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The Olympic rings.

The Olympic rings.

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New Doping Substance May Be Circulating in Sochi

As the Winter Olympics open today in Sochi, the race is on between athletes who try to get an artificial advantage from banned substances and the anti-doping experts trying to catch them. A new substance may be in the mix: On 2 February, television reporters for the German WDR network broadcast their undercover investigation (link in German) of a Russian scientist willing to sell them 100 milligrams of something called “full-size MGF” for $100,000. The reporters brought a sample to anti-doping expert Mario Thevis, a forensic chemist at the Center for Preventive Doping Research at the German Sport University Cologne. He confirmed the sample contained mechano growth factor (MGF), a variant of the human insulin-like growth factor-1 (IGF-1) protein, which can prompt muscle growth. It would be undetectable by current testing methods.

Thevis spoke with ScienceInsider from Sochi. The conversation has been edited for length and clarity.

Q.: What is the substance you found in the journalists’ sample?

M.T.: The closest way to describe it is human IGF-1 isoform 4. It’s a splice variant of the IGF-1 gene. The reason it’s called MGF—mechano growth factor—is that the mRNA [messenger RNA] of isoform 4 is elevated when mechanical stress is applied to muscle tissue.

Many gray market manufacturers offer something called MGF, but that usually refers to just a short peptide [at the end of the full protein]. That was claimed to be biologically active 15 years ago, but more recent studies have shown it has no biological effect. The full-size MGF is a molecule that according to the literature is biologically highly active, similar to IGF-1, but with different molecular weight and different size.

Q.: Can current doping screens detect it?

M.T.: Since we are using antibody-based or mass spectrometer-based detection assays, it has been more or less invisible. It has been under the radar of the doping control methods.  Even though we’re looking for modified IGF versions [and we can detect many of them], this particular version was not included with its particular structure and molecular weight. So if it has been misused, it might have gone undetected.

Q.: How were you able to tell what was in the sample?

M.T.: We have been looking into the literature—trying to keep track of what might come up. When we were confronted with a substance which should be related to IGF-1 but whose authenticity was not certain at all, we could deduce from the information we got from our analytical methods that we were dealing with a highly pure and therefore probably highly dangerous substance.

Q.: Highly dangerous?

M.T.:  There has been no clinical trial. There is no scientific data on long-term risks associated with injection or other use of this substance.

Q.: What might the side effects be?

M.T.:  We don’t know. There could be [immune reactions]. It could cause any of the side effects associated with IGF-1, such as cardiovascular issues.  Some of the growth factors also have cancer-causing effects. We can’t prove or rule out any of these. As far as the scientific literature goes, it has not been investigated in that regard.

Q.: Now that you know this might be in circulation among athletes, why can’t you add it to your battery of tests right away?

M.T.:  Practically we can, but we have to demonstrate that our test is fit for the purpose. We have to evaluate and assess whether our detection limits are in the range for physiological or therapeutic amounts, even though we have no idea how much that would be.

Since we do full-scan spectrometry on all our samples, it might well be that we have already captured it [in some samples], but we have to go back to our data and extract the molecular mass and see whether we see an indication for the presence of that molecule or not.

Q.: Could it occur naturally in athletes who are exerting their muscles to the extreme?

M.T.:  No. At least not according to the scientific literature that is available. It is a potentially naturally occurring substance, but it has never been seen in blood or serum, and you wouldn’t expect it to be in urine as it’s naturally produced.

But it’s true that if we see something that is positive, we would have to rule out that it could be a natural artifact.                                                                                                             

Q.: How clean will the games be?

M.T.:  Good question. The only thing I can say is that we have exceptionally good conditions here. The things we’re aware of, that we are testing for, can be very well detected. Any substance that would be known to provide an advantage and be misused in competition can be tested here on site.