In the run-up to the 2008 Olympics, scientists use live mice for the first time on the 'roof of the world' to develop new tests for gene doping
A team of researchers from the University of Pennsylvania is attempting to climb Mount Everest, taking with them for the first time live mice to the 'roof of the world'.
The effort is being supported by the World Anti-Doping Agency (Wada) and the molecular diagnostics company Qiagen.
The purpose of the researcher's historic climb is to investigate tissue and blood samples from the mice to create a molecular signature for altitude-induced hypoxia.
The scientists' ultimate goal is the development of novel testing methods for gene doping by comparing such natural molecular signatures with induced signatures that would be created by gene doping.
Such practices have been listed on Wada's index of banned substances since 2003, but the identification of athletes using gene doping is still not possible.
Accordingly, experts consider gene doping to be one of the most urgent problems in sports today.
The scientific team headed by Prof Tejvir Khurana and Gabriel Willmann is specifically looking to find those genes that are active in a low-oxygen environment and thus enable the organism to adapt to the altered environmental conditions.
In general, hypoxia has a positive influence on the body's performance as it stimulates the creation of erythropoietin (EPO), a naturally occurring hormone that promotes the production of red blood cells.
When applied artificially, EPO can be easily discovered.
However, if gene activity is manipulated in a way that the body produces more 'natural' EPO and therefore more red blood cells without being exposed to a low oxygen environment, existing doping-detection methods prove ineffective - at least so far.
Now, the University of Pennsylvania scientists intend to solve this problem by developing markers for a test that can discriminate between naturally induced activations and activations induced through gene doping.
"We are very excited that the attack on the summit is now beginning.
"From a research point of view, a major challenge of this endeavor will be the extraction of samples from the mice under these extreme conditions," said Gabriel Willmann, one of the initiators of the research project.
"The cooperation with Qiagen, as the world's leading provider of sample and molecular testing technologies, will help us enormously to successfully collect, process and analyse the samples.
"Therefore, we are confident that first results will be ready for presentation shortly after our return".
According to Peer Schatz, chief executive officer of Qiagen, this expedition shows how molecular biology is increasingly helping to find solutions for critical issues in many areas of our daily lives: "We are very pleased to partner with the team from the University of Pennsylvania in this exciting project, in which our sample and assay technologies will be used for the development of testing methods in the harshest of conditions.
"We are also proud to be contributing to the team's so important goal of making anti-doping controls more effective".
In addition to new testing methods for the identification of doping offenders, the scientists also hope to generate new data that may lead to a better treatment of muscular dystrophy.
The incidence of this genetic disease is comparatively low, yet it is also incurable and leads to a significant loss of expectation of life.
As the disease also affects respiratory muscles, patients in an advanced stadium experience a level of hypoxia comparable to the effects of exposure to extreme altitudes.
Background tp gene doping.
Gene doping as defined by the Wada encompasses the non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to enhance athletic performance.
An example for such doping approaches is a method to increase the organism's own production of EPO using an active agent called HIF-stabilisers.
Usually, a protein called hypoxia-induced factor (HIF) ensures the sufficient supply of oxygen to cells as it stimulates the production of EPO in low oxygen environments.
When the oxygen concentration rises, both the production of HIF and of EPO decreases.
This process is driven by an enzyme called HIF-PH, which reduces HIF.
So called HIF-stabilisers can be used to stop the enzyme from functioning, resulting in a slower reduction of HIF and thus higher EPO levels.
New products for the treatment of anemia currently under development tackle exactly this mechanism using HIF-stabilisers.
