By the Next Olympics, Athletes May Be Getting Routine Gene Doping Tests

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Overabundant skepticism about genetic manipulation in sports may be as dangerous as the hype that heralded its arrival.

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Alexis Madrigal

After Ye Shiwen shocked the Olympics with her performance in the 400 meter individual medley, swimming the last 50 meters faster than Ryan Lochte, the men's champion in the event, a long-time American coach ominously hinted that perhaps a new kind of performance enhancement had arrived on the athletic scene.

"If there is something unusual going on in terms of genetic manipulation or something else, I would suspect over eight years science will move fast enough to catch it," John Leonard, the American executive director of the World Swimming Coaches Association, said.

It's important to note that there is no evidence that Ye engaged in any doping practice, let alone something as new and high-tech as genetic manipulation.

But, the fact that genetic manipulation was even on the table or in the ether as the example Leonard gave in his accusation is remarkable. So I set out to find out how scientifically plausible it might be for Ye -- or any athlete -- to enhance his or her performance with current gene doping technology.

The context here could not get larger. Ever since humans deduced the powerful nature of DNA and all the associated molecules that do work in our cells, people have wondered: how long before we can simply change our own genes? On the one hand, all kinds of genetic diseases could be cured. On the dark side, if genetics sets the limits of human action, how long before we create genetically enhanced humans? And, like many things in bioethics, these thoughts are never very far away from the long shadow of the Nazis' eugenics program.

These fears and hopes have traveled with all kinds of work on the genome from Watson and Crick through the Asilomar Conference on Recombinant DNA to the earliest gene trials and the sequencing of the human genome. But until very recently, we had no evidence that transferring genes into human cells was helpful at all. In the early 2000s, gene therapy suffered a series of setbacks, including the high-profile death of a young patient. In the words of the Mayo Clinic, "The possibilities of gene therapy hold much promise. To date, however, that promise has not been realized."

Given that background, I was planning to write a story about how it was sort of nuts for John Leonard to talk about genetic manipulation, not because athletes wouldn't try it, but because it's unlikely to be effective.

But then I called up Richard Snyder, a University of Florida biologist who has a grant from the World Anti-Doping Agency to create reliable blood tests for gene doping. As as result, he's intimately involved in both what might be possible with current gene transfer technology -- and how we might detect any kind of illicit practice.

Snyder told me that gene doping of exactly the kind you'd expect high-level athletes to use is already effective in animals and that in the last few years, therapeutic gene therapies in humans have started to experience and sustain success, particularly in treating hemophilia and certain types of congenital blindness. And right now, there's no available test for gene doping. Put those three facts together and the idea that someone might be transferring genes into his or her body doesn't sound so outlandish.

"In the last five years, there have really been some dramatic examples of gene transfer being efficacious in humans. What we've been seeing in animals for a long time is coming to humans. We've optimized the delivery routes and the viral gene transfer vectors themselves. We understand the diseases better and know what genes we need to deliver to treat people," Snyder said. "This technology can also be usurped for illegitimate means."

He sent me over a paper his team published last year in the journal Gene Therapy, and began to walk me through how gene doping -- and his method of catching it -- could work.

How Gene Doping Works

Here is the basic idea of gene doping. First, you need a virus. Viruses work by going into the cells of your body and hijacking the machinery in there to make more of whatever they want, which in many cases is more viruses.

Second, you need to modify that virus. Scientists have been defanging viruses for a while and turning them into DNA delivery machines that they call vectors. These viruses are loaded with a "cassette" (this is actually what they call it) of DNA that the viruses then insert into cells within the mammalian body.

That DNA is the blueprint for whatever protein you are trying to make. In the case of doping, there's a protein hormone that your kidneys make called Erythropoietin, or EPO. Hormones control a lot of things in your body; in this case, EPO stimulates the production of red blood cells (erythrocytes). Because red blood cells carry oxygen, having more of them means more oxygen carrying capacity, a key factor in athletic performance. Simply put: inject yourself with EPO and your body starts cranking out more red blood cells.

There's a measure for the percentage share of blood that is composed of red blood cells. It's called hematocrit. Normally, it's about 40-45 percent, but by taking EPO people can boost that count to 50 percent or more. In fact, the only way to catch EPO cheaters for a while was to look for people with very high hematrocrit numbers. There are now more sophisticated ways to tell synthetic EPO from naturally occurring EPO, and people get caught even if their hematocrit numbers are in the normal range.

So here's the illicit promise of gene doping: your cells already make EPO, so what if you could get them to make more? Then, the EPO would be "natural," right?

ratEPO.jpgIn fact, this is the premise of Snyder's work. In the 2011 paper, he and his team injected monkeys with different doses of a virus carrying an EPO cassette. They are effectively transferring not the hormone itself, as in traditional doping, but the machinery to make the hormone inside the body.

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Alexis C. Madrigal

Alexis Madrigal is the deputy editor of TheAtlantic.com. He's the author of Powering the Dream: The History and Promise of Green Technology. More

The New York Observer has called Madrigal "for all intents and purposes, the perfect modern reporter." He co-founded Longshot magazine, a high-speed media experiment that garnered attention from The New York Times, The Wall Street Journal, and the BBC. While at Wired.com, he built Wired Science into one of the most popular blogs in the world. The site was nominated for best magazine blog by the MPA and best science website in the 2009 Webby Awards. He also co-founded Haiti ReWired, a groundbreaking community dedicated to the discussion of technology, infrastructure, and the future of Haiti.

He's spoken at Stanford, CalTech, Berkeley, SXSW, E3, and the National Renewable Energy Laboratory, and his writing was anthologized in Best Technology Writing 2010 (Yale University Press).

Madrigal is a visiting scholar at the University of California at Berkeley's Office for the History of Science and Technology. Born in Mexico City, he grew up in the exurbs north of Portland, Oregon, and now lives in Oakland.

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