A Very Muscular Baby Offers Hope Against Diseases
June 24, 2004
By GINA KOLATA
The moment the little boy was born, the hospital staff knew
there was something unusual about him. His muscles looked
nothing like the soft baby muscles of the other infants in
the nursery. They were bulging and well defined, especially
in his thighs and upper arms.
"Everybody noticed," said Dr. Markus Schuelke, a pediatric
neurologist at CharitÈ University Medical Center in Berlin.
The baby, it turned out in the first such documented case
in a human, had a double dose of a genetic mutation that
causes immense strength in mice and cattle. Drugs are under
development that, investigators hope, will use the same
principle to help people whose muscles are wasting from
muscular dystrophy or other illnesses. Experts say the
little boy, now 4Ω and still very strong, offers human
evidence for the theory behind such drugs.
The boy's story, written by Dr. Schuelke and colleagues,
appears today in The New England Journal of Medicine.
At the baby's birth, Dr. Schuelke said, his doctors were
worried. The infant was jittery, jerking his limbs, much
the way people sometimes involuntarily jerk their legs when
they are falling asleep.
"At first we thought it might be epilepsy," Dr. Schuelke
After two months, the jerking movements had subsided, but
the puzzle of the baby's muscles remained. Then Dr.
Schuelke had an idea. He knew that Dr. Se-Jin Lee at Johns
Hopkins University, working with mice, had found that when
both copies of a gene for a protein called myostatin were
inactivated, the animals grew up lean and so muscular that
Dr. Lee called them "mighty mice."
It turned out that cattle breeders, decades ago, had
stumbled upon the same genetic trick, developing a strain
known as Belgian Blue, or double muscle cattle. The cattle
are hefty, very meaty and lean, and they, too, researchers
later found, had inactive myostatin genes.
"We had a big discussion about what to do," Dr. Schuelke
said. "We remembered the mighty mice and the Belgian Blue
cattle. This child looked like that."
The child's mother was strong - she had been a professional
sprinter in the 100-meter dash - and she came from a strong
family. Her grandfather, a construction worker, had
unloaded curbstones by hand, hefting stones weighing at
least 330 pounds. (There was no information on the baby's
So Dr. Schuelke and his colleagues decided to test the baby
and his mother for mutations in the myostatin gene. The
mother had one nonfunctioning copy of the gene. In the boy,
both copies of the gene were inactive; he was making no
myostatin at all. No other family members agreed to genetic
The findings, researchers say, may help scientists pin down
why some people find it easy to get strong while others can
lift weights day after day to little effect. At least some
of this natural variation, they suspect, may be a result of
individual differences in myostatin levels.
"If you've looked at pictures of Arnold Schwarzenegger when
he was a teenager, he just looked naturally muscular,''
said Dr. Robert Ferrell, a professor of human genetics at
the University of Pittsburgh who in a small study found no
major genetic differences between professional bodybuilders
and ordinary people. "Everyone has run into people like
that who have great muscle definition and size. That's what
I'm interested in."
Certainly the baby's mutation was unusual, Dr. Schuelke
said. He and his colleagues tested 200 people not related
to the child and did not find it. But there are many ways
to disable a gene, and it is possible, researchers said,
that some naturally strong people have myostatin genes that
function poorly, or not at all.
Eventually, experts say, it may be possible to use drugs to
deplete myostatin. One way to do that could be with
antibodies that block it, a path that Wyeth is pursuing.
The company has begun safety tests in humans with the goal
of treating muscular dystrophy and muscle wasting.
Dr. Elizabeth McNally of the University of Chicago, who
wrote a commentary that accompanied Dr. Schuelke's paper,
is hopeful. In mice with muscular dystrophy, blocking
myostatin helped overcome muscle wasting, she said. There
is also the potential to help people who have muscle loss
from normal aging or from cancer and diseases like those of
the lung or kidneys.
In the future, people may be able to have their myostatin
genes tested to decide whether to train to become
"Although the ethics of using such genetic information is
questionable,'' Dr. McNally wrote, "the feasibility of
identifying this information should not be doubted.''
In addition, myostatin blockers could be used as
"Myostatin blockade," Dr. McNally wrote, "will probably
work its way into professional and amateur athletics, as
well as into the ever-growing business of physical
But, researchers say, it is too soon to know if such drugs
would be safe. While the mice and cattle seem normal, said
Dr. George Vlasuk of Wyeth Research in Cambridge, Mass.,
"the long-term effects of inhibiting this molecule aren't
Dr. Schuelke cited one concern: Muscle cells are surrounded
by immature satellite cells that lie dormant until the
muscle is injured. Then they migrate into the muscle,
replacing injured or dead cells. A recent paper indicated
that myostatin might normally function to keep satellite
cells quiescent. Without myostatin, he said, the satellite
cells might be so active building muscle that they become
depleted early in life.
For now, the little boy is healthy and very strong, able to
hold two 6.6-pound weights horizontally with his arms
extended. But while the muscles in his arms and legs are
twice as big as the muscles of other children his age, Dr.
Schuelke said, "he is not extreme: you wouldn't recognize
him if you saw him on the street."
The question is, What will happen when he grows older? Will
he be an athlete, a bodybuilder? Or will his satellite
cells be used up so that his muscles start to deflate when
he is 30 or so?
Dr. Schuelke said he and his colleagues would be following
the boy for years to come and eagerly watching what