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Unnatural Selection Genetic engineering is about to produce a new breed of athlete who will obliterate the limits of human performance

May 14, 2001
May 14, 2001

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May 14, 2001

Unnatural Selection Genetic engineering is about to produce a new breed of athlete who will obliterate the limits of human performance

In an unmarked cage in the bowels of the University of
Pennsylvania's Department of Physiology crawls the future of
sport. It is a genetically altered mouse. We'll call him He-man
because a creature of such import should be known by a name, not
a number.

This is an article from the May 14, 2001 issue

Soon after He-man was born, a team of Penn researchers led by Dr.
H. Lee Sweeney injected its muscles with a synthetic gene that
instructed its muscle cells to produce more IGF-1 (insulin-like
growth factor-1). IGF-1 is a protein that, in a nutshell, makes
muscles grow and helps them repair themselves when they've been
damaged. It is indispensable to the formation and maintenance of
strong physiques. For the most part, when those of us under 30
exercise vigorously, our bodies start producing lots of IGF-1.
Our muscles get bigger, and we get stronger.

As we age, the muscles stop producing IGF-1 in the quantities we
need to keep our muscles looking as they did when we were
younger. They sag, and they don't repair themselves as
effectively as they used to. We get slower and weaker. "Even if
you train," says Sweeney, "you lose speed."

It happened to Carl Lewis, Wayne Gretzky and Jerry Rice, among
others. But it hasn't happened to He-man. Because of the gene
that was injected two years ago, the mouse grew exceptionally
large muscles, and those muscles keep producing IGF-1. He-man, in
the throes of mouse old age, remains as mighty as he ever was, an
Arnold Schwarzenegger of mice. His muscle mass is 60% greater
than that of a normal mouse. He effortlessly climbs a ladder with
120 grams of weights--equal to three times his body
weight--strapped on his back.

"We showed that with a onetime injection of this gene we can get
bigger muscles in young animals and that, as they get older, the
muscles never change," says Sweeney, whose research is funded by
the National Institutes of Health. "The muscles maintain their
size through the whole life of the animal."

The implications for athletes are not lost on Sweeney. Implant
this IGF-1 gene into the proper muscles and Olympic sprint
champion Maurice Greene might be as fast at 48 as he is at 24.
Randy Moss might still outrun and outjump defensive backs in
2020. Pavel Bure might be skating as fast 30 years from now as he
does today.

Fanciful? Don't bet against it. Whether in one year, three years
or five years--the last of those being the prediction of most
experts--the first genetically engineered athlete will be secretly
competing. "It's not rocket science," says Theodore Friedmann,
director of the gene-therapy program at UC San Diego and a member
of the medical-research committee of the World Anti-Doping Agency
(WADA). "If you asked any molecular biologist, or even his
students, how he would implant genes to change muscle function,
within half an hour he could write down three or four ways to do
it. The same would apply if you asked him, How would you improve
oxygen transport? How would you change athletes so they could
jump higher and run faster? Be taller, stronger, whatever?
Because of the whole Human Genome Project [a federally funded
effort to identify the estimated 100,000 genes in human DNA],
synthetic genes are available, and putting genes into people to
express new functions is becoming reality."

"If this is being done on mice and rats, humans aren't far
behind," says Bengt Saltin, a Swedish professor of human
physiology at the University of Copenhagen and a member of WADA's
special committee on gene doping. "The only thing keeping it from
happening today is the control problem. For example, you can
insert a gene to increase EPO production"--EPO is a hormone some
athletes inject to illicitly boost the production of red blood
cells, thus enhancing their endurance--"but you can't shut [that
production] off when you want to." When the technology is
developed that will enable us to turn hormone production on and
off at will, says Saltin, we'll "have real problems."

Sweeney believes the IGF-1-inducing gene will slow the muscle
deterioration brought on by muscular dystrophy, and he had hoped
to have a clinical trial on humans under way by this spring. But
he has delayed seeking approval from the Food and Drug
Administration (FDA) because of the 1999 death of a patient in a
different gene-therapy trial at Penn. If approval is granted, as
is expected, and the synthetic IGF-1 gene proves safe in the
muscular dystrophy trial, the next step would be to conduct a
trial of the gene's ability to maintain a person's muscle
strength as that person ages. "All this is being driven by our
aging population," Sweeney says. "As people get old, they get
weak, and if they have an injury, [the muscle involved] doesn't
repair itself, so they lose even more muscle. They lose their
mobility. The ability to maintain muscle mass is [hugely
important] for an aging society."

