Gina Kolota
New York Times News Service
Jun. 24, 2004 07:10 AM

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 Markus Schuelke, a pediatric neurologist at Charite University Medical Center in Berlin.

The baby, it turned out, had a rare 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 4 years old and still very strong, offers human evidence for the theory behind such drugs.

The boy's story, written by Schuelke, appears Thursday in The New England Journal of Medicine.

At the baby's birth, 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," Schuelke said.

After two months, the jerking movements had subsided, but the puzzle of the baby's muscles remained. Then Schuelke had an idea. He knew that 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 inactive the animals grew up lean and so muscular that 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, meaty, extremely muscular and lean, and they, too, researchers later found, had inactive myostatin genes.

"We had a big discussion about what to do," 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 father.)

So 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 testing.

The findings, researchers say, may help scientists discover why some people find it easy to get stronger while others can lift weights day after day to little effect. At least some of this variation, they suspect, may be a result of individual differences in myostatin levels.

Robert Ferrell, a professor of human genetics at the University of Pittsburgh who did a small study looking for genetic differences between professional bodybuilders and ordinary people, noted that everyone has run into people "who have great muscle definition and size; that's what I'm interested in."

Certainly the baby's mutation was unusual, Schuelke said. He and his colleagues tested 200 people who were 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, mimicking the effect of the genetic mutation in the mice and cattle or in the German boy. One way to do that could be with antibodies that block myostatin, a path that Wyeth is pursuing. The company has begun safety tests in humans with the goal of treating muscular dystrophy and muscle wasting.

Elizabeth McConnell of the University of Chicago, who wrote a commentary that accompanied 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 with 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 professional athletes.

"Although the ethics of using such genetic information is questionable," McConnell wrote, "the feasibility of identifying this information should not be doubted."

In addition, myostatin blockers could be used as performance enhancers.

"Myostatin blockade," McConnell wrote, "will probably work its way into professional and amateur athletics, as well as into the ever-growing business of physical enhancement."

But, researchers say, it is far too soon to know if such drugs would be safe.

While the mice and the cattle seem normal, said George Vlasuk of Wyeth Research in Cambridge, Mass., "the long-term effects of inhibiting this molecule aren't known."

Schuelke added another 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 the 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, 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?

Schuelke said he and his colleagues would be following the boy for years to come and eagerly watching what happens.