensitivity. I see no references to scientifc articles appearing in
peer reviewed journals that suggest otherwise.
If the test has been shown to be valid then all of the bogeymen you are
throwing up have been looked at and rejected. You are simply listing a
bunch of "what ifs" without any knowledge about how they have been
addressed.
Get over it- he failed the test. Even Floyd has backed down from
claiming there is a problem with the test itself and has moved on to
tryon to explain where/how someone somehow got the stuff into him. Now
that is certainly a possibility even though the Why? part of that
escapes me.
Simon Brooke
('fi...@head-cfa.harvard.edu') wrote:
> Nobody in the media is extending the tiniest bit of effort to
> question this exogenous testosterone test. They quote experts
> and use words like "irrefutable", "proof", "perfect", etc.
Because the serious chemists all seem to say the test is bombproof, and
the only people saying it's not are Landis' legal team and wild-eyed
American tifosi.
--
si...@jasmine.org.uk (Simon Brooke) http://www.jasmine.org.uk/~simon/
;; So, before proceeding with definitive screwing, choose the
;; position most congenital.
-- instructions for fitting bicycle handlebars
photos...@gmail.com
His legal tactics are strong indicators of his guilt or innocence (I
believe). If he truly had no idea on earth how he might have tested
positive, he would have had scientific experts observe the testing of
the b-sample. Instead, he sent two lawyers. And instead of attempting
to prove his innocence AND his lack of guilt, he has very quickly
jumped to the "entrenchment" tactic. Obviously, he believes there is
something to these tests. Current strategy: plant a billion seeds of
reasonable doubt. Come up with every possible incredible explanation
until they find one good enough to go to the appeals panel with. And he
can watch the public critical reaction to all of these explanations.
If it had been my sample, I'd have my team all over the carbon isotope
test, the lab's competence in performing it and the chain of custody
issues that seem to be of concern to many these days.
Tom Kunich
news:1155156587.6...@h48g2000cwc.googlegroups.com...
> Read this page.
> This blog is done by a real chemist who works for a large pharma.
>
> http://pipeline.corante.com/archives/2006/08/01/testosterone_carbon_isotopes_and_floyd_landis.php
Unfortunately he doesn't actually know what the test is or how it's derived.
He is only commenting on the theoretical underpinning of such a test.
There's no question that a mass spectrometer can tell C12 from C13. No one
is questioning that.
What is being questioned are things like:
How many peaks are near the testosterone peak?
Is there any over lap of the peaks (normal)?
Since the total volume of testosterone is so small, how many atoms are we
talking about here? After all, since it is common for peaks to overlap, if
they are using all of the testosterone peak in order to obtain the maximum
volumn to test this would include components from the overlap.
As Mr. Fine pointed out, cholesterol and testosterone are derived from
different bodily functions and the diet has a notable lag time in production
of the testosterone whereas the cholesterol is almost immediately available.
I keep going back to one point - the 4:1 e/t ratio. That is a BOGUS value
from the start since the literature quotes NORMAL spikes up to 20:1.
Apparently it is the judgement of WADA and UCI that they can lose a few
riders here and there to false positives. They simply don't care.
chester
>
> I find most of your premises plain wrong. The test being run is an
> accepeted test that has been well researched for validity, reliability
> and sensitivity. I see no references to scientifc articles appearing in
> peer reviewed journals that suggest otherwise.
>
> If the test has been shown to be valid then all of the bogeymen you are
> throwing up have been looked at and rejected. You are simply listing a
> bunch of "what ifs" without any knowledge about how they have been
> addressed.
>
> Get over it- he failed the test. Even Floyd has backed down from
> claiming there is a problem with the test itself and has moved on to
> tryon to explain where/how someone somehow got the stuff into him. Now
> that is certainly a possibility even though the Why? part of that
> escapes me.
>
Again, the problem is that you simply accept whatever someone tells you
at face value, with little ability, or desire, to question it. It is a
real problem in society, and has been for centuries. In the US the
problem has reached epidemic levels, and has resulted in a huge moron
running (ruining?) the world
Perhaps Landis is guilty, but to simply state that the test results are
always without question is itself moronic and contradicts the test
equipment manufacturer's own comments.
It is NOT an "is it there or not" test, like some other steroid tests
are. It is a test that requires interpretation, and as the OP said,
there are crossovers in the values of natural vs synthetic. That is a fact.
mal
".
