Gene Doping – The Lab Cheat

27. May 2008
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Protests against China just don't seem to stop. The Olympic Games 2008 already seem to become a debacle. And another adversity raises from yet a different direction. Will Peking be the venue of the first gene doping wave? Or is it just fiction? Experts are groping in the dark - DocCheck spoke with Dr. Partick Diel at the Cologne Physical Education College.

Just recently, the Sportausschuss des Deutschen Bundestags invited to a public technical discussion on the topic of gene doping. The text says among others “It seems that molecular biotechnology and the knowledge about the function of genes and cells lead to new substances and methods contributing to the genesis of a new “quality” of doping. … To the possibility of manipulating genes for physical increase of performance adds the problem to prove gene doping … Although currently it is difficult to make a statement regarding how much it is spread or used,…”

Dr. rer. nat. habil. Patrick Diel, Adj. Professor and researcher at the Deutschen Sporthochschule in Cologne/Germany, department of molecular and cellular sports medicine and member of the center for preventive doping research, was among the invited experts. He and his colleagues were assigned for the issue of an expert report concerning this group of themes by the committee. DocCheck spoke with him about facts and risks of gene doping.

DC: The questions whether there is gene doping in sports or not is being taken up by media rather diffusely and – as you say – with non-scientific interpretations. What are we supposed to believe? Is gene doping reality or not?

Diel: I am one of those convinced that gene doping is being practiced already. But we do have to agree on how to define the term gene doping since this is essential for the question.

DC: Does that mean that already at the Olympic Games in Peking athletes will participate who made themselves genetically fit?
Diel: I consider it not unlikely that within the frame of my definition there will be cases of genetic manipulation.

DC: And how do you define gene doping?

Diel: We are looking at two different thesis here: One sets gene doping equivalent to gene therapy, the other says that first of all it is much more and secondly something completely different. The latter is also my opinion. The definition of the World Anti-Doping Agency (WADA) is the one relevant for me. It says: Gene doping is the non-therapeutic application of cells, genes, genetic elements or the modulation of gene expression, capable of improving the sportive performance. The first aspect includes that additional artificial genes are brought into the body. And the second aspect includes that methods, drugs or strategies are developed in order to influence the activities of body-owned genes. On the other hand, gene therapy targets to substitute genes respectively neutralize surplus or faulty genes.

DC: The sports committee notes that up to now there is a lack of methods to detect gene doping.

Diel: That’s right. We cannot prove it yet. That is and will remain a difficult topic because we are facing a vast number of possibilities of how to practice it methodically.

DC: Such as?

Diel: For example there are viruses used classically in gene therapy. Or Si-RNA-methods which are very important for medical basic research, especially for pharmacological use as well. Or anti-sense-RNA basic approaches. Just now an article was published in the magazine Gene Therapy (GeneTherapy (2008) 15, 155-160). Peking scientists describe how they were able to stop myostatin-expressions in skeletal muscles of mice by applying anti-sense-RNA which resulted in muscle growth. All this is commented strictly scientifically. The most disquieting about this is that they administered by injection and via the food. Both worked out. Transferred to humans, this would mean that athletes could be doped without knowing it. Despite all the risks involved.

DC: What do we know about health risks or side effects of gene doping?

Diel: The risks are not any smaller or higher that in any type of doping. Referring to genetic manipulations there is a wide-spread misunderstanding existing among expert report-colleagues from the field of gene therapy. You know like ‘nobody will take such a vector he doesn’t have the foggiest idea about. After all it’s perilous. Nobody would be so stupid to risk his health.’ But that is exactly what athletes have been doing for decades and they will continue doing it whether there is a “gene” in front if it or not. That’s why gene doping is no new dimension for me. It is not any worse that other known methods. It’s just simply a new technical version adding to the other procedures.

DC: And it what state is the research of this new technical version currently?

Diel: There are clinical studies in this field, for example for pharmacological products. But those studies normally do not target on doping. In general we have to distinguish between two scenarios. On one hand new drugs and strategies are developed which could be abused as doping drugs. On the other hand there are certain groups developing strategies targeted on doping. Regarding the latter we do not know exactly whether it is actually happening or not.

DC: And if – could it happen in the laboratory?

Diel: Of course! And with the most simple tools. Theoretically each and every of my doctorands could make it real within a couple of days. He just needs a short molecular biological training. And the reasoning regarding safety regulations readily quoted by gene therapists won’t do it either. Those people targeting on gene doping are not interested in regulations.

DC: Some claim that single genes applicable for increase of performance are already known. Is that right?

Diel: That is one of the things we discussed during the drawing up of the expert report for the Bundestag committee as well. One of us, Dr. Wohlfahrt of the Technischen Universität in Munich is an expert for genes concerning performance. Together with Claude Bouchard he publishes an up-dated list once a year informing particularly on those genes. Even those two say that genes responsible for performance in its actual meaning cannot be identified conclusively. But this is not what it’s all about.

DC: If it’s not the genes, what else is it?

Diel: It’s solely about creating physiological framework conditions enabling outstanding performances. Here the gene does not interest but which parameters have the largest influence on the performance. If for example we are talking about endurance, then the supply with nutrients and the availability of oxygen are determining. The latter can be improved with Epo. Although detection of Epo is theoretically possible, it de facto shows to be rather unreliable in practice. In regard to muscle mass we know myostatin with an abundance of possibilities to influence this gene. And the article in Gene Therapy I mentioned before describes that the mice gained both, muscle mass and muscle power. So the question is just how this is working with humans. No studies are available on that yet.

DC: And what about the studies in gene therapy?

Diel: Now we are back on gene therapy. That really makes me angry. People reason that gene therapy is just not at that point yet. But again: Gene therapy and gene doping have only very, very little to do with each other – both, methodically and also concerning the aim.

DC: Currently people are still groping around in the dark regarding what the reality in gene doping is. How long do you think this will continue?

Diel: As a matter of fact, gene doping is possible today. The question is to what extent it is practiced.

DC: Do you do here – at the Institute for molecular and cellular sports medicine – in particular research in the field of gene doping?

Diel: First and foremost we are interested in physiological coherencies and the activities of the corresponding genes such as for example myostatin. This we do within the framework of basic research. In addition we do projects in cooperation with pharmaceutical companies. For instance how do the female sex hormones influence the skeletal musculature. As regards to gene doping, we have a research project together with the biotech company Chimera in Dortmund/Germany, which is sponsored by WADA and has the target to detect gene manipulations regarding myostatin.

DC: Thank you very much for this interview!

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