The Olympic Mutant
Genetic Modification Could Be New Wave
Of Illegal Performance Enhancement

By Anne McIlroy
The Globe and Mail
Even as a newborn, he had bulging muscles that attracted the attention of curious doctors. By the time he was 4, he could lift almost seven pounds with each hand, with his arms fully extended -- something adults can find difficult.
There was something so innocent in the baby Popeye pictures published this summer in the New England Journal of Medicine, along with details about the genetic mutation that explains the German boy's extraordinary strength. (It has nothing to do with spinach.)
But there was nothing innocent in the buzz his strong arms and legs created in the athletic world. It had little to do with the fact that the baby, whose mother is a former professional sprinter, has the potential to be a future champion.
The ugly truth is that the German super baby may offer a genetic template for cheaters of the future. By the time he is 20, Olympic athletes may be genetically modified to grow muscles like his.
Forget about the next generation of steroids or growth hormones. Researchers say the future of cheating is athletes who have been genetically altered so that their bodies produce performance-enhancing substances on their own.
Many experts believe that the first genetically modified athletes could be competing at next Summer Olympics.
"I would think the Beijing Olympics may be the time to pick it up on a widespread basis," says Geoffrey Goldspink, an expert in muscle regeneration at the University College Medical School in London. He is already working on a test to detect genetic cheaters for the U.S. anti-doping agency.
The technology for gene therapy already exists. It involves using viruses to deliver new genetic instructions that become incorporated into muscle or other tissue and change the way they work. It has already been used in several labs around the world to create super-muscular rodents, dubbed mighty mice or Schwarzenegger mice. In many cases, the new genes often don't work all the time -- only when researchers deliberately turn them on by a simple action such as rubbing a leg muscle.
Some, including Dr. Goldspink, suspect that the practice -- dubbed gene doping -- is already being used in thoroughbred horse racing.
In humans, experts say, the only issue is safety. This means that there is a good chance that in a private lab somewhere in the world, researchers are getting ready to make a performance-enhancing addition to an athlete's DNA.
The World Anti-Doping Agency, led by Canadian Dick Pound, has pronounced that gene doping is cheating and has added it to the list of banned substances and methods for Olympic athletes.
Still, many athletes and their coaches are avidly following the latest scientific developments, which have been made by doctors hoping to find cures for muscle-wasting diseases such as muscular dystrophy or for blood disorders such as anemia.
When H. Lee Sweeney, a professor of physiology and medicine at the University of Pennsylvania, first used gene therapy to create super-muscular mice in 1998, he was swamped by e-mail messages from athletes and coaches wanting to use his discovery to improve athletic performance. One request came from a high-school football player who wanted to inject all the kids on his team.
They were excited by the news that Dr. Sweeney had found a way to inject a gene into rats and mice that instructs their bodies to make a hormone called insulin-like growth factor. The mice also take part in an exercise program, and after two months, they can lift 30 per cent more weight and have a third more muscle mass than normal mice.
Dr. Sweeney is still years away from testing his discovery in humans, but that didn't seem to matter to the would-be athletic guinea pigs who contacted him offering to volunteer.
Given the level of interest, and the millions of dollars at stake for those competing for Olympic gold in high-profile sports, the fact that gene therapy has so far proved risky for humans is probably not a deterrent for some athletes.
At the University of Pennsylvania, where Dr. Sweeney works, 18-year-old Jessie Gelsinger died in 1999 after receiving experimental therapy for an inherited liver disease that was treatable with drugs and diet.
For reasons researchers don't understand, the virus used to deliver the DNA they hoped would cure the young man caused his fever to run dangerously high. His major organs began to shut down, and his father made the decision to take him off life support.
Two "bubble boys" in France were successfully injected with genes to build their non-existent immune systems, but later developed leukemia.
Setting the safety issue aside for a moment, genetically altered athletes raise interesting ethical questions. In the years to come, gene therapy may not have the same Frankensteinian overtones it has now. It may turn out to be the best way to save the lives of patients with serious diseases, or even to help heal sports injuries such as torn muscles.
It is clear simply by looking at the bodies of many gold-medal Olympians that they have a natural genetic advantage.
In 1964, Finnish cross-country skier Eero Mantyranta was suspected of blood doping after winning two gold medals because he had so many red blood cells in his system. Three decades later, he was cleared when researchers found that he and many of his family members have a genetic mutation that increases their red-blood-cell count by 20 per cent.
Is it so wrong for athletes without this kind of extraordinary natural capacity to want to level the playing field?
It's cheating, says Mr. Pound, head of the World Anti-Doping Agency. At a recent meeting of the American Association for the Advancement of Science, he suggested that regulators not approve clinical trials for gene-transfer therapy unless the scientists have developed a way to detect if the procedure has taken place. He urged researchers developing gene therapies that might have athletic applications to work on detection methods.