>
> Apparently it is the judgement of WADA and UCI that they can lose a few
> riders here and there to false positives. They simply don't care.
And that's why this whole doping stuff is so hipocritical. They'd rather
hang ten innocent riders to preserve the impression that they are doing the
right thing.
The wankers in senior positions are guilty of it, and Dick Pound is the
master.
They are self righteous ponces.
mal
NEVER claim anything is irrefutable or bombproof. Only those who quote them.
Experts are like hookers. They have different specialties, and will do
anything for money.
This is the reason they replaced rats with lawyers in scientific
experiments.
There were things that rats just wouldn't do.
"Simon Brooke" <si...@jasmine.org.uk> wrote in message
news:g70qq3-...@gododdin.internal.jasmine.org.uk...
Ray_...@hotmail.com
gds wrote:
"If the test has been shown to be valid then all of the bogeymen you
are
throwing up have been looked at and rejected. You are simply listing a
bunch of "what ifs" without any knowledge about how they have been
addressed."
Well that is my problem, I don't know that their test has been shown to
be valid as they us it. The criticism of WADA/UCI has been the lack
of transparency. If they have proof the test works, then they should
release the data.
As part of lab certification process blind samples are sent to the labs
for testing and the results compare to the known content. These
results for ALL labs should be released for public examination. What
has WADA/UCI to hide?
Thomas A. Fine
Tere <terence...@nist.gov> wrote:
>How much does diet effect 13C? Would one have to be vegetarian or even
>vegan to see a significant elevation of C13? I assume that other
>animals have 13C level similar to humans, so eating meat or dairy
>products may mitigate any effect diet has on !#c.
No, when you look at the meat, the carbon-13 is based on what the
meat ate. In an experiment with cows, they were able to alter
the delta 13C by 9 permill, which is a very wide range.
The biggest variant are how much of your diet is C3 plants (which is
most plants) or C4 plants (which is mainly corn and sugar cane, as
far as food goes). C4 plants drive your results to higher
carbon-13, which is a less negative d13C value, which makes you
more different from the synthetic. Not eating C4 plants will
cause you to have less carbon-13, and more negative d13C value,
closer to the synthetic value. It depends on which things you eat,
as C3 plants can range anywhere from -22 to -30 permill, with the
soy that's used to make testosterone apparently near the -30 permill
end of the range.
>Wouldn't a dietary source of 13C would effect all or many of the
>compounds in the body.? Therefore they might be able to test the
>background level of 13C in the urine and compare that to the 13C in the
>testosterone
They can and do compare to background value - of another natural
steroid. However, due to different rates and processes of production,
they are not expected to be identical, merely similar.
tom
Thomas A. Fine
Salvelinus <troy....@ipi.com> wrote:
>Read this page.
>This blog is done by a real chemist who works for a large pharma.
>
>http://pipeline.corante.com/archives/2006/08/01/testosterone_carbon_isotopes_and_floyd_landis.php
Yeah, I've seen it.
There's nothing in there that answers any of my open questions. He
doesn't talk about how quickly a dietary change can alter carbon-13
ratios.
He writes:
"The typical Western industrial-country diet is derived from a mixture
of C3 and C4 stocks, so the appearance of testosterone with a C3-plant
isotopic profile is diagnostic."
What if the diet isn't typical. What if it was typical last week,
but today the diet was not typical, how does that alter tomorrow's
testosterone carbon-13 content?
tom
Thomas A. Fine
gds <gary...@msn.com> wrote:
>I find most of your premises plain wrong. The test being run is an
>accepeted test that has been well researched for validity, reliability
>and sensitivity. I see no references to scientifc articles appearing in
>peer reviewed journals that suggest otherwise.
Is there a specific thing that you can point to that's wrong, that
you can show how it is wrong? Or do you just always blindly trust
"experts"?
>If the test has been shown to be valid then all of the bogeymen you are
>throwing up have been looked at and rejected.
As if there is some "valid" stamp, that once used can never be revoked?
This is not how the real world works. Tests are rushed into place with
little validation, because the war against drugs has to be fought.
And because many of these tests are commercial products, and performing
too much validation is too expensive, and decreases profits.
There's a deeper problem too. You can't test athletes in these tests,
because they might lie about doping, and skew the results. So you
have to test "normal" people, and then assume that athletes will
behave the same. But this is demonstrably false - elite athletes
exceed normal parameters in many different ways.
