Introduction Goals Methodology Programs Results Conclusions References Authors Acknowledgements

INTRODUCTION


DOPING

Doping has covered newspaper's front pages, always relation to sport. One of the main doping problems in sport is the danger that it could become a sad media-press spectacle: the abuse of narcotics and stimulants by athletes (normally famous) has obvious consequences far away from the illegality of consuming prohibited substances in sport competitions. In one hand, creates a bad example of success to the young people and, in the other hand, the impact for the athletes sponsor's image.

The meaning of doping hasn't a clear root, but the more mentioned versions localize its origin in Southern Africa, where "dope" was a alcoholic drink used as a stimulant in ceremonious dances. Its origin also is attributed to a flamenco root's word that means blend (doop). Doping is as well relation to the English word dope, referred to grease used as a lubricant. Finally, is also relation to DOPA amino acid and dopamine. In spite of its etymological meaning is not clear, the general concept of doping is more widely than the illegal substance list. According to International Olympic Committee (IOC), dope or "taking drugs" is the use of a substance or method, which is potentially danger for athletes health and improvable of his performance, or the presence in the athletes organism of a substance, or the ascertainment of a method, that figures in the annex list of Olympic Movement Antidoping Code (Word Conference about Sport Doping, Lausanne's Declaration, 1999). (For further details, click here.)

         History
Doping and the intention of getting through the physiologic limitations with health risks exist since the first populations.

Nordic mythology explains that Vikings increased their combative strength eating fungus. The jumpers and runners, participants in classic Greek Olympic Games, used plant extract infusions and spleen extirpation to enhance their performance. American originated populations took coffee or cacao as energetic food.

Caffeine was used since 1805 in swimming, athletics and cycling, sport in which it was registered the first mortal case for doping: the cyclist Linton dead in 1866 during the race Paris - Burdeos. During this and next century, athletes achieved an important social position and sport turn to, a part from a big business, a significant social institution: sport success started to being highly appreciated, with the consequence pressure to athletes for being the best.

During the Second World War the knowledge of doping substances increases. Finishing the war, the athletes used different methods of doping, which resulted in hormonal doping with anabolic steroids that were introduced in sport's world in 1960.

Suddenly increase highly the number of documented cases and, in the sixties, federations and associations began to regulate antidoping controls, due to in Helsinki 1952 and Melbourne 1956 Olympic Games existed informs about the use of drugs by athletes.

One of the first international antidoping affairs was the publication in 1960 of the European Council's resolution against the use of doping substances in sport. Only after Tommy Simpson cyclist's death, that we could saw an important change in elite sport protagonists: in the same year, International Olympic Committee (IOC) created Medical Commission, and in the Grenoble 1968 Winter Olympic Games officially started the antidoping samples gathering.

In the next years, happened the famouse case of Ben Johnson, who lost the hundred meters gold medal in Seul 1988, and others cases such as Maradona in EEUU 1984 Football World cup and erythropoietin appearance in France Tour 1998. All this caused the creation of the World Anti-doping Agency (WADA, during the Word Conference about drugs in sport, organized by IOC in Lausanne (Switzerland). WADA is an international and independent organism, which promotes and coordinates the fight against doping in sport. One of its goals is accredit antidoping laboratories over the world to analyze antidoping samples, and in one of these we can find Barcelona Antidoping control laboratory.

         Drugs categories
Classification of the different types of drugs and methods used in the practice sport:

  • Leisure / Free time
    All the substances that can alter the perception (illicit drugs or the abuse of medical prescription drugs).
  • Therapeutics
    Substances used by medical indications.
  • To improve the performance
    The use of drugs (like amphetamines) or methods (like blood transfusions) in order to get athletic advantages: an increase of the energy use, including its production, control and efficiency, in a way that increase the performance and the chances to win a competition.
    Inside this category, WADA classifies drugs and methods of doping in two groups:
    • In particular sports
      • Alcohol
      • ß blockers
    • Prohibited in competition
      • Substances
        • Stimulants
        • Narcotics
        • Cannabinoids
        • Glucocorticosteroids
    • At all times (in- and out- of competition)
      • Substances
        • Anabolic agents
        • Hormones and related substances
        • ß 2-agonists
        • Agents with anti-estrogenic activity
        • Diuretics and other masking agents
      • Methods
        • Enhancement of oxygen transfer
        • Chemical, physical and pharmacological manipulation
        • Gene doping: The non-therapeutic use of cells, genes and genetic elements or the modulation of gene expression, having the capacity to enhance athletic performance.

