Juicing 3.0

02 Jul 2008, Posted by Steven Kotler in

The history of sports is really the history of drugs in sports. From Roman gladiators hopped up on herbal stimulants to distance runners downing brandy-and-strychnine cocktails (a combination that helped American Tom Hicks win the 1904 Olympic marathon), athletes have always found ways to augment their bodies.

Steroids and human growth hormone are yesterday’s headlines. The future of performance enhancement belongs to a dizzying array of medical wizardry, including manipulating stem cells and inducing euphoric mental states, that could make the cheaters stronger and faster than ever—and catching them nearly impossible.

Enhancing Your Brain

Timeline: Within 3 Years

BACKGROUND: At the 2003 Track and Field World Championships in France, American sprinter Kelli White shaved a whopping second and a half off her 100- and 200-meter race times and swept the races. White’s postrace blood tests, however, turned up higher-than-allowed levels of modafinil, a prescription anti-narcolepsy stimulant that helped her jump out of the blocks and sprint down the track faster. Modafinil is but one of a dozen or so “neural enhancers” currently available in pharmacies that scientists say could enhance athletic performance. Popping FDA-approved Parkinson’s meds and antidepressants might not seem like cheating, but studies suggest that a positive mental attitude improves mental focus, contributing to superior performance. Various antidepressants boost dopamine, norepinephrine and serotonin levels. For a healthy athlete, that extra serotonin may foster a more positive mood, while both dopamine and norepinephrine seem to enhance motor control and muscle reaction time—an edge in any sport.

WHERE IT’S AT: “Within the next few years, we’ll see the second generation of these drugs,” says Mark Gordon, an endocrinologist in Los Angeles. “Like all second-generation drugs, they will be stronger, longer-lasting, and have fewer side effects.” The pharmaceutical industry makes a fortune on these drugs, so nearly every major company has a brain booster or two in the works.

DETECTION: Most governing bodies allow exemptions for athletes with diagnosed conditions. Scientists can detect neurochemicals in blood and urine samples, but a brain-tissue biopsy is the only way to determine if athletes are abusing the drugs.

Muscling Up

Timeline: 3–5 Years

BACKGROUND: In 1997, geneticists Alexandra McPherron of the National Institutes of Health and Sie-Jin Lee of Johns Hopkins University discovered that “turning off” the protein myostatin can double the size of muscles in mice. Myostatin keeps muscle stem cells inactive during normal use. Turn off the protein’s signaling ability, and those cells turn their host into the Hulk. Last year, researchers at the Human Genome Research Center found the same mutation occurring naturally in a few Popeye-esque whippet dogs—typically a skin-and-bones breed—called bully whippets. In races, bully whippets run almost twice as fast as genetically normal whippets.

WHERE IT’S AT: As soon as McPherron and Lee announced their myostatin discovery, weightlifters were quick to offer their services as human test subjects. But a better test case came along by accident in 2000, after a German baby born without the protein exhibited extremely overdeveloped muscles. Today, though still extraordinarily muscular, the boy is in perfect health, suggesting that safely blocking myostatin in humans is a real possibility. In lab tests, two injections of one mysostatin blocker produced a permanent 50 percent muscle gain in mice. “Just about every major pharmaceutical company is developing a myostatin-blocking drug to treat muscle-wasting diseases like muscular dystrophy,” Lee says. Because these medicines will use traditional antibody-based drug-delivery methods, a myostatin inhibitor could be on the market in five years.

DETECTION: Myostatin blockers that use antibodies should be pretty easy to detect, since similar tests already exist. But alternative delivery systems like RNA interference and gene therapy, probably the norm for drugs in a decade, would make catching abusers near impossible. And although an athlete sporting a 50 percent increase in muscle mass might be a dead giveaway, partial inhibition of the myostatin pathway could lead to less obvious effects.

Gene Doping

Timeline: 5 Years

BACKGROUND: Gene doping is the sneaky side of gene therapy, in which scientists use modified viruses to insert healthy genes into flawed parts of the genetic code. The cells follow the new instructions, and presto—stronger body. Recent studies looking into boosting muscle mass to treat muscular dystrophy have caught athletes’ attention.