"When [Sweeney's work] is done, it will decrease the incidence of
hip fractures in the elderly," says Gary Wadler, associate
professor at the New York University School of Medicine and an
adviser to the White House Office of National Drug Control
Policy. "But you'd better start inventorying the genes because
athletes will be trying to get them. That's the plain truth. His
work has the potential to be misused. It won't be long before
someone does a kinesiologic study of a pitcher's motion, say, to
determine which muscles should be enhanced for throwing a
baseball. Then with the injection of the IGF-1 gene you create a
superpitcher. The only way you'll be able to prove an athlete is
cheating is through a muscle biopsy, and that's not going to
happen."

WADA, a two-year-old organization that was founded by the
International Olympic Committee (IOC), is so worried about the
possible impact of genetic research on sport that it's hosting a
symposium on gene manipulation in September in Cold Spring
Harbor, N.Y. The purpose is to discuss the ethics of the matter.
Is gene therapy, the medical use of genes to repair an illness or
injury, acceptable for Olympic athletes? Is gene enhancement, the
implantation of genes to increase the performance of a perfectly
healthy body, unacceptable? Are there gray areas somewhere in
between?

"I am very clear on this," says IOC Medical Commission vice
chairman Jacques Rogge of Belgium, an orthopedic surgeon who may
succeed Juan Antonio Samaranch later this year as head of the
Olympic movement. "Genetic manipulation is there to treat people
who have ailments, not there to treat a healthy person."

However, the IGF-1 gene repairs and enhances muscle tissue. It
also keeps the muscles churning out insulin-like growth factor-1
indefinitely, which theoretically could allow the athlete to
perform at an optimal level years past what is now considered his
prime. Is WADA going to forbid the injured athlete from using
that particular form of gene therapy--one that may well be
available to the public--on the grounds it might fix him better
than new?

In fact, there's a tremendous upside to these forays into the
genetic minefield that even the naysayers see. "This gene
manipulation is not all bad," says WADA's secretary general,
Harri Syvasalmi of Finland. "We have to accept that some of these
enhancements will be wonderful, especially for athletes who are
injured."

It isn't only professional athletes who stand to benefit.
Weekend warriors could see a marked improvement in the quality
of their lives and athletic performances. More than 100,000
anterior cruciate ligaments are torn annually in the U.S. Damage
to knee cartilage is also common. Stress fractures account for
15% of all injuries to runners. These statistics are cited in a
February 2000 report published by three researchers from the
University of Pittsburgh, Dr. Freddie H. Fu, Dr. Johnny Huard
and Vladimir Martinek, who write that their early findings show
recovery from sports-related injuries involving slow-healing
tissues can be significantly sped up and enhanced through gene
therapy--specifically, by introducing genes, like the synthetic
IGF-1 gene, that express growth factors. "One day injured
tendons, cartilage or ligaments will be repaired through an
injection," says Wadler. "It will be like a salamander regrowing
a tail."

Bobby Orr, his knees crippled from six operations, would not have
had to retire at age 30. Joe Namath would not have limped off the
field for the last time at 34. His elbow pain gone, Sandy Koufax
could have pitched past 30. Tantalizing, yes? A little
frightening too. As at the dawn of any age, man's venture into
genetic engineering will have its champions and its detractors.
But it won't be stopped. Time will tell whether we are on the
brink of enrichment or the brink of disaster.

"The sports world was not prepared for anabolic steroids," says
Syvasalmi. "We can't get behind [on a doping trend] again. By
looking at gene enhancement now, we hope to raise the ethical
issues and appeal to the ethics of athletes."