>You are simply listing a
>bunch of "what ifs" without any knowledge about how they have been
>addressed.
Yes, this is the point. I want answers to these questions. It's
not so much that I don't know how they've been addressed -- I don't
know IF they've been addressed. So far, I've come up empty, and I
want to see if the power of the Internet can do better. So far,
not.
tom
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Thomas A. Fine
<photos...@gmail.com> wrote:
>His legal tactics are strong indicators of his guilt or innocence (I
>believe). If he truly had no idea on earth how he might have tested
>positive, he would have had scientific experts observe the testing of
>the b-sample. Instead, he sent two lawyers. And instead of attempting
>to prove his innocence AND his lack of guilt, he has very quickly
>jumped to the "entrenchment" tactic. Obviously, he believes there is
>something to these tests.
You've seen here that there are many people who tend to blindly trust
experts. So if assume that there exists an innocent Floyd Landis who
tends to trust authority, then he would act exactly as we've seen -
he'd desperately thrash about for an explanation that somehow fits,
since he knows he didn't dope. That would look pretty much like
what we're seeing.
I really don't think you can tell just by watching outward behaviour.
It's entirely consistent with how some personality types might react in
either the innocent or the guilty scenario. Maybe if you knew Floyd
personally, and knew what his true personality was (as opposed to his
public persona) then you might be able to guess.
tom
RonSonic
>I find most of your premises plain wrong. The test being run is an
>accepeted test that has been well researched for validity, reliability
>and sensitivity. I see no references to scientifc articles appearing in
>peer reviewed journals that suggest otherwise.
>
>If the test has been shown to be valid then all of the bogeymen you are
>throwing up have been looked at and rejected. You are simply listing a
>bunch of "what ifs" without any knowledge about how they have been
>addressed.
And you seem to be blindly assuming that they have been addressed. If I'm wrong
and you've got some real science that answers this please present it so we can
get smarter.
Ron
Thomas A. Fine
Tom Kunich <cyclintom@yahoo. com> wrote:
>I keep going back to one point - the 4:1 e/t ratio. That is a BOGUS value
>from the start since the literature quotes NORMAL spikes up to 20:1.
Do you have a reference for this? I've looked around for a study that
measures T/E ratio after a testosterone surge, but haven't found anything.
I also haven't seen any references myself to a normal value that was
that high.
tom
RonSonic
>The serious chemists, or pharmacists as they are called in civilization,
>NEVER claim anything is irrefutable or bombproof. Only those who quote them.
Except the director of this particular lab, who insists there is no possibility
of error in this test.
I don't personally think he's serious, but a lot of other people do.
Ron
Chris
playing the ignorance of the general public, skewing public opinion where as
this needs to be tried in a real court not the court of public opinion.
"Thomas A. Fine" <fi...@head-cfa.harvard.edu> wrote in message
news:44da358a$1...@cfanews.cfa.harvard.edu...
seatos...@yahoo.com
is innocent.
Mark
Ray_...@hotmail.com wrote:
> I don't know that their test has been shown to be valid as they us it.
This is perhaps a two part issue. The first part is to validate the
analytical part of the test and to understand how a test performs. This
can be done to a reasonable degree for many analytes. Let's assume for
discussion that the lab involved is competent and test validation has
been carried out properly. The second part of a test validation is to
understand the biologic variance and how different physiology impacts
interpretation of a properly carried out analytical test. This is the
part that is troublesome because it's not at all clear that there
exists a large enough database to ensure that the results are being
interpreted correctly. It's one thing to measure something accurately
and it's entirely another to understand what that measurement means. Of
course even with a very good test there will still be outliers and
false positives and negatives. All of this complicates interpretation
when important results are at stake.
>The criticism of WADA/UCI has been the lack of transparency.
There are a lot of imperfections in the whole WADA mission and
execution thereof. What I find most troublesome is that in speaking to
some WADA reps is that they appear to have crossed over from medical
science and pragmatism to more of a religious pursuit of catching the
dopers. While there are certainly dopers to catch, once a group moves
toward a "burn the witches" perspective I find it hard to blindly
accept a priori interpretation of results.
To be fair, the WADA mission is difficult as they are trying to catch
people altering their physiology who obviously do not want to get
caught and who clearly have resources available to be creative about
performance improvement. It's nice to ask for transparency (and I
agree) but transparency makes it somewhat easier to cheat. To me, that
is the reason why WADA and the labs involved need to be beyond reproach
and so squeaky clean that they are to be believed. As many have pointed
out in this forum over the years, the anti-doping groups have lost a
certain amount of credibility and that is a shame as their overall
mission remains valid.
