SAN FRANCISCO (AP) Researchers on Monday unveiled genetically
engineered mice that can run farther and longer than their
naturally bred brethren, bringing the ``genetic doping'' of elite
athletes a mouse step closer to reality.
The creation of the so-called marathon mice, announced Monday,
follows earlier genetic engineering work that created
``Schwarzenegger mice,'' rodents that bulked up after getting
injected with muscle-building genes.
The engineered mice racing away on their treadmills are bound to
add to the furor over performance-enhancing substances, just as the
world's best marathoners prepare for the Olympic event Sunday.
The gene engineered in these mice essentially mimics exercise:
Researchers say it conferred endurance and prevented the modified
mice from becoming obese even when they were kept inactive and
fed a high-fat diet.
``This is a real breakthrough in our understanding of exercise
and diet and their effects on obesity,'' said lead researcher
Ronald Evans of the Salk Institute in San Diego. ``The practical
use of this discovery is the implication in controlling weight.''
The paper describes how engineered mice, even the couch potato
variety, were able to run farther and longer if their ``fat
switch'' genes remain switched on continuously. The engineering
also appeared to make them immune to obesity.
Evans found the gene he dubbed the ``fat switch'' more than 10
years ago, but it is only just now that its broad implications are
being understood. Evans now believes his work has implications for
just about every disease of the metabolism, from obesity to heart
disease.
``This gives us a real lever on metabolism,'' Evans said.
Of course, nobody cares more about the intricacies of the human
metabolism than Olympic athletes and for better or worse, Evans
is bracing for a flood of inquiries from their trainers now that
his research paper has been published in the online journal Public
Library of Science Biology.
Many predict that steroids, growth hormones and other drugs and
chemicals that cheating athletes take to shave the smallest sliver
of a second off their times will soon seem quaint replaced by
hard-to-detect genetic engineering, which could become commonplace
as soon as the Beijing Olympics four years from now.
Instead of improving times by fractions of a second, the
genetically enhanced marathon mice ran twice as far and nearly
twice as long as naturally bred rodents.
The engineered mice ran 1,800 meters before quitting and stayed
on the treadmill an hour longer than the natural mice, which were
able to stay running for 90 minutes and travel 900 meters. Evans
said he has not seen any adverse side effects in the engineered
mice.
Evans expects his research will be of keen interest to the
Olympic officials who struggle to keep athletes honest. ``It's a
bit ironic that we developed these marathon mice at the same time
of the Olympics,'' he said.
Evans and his team made the marathon mice to help them better
understand diseases of the metabolism such as obesity and diabetes.
The bulked-up ``Schwarzenegger mice'' serve a different purpose
research into muscular dystrophy treatments.
The ``fat switch'' gene, when switched on, begins the process of
creating ``fatigue-resistant'' muscles while helping the heart and
nervous system create endurance.
Humans run and jump thanks in large part to two types of muscle,
known as ``fast twitch'' and ``slow twitch.'' Depending on workout
regimens, fast twitch is converted into slow twitch or vice versa.
Sprinters crave fast twitch, which confers speed at the cost of
endurance. Marathoners work to bulk up slow twitch for the opposite
reason. Elite athletes are continuously probing their muscles to
ensure they have the right ratio of fast- and slow-twitch muscles.
Evans' team found that slow twitch converted into fast twitch
only when the gene in charge of the process kicked on, which was
only when the mice exercised. That is a problem for couch potatoes
with Olympic-sized goals.
So Evans took a piece of genetic material known as a promoter,
or ``gene switch,'' and injected it into the mice, keeping the gene
on continuously. As a result, even the laziest mice increased
endurance.
``The enhanced performance of the mouse could translate into
human athleticism,'' Evans said.
There's a big gulf between mice and men, and the field of gene
therapy has yielded mixed results over the last decade, including
the death of a human subject five years ago.
Still, Evans' earlier work is already being tested in people.
The pharmaceutical company GlaxoSmithKline PLC is conducting
mid-stage human experiments with a chemical that turns on the ``fat
switch'' in hopes of developing a drug to raise levels of ``good
cholesterol.''
``This may represent a significant role in exercise endurance,''
said Glaxo spokesman Rick Koening.
After Evans' latest work was published on Monday, Koenig added a
cautionary note: ``We do not condone the pharmaceutical enhancement
of athletes.''
(Copyright 2004 by The Associated Press. All Rights Reserved.)