The
HULK Gene
Scientists have unlocked the code for unlimited
muscle growth, a breakthrough that has the
potential to save millions of lives—and create
lots of really muscular people.
BY SHAWN PERINE /// PHOTO-ILLUSTRATION BY ERIC HEINTZ
IN 1997
Se-Jin Lee, M.D., a professor of molecular biology and genetics at Johns
Hopkins’ Institute for Basic Biomedical Sciences, with the assistance of then-
graduate student Alexandra C. McPherron, made a groundbreaking discovery. While studying
cell growth and diferentiation in mice, Lee and company found that by knocking out a previ-
ously unidentified gene in embryonic mouse cells, they could create “mighty mice”—animals
that carried twice as much muscle mass as their normal siblings. Lee dubbed the previously
undescribed gene “myostatin,” after the protein whose release it is coded to trigger.
Myostatin protein limits muscle growth in a number of animals during the developmental
and adult stages. The myostatin gene regulates it in much the way a spigot regulates the flow
of water. Normally, the spigot is left open, myostatin is released into the bloodstream, and
skeletal muscle growth is kept in check. When the spigot is turned of, however, as in the case
of Lee’s mighty mice, muscle growth is unimpeded. McPherron et al. described the phenom-
enon in the May 1997 scientific journal Nature. A
startling photo of a transgenic mouse side by side with
Magazine as saying that “they look
its genetically unaltered brethren reveals that the
like Schwarzenegger mice.”
genetically altered mouse sports bulging calves, round
It wasn’t long before Lee noted
sweeping thighs, and knotty back muscles, but the
that his heavily muscled mice bore
control mouse is typically mouselike. In describing his
a close resemblance to a couple of
muscular subjects, Lee was quoted in Johns Hopkins
other Mr. Olympias of the animal
kingdom, namely the Belgian
Blue and Piedmontese breeds of
cattle. Like the mice, the beefy
bovines are the result of genetic
manipulation, but not the kind
done in a lab.
In the early 1800s, Belgian
livestock breeders noticed that
some of their cattle possessed
much more muscle and less fat than
others. Seeing the upside to lean,
meaty stock, they crossbred the
biggest of the big to create a lineage
of supermuscular cattle, commonly
MIGHTY MOUSE At left, the “Schwarzenegger” mouse.
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MUSCLE & FITNESS
FEBRUARY 2016