Of course none of this means that an athlete did or did not dope.
Simply suggests that folks who blindly accept that the assays under
discussion are without flaw and that the results available at present
time are perfectly conclusive are as naive as folks that believe doping
is not widespread in high level sport.
In any case at least this gives RBR something to prattle on about until
next July.
Mark
Michael Press
> The test being run is an
> accepeted test that has been well researched for validity, reliability
> and sensitivity. I see no references to scientifc articles appearing in
> peer reviewed journals that suggest otherwise.
Do you have citations for the articles that form the basis
for the test?
--
Michael Press
Michael Press
<r7ednYIP-4OJ5EfZ...@comcast.com>,
"mal" <malco...@comcast.net> wrote:
> The serious chemists, or pharmacists as they are called in civilization,
> NEVER claim anything is irrefutable or bombproof. Only those who quote them.
> Experts are like hookers. They have different specialties, and will do
> anything for money.
>
> This is the reason they replaced rats with lawyers in scientific
> experiments.
They're plentiful, and the laboratory assistants do not
become attached to them
> There were things that rats just wouldn't do.
Problem is that experimental results cannot be
extrapolated to humans.
--
Michael Press
Tom Kunich
Sorry that I don't have it now but it was referenced on this group and I
read it. Can't remember which thread however.
Donald Munro
>> This is the reason they replaced rats with lawyers in scientific
>> experiments.
Michael Press wrote:
> They're plentiful, and the laboratory assistants do not
> become attached to them
What ? rbr has become quite attached to Lafferty.
Tom Kunich
news:44daefd1$0$9471$ec3e...@news.usenetmonster.com...
The term is "infected".
gds
Thomas A. Fine wrote:
> Is there a specific thing that you can point to that's wrong, that
> you can show how it is wrong? Or do you just always blindly trust
> "experts"?
Sure, you allege that no one in the media is questionaing the tests. I
have seen interviews with numerous people who are saying the test are
quite valid and reliable. These are folks are scientists in the field.
So, the media did raise the question and it seems it is being answered,
though not in a way you would prefer
>
>
> As if there is some "valid" stamp, that once used can never be revoked?
> This is not how the real world works. Tests are rushed into place with
> little validation, because the war against drugs has to be fought.
> And because many of these tests are commercial products, and performing
> too much validation is too expensive, and decreases profits.
What is the point of this argument? At it s core you are saying that
you don't believe that nay of the tests that come to market are any
good becasue they are all tainted by a variety of economic motives.
That has not been my experience. I have a number of years working in
labs and on the faculty of a medical school. My wife has over 20 years
of experience in large Pharma. Our experience is that overall
procedures for establishing validity and and reliability are pretty
good.
Does this mean that the system is perfect? Of course not, but you are
suggesting you don't believe anything and that is just silly.
>
> There's a deeper problem too. You can't test athletes in these tests,
> because they might lie about doping, and skew the results. So you
> have to test "normal" people, and then assume that athletes will
> behave the same. But this is demonstrably false - elite athletes
> exceed normal parameters in many different ways.
Right! Of course you establsih the test parameters on groups like what
you want to study. When I was involved in testing of this sort in the
military we found huge differences in the response to various stress
stimulii between regular infantry and elite troops. This is a
fundamental research issue. Why are you assuming that the testers
haven't figured this out? You are attacking with passion but no
ammunition.
>
> >You are simply listing a
> >bunch of "what ifs" without any knowledge about how they have been
> >addressed.
>
> Yes, this is the point. I want answers to these questions. It's
> not so much that I don't know how they've been addressed -- I don't
> know IF they've been addressed. So far, I've come up empty, and I
> want to see if the power of the Internet can do better. So far,
> not.
I guess its fine that you want these answers but who is that is
responsible for providing them? You are a paying client of whom? Sure
ultimately if fans desert the sport the sponsors and the sport itself
will suffer. But seriously, in the short run it does't seem to me that
you are a direct client.
I'll go back to the issue that all of the procedures were in place and
agreed to by the athletes before competing. I'm not talking aobut
leaks, that's plain wrong; but the testing procedures and the outcomes
were very clear.
aco...@earthlink.net
> Since the total volume of testosterone is so small, how many atoms are we
> talking about here?
