Risks & effects of doping

The list of doping products contains not only prohibited substances but also prohibited methods. The manipulation of blood and blood components as well as the supply of synthetic blood products (eg perfluorocarbon emulsions), are among these prohibited methods which improve the body's oxygen supply.

The improvement of endurance capacity by the supply of allogenic blood was first described in 1947. This method aimed to improve the performance of athletes exposed to oxygen depletion at high altitude. This process entered the sport in the 1980s and has been officially banned since 1985.

EPO VERSUS BLOOD DOPING

In the 1990s, blood doping was eclipsed by erythropoietin (EPO) doping. EPO doping produces comparable results, but it is less complicated and poses fewer health risks. Since 2000, since synthetic EPO can be detected in urine, blood doping has experienced a marked resurgence of interest. While it is easy to prove the use of blood doping based on allogeneic blood (blood from a third party), there is still no direct method for detecting blood autotransfusions. This is why in endurance sports at risk one establishes more and more long-term blood profiles (biological passport of the athlete) which can give information in the event of manipulation of the blood.

EFFECTS OF BLOOD DOPING

Blood doping is the taking of blood from the athlete a few weeks before the competition. Red blood cells (erythrocytes) are isolated from the blood collected and stored under refrigerated conditions. The body responds to this blood loss by the accelerated formation of new erythrocytes. Shortly before or during the competition, the red blood cells collected and stored are reinjected (transfused) again. Thus, the number of oxygen-carrying red blood cells is increased, thus improving the oxygenation of the muscles and therefore endurance performance.

When blood doping with allogeneic blood, a concentrate of red blood cells (erythrocyte concentrate) from a donor is infused, as is the case with blood transfusion in anemic patients. Instead of conventional blood transfusions, synthetic products can also be used. These molecules cause an increase in the uptake, transport or release of oxygen in the body, depending on the type of molecule.

SPORTING DISCIPLINES CONCERNED

Blood doping improves endurance capacity and therefore finds its field of application in classic endurance sports (eg cycling, cross-country skiing, etc.)

Direct detection of doping based on allogeneic blood

The direct detection of doping based on allogeneic blood is now easy.

Indirect detection of doping based on autologous blood

Since there is as yet no direct detection method for doping based on autologous blood, most cases of autotransfusion are discovered during police investigations or confessions by athletes. In addition, in high-risk sports disciplines, long-term blood profiles (athlete's biological passport) are increasingly established which can provide information in the event of blood manipulation.

ADVERSE REACTIONS AND CONSEQUENCES OF BLOOD DOPING

Too high a hematocrit level is a real danger. Blood doping and the administration of synthetic EPO increase the number of red blood cells and therefore the hematocrit level. Such an increase in the hematocrit, whether abnormal or natural, by dehydration (lack of water), for example, reaching a value of 60% or more, represents a serious danger to health.

Indeed, this increase in the number of circulating red blood cells leads to a significant decrease in the fluidity of the blood, leading in particular to an increase in the risk of thrombosis (formation of blood clots) and embolism (obstruction of a vessel by a blood clot). blood) with the risk of fatal outcome.

Inappropriate handling of canned blood

There are several documented cases of athletes who have exposed themselves to serious risks to their health as a result of improper handling during the collection, storage, transport or transfusion of doped blood which can lead to potentially fatal sepsis. Other complications can arise from doping with allogeneic blood. Pathogens such as hepatitis or AIDS viruses can be transmitted during blood transfusion. This can also trigger a reaction of incompatibility with allogenic blood, resulting in anaphylactic shock (allergic), or even a fatal state of shock.

Physical and chemical manipulation is the act of using substances or methods to modify a urine sample.

Adverse effects and consequences of blood doping

Physical and chemical manipulation is the last category of doping in terms of frequency of use and represents only a very small percentage of positive results worldwide (<0,1%). Physical manipulation is generally preferred over chemical manipulation.

Doping tests attempt to screen for masking agents and analyze a variety of physical and chemical properties of urine to detect any signs of manipulation of the sample.

MODE OF ACTION

Chemical and physical manipulation is the use of substances and processes which modify, attempt to modify or reasonably threaten to modify the integrity and validity of Samples used in doping controls. These substances and methods include, among others, catheterization, substitution or alteration of samples, but also intravenous infusions and / or injections of more than 50 ml per period of 6 hours (with the exception of those legitimately received in the during hospital admission or during clinical examinations).

SIDE EFFECTS

The side effects of physical and chemical manipulation of the urine sample are limited and depend on the type of manipulation. Many of the methods used to handle urine samples have harmful side effects.

