Is it Ethical to genetically engineer humans to have certain desirable traits? What traits would be okay and what traits wouldn't be? You probably have already eaten genetically engineered vegetables and fruit, but would you eat genetically engineered meat (like from Big Blue up above)?
Think performance enhancers are a problem now?
Welcome to the era of the
genetically engineered superathlete
Posted:
Tuesday March 11, 2008 12:27PM; Updated: Wednesday March 12, 2008 10:52AM
By
David Epstein
I am one of the
most avid sports fans you'll find," Se-Jin Lee says. It's true. He'll
watch anything. Basketball. Football. Fútbol.
Billiards on channel seven-hundred-whatever. As a graduate student in the '80s
Lee used to sit in his car in the driveway with the radio on to listen to the
games of faraway baseball teams. Even now, in his lab at Johns Hopkins Medical
School in Baltimore, he easily rattles off the NCAA basketball tournament
winners in order from 1964 to 2007. And, like anyone who values fair
competition these days, he's disturbed by the issue of performance-enhancing
drugs in sports.
Why, then, is Lee
working to usher in technology that will make even today's most inventive
doping methods look primitive? A professor of molecular biology and genetics,
the 49-year-old Lee studies genes that tell muscles what to do -- genes that he
knows how to change. As clever as chemists are in altering steroid molecules to
avoid detection (recall BALCO's THG, a.k.a. "the Clear"), those
designer drugs can be spotted once antidoping agencies know what to look for.
Even human growth hormone will be detectable soon, after a valid blood test
becomes commercially available. But if athletes develop ways to alter their
genes, the very blueprints for their own muscles, there may be no test of blood
or urine that can pick that up.
Lee is pushing the
frontier of genetic research into muscle building because the same
breakthroughs that could boost performance in sports might also bring about a
medical revolution. Advances could not only reduce or eliminate the effects of diseases
like muscular dystrophy but also give senior citizens back their strength --
which, often, would amount to giving them back their lives.
In 1995 in his lab
on North Wolfe Street, Lee and two colleagues identified the function of
myostatin, a protein that tells muscles when to stop growing. It does so,
scientists believe, by signaling "satellite cells," or stem cells
that lie dormant around the muscle until they're needed to build or repair it.
Experimenting on mice, Lee inactivated both copies of the gene in the animal
that code for myostatin. The result: Over four to six weeks the rodents
developed twice their normal muscle mass without a formal exercise regimen.
After Lee's results were published in 1997, he was awash in e-mails from people
with muscle-wasting disease (no surprise) offering themselves as subjects for
human experiment. He got similar offers (surprise!) from bodybuilders and
athletes. Imagine: double the muscle mass. Could he do to them what he had done
on the mice?
Some of the athletes
barely knew what they were inquiring about. They'd ask Lee where they could
purchase some myostatin. "Of course, they didn't want myostatin," he
says. "They wanted to block it." But if they could block it with a
synthetic gene, the alteration would be a part of their DNA, and it would last
for years at the center of their cells. The most straightforward way of
detecting the new gene would be to remove a piece of the muscle and probe for
it, a procedure most likely too invasive for widescale use. It would be enough
to make one long for the simplicity of the steroid era.
The year after Lee's mice results went
public, H. Lee Sweeney, a physiology professor at the University of
Pennsylvania, published a paper detailing his own mighty mice, which he had
injected with a gene engineered to produce a muscle builder called insulin-like
growth factor (IGF-1). Sweeney, too, was inundated with inquiries from
athletes. He says a high school football coach and a high school wrestling
coach volunteered their entire teams as guinea pigs.
Since the gene
genie escaped from the bottle a decade ago, researchers have discovered dozens
more genes that appear to affect athletic performance. This is old news in the
rodent community. Scientists have created mice whose bodies are flooded with
oxygen-carrying red blood cells, creating greater endurance. Other mice have
been engineered to produce extraordinary amounts of growth hormone, while still
others metabolize fat and carbs in such a way that they can live like couch
potatoes yet run like marathoners.
Significant safety
hurdles remain before gene therapy is widespread for humans. The most efficient
means of delivering a synthetic gene is by attaching it to a virus that
shuttles it into human cells. Viruses are great at that. They can also trigger
the immune system in a way that can lead to fatal results. In 1999 Jesse
Gelsinger, an 18-year-old with a rare liver disease who had volunteered for a
gene-therapy trial, died from a massive immune response to the virus used in
the treatment. And the dangers extend beyond the immune system. In a
gene-therapy trial in France, 12 boys were successfully treated for X-linked
severe combined immunodeficiency, commonly known as Bubble Boy syndrome, but at
least three of them developed leukemia.
One delivery
method -- flushing the bloodstream with the desired gene -- is simple enough,
says Sweeney, that it could be achieved by a clever undergrad in a molecular
biology lab. The method is not very efficient and hasn't been thoroughly
tested, but it hints at the possibilities for the spread of gene tampering in
sports. Despite the unknowns and the dangers, chances are good that someone at
the Beijing Olympics in August, someone willing to weigh his or her mortality
in gold, will have undergone gene transfer in an attempt to enhance
performance. "Even when I tell them it's not safe," Sweeney says,
"some athletes are willing to try anything."