The ethics of athletes? That's a good one. If history has taught
us anything, it's that athletes will do anything, try anything
and risk everything to win. "Go all the way back to the ancient
Greek Olympics and you'll find stories," says Saltin. "Man has
always believed there was something he could put in his mouth to
help him win. Gene manipulation is only the next step. I guess
I'm naive, but I hope that ethics will win out. If I'm wrong,
it's the end of sport as we know it. Sport will be a circus of
unbelievable performances."

Norwegian speed skater Johann Olav Koss, a triple Olympic gold
medalist in 1994, knows something about both unbelievable
performances and the nature of athletes. A recent graduate of the
University of Queensland medical school in Australia and an
athlete's representative to both the IOC and WADA, Koss doesn't
know whether to be more frightened of gene manipulation from an
athlete's perspective or a doctor's. "Athletes should realize the
research that's been done in this field is absolutely not good
enough to know the risk of long-term damage," he says. "Don't let
the doctors tell you differently. There is no knowledge about the
potentially damaging side effects of genetic changes. Saying
that, we also know some athletes don't care about long-term risk.

"This is an ethical question, not only for sport, but for the
human race," Koss continues. "You are tinkering with nature. How
far are you going to go? What is acceptable? What will be the
effect long term? Why shouldn't we create something genetically
that is much smarter, stronger and better than a human? Why
shouldn't we put wings on a human? Why shouldn't we give humans
the eyes of a fly? Then we are no longer human, we are something
else. You could eliminate the human race."

There are many reasons that we should not go down that road.
Trouble is, world-class athletes, even without genetic
enhancement, are a different breed. "An atmosphere has been
created in which it doesn't matter if you cheat," says Koss, "as
long as you win."

Over the years sports officials from many countries have proved
they're as prone to embrace that mentality as the athletes they
oversee. East Germany's state-run steroid program, which has come
to light in the last couple of years, exacted a terrible physical
and psychological toll from a generation of that country's
athletes. No nation's ruling sports bodies are above suspicion,
including those from the U.S. Small wonder, then, that among
WADA's long-term fears is state-sponsored cloning. "It's a real
issue for sport," says Saltin. "If you're a country, why not take
the chance and clone Pele--or 25 Peles--and engineer an entire
team?"

A Quebec company called Clonaid may have already begun human
cloning experiments. Using the DNA of a dead infant, the company
is supposedly trying to clone another child for the bereaved
parents for $500,000. Since DNA can be obtained from a strand of
hair, the imagination races with visions of molecular biology
students of an entrepreneurial bent swooping in to gather hair
after Tiger Woods leaves a barbershop and then selling the
strands for underground cloning experiments.

"I honestly believe that if the Soviet Union hadn't fallen apart,
it would be genetically altering humans by now," Sweeney says.
"The Soviets were always more willing to push the envelope than
we're allowed to here. And the next step would be to pick mothers
and fathers of the next generation of athletes, give their
children altered genes to determine all kinds of talents, then
watch them grow. Who knows where it would go?"

No one. Athletes, though, are sure to step forward for many of
the experiments. Even after knowing the potentially damaging,
sometimes fatal, side effects of the performance-enhancing drugs
now available, athletes of all cultures have not hesitated to
experiment with steroids, EPO, human growth hormone, blood doping
and God knows what else. They're 21st-century Fausts, willing to
bargain future health for present glory.

Sweeney has certainly discovered that. He has already been
contacted by several athletes, most of them weightlifters, who
have heard about his research and wonder if he's looking for
human volunteers on whom to test the IGF-1 gene. "They wanted to
know what I thought it would do for them and what the safety
issues were," Sweeney says. "Then the main question was how they
could get it. I told them I had no safety data on humans
whatsoever, but based on the mice, I didn't think it was a big
risk. They were fine with that. Safety data didn't mean anything
to them. They basically said they were willing to do it right
now. I told them the FDA wouldn't be fine with that and I could
go to jail if I helped them."

What are the risks of genetic engineering? The theories range
from Koss's worries about the elimination of the human race as we
know it, to only slightly less apocalyptic scenarios involving
genetically altered viruses running amok and genes spinning out
of control. Right now the preferred delivery vehicle for a gene
like the one Sweeney implanted in He-man is a common virus.
Essentially, the virus is denuded of its illness-causing
characteristics and all genes, then stuffed with a synthetic gene
and injected into a particular muscle or organ. If all goes well,
the new gene will live harmoniously within the host for the rest
of the host's life, reproducing itself in the new cells it helps
create and merrily expressing whatever function it was selected
to express.

