Drug running

by Jon Entine

ALAIN BAXTER’S positive drugs test has drawn attention, yet again, away from athletic achievements at the Olympics and back onto the role of the science lab in professional sport. But forget mistakes with a cold cure, genetic engineering is the real threat for the world’s doping agencies. A doomsday scenario in which sport is dominated by users of performance-enhancing, gene-altering drugs that are totally undetectable is nearer than most in the West would dare to contemplate. Science fairs displaying rabbits with human ears are already being regularly held in China.

"Genetic research is like unlocking the secrets of the atom," waxes Chen Zhang Liang, vice president of Beijing University, which is bidding to become a world centre of genetic engineering. "We need to push forward."

According to sports scientists, China’s next great leap forward is already well underway. Consider some of the results from the Chinese Games in Guangzhou as possible evidence. Guo Lingling, just 15, finished second in the women’s 400m hurdles. And just 11 days past his 14th birthday, Li Huiquan won the 800m in world class time, only a few days after nearly cracking 3:45 in the 1500m.

Bear in mind this was not the junior games but the quadrennial showcase of the best Olympic athletes China has to offer. The results in swimming by a band of unknown teenage girls, most not listed in the world’s top 200, were equally mind-boggling. If the Chinese females perform at the Athens Olympics as they did at the event in November, they will win two out of three medals in every freestyle event from the 100m to 800m.

There is no hard evidence to suggest these unprecedented performances were the result of genetic manipulation but China now has one of the more rigorous drug-testing programmes in the world. Since nearly everyone believes that these results are at the edge of, or beyond, natural human performance limits, speculation has run rampant. After all, it was only four years ago that Australian police nabbed Chinese swimmer Yuan Yuan red-handed with 13 vials of genetically engineered human growth hormone (hGH).

"Genetic engineering may have already started," warns Norwegian speed skating champion Johann Olav Koss, with an eye toward China. A doctor and member of the International Olympic Committee’s World Anti-Doping Agency (WADA), Koss believes that: "We can’t be na•ve. We have to be realistic."

FIFA, international football’s governing body, has become so alarmed about the surge in use of another genetically-engineered drug, EPO (erythropoietin), that it is introducing a test for it at the World Cup.

There is little doubt that the genetic revolution threatens to alter permanently the nature of sport. As WADA chairman Dick Pound recently said, "we will look back on Ben Johnson with his Stanoloxol [anabolic steroid scandal in 1988 for which he was stripped of the 100m gold medal] and say ‘that’s like an ancient rock painting in a cave compared to what we face now with genetic engineering.’"

Genetic engineering is one of those concepts that stir a powerful gut reaction. In recent years, biomedical researchers have made measurable strides in gene therapy, which involves injecting the body with artificial genes that help block diseases such as cystic fibrosis. The technique, while still being tested experimentally on humans, has been used successfully in animals. Many look forward to an age when some diseases will have been wiped out and hospitals will be obsolete except to treat trauma.

Others fear the creation of soulless cyborgs that make Orwellian predictions look timid. Almost always the controversy is projected as a future

concern. That may be true in medicine, but in athletics, genetic engineering is not a theme of science fantasy, but a sobering fact of our cyborg present.

"Why would anyone who is willing to cheat use stimulants and steroids when they can use genetically-engineered drugs, which are virtually undetectable?" asks Charles Yesalis, a Penn State University epidemiologist and world expert on doping.

Considering the high risk/high return nature of big time sports, athletes are the ‘canary in the mine’, willing to experiment with magic elixirs in the quest for gold. The temptation is enormous. Everyone from an ageing footballer to a Kenyan-chasing British distance runner could see their prospects brighten with the right genetic cocktail.

Unfettered by fears of being caught, athletes will likely shatter accepted limits of human performance - but at an unknown and potentially disastrous cost to their health. "If things spin out of control," Yesalis warns, "it could be a freak show in athletics." And that show, warns sport scientists, may come as early as the 2004 Athens Olympics.