Dr. Goldspink is happy to help. He is developing a test to look for traces of the viruses scientists would use to deliver new DNA into an athlete's body. Those viruses have been altered so they don't cause disease, and so can be detected, he says. All that would be required would be a scraping of cells from inside an athlete's mouth. "We've got the techniques."
Others researcher, including Dr. Sweeney, argue that it won't be that easy to catch genetic cheats and may require invasive tests such as muscle biopsies, which wouldn't be practical at the Olympics.
Dr. Goldspink says it makes him feel better to try. After all, it bothers him to think that a lifetime of work designed to prevent muscle wasting in the sick or the elderly might help a sprinter gain an advantage over a competitor.
It is true, he says, that many elite athletes already have a natural genetic advantage over some of their competitors. For example, the ancestors of Kenyan long-distance runners needed to be able to cover a lot of ground at great speed to keep track of their cattle and stay out of the jaws of predators.
"Why can't other athletes do what evolution had done for the Kenyans over thousands of years, but speed it up by injections and genes?" Dr. Goldspink says. "I think, once you open that door, the whole thing becomes meaningless. It all comes down to who has access."
Others disagree.
Andy Miah, a lecturer at the University of Paisley in Scotland and author of the book Genetically Modified Athletes: Biomedical Ethics, Gene Doping and Sport, says it is wrong to ban gene doping without a broad, social debate.
"What is the rationale for banning genetic modification? If we are concerned about fair play, then actually gene doping might promote fairness. If we are concerned about health, then getting the technology right could actually be safer for athletes than current forms of doping," he says.
He argues that Mr. Pound and the World Anti-Doping Agency have acted precipitously in lumping genetic modifications in with taking steroids or growth hormones.
No question, there are going to be some blurry lines to define. What, for example, is the difference between an athlete who was selected as an embryo in a lab for genes that would make her a good sprinter and one who is modified as a teenager to have the same advantage?
Researchers are already studying the genetics of strong athletes. In the United States, scientists have recruited 900 subjects in a bid to find which genes predict who will have a muscular body and who is doomed to get sand kicked in their face at the beach.
Volunteers are asked to lift a weight with their weakest hand, and then to lift weights with that arm twice a week for three months. The researchers then look at the genes of the 10 per cent of subjects who bulked up after the training, and the 10 per cent who stayed pretty scrawny. So far, they've identified 25 different genetic differences between the two groups.
It is not hard to imagine the day when genes for athletic prowess can be screened for, either in sperm, eggs, embryos or children.
Mr. Pound, for now, is focusing on athletes who choose to become genetically modified. He has warned that if the practice becomes widespread, and goes undetected, it will be the end of sports as we know it.
"I want human beings," he told the American Association for the Advancement of science. "Not mutants."
How to do it
Scientists willing to overlook serious safety concerns could inject new genes into muscle or other tissue in an athlete's body. Viruses would be used as the delivery vehicle, a way to get the new genes into cells.
This is a localized approach to genetic engineering. Egg or sperm cells would not be altered, which means that the changes would not be passed on to any offspring produced by a genetically altered athlete.
Here are a few of the possibilities for using gene therapy, also known as gene doping, to build a winning athlete:
Boosting red-blood-cell production. In our bodies, a protein called erythropoietin, or epo, regulates the production of red blood cells, which carry oxygen to our muscles. The more epo you have, the more red blood cells you make. Cheaters are already using a synthetic version of epo designed to treat anemia. Researchers are working on injecting a gene that would allow the body to make far more epo than normal, without thickening the blood with too many red blood cells. This would help patients with blood disorders, as well as cyclists, runners and other long-distance athletes.
Encouraging muscle repair and growth. Insulin-like growth factor, also known as IGF-1, is produced by our bodies and repairs the everyday damage caused to muscle fibres when they are used. Cheaters are now orally taking versions of IGF-1. Researchers in the United States have turned normal mice into super rodents by injecting the gene for IGF-I directly into their muscles. Other researchers are working on other even more effective growth factors, including one called mechano growth factor. Their work could help people with muscular dystrophy and other muscle-wasting diseases, as well as sprinters and weightlifters.
Removing the natural check on muscle growth. Myostatin is a protein that regulates muscle growth in normal humans. The New England Journal of Medicine recently reported that a German baby born with bulging muscles had a mutation that blocked the production of myostatin. Researchers may be able to do the same thing for athletes through gene therapy. This could help sprinters, weightlifters and football players.
- Anne McIlroy is The Globe and Mail's science reporter
© Copyright 2004 Bell Globemedia Publishing Inc. All Rights Reserved.



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