Re: Re:
thehog said:
Because EPO at altitude or just prior to altitude, rather than using it as a pure performance enhancer, stimulates & speeds the natural effects and altitude acclimatisation for an increase in RBCs. The EPO test does not look for levels of EPO rather than recumbent EPO - smaller cell size etc. due to synthetic use rather than natural occurring. The test simply can't yield a result. Addtionally the legal aspect, its way too open for legal challenge making the already flakey test redundant.
People oft forget that the medical use of EPO is to stimulate the natural production of EPO rather than supplement a patient with EPO. A patient generally would receive a blood transfusion followed by a course of EPO.
No, that's a muddled and inaccurate explanation. Like many biological processes there's a long and complex pathway, but for now let's just worry about two bits: EPO and the EPO receptor. This is your standard lock and key model: EPO fits into the EPO receptor, which in response kicks off a cascade of signalling that results in more red blood cells.
That's the natural EPO that your body produces, so what's the artificial EPO that athletes take? It's recombinant human EPO, so it's the same sequence of amino acids as human EPO (other animals will have their own EPOs with very slightly different sequences), but made in a lab instead of the ribosomes of your cells. A protein is made as a 2D string, same as it's stored in DNA, but after the string is made, it's folded into the shape it needs to be to do its job, often with the help of special chaperone proteins. It may also have parts of the ends of the string chopped off, and can have sugars attached at certain places (this is called glycosylation and can help folding or tag a protein for immune system reasons etc.).
So even if recombinant EPO was made from the same DNA/amino acid sequence, it will end up looking different, because it was made with different biological machinery, inside bacteria or another non-human cell in a lab instead of your own cells. Also some manufacturers change the sequence slightly (e.g. Amgen's darbopoeitin alpha) to make the resulting EPO more stable etc. But these changes are still small enough that the key still fits in the lock.
So how does the EPO test work? Because of the different glycosylation, electrical charge is distributed differently around the artificial EPO. If we put a mix of natural and recombinant EPO in a gel and apply an electric current (electrophoresis) they will separate out.
https://gbiomed.kuleuven.be/english/research/50000618/50753339/files/revepo.pdf
But back to the original point: there is nothing that would cause the test to not work on athletes who were at altitude. They may have produced more natural EPO due to hypoxia, but if they've taken artificial EPO it'll still separate out. It'll be more difficult to indirectly detect EPO usage via HgB/reticulocytes etc., but that's not the EPO test, that's the biological passport.
There's also the wider class of continuous erythropoietin receptor activators (CERAs) like Mircera of Ricky Ricco fame that are often based on the basic EPO protein, but modified enough that they need their own test to detect. You can also design drugs that target other earlier or later steps of the hypoxia pathway, like HIF-1 (hypoxia-inducible factor) that the Russians found was boosted by xenon. It's inaccurate to call any of those other substances EPO though.
thehog said:
As an aside; Wiggins most likely took a EPO shot in the back of the bus; he was just drugged tested and about to be in transit for 6 hours and overnight (testing stops), so no chance he'd be tested again in the short window for the microdose to leave the body. Perfect opportunity to use EPO prior of going to altitude and minimising any chance of being tested.
Yep EPO or similar is the most obvious answer to "what drug would a professional cyclist get couriered several hundred miles and not want to talk about it?".