It may be a decade or more before doctors can remove embryonic fluid and generate a read-out of the predicted sporting accomplishments of our prodigies in waiting, but synthetic drugs are already in widespread use. The revolution began more than a decade ago with the introduction of hGH and EPO, which are now as popular with some athletes, and as available as vitamin pills. A rich array of drugs is in the pipeline, including a concoction that would postpone sexual development to keep pre-adolescent female gymnasts in their performance prime. Scientists and guinea pig athletes are also busy experimenting with various gene therapies to regenerate the body after cartilage damage and fractures.

The next giant step in the genetic revolution in sport will come within the year as geneticists begin experimenting with the direct injection of artificial genes that would self-regulate muscle growth. Bulging biceps, svelte calves and women-attracting pectorals may be just a few injections away.

While hGH and EPO are extremely difficult to detect, the direct delivery of artificial genes means that sport can kiss goodbye effective dope policing. "If direct injection is used, the DNA will only be present in that specific muscle," says Peter Schjerling of the Copenhagen Muscle Research Centre. "A positive test would require coring out actual muscle tissue. Not many athletes would allow that. And even if they agreed, the sample would have to be at the exact spot of the injection. That’s just not feasible."

For a glimpse of what the future cyborg athlete might look like, one might peek into a dark basement laboratory at the University of Pennsylvania. There, running tireless circles on a wheel inside a cage, is He-Man. A few years ago, physiologist H Lee Sweeney injected a tiny white mouse with a synthetic version of a gene called Insulin-like Growth Factor 1 (IGF-1), a protein that makes muscles grow and repair themselves.

As Sweeney tries to remove him from his pen, He-Man clings stubbornly to the cage bars. "He’s just showing off," says Sweeney, who is only partially kidding. The IGF-1 boosted his muscle mass by more than 60%. Today, deep into old age, this gene-modified giant looks like the Turkish heavyweight icon Naim Suleymanoglu. He-Man can still climb a ladder carrying three times his body weight.

Researchers at London’s Royal Free hospital and University College London’s medical school have developed a similar muscle-building protein dubbed mechano-growth factor (MGF). As yet, scientists have detected no health problems. The rodent-athletes, with no exercise, balloon to four times their natural muscle mass but weigh only 30% more.

"We call them the Schwarzenegger mice," says geneticist Nadia Rosenthal, who co-authored a study with Sweeney. "I’d be totally surprised if it was not going on in sports."

Injections that would beef up muscles with limited weight gain would be a magic elixir for sprinters, footballers, lifters, shot-putters and other athletes who need quick bursts of power. Endurance athletes - cross country skiers, marathoners, and cyclists - can turn to a different set of promising genetic therapies.

Athletes and their scientist enablers are also eyeing the gene for EPO, a hormone which is used by doctors to treat anaemia. The drug version has become a dietary staple on the cycling circuit. The more revolutionary injectable version has been shown to boost red blood cell concentration by 60%. That is far more than the difference between Olympic gold and also-ran status, as the case of skier Eero MS

ntyranta aptly demonstrates. Boosted by a genetic mutation that churned out natural EPO at astronomical levels, MSntyranta won seven medals over three Olympics in the 1960s.

As is frequently the case with genetic advancements, there’s good news and bad. A single injection could elevate red blood cell levels indefinitely. On the other hand, without a mechanism to shut down production, the body could turn into an out-of-control EPO factory, leading to the thickening of the blood with excessive blood cells, strokes, heart attacks, and eventually death. But such problems offer only temporary barriers. Helen Blau, chairwoman of the department of molecular pharmacology at Stanford Medical School, has demonstrated that a gene could be introduced into a mouse to stimulate growth hormone in the bloodstream and then be switched off using an oral antibiotic.

"In theory, it is possible that an athlete could be genetically engineered to have a gene so you could increase muscle strength, train with it and shut it off when you want to," she says. "Not only would such a development prevent inserted genes from spinning out of control, they would render drug screening almost impossible."

World-record running times are made to be broken. Many performances that were world-class only 50 years ago are routine now. In 1954, Roger Bannister stunned the world when he broke the four-minute barrier. But within six weeks his improbable record fell. Fast-forward to 1999 and Moroccan Hicham El Guerrouj lowered the record to 3:43.13.

