The night Barry Bonds drove number 756 sailing over the right center wall at AT&T Park, I watched one sports commentator who speculated that it might be the event that brings to a close the steroid era in baseball. The Giants' slugger, the subject of allegations that he used performance-enhancing drugs, has denied knowingly using steroids.

 

The commentator was referring to what he viewed as greater vigilance on the part of Major League Baseball to put an end to the use of performance-enhancing drugs. But there may be another reason that steroids soon become a quaint reminder of a bygone era of sport when towel-clad ballplayers stuck hypodermic needles filled with bull testosterone into their each other's assess.

 

Thanks to scientific advances, athletes may instead be injecting themselves with new genes. At least that seems to be the concern at the World Anti-Doping Agency or WADA, the independent foundation formed through an initiative led by the International Olympic Committee to fight doping in sports. With ongoing scandals at the Tour de France and the 2008 Olympics on the horizon, the Agency is now developing means for detecting which athletes may have inserted genes into their bodies to produce performance-enhancing substances that might fly below the radar of the doping police.

 

An Emerging Technology
In 2003, WADA officially banned gene doping. Athletes started showing an interest in the practice the following year with the publication of research from scientists at the University of Pennsylvania that reported muscle-boosting gene therapies in mice. But the practice entered the public mind in 2006 when, as part of a trial of a running coach in Germany accused of providing performance-enhancing drugs, emails in which he discussed ordering Repoxygen became public.

 

Repoxygen is an experimental therapy that delivers into patients the gene that encodes for erythropoietin, a hormone that stimulates the production of red blood cells. It is used to treat anemia, but elite athletes have used erythropoietin to enhance their endurance. Several other genes, including the one that encodes for the production of insulin-like growth factor, which helps increase muscle mass, are also seen as likely targets of gene doping.

 

"WADA has been aware for the potential for some years of using the techniques that have been developing so rapidly in gene therapy and applying those same methods to sport—not to cure anything, but to modify traits that are changeable," said Theodore Friedmann, head of the agency's panel on genetic doping and director of the gene therapy program at the University of California at San Diego. "It certainly is not in the same league yet as traditional drug doping, but I think that everybody understands that the techniques are moving quickly and could be applied eventually in sport."

 

One Step Ahead
Friedmann said he's not aware of any serious case where there was a likelihood of gene doping having taken place. Nevertheless, WADA is trying to stay ahead of athletes looking for an edge at any cost by developing detection methods now, before use of gene doping becomes a problem.

 

To do that, Friedmann said traditional assays used today to detect elevated levels of banned substances or their byproducts will still be needed, but WADA will also need to develop new molecular tools. Already, the agency has assembled researchers at about a dozen labs throughout the world to come up with such tools. These researchers are trying to determine how to detect the presence of foreign genes, find the effects of them, determine if they are switched on or off, and find where they have been put into the body. Added to that challenge is the need to be able to do all of this by testing easily obtained biological samples such as blood, urine, and saliva.

 

"You can't go around requiring muscle biopsies and so on to see if a gene has been put into a muscle, so there's a requirement to develop new kinds of tests that will find footprints of exposure to gene X or gene Y in tissues that are accessible and standard kinds of materials for doping testing," said Friedmann. "There are limits, of course, on what tissue you can look at in an athlete."

 

One of the researchers working with WADA is Richard Snyder, an assistant professor of microbiology and molecular genetics at the University of Florida in Gainsville and director of its Center of Excellence for Regenerative Health Biotechnology, who for 16 years has worked to track the distribution and activity of genes injected into a subject. He's now taking these techniques and modifying them to minimally invasive methods that can reliably detect illicit use of the technology. He expects to have preliminary results this year on his work and said he will continue to work on increasing the sensitivity of the tests and broaden the number of genes WADA will be able to detect.

 

Accessible Technology
Snyder describes WADA's efforts as "preemptive." Therapeutic efforts at the clinical stage are still dogged by safety concerns. Last month 36-year-old Jolee Mohr died during a trial of a gene therapy by Seattle-based Targeted Genetics to treat arthritis, although it is not yet known whether the gene therapy caused her death. But WADA's concerns also point to how available and easy to use the tools for gene transfer have become.

 

Despite hurdles therapeutic efforts face, Snyder said the ability to use viral vectors to transfer genes and affect therapeutic responses in animals has been well-established. And, for anywhere from $500 to $2,000, people can buy kits from a catalogue to produce viral vectors, clone genes, and purify them.

 

"If you have a small laboratory with the proper equipment, you can grow the cells, grow the virus. They actually have this simple, handheld method to purify the vector right there on your bench, and that would be enough to inject," he said. "I wouldn't do that because the purity standards don't meet clinical and medical muster, but if you are going to gamble and go down that path, you may not care that much if it's a research-grade vector or a clinical-grade vector you are making."

 

Unfortunately, it's going to take a lot more than a mere vial of Repoxygen to correct the cruel combination of my innate genome coupled with years of neglect and abuse. Bonds has nothing to fear from me.