You usually need ~1 umol of material, or 6.02 x 10^17 molecules, for
standard dual-inlet IRMS analysis. However, the test here uses a
GC/C/IRMS, which operates in a continuous flow manner analogous to a
GCMS, such that the sample requirement is significantly less. How much
less in this case, I don't know, but for standard GCMS analysis ~1 nmol
of material, or 6.02 x 10^14 molecules, injected onto the column is
plenty, and you can get by with much, much less.
Andy Coggan
Jeff Jones
>
> You usually need ~1 umol of material, or 6.02 x 10^17 molecules, for
> standard dual-inlet IRMS analysis. However, the test here uses a
> GC/C/IRMS, which operates in a continuous flow manner analogous to a
> GCMS, such that the sample requirement is significantly less. How much
> less in this case, I don't know, but for standard GCMS analysis ~1 nmol
> of material, or 6.02 x 10^14 molecules, injected onto the column is
> plenty, and you can get by with much, much less.
>
Extending this: molecular mass of 1 mol of testosterone = 288.43g.
Thus, 1 nmol = 2.88 x 10^-7g of material. Or buggerall, in layman's
terms.
One study I saw showed natural testosterone excretion was about an
order of magnitude greater than this (3 x 10^-6g/hour). And although
you could argue that 10 times buggerall is still buggerall, it's good
enough for GCMS.
Jeff
Thomas A. Fine
gds <gary...@msn.com> wrote:
>Sure, you allege that no one in the media is questionaing the tests. I
>have seen interviews with numerous people who are saying the test are
>quite valid and reliable. These are folks are scientists in the field.
>So, the media did raise the question and it seems it is being answered,
>though not in a way you would prefer
I've seen shallow empty things like "is this test reliable?" "Oh
yes, absolutely reliable" and that's it. But when I repeatedly see
these results reported as "exogenous testosterone detected in Floyd's
urine", I know for a fact that they simply don't get it.
I want someone to ask the deeper questions. Is there a measure for the
accuracy of the test? A false positive rate? Known factors that
can affect the outcome? That would be a start.
>Does this mean that the system is perfect? Of course not, but you are
>suggesting you don't believe anything and that is just silly.
I'm not suggesting that. I love to believe in things. Show me that
diet and/or testosterone surges have been studied in conjunction with
this test, and I'll be very interested. If no body can show me that,
then I have serious doubts, and anyone with training in lab testing
ought to have those same doubts.
>I was involved in testing of this sort in the
>military we found huge differences in the response to various stress
>stimulii between regular infantry and elite troops. This is a
>fundamental research issue. Why are you assuming that the testers
>haven't figured this out?
You keep saying that I'm assuming. I've spent quite a bit of time looking
for these papers on line. I assumed I would find them and so far I have
not, so now I want to see if anyone else can find them. Then, if no one
else can find them, I'll might assume they don't exist, depending on
how many people I've asked.
> I guess its fine that you want these answers but who is that is
>responsible for providing them? You are a paying client of whom? Sure
>ultimately if fans desert the sport the sponsors and the sport itself
>will suffer. But seriously, in the short run it does't seem to me that
>you are a direct client.
I'm a client of the media, and I expect the media to do its job. And
so far, it has not. If Reuters editors can accept a photo with the
worst photoshop alteration ever seen, then I can wonder how deeply
the media is really probing this issue, and I can try to probe more
deeply.
>I'll go back to the issue that all of the procedures were in place and
>agreed to by the athletes before competing. I'm not talking aobut
>leaks, that's plain wrong; but the testing procedures and the outcomes
>were very clear.
This is simply not true. The athletes agree to the testing. But not
the procedures -- the procedures are kept as secret as possible by the
testing agencies. I think that the athletes have been entirely too
trusting with respect to these procedures.
tom
mcc...@usa.net
on the isotope composition of steroids
http://www.wada-ama.org/rtecontent/document/b5_2003.pdf
Raptor
> Apparently it is the judgement of WADA and UCI that they can lose a few
> riders here and there to false positives. They simply don't care.
We must destroy cycling in order to save it.
--
Lynn Wallace http://www.xmission.com/~lawall
I have nothing but contempt and anger for those who betray the
trust by exposing the name of our sources. They are, in my view,
the most insidious of traitors."
George H.W. Bush, April 16, 1999,