For example:

Catheterization can lead to cystitis caused by infection of the bladder and inflammation of the lower urinary tract.

Urine replacement can also lead to various infections.

The difference between genetic doping and classical doping methods lies in the fact that the body's supply of doping substances (eg: anabolics, hormones or blood) is replaced by the supply of genetic material. In the context of genetic doping, the World Anti-Doping Agency (WADA) prohibits, because of their potentially doping effect, the following practices:

The transfer of nucleic acids or their analogues.

The use of genetically modified cells or not.

It is a genetic material capable of directly influencing muscle growth, fat catabolism or the production of corresponding hormones in the body. Thus, genetic doping could, in the future, supplement or even render superfluous conventional doping methods, since it turns the body into its own doping factory. But this is precisely the origin of the enormous danger generated by gene doping, because once started the processes are irreversible.

ROLE OF GENOA IN SPORT

Each human being carries genes that determine his ability to exercise a particular activity. Thus, in sport, some are, from an early age, faster than others, stronger, taller or more skillful in terms of psychomotor coordination. It's all in the genes. Nevertheless, the final formation of an individual's genotype (character, preferences, physical characteristics, etc.) is also determined by the influence of his environment.

Science is gaining ground

Science continues to discover new genes important for physical performance (e.g. genes determining the structure of muscle fibers, synthesizing growth factors or hormones such as the hormone responsible for blood formation (Epo), regulating blood energy balance of the organism,…).

WHAT IS A GENE?

A gene is a unit of information for a specific characteristic of the body. Hereditary information houses, so to speak, the "architectural plan" of a living being. It is memorized chemically and is present in the nucleus of every cell.

Deoxyribonucleic acid - DNA

The building block of genes is called “deoxyribonucleic acid” (DNA). DNA is a very long, threadlike molecule. To prevent it from tangling during cell division, it wraps around its own axis and forms what are called chromosomes.

The chromosomes are visible under a microscope. The human being has 46, of which 23 come from the father and 23 from the mother. The structure of DNA resembles a rope ladder with two strands of filaments linked together by rungs, twisted like a spiral staircase. The rungs of this ladder are made up of four molecules called: Adenine, Thymine, Guanine and Cytosine. They are generally designated by their abbreviations: A, T, G and C. Associated two by two, they form a base pair which then represents a rung of the rope ladder. All the genetic information of a living being is thus encoded in the almost infinite succession of these four letters: this is called the genome. Human beings have about 10 billion such base pairs. We could say that the genome is the book of life written only using four letters but, on the other hand, having 10 billion characters.

The information in the genome must be transformed into a genetic product capable of performing a function in the body. This transformation of genetic information, allowing it to be used by the cell, is called gene expression. The two major steps in gene expression are the transcription of DNA into ribonucleic acid (RNA) and then the translation of RNA into proteins. The latter process takes place in the cytoplasm and involves synthesizing proteins based on the genetic information copied into messenger RNA (mRNA) molecules.

Proteins take on very diverse functions in the body, they represent real molecular machines. They transport the intermediate products of human metabolism, they ensure the "pumping" of ions, play a role of catalyst of chemical reactions, can pick up signals or act as hormones.

GENETIC DOPING BY DIVERSION OF GENE THERAPY

The aim of medical research is not to develop genetic methods for the purpose of gene doping in sport, but to use them to cure hereditary diseases with the help of gene therapy. Indeed, many diseases are of genetic origin (eg immunodeficiency, muscular dystrophy….). The idea of ​​gene therapy is to cure such diseases at the genetic level by replacing faulty or missing genes with healthy copies of those genes.

GENETIC DOPING BY GENE TRANSFER

Basically, gene doping can be done by two different methods:

- By the transfer of genes in the athlete's body

- By influencing their own genes.

Genetic doping by gene transfer

It is not as easy to fill a syringe with genes as it is with anabolics or EPO. The transfer of genes from one person to another can only be done using a vector. Genetically modified viruses are used for this purpose, which can be injected into the athlete directly through the blood. Another method is to take cells eg. of the athlete's bone marrow, containing the hematopoietic system, and to bring them into contact with viruses outside the body, before reintroducing them into the athlete's body.

Viruses as carriers of "sports genes"

Viruses are not considered to be living beings: they are formed only of an envelope which contains a certain amount of hereditary substance. Viruses are incapable of reproducing on their own, but they are very clever: with the help of special detection systems, they are able to find their target in an infected organism, for example blood or muscle cells. This is where they pass their own hereditary substance inside the target cell. Then, the hereditary substance of the virus reprograms the target cell. From this moment, this cell obeys the commands of the virus. So, if genetically modified viruses transfer “sport genes” instead of diseased genes, they do not weaken their prey, but give it strength, endurance or speed.

