Are athletes turning to genetic modification and is drug abuse in sport getting worse?

Genetic engineering and drug abuse

It's a crying shame when a once proud athlete hits the bottle. It can be even more of a shame - and frightening too - if that bottle contains a genetic cocktail that might forever change the competitive balance in sports. And in this Frankenstein world where genetics meets athletics, the future is now.

'I think certain methods could have already started,' says Johann Olav Koss, the 1994 speed skating champion from Norway who is a member of the International Olympic Committee (IOC) and a doctor.

In many competitive sports, the difference between the gold medal and also-ran status is a fraction of a second. No wonder everyone is looking for any edge that technology might offer. Athletic improvements over the past decade have come to depend more and more on scientific advances in training, nutrition, and even surgical enhancements. But perhaps the biggest boost has come from performance-enhancing additives.

With the widespread use of steroids, human growth hormone and EPO (Erythropoietin, a hormone that regulates red blood cell production, used to increase the oxygen-carrying capacity, and hence the performance, of endurance athletes), runners, bikers, or swimmers leaning into the wind and water have every reason to eye their competitors suspiciously. Now the cornucopia of easily available and easily disguisable pharmaceuticals is joined by the latest and most controversial competitive weapon - genetic engineering.

Several promising performance-enhancing gene modifications have already been successfully tested on animals. They include generating the growth of explosive, fast-twitch muscle fibres and stimulating the release of growth-hormone-releasing hormone (GHRH), which can make recipients both stronger and leaner.

Medical applications of gene therapy on humans to cure or prevent disease are at a rudimentary but fast-evolving stage. Instead of treating deficiencies by injecting drugs, doctors soon will be able to prescribe genetic treatments that will induce the body's own machinery to produce the proteins needed to combat illnesses.

'It's not rocket science,' says Theodore Fridemann, director of the gene therapy programme at the University of California at San Diego and a member of the medical research committee of the World Anti-Doping Agency (WADA). 'If you asked any student of molecular biology how he would implant genes to change muscle function, he could cite three or four ways to do it.'(1)

The model cited by scientists on the cutting edge of sports science - the experimental patient that sends shivers down the back of the Greenes, the Kipketers, and the Khannouchis of this world - is 'He-Man', a mouse running endless, tireless circles in his basement laboratory cage at a University of Pennsylvania physiology laboratory.

Two years ago, He-Man was injected with a synthetic version of a gene called Insulin-like Growth Factor 1 (IGF-1), a protein that makes muscles grow and repair themselves. Today, deep into old age, the once tiny mouse and his gene-modified brothers and sisters look more like the Turkish weight-lifting icon Naim Suleymanoglu. After the IGF-1 boosted He-Man's muscle mass by more than 60%, he can now climb a ladder carrying three times his body weight. 'We call them the Schwarzenegger mice,' says Nadia Rosenthal, an associate professor at Harvard Medical School who co-authored the study. 'I'd be totally surprised if it was not going on in sports. Those with terminal cancer and Aids want to know 'What will keep me alive?' Athletes want to know 'What will help me win?''(2)

As the drug-addled East German and Soviet sports systems demonstrated, athletes and their managers are willing to strike Faustian bargains to achieve immediate glory. But this was no Communist-specific phenomenon: in a 1995 survey of nearly 200 aspiring American Olympians, more than half said they would take a banned substance that would guarantee victory in every competition for five years even if it would lead to certain death.

Where mice lead in the lab, athletes will follow in the field
'I have no doubt that if this is being done on mice, humans aren't far behind,' says Bengt Saltin, a former competitive runner, head of the Copenhagen Muscle Research Institute, and also a member of WADA. 'It would be risky because of unknown side effects but the basic genetic advances have been made. If scientists are willing to cooperate, athletes will experiment on themselves.'

Like ordinary genes, the artificial genes consist of DNA, the basic raw materials of human life. The direct delivery approach would be to inject the DNA into the muscle. The fibres would then take up the DNA and add it to the normal pool of genes. As this method is not yet very efficient, researchers often use viruses to carry the gene payload into a cell's nuclei. That's how the IGF-1 gene was delivered to make He-Man. Unfortunately, in contrast to the direct injection, the genes are also delivered to many other cells, such as those of the blood and liver, in addition to the intended target. A third approach entails removing specific cell types from the patient, adding the artificial gene in the laboratory and reintroducing the cells into the body. Since the artificial genes would produce proteins that in many cases are identical to the normal proteins, that means you can kiss good-bye to effective policing by sports agencies.

Bengt Saltin has a recurring nightmare. He imagines a scenario in which an already elite sprinter obsessed with becoming the world's fastest human turns to a renegade geneticist familiar with the latest research on the genetic modification of muscle fibre types. As powerful as the human musculature may appear to be to the layman, it can't hold a candle, relatively, to the explosive capacity of the muscles of many mammals, including mice, who call on energy bursts to elude predators. Although the fastest muscle fibre types are not found in human skeletal muscle, the potential for developing such fibres are imbedded in long dormant genes. Geneticists have recently developed a protein known as a 'transcription factor' called Velociphin, which can activate these genes.

Just a few injections of this DNA into the quadriceps, hamstring, and gluteus, and the muscle fibres will start cranking out Velociphin, which will activate the fast myosin gene. In weeks, the muscles bulge and burst with energy. There are no visible side-effects and without a muscle biopsy directly into manipulated muscle, the genetic modification is undetectable.