The steady improvement in records of all sporting events may, at first glance, look like biological evolution at work, but that is far-fetched. Genetically we are much the same as we’ve been for millennia. And the last 100 years, which have seen the most dramatic improvements, represent but an eye-blink of evolutionary time. Moreover, any mutation that might crop up and that could be of value for athletic performance (such as enormously large lung capacity for marathoners) would quickly be diffused in the gene pool. After all, humans like to ‘fool around’.

That said, genes matter. Elite athletes are by definition, freaks of nature. "Very many in sports physiology would like to believe that it is training, the environment, what you eat that plays the most important role," says Bengt Saltin of the Copenhagen Muscle Research Centre. "But we argue based on the data that it is ‘in your genes’ whether or not you are talented or whether you will become talented. The extent of the environment can always be discussed but it’s less than 20, 25%."

Geneticists are trying to bottle this wisdom. The question remains: will we ever be able to isolate individual genes, that will radically change physiology - and therefore alter the competitive balance in sports? The answer is a qualified ‘yes’.

"It would be risky because of unknown side-effects but the basic genetic advances have been made," asserts Saltin, who is himself a former competitive runner. "I have no doubt that if this is being done on mice, humans aren’t far behind. If scientists are willing to cooperate, athletes will experiment on themselves. And it will fundamentally change sports as we know it."

He imagines a scenario in which an ambitious sprinter sick of running in Maurice Greene’s tailwind turns to a renegade geneticist for help. This scientist is familiar with the latest research on muscles, including the discovery of fibres that fire even more quickly than human fast twitch muscles. This rebel geneticist readies a syringe of a synthetic protein that can turn on these genes. Just a few injections of this DNA into the quadriceps, hamstring, and gluteus, and the muscle fibres start cranking out Velociphin, which activates the fast myosin gene. In weeks, the muscles bulge with energy. As Saltin spins the tale, this desperate athlete faces his long-awaited race into Olympic immortality.

Bang! The genetically-doped athlete dashes into the lead, extending it with every stride. Then at 65m, far out in front of the field, a sudden twinge tickles his thigh. Saltin picks up the story:

"At 80m, the twinge explodes into an overwhelming pain as he pulls his hamstring. A tenth of a second later the patella tendon gives in - because it is no match for the massive forces generated by his quadriceps muscle. The tendon pulls out part of the tibia bone, which then snaps, and the entire quadriceps shoots up along the femur bone. The athlete crumples to the ground, his running career over."

"This is not the scenario that generally comes to mind in connection with the words ‘genetically engineered super athlete,’" notes Saltin, "but it is very much a part of the reality."

The sports community, and ethicists in general, are understandably on edge. "Biological variation is fundamental to sport," Saltin asserts. "You could say it is what gives a person their talent. This can now be affected with genes, and this must be wrong."

The same line is espoused by the international Olympic movement. "Anything you did not get from God is illegal," asserts Tim Conrad, a US Olympic scientist. According to new IOC president Jacques Rogge, "Genetic manipulation is there to treat people who have ailments, not to treat a healthy person. I am very clear on this."

Few scientists see the medical or ethical issues as so black and white. There is a hazy line between ‘health restoration’ and ‘performance enhancement’. Imagine an athlete using gene modification to overcome congenital asthma. What about genetically aiding someone who is destined to be short? Should people be punished because the roulette wheel of genetics did not land on their number?

Genetic enhancement obviously offers promising medical benefits, as do tendon surgery and any number of treatments that are the result of breakthroughs in medical technology. Do we want to leave it up to sports officials or ethical arbiters to make life-altering decisions about which therapies cross some line when genetic therapy becomes unfair genetic enhancement? We can expect this debate, both medical and ethical, to rage for decades.

"While the information from genetic science will feed through into better treatments for disease," warns Bruce Lynn, a neurophysiologist at University College London, "it is presenting the sports industry with a Pandora’s box.

Wake up sports world. The Pandora’s box is open. There are cyborg athletes among us.

Jon Entine is author of Taboo: Why Black Athletes Dominate Sports and Why We’re Afraid to Talk About It