If things go badly, the gene could sit sullenly in its new home
and refuse to express. Far worse, the body's natural defense
mechanisms could kick into gear and attack the virus or the
synthetic gene, as happened in the gene-therapy trial at Penn two
years ago, when a young patient who'd had a gene injected into
his hepatic artery died after his body's immune system shut down
his liver.

Then there are the control issues to which Saltin referred.
Who's calling the shots, you or your new gene? What if in its
enthusiasm, your new gene overdoes it and gives you too much of
a good thing? Be careful of what you wish for. Visions of
12-foot-tall basketball players come to mind, and football
players with muscles so immense and powerful that they can't be
supported by the surrounding tendons and skeletal structure.

Genetically altered houseflies demonstrated a variation of the
latter problem. Researchers found that they could genetically
enhance a fly's flight muscles so that they were 300% stronger
than normal. That was the good news. The bad news was that the
fly couldn't get off the ground. "The fly actually lost power
because it couldn't make its wings move fast enough," explains
Sweeney. "It's a good example of why we need to learn more about
how muscle groups work and interact."

Try to explain that to a college lineman yearning to be drafted
by the NFL, who learns that with one injection of something
called growth-hormone-releasing hormone (GHRH) he could gain 70
to 80 pounds of muscle. "If athletes are willing to take hGH
[human growth hormone]," says Sweeney, referring to a banned
substance believed to be widely used among Olympic athletes,
"this is, in my opinion, safer, cheaper and probably gets better
results. GHRH will be the next great problem for athletics."

In research conducted by Dr. Robert Schwartz of Baylor College of
Medicine, piglets injected with GHRH grew 37% heavier than their
siblings and had 10% less fat. The pigs were stronger and leaner.
GHRH is different from HGH in that it sends a signal to the
pituitary gland to start cranking out growth hormones. And keep
cranking. The growth hormones aren't introduced externally, so
the body tends to accept them. "This has got the pig farmers all
excited, but I know that athletes read many of these scientific
journals," says Sweeney. "So I'm sure some out there are already
looking into it. The only thing I'd advise is to be sure to put
it into a muscle you're not too fond of, in case one day you want
to stop growing, you could just cut that muscle out."

One thing is clear. We'll all share an interest in genetic
enhancement, whether for something as simple as a hair-growth
gene to end our baldness or as potentially life-changing as the
ability to remain mobile, even spry, in our dotage. "The public
will accept genetic interventions because it will want them,"
says Sweeney. "I see a day when this is going to be commonly used
in the population because the population does not like getting
old and weak and ending up in a wheelchair. Once society accepts
it, the Olympic committee is going to have to deal with it. The
days that it can try to stop it are numbered."

COLOR PHOTO ILLUSTRATION: PHOTO ILLUSTRATION BY AARON GOODMAN [T of C]COLOR PHOTO ILLUSTRATION: PHOTO ILLUSTRATIONS BY AARON GOODMAN/ J&P WEGNER/ANIMALS ANIMALS (CHIMPANZEE); AMANDA CLEMENT/PHOTODISC (BEACH)COLOR PHOTO ILLUSTRATION: PHOTO ILLUSTRATIONS BY AARON GOODMAN/ JOHN IACONO, CHUCK SOLOMON (RODRIGUEZES)COLOR PHOTO ILLUSTRATION: PHOTO ILLUSTRATIONS BY AARON GOODMAN/ BRIAN SMITHCOLOR PHOTO ILLUSTRATION: PHOTO ILLUSTRATIONS BY AARON GOODMAN/ JOHN BIEVER (POLE VAULTER); ADALBERTO RIOS LANZ/SEXTO SOL/PHOTODISC (STADIUM)
Why not clone A-Rod--or 25 A-Rods--and engineer an entire team?
With gene therapy, Joe Namath wouldn't have limped off the field
for the last time at 34.
"Sports will be a circus of unbelievable performances."
"An atmosphere exists in which it doesn't matter if you cheat,
as long as you win."