Friday, August 15, 2008

Wired - Cheats of Strength: 10 Next-Gen Olympic Doping Methods

Wired looks at the top 10 next-generation doping methods in sports.

Despite the title, this isn't really just about the Olympics. The testing ground for endurance athletes is pro cycling. The testing ground for strength athletes is body building. If you want to know where doping is going in the future, look at those sports.

Pro body building has been working with IGF-1 and insulin for years. I'm pretty sure they'll be the first to test myostatin inhibitors and selective androgen receptor modulators, if they aren't already.

Pro cycling has tried every conceivable method of increasing red blood cell levels, including blood doping with other people's blood. EPO and all of its next-gen variants have been around for years. And Id wager there are cyclists who will be willing to try vascular endothelial growth factor, despite the possible pain factor and unknown consequences.

Cheats of Strength: 10 Next-Gen Olympic Doping Methods

By Jim Feeley

Anti-doping officials hope to keep lab tests ahead of dopers' ability to create and hide new means of chemically augmenting their performances.

While the International Olympic Committee is busy trying to catch today's performance enhancers, athletes are already looking for the next big boost that will give them the edge in 2012.

Most of the positive doping tests in Beijing -- and the IOC president estimates there will be as many as 40 -- will likely be for steroids and the blood-boosting hormone erythropoietin, known as EPO.

But the future of doping could get a lot more complicated. Here are some of the most promising -- or threatening, if you're the World Anti-Doping Agency -- candidates for the next Olympics.

Use your genes to grow more muscle

Manipulating genes to block naturally occurring muscle-growth inhibitors could allow athletes to boost their muscle mass. A lot.

In tests on mice, blocking the protein myostatin gave the mice up to 60 percent more lean muscle mass. Even more promising, Johns Hopkins' Se-Jin Lee recently found that overproduction of one myostatin inhibitor pumps the mice up even more: up to 81 percent in females and a whopping 116 percent in males. Results of human clinical trials are pending.

Complicating the picture, particularly for WADA, is a small number of people with naturally inhibited myostatin who will have to be distinguished from the dopers somehow.

Pop a blood-boosting pill

Who wouldn't love a pill that delivers the same record-breaking benefits of synthetic EPO without the hassle of injections or getting caught?

Clinical trials are under way for a pill that tricks the body into thinking blood-oxygen levels have dropped, causing it to produce more red blood cells, thus improving muscle endurance.

When blood-oxygen levels drop, hypoxia-inducible factor, or HIF, kicks in to stimulate red blood cell production. Once oxygen is back to normal, the HIF breaks down and cell formation stops. The drugs, known as HIF stabilizers, stop the breakdown and keep blood production up.

Some suspect athletes may already be using HIF stabilizers, but the health risks are unknown.

Grow more blood vessels

If you don't mind injections directly into your heart and limbs, vascular endothelial growth factor may be for you. VEGF causes new blood vessels to grow, which in theory could move more oxygen and nutrients between muscles, lungs and the heart with less effort. So more effort could be expended on athletic performance. VEGF gene therapy could potentially help patients with heart and arterial diseases form new blood vessels, keeping them alive and avoiding amputation. But it's not a simple hack, and a failed gene-doping test isn't the only risk. Unregulated VEGF-induced vessel growth appears to also promote tumor growth and metastasis.

Feel less pain, get more gain

Athletes know how to suffer. Raise an athlete's pain threshold, and suffering will occur at a higher level of exertion.

Tests on rats suggest that injecting the beta-endorphin gene into spinal fluid through a spinal tap causes the body to release its own painkilling endorphins. Pain signals get blocked before they reach the brain, without the sleepiness and cloudiness associated with morphine and other painkilling opioids.

Raising an athlete's pain threshold may improve performance, but it may also cause them to ignore warnings of overexertion and injury.

