Popular media has suggested there are 80-100 undetectable substitutes for EPO. I know EPO is a naturally occurring hormone in the body but know next to nothing beyond that. I am wondering if someone with a solid background in chemistry, physiology, bio-genesis, etc. can take the time and explain how it all works, injection to detection. For instance, I can't imagine a 3:42.7 guy takes EPO or a substitute the night before and all of a sudden magically runs 3:28.81 on race day.
Unless everyone here is a PhD in biochemistry or a laboratory scientist of the sort I am guessing others are in similar positions. They know what EPO is but not how it works and enhances performance. It would help if examples were catered to the running perspective (ex: effects on training) and wasn't overly loaded with jargon. I am also personally very interested in:
- "gene doping" vs "traditional doping"
- intricacies of testing methods
- why "substitutes" are undetectable
For some reason, I decided to write a response to this poster, and I think that it would be worth posting again here.
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| EPO |
As has been previously stated, erythropoietin, or EPO, is a signalling molecule (cell signaling) that eventually leads to the production of more red blood cells (erythrocytes). EPO binds to a receptor on the outside of the cell, causing that receptor to change shape (known as conformation; the change here is a dimerization). The newly changed receptor can then bind and activate another protein (a protein kinase), and then after several more steps, molecules (transcription factors) reach the DNA and causes more production of proteins that are necessary for red blood cell maturation (transcription factors cause increased synthesis of mRNAs that code for proteins required for erythrocyte maturation; this is an example of a JAK-STAT system). Source: Lehninger 443-4.
1. Regarding substitutes.
In chemistry, molecules can be analogues of one another. That is to say, they are structurally basically the same, but have a minor difference that may or may not affect function. An example of this would be sucrose (table sugar) vs. sucralose (Splenda).
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| Sucrose (sugar) vs. sucralose (Splenda) |
Now, what does this have to do with EPO? Proteins, as they are molecules as well, can have analogues much in the same way small molecules can. These analogues can have essentially the same structure and function, but small variations in the structure (amino acid sequence) can change their detectability. This is similar to how your body does not "detect" Splenda--you reap the benefits of sucralose, but you don't pay the caloric price of sugar because your body doesn't have the receptors. When you mention that there are 80-100 "substitutes" for EPO, they are undetectable insofar as they have subtle differences that prevent them from being picked up by the test but do not change their overall function. I don't know how synthetic EPO is tested for (other than way back when they would test for plastics found in the bags they were stored in), so I can't give any more insight into where and what these changes are.
2. How EPO affects performance.
As we have said, EPO leads to the increased production of red blood cells. I'm not sure the time between injection and RBC production, but I would guess that it's on the order of hours, and I think I've read that RBC levels normalize after about 3 days. So, one would benefit from shooting up the night before, but it isn't going to take you from 3:42 to 3:29, no way, no how. The strength of EPO, and any PED, comes from what they allow you to do in training. If you have more RBCs, you're going to able to run faster and longer in your workouts, do more miles per week, etc. If you're on the juice for 9 months and your training load is exceeding what you're body can naturally handle, when you come off it, you're going to be in ridiculous shape. You come off the juice, ramp down your training, and race. You'll pass your in-season tests because you're off the stuff, but you've already reaped the benefits of the PEDs because you were able to have higher quality and quantity of training over the previous nine months. The competition season becomes about doing maintenance work to keep that level of fitness. Your body can also probably now handle a higher level of training, but not as high as when you were on the juice. A program like this is probably what lead to Ramzi's stupid drop in time between 2003 and 2004.
It is also worth mentioning that young RBCs are more efficient oxygen carriers than are older RBCs (RBCs have a life cycle of ~120 days). It is thus beneficial to induce the production of RBCs because your body will have a higher percentage of newer and more efficient cells delivering oxygen to the muscles (source). Tyler Hamilton talks about the use of EPO between stages on the Tour in his book (which is worth reading).
See also: http://www.sportsscientists.com/2007...mance-who.html
3. Gene doping vs. traditional doping.
WADA defines gene doping as "the non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". EPO abuse is a form of gene doping; as I previously explained, EPO increases the expression of genes important in RBC production. Read more here.
I'm not exactly sure what you mean by "traditional doping", but if you provide an example of what you mean, I'll try to expand.
4. Intricacies of testing methods.
I don't know too much about how EPO is tested for--I don't think that information is out there. Here are some general testing methods:
-Biologic levels: some PEDs alter the levels of certain naturally occurring compounds in the body. So, while the drug itself isn't being tested for, the effects of the drug are. An example of this is the testosterone/epitestosterone ratio (although this is a little more direct). In normal humans, these are produced in roughly the same amounts (an Australian study found the mean T/E ratio to be 1.15:1). But, when Mary Slaney pops a T/E of greater than 6:1, you know something's up. Sometimes epitestosterone is administered as a masking agent for synthetic testosterone to keep the T/E ratio down. A second example is measuring hematocrit (% RBC in blood) for blood doping. Back in the late 90s and early 2000s, the UCI allowed hematocrit levels of up to 50. As long as you were under that number, you were good to go. If you tested higher, you got popped, as you basically had to be on something to get that level of RBCs.
-Testing for the compound itself: not sure how often this is done, but in the case of a synthetic compound that has a long half-life, a chemist could design a test to look for the presence of the molecule.
-Testing for carrying devices: as I previously mentioned, tests used to be done for the plastics in blood bags. Those aren't supposed to be in your body.
Post by AJ Acosta in the same thread:
Doping programs are incredibly sophisticated and the new rage these days is "microdosing."The idea is that by using a patch or fast acting cream, the steroids or whatever drug you are using is out of the system fast. Remember, the half life of EPO is something ridiculously short like 5 hours, so by microdsoing you significantly decrease your chances of being caught. And as other and smarter posters have laid out, the chemists will change chemical compositions of the drugs to make it even harder for hte drugs to be detected.
My response: Yes. Tyler Hamilton talks about this.
Another post by AJ:
You dont "use" up blood cells technically, although i suppose when you dig in the well a little too deep you start using your iron storage levels a bit.
My response: This sounds about right. My understanding is that stressful exercise can lead to RBC destruction due to depletion of protectants (eg antioxidants).
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