It's the long-awaited race for Olympic immortality. BANG! The genetically doped athlete dashes into the lead, extending it with every stride. Then at 65 metres, far out in front of the field, a sudden twinge tickles the hamstring. 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 patella 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 part of the reality.(3) For example, researchers have genetically altered a housefly with muscles 300% stronger than normal. It may sound promising, but 'the fly actually lost power because it couldn't make its wings move fast enough' to support the added muscle weight, notes H. Lee Sweeney, co-author of the He-Man study.(1)
While society has come to view the human body as an invincible machine, it is in fact a resilient but still delicate balance of tendons, cartilage, muscle, and fat. This is a balance that some fear may be altered radically, permanently, and perhaps perilously by genetic manipulation.

Aside from ethical concerns, there's a practical problem. This has understandably provoked a host of medical and ethical concerns. 'The only thing keeping athletes from using genetic manipulation today is the control problem,' says Saltin. 'You can't shut the production off when you want to.' For example, muscles injected with Velociphin will continue to produce the explosive fibres without further injection. Geneticists experimenting with the gene that codes for EPO have discovered that a single injection into the leg muscles of monkeys produced significantly elevated red blood cell levels for 20 to 30 weeks. That could prove to be a boon for anemia patients and provide a performance boost for endurance athletes except for one key problem: in the absence of a mechanism to shut down production, the body could turn into a 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 with the use of 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.(4) Not only would such a development prevent inserted genes from spinning out of control, they would render drug screening almost impossible.

With all of these Frankenstein-like scenarios, it would seem an easy decision to ban genetic engineering of athletes on ethical grounds. 'The argument in favour of allowing people to do this is based on our tradition of giving individuals a huge amount of autonomy over their own bodies,' says Eric Juengst, an ethicist at Case Western Reserve University in Cleveland. 'The limits on that kind of freedom are interpersonal. Once your actions cross the line of affecting just yourself and begin to affect other people, we have licence to step in.'(5)

Surprisingly, not everyone agrees, and in fact the ethical issues turn very murky on close examination. The current anti-doping rules do not permit the use of steroids even if prescribed for genuine medical reasons, eg to hasten recovery after an injury. Yet that is exactly how gene modification in athletes will first be used - say an injection of IGF-1 to stimulate muscle regeneration. Its use could theoretically allow an athlete to perform at an optimal level years past what is now considered his prime. Or imagine an athlete using gene modification to help overcome congenital asthma or some other genetic abnormality.

IOC President Jacques Rogge waded into this ethical thicket earlier this year. 'Genetic manipulation is there to treat people who have ailments, not there to treat a healthy person,' he says. 'I am very clear on this.' Very few geneticists or ethicists have quite the same level of clarity. There is a very hazy and debatable line separating 'health restoration' and 'performance enhancement'.(6)

The case of Helen Smith, an internationally renowned swimming star from Britain comes to mind. Smith who competes as a quadriplegic was threatened with a ban at the 2000 Sydney Paralympics for receiving medication that is life-sustaining for her but was deemed performance-enhancing by Olympic officials. There is already an equal access controversy in elite sports between wealthier countries which employ cutting edge technology in equipment, nutrition, and medicines versus the rest of the world who just muddle along. What makes genetic engineering any different as long as its focus is in overcoming some real - or perceived - injury-related performance deficiency?

A further question arises about any kind of genetic manipulation that is introduced before birth by a well-meaning parent. As Maurice Greene has noted: 'What if you're born with something having been done to you?' Would manipulation of an egg or an embryo be considered cheating, if as Greene hypothesises, 'you don't have anything to do with it?'(7) It might be unfair to penalise someone for an enhanced genotype but it is understandably problematic to have that person compete against a non-enhanced athlete.

Considering the health dimension of genetic enhancement, it certainly appears to be a more acceptable method of performance enhancement than drugs. The IOC has set up a 'gene doping' advisory group but seems befuddled by these complex issues. 'The information from genetic science will feed through into better treatments for disease, but it also going to present the sports industry with a Pandora's box within the next five to 10 years,' says Bruce Lynn, a senior neurophysiologist at University College London's School of Human Health and Performance.

There has even been talk of introducing a handicap for genetically enhanced contestants or even setting up official performance-enhanced competitions. 'That's a terrible idea,' bemoans Saltin. 'If genetic engineering is sanctioned, it's the end of sports as we know it. Sports will be a circus of unbelievable performances.'

Perhaps. From a purely competitive standpoint, athletics might be more exciting, pushing the edge of human capability, testing the limits of speed and endurance well beyond those that science currently accepts.
Until the patella tendon and quadriceps snap and a once valiant athlete is carted off the track, perhaps never to walk again.



Jon Entine

References:
1, Swift, EM & Yaeger, D, Irish Examiner (July 10, 2001)
2 Cromie, WJ, Harvard Gazette (Feb 11, 1999)
3 Andersen, JL, Schjerling, P & Saltin B, Scientific American (Sept 2000)
4 Longman, J, New York Times (May 11, 2000)
5 Compton M, DNA Dispatch (July 2001)
6 Clarey, C, Intl Herald Tribune (Jan 26, 2001)
7 Chandel, A, Tribune (India) (May 18, 2001)

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