DOPING BY THE INFLUENCE OF ENDOGENOUS GENES

Genetic expression can also be influenced from the outside. That is, endogenous genes can be turned on or off, or their effect can be enhanced or inhibited.

This is possible in two ways:

- using small genetic elements;

- by the influence of certain drugs.

These two methods have the common feature - unlike gene transfer - of not placing exogenous genes in the genetic heritage (genome) of the individual.

Doping by genetic influence:

Instead of modifying gene expression, it is possible to render mRNA inoperative by integrating tiny RNA elements synthesized by genetic engineering (siRNAs or small interfering RNAs) and perfectly adapted to the desired gene. Such an element clings to mRNA before it is translated. The body perceives the artificial and natural RNA product as a foreign body and destroys it. This is how the interruption of the translation of a gene into its product works, a method known in scientific circles as “RNA interference”. All over the world, efforts are currently being made to develop, in this way, treatments for a wide variety of diseases: for example viral infections such as AIDS, hepatitis or even cancer.

Drug-induced doping

Until 2011, all substances directly or indirectly modifying gene expression were considered as means of gene doping. In the current prohibited list, such substances have the more correct name of metabolism modulators and are assigned to the class of substances “S4 Hormonal and metabolic modulators”.

RISKS OF GENETIC DOPING

Genetic doping presents multiple risks.

Risks during production, when a gene therapy method, still in development, is produced in a “clandestine laboratory” and illegally applied for doping purposes.

Gene vectors

For gene therapy, genes are carried by viruses. Although these viruses are previously modified so that they are no longer infectious, viruses in general, even in the neutralized state, still present a certain residual risk as a pathogen.

The environment

The risk is much higher in the illegal production of substances used for gene transfer than in the development of medical gene therapy. It is in fact possible to envisage the use of only partially neutralized viruses, of contaminated preparations or of infected instruments.

Risks during transfer

Even properly inactivated viruses remain foreign bodies in the patient's body that must be fought off by the immune system. The consequences generated by the activation of the immune system in the face of these proteins produced by injected genes are much more serious, which can cause allergic reactions up to a fatal allergic shock.

Genetic risk

When a gene is administered to a patient as part of gene therapy, it is not possible to determine exactly where the gene will fit into the genome. This could have fatal consequences. It is indeed possible that neighboring genetic sequences cause an undesirable or unpredictable reaction with the new introduced gene. All the possible effects of gene therapy are far from known.

POSSIBLE SIDE EFFECTS OF GENETIC DOPING

According to the current level of knowledge, modifications of genetic material by gene doping cannot be completely undone. While in conventional doping many side effects diminish after stopping doping, the effect of gene doping and its side effects is long lasting.

It is not yet possible today to be certain about the feared side effects of gene doping - we can only imagine scenarios like the following: a growth factor such as IGF-1 promotes the growth of genes. muscle cells, but could also stimulate the development of tumor cells. As a result, an isolated altered cell which, under normal circumstances, would be eliminated by the control mechanisms of our body, would quickly become a tumor.

GENETIC DOPING DETECTION

The detection of genetic doping is particularly difficult because the product of the injected gene does not differ from that of the endogenous gene (therefore created by the organism). It would be easier to directly prove the presence of genes injected into a tissue sample. This would require removing a small piece of muscle from the athlete and testing it for the possible presence of exogenous DNA. However, taking tissue samples is a significant invasive procedure for the athlete and is not provided for in the World Anti-Doping Code. Therefore, the method of detecting gene doping by tissue sampling is excluded as a standard method.

However, the first methods have been developed or are still in the development phase in order to detect genetic doping.

It is true that the products made by the artificially introduced genes and the natural genes are indistinguishable, but the genes themselves are not completely identical. DNA produced by genetic engineering is always shorter than its natural model. This is because natural DNA always contains sequences that do not serve directly for encoding the gene product, thus allowing investigators to distinguish natural DNA from artificial DNA. Here is a technique that works well and the first experimental doping tests have already been carried out.

The doping genes becoming active in the body, cause changes in the metabolism of the tissues. This altered activity could be proven using imaging techniques.

A similar method is to look for gene activity in unusual tissues. The sudden production of EPO in the muscle cells instead of the kidneys of an athlete would be highly suspect. It is very likely that one can assume that an EPO gene implantation has taken place at this location.

We could also look for the constituent elements of the vector genome. A few tiny components of the virus's envelope are preserved upon entry into the host cell - and these components are detectable.