Beef up specific muscles

Say you're a cyclist who wants powerful legs but a light upper body so you don't have to haul the extra weight when riding uphill. Or a tennis player who needs a bit more shoulder muscle. Injecting insulin-like growth factor, or IGF-1, into specific muscles sparks those muscles to grow while avoiding the full-body muscle growth usually associated with IGF-1. Physiologist H. Lee Sweeney at the University of Pennsylvania discovered this while looking for a treatment for muscle-wasting that avoids side effects from unwanted growth, such as cancer and heart enlargement. The targeted therapy may also make IGF-1 harder to detect in a doping test. Sweeney estimates that since his research was published, half of his e-mails are from athletes. He has worked with WADA, but others developing similar techniques may not.

Get more muscles, fewer zits

Want the muscle-building benefits of steroids without the testicle-shrinking, moob-growing, acne-popping side effects? That's the promise of selective androgen receptor modulators.

SARMs bind to specific tissues, such as muscle and bone. Unlike some steroids, they don't indiscriminately also bind to prostate, liver and other tissues. And SARMs come in a pill. No needles or skin patches.

These pills could be a boon to people suffering from muscle-wasting diseases and for athletes concerned about health risks associated with steroids. Sound too good to be true? Perhaps: A test to detect SARMs may be ready before the drugs are widely available. WADA won't tell until they catch an athlete.

Fill up with new blood substitutes

With EPO and blood transfusions increasingly detectable, athletes could return to blood substitutes for an extra hit of oxygen. Several athletes reportedly used substitutes in the past, and one cyclist may have almost died as a result.

Some new substitutes could have similar problems. A report in the Journal of the American Medical Association in April criticized blood substitutes such as PolyHeme and Hemopure for causing heart attacks and deaths in test subjects. But there are alternatives. Oxygen Biotherapeutics claims their experimental substitute, Oxycyte, carries oxygen 50 times more efficiently than natural blood without the risks of older substitutes. And Dendritech patented a blood substitute built from 3-D nanoparticles that the company builds in precise oxygen-carrying shapes. At least some blood substitutes may be easy to detect, but there are rumors the test isn't regularly used.

Take a next-gen EPO

At the Tour de France in July, Ricardo Ricco got caught using a new EPO-like blood booster, CERA, recently released by Roche.

Before CERA was on the market, the pharmaceutical giant cooperated with WADA to have a test ready to trap cutting-edge dopers like Ricco, a sign that WADA is catching up to, and perhaps even staying ahead of, dopers.

Or it's a sign that WADA needs help developing tests to detect each EPO variant, a tall order considering EPO and related drugs make up a $12 billion market. There are also dozens of EPO-stimulating agents available or in the works around the world.

Pump up your muscle fiber

Athletes already have more fatigue-resistant muscle fibers than couch potatoes. But new research shows they may be able widen that gap further by boosting levels of the gene responsible for adding new fibers.

Recently, researchers at the Salk Institute in San Diego found that an existing medication, called GW1516, raises the levels of this gene, resulting in a 68 percent endurance improvement in fit mice.

The Salk researchers are working with WADA on a test to detect use of GW1516. But several other drugs are known to manipulate the muscle-fiber genes, and others are believed to do the same. A test to detect this type of gene doping would need to cover a lot of uncharted territory.

Lastly, use mustard?

Athletes turned off by the latest biotech breakthroughs can try this recipe: Strip down and rub mustard oil all over your body.

While exploring the role skin plays in the production of red blood cells, Randy Johnson's team of researchers at UC San Diego found that rubbing mustard oil on mice caused spikes in natural EPO production, and that led to increased red blood cell levels.

It's unclear how much mustard oil a human athlete would need to enhance performance, or how much mustard oil could lead to strokes and heart attacks.

With all the crazy, complicated doping schemes out there could the journey to the top of the podium simply require a trip to the grocery store?

I support legalized doping, and part of that support comes out of the hope that if athletes can dope with things we know will work, and not kill them, then they might not risk the methods that are seriously dangerous or that might have unknown long-term consequences.

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