WHERE IT’S AT: In 2006, German track coach Thomas Springstein was arrested after attempting to get his hands on a Repoxygen virus that ramps up production of oxygen-carrying red blood cells in humans. This drove mass speculation that gene dopers will dominate the 2008 Olympics. Scientists disagree. “Developing techniques that really work has been much harder than people first thought,” says Theodore Friedmann, director of the Human Gene Therapy Program at the University of California at San Diego and a consultant for the World Anti-Doping Agency (WADA). There have been a few successes with gene therapy—in 2000, scientists “cured” severe combined-immune-deficiency syndrome in nine infants. But results are inconsistent, and although side effects are typically limited to flu-like symptoms, sometimes they’re worse: Five of the babies have since developed leukemia. Because the tech is still in its infancy, gene dopers, Friedmann says, won’t be grabbing medals until the 2012 Games at the earliest.

DETECTION: WADA scientists are testing the theory that foreign genes introduced into the body will produce identifiable by-products that will show up in bodily fluids. If so, a test should be easy to develop.

Bulking Up With Stem Cells

Timeline: 10 Years

BACKGROUND: The potential uses of stem-cell therapy seem endless: from treating cancer and neurological diseases, to increasing muscle mass and bone density in the weak, to cultivating new organs in petri dishes. It’s those last two items that have piqued the interest of athletes looking to beef up or repair game-worn bodies. Although these applications might be considered outright cheating, they fall onto what Tom Murray, the president of the bioethical institute the Hastings Center, calls “the fault line between enhancement and highly sophisticated injury prevention.” If a basketball player goes in for a stem-cell treatment for the ailing bones in his feet, is it cheating or just good medicine? No governing body has yet stated a position on stem-cell therapies, but the issue will need to be addressed soon.

WHERE IT’S AT: “We can already make adult stem cells form muscle,” says Chris Evans, a professor of orthopedic surgery at Harvard Medical School. “But how to deliver stem cells to the appropriate muscle, and how to get that muscle to integrate these newcomers and gain additional function, remains a mystery.” Scientists expect this barrier to fall in a decade.

DETECTION: “You’re using the body’s own cells for this procedure,” Evans says, “so it’s going to be horribly difficult to detect.” If athletes were to grow replacement parts from the stem cells in their kids’ cortical blood, however, those would be genetically different from their own tissue and thus detectable with simple DNA tests.

Getting Into the Zone

Timeline: 15 years

BACKGROUND: In the past 30 years, hundreds of scientists have investigated the “in-the-zone” feeling that athletes say gives them the sense that they can accomplish anything. When Boston Celtic Larry Bird talked about the game seeming to actually slow down during crunch time, helping him to read defenses more clearly and feel more fleet-footed, he was probably experiencing a natural dopamine high. Dopamine increases muscle-reaction speed and alters the perception of time. But these flow states, as they’re known among psychologists, are probably triggered by a surge of several mindscrambling, euphoria-inducing, reflex-quickening neurochemicals, such as norepinephrine and serotonin. Although studies have yet to quantify how much flow states actually raise an athlete’s performance, anecdotal evidence has convinced Michael Sachs, a sport psychologist at Temple University. “Athletic abilities are so elevated by the experience,” he says, “that just about any championship-level, gold-medal peak performance has a flow state at its core.” Elite athletes would do anything for a pill or injection that stimulates this feeling.

WHERE IT’S AT: In 2004, neuroscientist Arne Dietrich, then at the Georgia Institute of Technology, identified anandamine—the body’s version of THC, the psychoactive chemical in marijuana—as the chemical most likely responsible for flow states. This theory received a boost this spring, when scientists at the University of Bonn in Germany found elevated levels of endorphins in the brains of test subjects. These molecules are too big to penetrate the blood-brain barrier on their own, so the current thinking is that anandamine ferries them in and that it’s the endorphins that provide the actual high. Still, most scientists think there are other neurochemicals in play, and figuring out the exact combination may take years. With so much pharmacological interest in neuro-enhancement, though, scientists in the field say it’s only a matter of time.

DETECTION: To spot cheaters, Sachs says, you’ll need to differentiate between the neurochemicals responsible for a natural flow state and one that’s triggered artificially. “But these chemicals may be perfectly identical to the natural stuff,” he says. “I just don’t think detection may ever be possible.”

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