The signs are
ominous. In January 2006, during German track coach Thomas Springstein's trial
on charges of providing performance-enhancing drugs to minors, evidence emerged
indicating that Springstein had attempted to procure Repoxygen, a gene-therapy
drug developed to treat anemia by prompting cells to produce EPO and, in turn,
red blood cells. (He was found guilty of giving illegal substance to minors and
received a 16-month suspended sentence.) In addition, Mauro Di Pasquale, the
1976 world powerlifting champion and an Ontario physician who has written
several books on sports doping, says he knows that athletes are experimenting
with gene doping, with the help of Chinese doctors and researchers.
Human data
relating to myostatin has been hard to come by. Soon after his discovery, Lee
attempted to identify potential test subjects with natural mutations in their
myostatin genes. He placed an ad in Muscle
and Fitness, and close to 1,000 muscle-bound men and women responded. But
after collecting samples from 150 of them, he has yet to find a single one with
the myostatin mutation he had engineered in his mice.
From his study of
Belgian Blue cattle, Lee knew the mutation could occur naturally. A cross
between the Shorthorn and the Holstein, which have been bred for some 150
years, these massive animals look as if their skin has been stuffed with
watermelons. Lee got in touch with Dee Garrels, owner of the Lakeview Belgian
Blue Ranch in Stockton, Mo., who sent him samples for testing. Garrels knew
Belgian Blues were strong -- her 2,500-pound bull once ripped a metal
restraining gate off its hinges with its horns to get at a cow in heat -- and
Lee found out why. He discovered that they had mutations in their myostatin
genes.
Lee didn't see the power of a human
myostatin mutation until Markus Schuelke contacted him in 2003. A pediatric
neurologist in Berlin, Schuelke had been summoned three years earlier to
examine a jittery baby in the nursery at Charité hospital in Berlin, where he
was taken aback by the newborn's chiseled calves and sculpted quads. By the age
of four the boy could hold up a pair of 6.6-pound dumbbells at arm's length.
Schuelke had been monitoring the boy's development, and he got in touch with
Lee, who confirmed the boy had mutations on both myostatin-coding genes,
leaving no detectable amount of the protein in his body.
Apparently it ran
in the family. The boy's mother, who was 24 when she gave birth to the
"superbaby," had a mutation on one of her two myostatin genes,
presumably leaving her less of the protein than normal but not so little that
she was as muscle-bound as her son. Nevertheless, she is a testament to the
tantalizing temptation of gene-doping. Superbaby's mother, the only adult in
the world with a documented myostatin mutation, was a professional sprinter.
The world
anti-doping agency has banned gene tampering in athletes and spent millions
attempting to develop tests to identify it. Such a procedure will require
technology unlike any employed by antidoping scientists. The theory, according
to Ted Friedmann, the scientist leading WADA's search for gene-doping
countermeasures, is to fight genes with genes. If one medical breakthrough is
revolutionizing doping, perhaps another can beat it back.
Thanks to the
Human Genome Project, someday all of us could carry our entire genetic
blueprint on a microchip, which we'd present to doctors during medical treatment.
As that technology matures, Friedmann hopes athletes' genomes can be screened,
and that gene-doping markers or signatures will emerge.
As pharmaceutical
companies race to turn genetic research into medicine, new gene-therapy drugs
could come to market en masse over the coming years. In practical terms it will
be impossible to develop specific tests for each of them. "We can keep
buying instruments and keep building labs," says pharmacologist Don
Catlin, founder of the UCLA Olympic Laboratory, "but [the antidoping]
industry isn't like Exxon. There are certain limits."
Perhaps a time
will come when there is no longer a need to define those limits -- not because
of new artillery in the war on doping but because gene therapy will have become
so widespread that it will be as controversial as Flintstone chewables. So far
Sweeney has aided antidoping officials. "But I've often told WADA my
position would change if [gene therapy] is proven to be safe," he says.
"Then we're withholding something that would make the athletes
healthier."
That would, in
turn, raise a new series of questions: What is it we seek to gain from sport?
Do we want to see larger-than-life
behemoths swatting 600-foot home runs? Or do we prefer to see people more like
us pressing the limits of their strength and skill? After all, with their
doctors and coaches and cutting-edge equipment, professional athletes, doped or
not, are hardly us.
The gravest danger
in the debate over gene transfer is not that athletes might taint sport by
tampering with their genes. It's that by abusing such treatment, they'll create
the same stigma for gene therapy that they have for steroids.
Pat Furlong has
felt the effects of that stigma. She is the head of Parent Project Muscular
Dystrophy. Her two sons began life happy and healthy, "and then over 10 to
15 years, you watch them go away, helpless," she says. Part of her job is
to persuade parents of kids with muscular dystrophy and their doctors that
anabolic steroids are beneficial. "I get calls from parents nervous about
steroids because of what they've heard," she says. "But the flip side
is that steroids have benefits in people who are losing function. In Duchenne
muscular dystrophy, it's all we have.
"We know
there's no drug that will come without side effects, but steroids are an option
to preserve and protect muscle for a few minutes longer, or a few months
longer, or a few more years." The local newscasts, and Congress, rarely
mention the part about how they can help kids with MD walk longer, which keeps
their spines straighter and helps them breathe better.
As he stands at
the edge, looking over the gene-doping precipice, Se-Jin Lee has similar
concerns. The hysteria that will ensue when an athlete is caught gene-doping,
Lee frets, will result in restrictions on gene-therapy drugs, making them hard
to obtain by those who truly need them.
"If [an athlete] did cheat, it was
his choice," Lee says. "If [the league] turned its back and allowed
that to happen, it was their choice. Patients with debilitating diseases did
not get there by choice."