GENE DOPING

There may come a day, in the not too distant future, when diseases such as Parkinson, cystic fibrosis or some cancers, and others that have plagued mankind become a distant memory, thanks to research into genetics. Once this has become a real fact in regular medicine, they may be very useful to treat injuries and acceptable for the sport world as well.

Gene therapy - the ability to manipulate the human genome to prevent or cure diseases - is still a highly experimental procedure performed by very few research and clinical centers. However, the potential to abuse such therapies to enhance sport performance in otherwise perfectly healthy individuals can be considered a threat. Unfortunately, advancements in this field of science also may someday be used by athletes. For some, the lure of becoming better, stronger and faster than their competitors through tinkering with their genes may be too strong a temptation to resist.

The elucidation of the complete human genome with approximately 25.000 different genes leads to new possibilities for diagnosis and prevention of a wide variety of genetic diseases. In addition, this knowledge may be used for the design of new therapeutics, including gene therapy, based on the DNA sequence information. The principle of gene therapy is based on the delivery to a cell, of a therapeutic gene which may compensate an absent or abnormal gene. The genetic material (DNA) is mostly encapsulated and is introduced into the body by direct injection into the target organ. The most relevant genes are Erythropoetin (EPO), Growth factors, Myostatin and Endorphins.

Gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance sport performance". While it is doubtful that gene doping is already a reality, WADA and its partners in the fight against doping have already made it a top research priority. The International Olympic Committee has included the method of gene doping in their list of prohibited classes of substances and prohibited methods (to see the completed list click here). This organism has created a international research group in order to detect when and where it can appear this new kind of doping, what can do for preventing its use and, finally, to detect it when exists. At this moment, WADA has celebrated two symposiums about the theme: in New York, in March 2002, and in Stockholm, at 4th and 5th in December 2005.

The threat of gene doping is very real. We need to start fighting this threat now, before it becomes a reality. It is easier to prevent a problem than it is to solve it!

         Risks
The risks involved in gene doping are several, and are related to the vector used (DNA, chemical, viral) and related to the encoded transgene. So far, gene therapy has been relatively safe; thousands of patients have been treated in well controlled clinical gene therapy trials with pharmaceutical grade gene therapy vectors and have shown few side effects. With gene doping, gene transfer vectors may be produced in non-controlled laboratories.

DNA can be easily and cheaply produced with materials available from legally. These preparations may be contaminated with chemicals and other impurities from the production. In the case of virulent viruses, these are not only harmful to the athlete, but also pose a health risk for the general population who might get infected.

Health risks resulting from expressed genes are similar to those of other doping forms. However, the level and duration of protein production is less controllable when compared to conventional protein administration. For example EPO delivered by gene therapy could result in sustained high EPO levels which would increase the chances of stroke and heart attack.

         Detection
Detection of gene doping is very difficult. Gene therapy vectors may be measurable only shortly after administration and in many cases would require tissue sampling. Taking muscle biopsies from athletes is no option, thus eliminating this form of detection. In addition, many forms of genetic doping do not require the direct injection of genes in the desired target organ. Finding the site of injection will be like looking for a needle in a hay stack.

The protein resulting from gene transfer is not different from the endogenously produced protein and as such detection of the protein itself is no indication for doping. It will therefore only be possible to monitor the use of gene doping by repeated physiological protein profiling of athletes, allowing changes in protein levels to be perceived. These assays, which require the simultaneous measurement of many (possibly up to one thousand) different proteins and establishing ranges of normal values need to be developed.

Another unique idea being looked at is imaging, where a process similar to magnetic resonance imaging would be used to scan the body and search for unusual locations of gene expression.

For this purpose, imaging will be used to detect the RNA being formed in unusual tissues after the gene transfer process. This approach is applicable to any gene transfected to tissues not usually expressing the "doping" protein, such as muscle for EPO. Imaging of mRNA will be carried out by the use of antisense peptide nucleic acids oligonucleotide probes labelled for tomographic detection.