GENETIC DOPING - article

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posted by MarkyM

Got this from the Houston Chronicle, thought ya'll might like it.

Good for medicine, but bad for sports
Building better muscles could help save lives — and taint athletic feats
By ERIC BERGER
Copyright 2004 Houston Chronicle

Baseball superstars Barry Bonds and Jason Giambi can't hit a home run without facing questions about steroids. Lance Armstrong just won a record sixth Tour de France, but did so amid suspicions by a few that he doped his blood.

And the signature contests of the 2004 Olympic Games that open this week in Athens — track-and-field events — will undoubtedly unfold under a pall of cynicism: Did the gold medalists, as many have in the past, take steroids?

With ever-increasing pressure to win, it's difficult to find a major sport where elite athletes haven't been accused of juicing their bodies.

Now, here's the bad news: These may be the halcyon days of fair athletic competition.

By understanding how the body works on a molecular level, and decoding the human genome, scientists are beginning to tailor treatments that target the biological roots of health problems. And as genetics revolutionize medicine, new treatments to build muscle more naturally, safely and quickly than steroids could be one of the first applications.

Though the manipulation of muscle-building genes may prove a godsend for people with diseases such as muscular dystrophy, it would be a nightmare for anti-doping agencies.

"This is scary stuff, and it's right around the corner" said John Eliot, a Rice University lecturer and consultant to Olympic athletes and teams.

"This is the next step in artificial enhancement, and it's far ahead of testing."

Anti-doping officials say they don't think these genetic techniques will be used in this summer's games. But when the Olympics reach Beijing four years from now, the games may enter the genetic age.

"Certainly, by 2008, the entire gene therapy field will be much more developed, and the World Anti-Doping Agency is very concerned," said Dr. Carlos Hamilton, a committee member of the agency and an executive vice president of the University of Texas Health Science Center at Houston.

How it works
Gene therapy has already worked in rats, and scientists have identified a gene in humans that gives a tremendous advantage to weight-lifting. These therapies are on the cusp of, or are already in, human trials for muscle-loss diseases.

The critical scientific work in this area is new, started less than a decade ago, when scientists began understanding precisely how muscle is built.

A normal workout microscopically tears muscle fibers, triggering a chemical alarm in the form of a protein called IGF-I, which calls nearby cells to make multiple copies of themselves by the normal process of cell division. Some of these cells then merge with the muscle fibers, adding bulk and strength. When the muscle is rebuilt, another protein, called myostatin, tells the nearby cells to stop.

In recent years research groups have begun working to boost IGF-I in human muscle cells, or block myostatin, with the thought that doing one or the other would lead to beefed-up muscles.

Simply injecting IGF-I into muscles would have little effect, because it dissipates quickly. So scientists at the University of Pennsylvania designed a mechanism to insert a synthetic IGF-I gene into muscle cells, where it should last for the life of a cell. Since muscle cells live a long time, a single dose could last for a decade, or more.

The researchers used a harmless virus to smuggle the gene into muscle cells, where it mingles with the existing DNA in the host cells and begins raising production of IGF-I.

The team then turned to the Austin-based laboratory of Roger Farrar, a University of Texas professor of kinesiology. They injected the modified virus into one leg of lab rats, then gave them eight weeks of resistance training.

The injected muscles performed like champions — they gained twice as much strength as the non-treated muscles, and after training stopped, they lost mass twice as slowly. Even rats that received injections but did not work out saw a 15 percent gain in muscle mass. The ones who received injections were otherwise normal and healthy.

"There are some real benefits, healthwise, you could see in this," Farrar said. "But you can also see how it could be abused by an athletic population with sufficient resources."

For now the IGF-I researchers plan to continue their work in larger mammals, such as dogs, before moving to humans.

Successful studies

Studies on the other muscle-building pathway, blocking myostatin, are further along.

In 1997, scientists found the gene in mice that produces myostatin, and determined that mice without the gene had twice the muscle mass of normal mice. Earlier this year, the same group, led by Dr. Se-Jin Lee, a genetics professor at Johns Hopkins University, found similar evidence in a child.

At about the same time, based partly on Lee's research, Wyeth Pharmaceuticals announced a clinical trial to study the safety of a myostatin-blocking drug. It is just the first round of trials, so the drug remains several years away from the market. Such tests will determine whether gene therapy has serious health implications like those caused by steroid use.

Lee said he fears the brewing furor over genetic doping in sports will overwhelm the medical advantages.

"There certainly is the potential for abuse, so clearly we'll have to do whatever we can to prevent the misuse of these drugs," he said. "At the same time, the potential medical uses are enormous. If this really does work like we think it can, it really could provide some profound benefits for people with some pretty devastating diseases."

Clear health benefits

As much as 50 percent of a fit person's body weight is muscle mass, but between middle age and old age, people lose as much as a third of their muscle. As a result they become weaker, fall easier and see a decline in their quality of life.

For people with some forms of muscular dystrophy, muscle loss can mean a childhood spent in a wheelchair, and death by the age of 20 or 25.

Muscle wasting is a health problem for people with chronic diseases such as AIDS and cancer, too, and can affect people recovering from surgery, those in comas and those with injuries that force them to remain sedentary.

The vast potential of gene therapy has groups such as the Muscular Dystrophy Association talking confidently about a cure, perhaps for the first time.

"We've known about these muscle-wasting diseases for 200 years, but they really have never been treatable," said Sharon Hesterlee, the MDA's director of research development. "Gene therapy is an amazing breakthrough that may solve the problem."

Very hard to test

Anti-doping officials have expressed the most concern about IGF-I gene therapy because it is injected directly into the muscles. There would be no evidence of it in blood or urine, which Olympic officials test.

To find any evidence at all officials would have to perform an invasive muscle biopsy to detect the virus or synthetic gene. Even such a test, however, might be inconclusive, and it is difficult to imagine an athlete consenting to a procedure that would damage muscle.

Myostatin blockers may pose less trouble for testing, at least for now. Lee said it would not be too difficult to develop a test for the drug in development by Wyeth. But certainly there is potential for abuse with the myostatin-blocking gene as well, experts said.

"I would not underestimate the cleverness of those that would abuse any potential way to enhance performance," said Hamilton, of the anti-doping agency.

As evidence, he cited Balco Laboratories, which has been investigated by the IRS and other federal agencies, and is accused of creating a so-called "designer steroid" for athletes to evade drug testing. Bonds, Giambi and sprinter Marion Jones headline a list of several dozen top athletes who reportedly received the steroid, THG.

"The THG saga is evidence that the science available to the 'dark side' is formidable, and it is only by a degree of luck and the persistence of the IRS that Balco was even suspected of evil intent," Hamilton said.

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