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Gene doping

The Prohibited List defines gene doping as follows:

The following, with the potential to enhance sport performance, are prohibited:

1. The transfer of nucleic acids or nucleic acid sequences;
2. The use of normal or genetically modified cells.

In narrow molecular biological terms, gene doping is referred to as the introduction of DNA or RNA molecules to the human body for the purpose of permanently enhancing performance. No research findings or observations for humans exist yet, and the risk for athletes cannot be estimated. Nonetheless, initial indications of experiments with an EPO gene construction exist.

Is it possible to test for gene doping?

Anti-doping organizations all over the world originally feared that gene doping could not be detected using traditional urine and blood sampling. Yet, the technique leaves behind traces that can be identified. The most recent research has additionally demonstrated that methods do indeed exist for detecting an illegal enhancement of performance using genetic material. Various researchers and institutions are currently active under a mandate from WADA to develop a gene doping detection method.

Why is it so difficult to detect gene doping?

The crux of the problem is that there is no difference between the product of an artificially introduced gene and one produced naturally in the athlete's own body. Detecting doping with hormones, for instance with EPO, is possible because the molecular structure of natural, endogenous EPO differs from that of exogenous EPO (originating outside the body). The differences, while very minor, can be detected in the laboratory using modern analysis techniques. This is not possible with gene doping, because the athlete engaged in doping produces the doping substance in his or her own body.

What might a gene doping test be based on?

Researchers rely on three clues for unmasking gene doping violations:

1. Identification of gene sequences characteristic of a gene transfer
2. Direct detection of the introduced gene sequence
   
3. Identification of changes in the activities of other genes influenced by gene doping

1. Detection of characteristic gene sequences - transgenic DNA

While the products of artificially introduced and natural genes cannot be distinguished from each other, the genes themselves are not quite identical. The differences may be the key to a gene doping test. Artificially introduced or transgenic DNA lacks certain sequences present in almost every gene in the human body, the so-called introns. These are sequences within the genetic material that contain control information instead of information defining the later gene product. In the body, introns are removed or "spliced out" of the gene after transcription. These segments, which are "superfluous" in terms of actual gene information, are not built into artificial DNA in the first place. This is the opportunity that investigators have been looking for. They need to search for such introns in order to distinguish natural from artificial DNA.

2. Direct detection of the introduced gene sequence

The simplest method would be to perform a biopsy of suspicious tissue in order to identify the introduced gene sequence directly. In this case, a tissue sample would be taken from the athlete's muscle for instance, and subsequently tested for the presence of foreign DNA. Yet, for the athlete this would represent a fairly major operation, one for which no provision is made in regulations. For this reason, a biopsy is not feasible as a standard method for detecting gene doping.

3. Detection of altered gene activity

Genes introduced to the body through gene doping become active and cause uncharacteristic changes, in tissue metabolism for instance. These changes can serve as an indication of gene doping and thus help to unmask anti-doping rule violations. Imaging techniques such as magnetic resonance imaging (MRI) are one possible method for detecting altered metabolism processes. The MR image would even indicate the position within the body where uncharacteristic gene activity was occurring. This technique is highly complicated, however.

WADA supports research to detect gene doping

Some examples:

• Theodore Friedmann at the University of California is studying various types of cells to determine the changes in gene activity that are triggered when the growth factor IGF-1 is used in doping.
• Günter Gmeiner at Austria's ARC Seibersdorf Research is involved in research to determine whether doping with an artificial growth hormone causes altered gene activity in white blood cells.
• Geoffrey Goldspink at University College London is investigating possible changes in the IGF-1 content of muscle tissue in response to doping with the growth hormone HGH.
• Jane Roberts of HFL Laboratory Inc. in the UK is seeking to utilize the fact that the activity of various genes in a variety of cells is altered after gene doping. It might thus be possible to identify gene doping violations by looking for altered gene activity in the cells of a blood sample or from an oral smear.
• Perikles Simon at the Department of Sports Medicine of the University Hospital in Tuebingen, Germany, presented a technique in 2006 that allows the identification of even very small traces of transgenic DNA in the blood on the basis of missing introns. Yet, the very low concentration of transgenic DNA poses a major challenge. The technique continues to be improved and refined.
• Jordi Segura of the Pharmacology Research Unit in Barcelona is investigating unusual gene activity in unusual tissues. One example is the production of the hormone EPO in muscle cells.