Man-Made Monkey
For the First Time, Researchers Have Altered the DNA of a Primate

By Amanda Onion


Jan. 11 — His fur is light brown and black, he weighs just over 3
pounds, he is frisky and has long white fingers and big brown eyes.
But the most distinguishing feature of ANDi, a 3-month-old rhesus
monkey, is that every cell of his body has been altered by man.



For the first time, scientists have modified the DNA of a primate species, whose genetic coding
varies from people's by only slightly more than 1 percent. Scientists at Oregon Health Sciences
University inserted a variation of a gene, plucked from a fluorescent jellyfish, into the DNA of an
unfertilized egg. The egg was then developed into ANDi, which is a backward acronym for
"inserted DNA" and scientists expect it should make the monkey's cells glow — glow green, in
fact — under fluorescent light.

A Close Human Model

By altering the genetic makeup of ANDi, researchers hope they have demonstrated they will be
able to introduce into monkeys other genes that cause a host of diseases in people. Such work
could provide living laboratories to analyze the effects and possible treatments for diseases like
Alzheimer's, breast cancer or diabetes.

"The fact that this has been done in a monkey is exciting because the physiology of a rhesus is
very similar to human beings as is the genome, itself," says Kathleen Grant, a researcher at
Wake Forest University Baptist Medical Center, who studies possible genetic links to alcoholism.
"So then you have a close model to the human condition."

Scientists first altered the genes of an animal — a mouse — in 1976. Since then they have
tinkered with the DNA of fruit flies, sheep, goats, rabbits, cattle and pigs. The rhesus monkey is
the closest relative to humans to be genetically altered. The jellyfish gene that was added to
ANDi has no medical value in itself, but it can serve as a dramatic marker since it makes the cells
of an animal glow green when exposed to fluorescent black light.

Lead author of the study to be published in Science, Anthony Chan, says his team's work is "a
success in showing that we are capable to deliver a new gene into the genetic blueprint of
non-human primates." But so far there is a slight wrinkle in the results: ANDi doesn't glow green
— at least not yet.

Waiting For ANDi to Glow

Chan, a scientist at the Oregon Regional Primate Research Center, has tested cells from ANDi's
blood and from skin cells taken from the inside of his cheek and found they do carry the
introduced gene. But when exposed to fluorescent light, they don't glow green as do the cells of
the gene's original jellyfish host.

Chan says this could be due to one of two reasons. Either the gene they introduced isn't
producing enough of the fluorescent proteins to detect, or the altered bit of DNA has yet to be
translated by the body's so-called gene messenger, RNA, to produce the glowing proteins in
young ANDi.

"It will be important to learn why we can't see it for learning how the transgene is regulated in
the monkey," says Chan, who says they expect to understand the problem soon.

Once the glitch is fixed or understood, the technique
developed at the Oregon center should produce
rhesus monkeys that glow green under special light.
This isn't the first time that fluorescent animals have
been produced. In 1994, scientists used the same
jellyfish gene to make a worm glow green and in 1997,
Tokyo scientists created green fluorescent mice. Last
September, Eduardo Kac, a Chicago artist created a stir when he
had French scientists develop a fluorescent rabbit he named Alba.

Tagging Diseases by Fluorescence

Although Alba, the fluorescent rabbit, was designed
for show, adding luminescent jellyfish genes to other
species holds great scientific value. The fluorescent
genes can be used to tag other genes or proteins.
When that protein is active, scientists can detect its
fluorescence under a black light. When it's inactive, no
fluorescence appears.

Robert Hoffman, a researcher and chairman at the
biotech research company, Anticancer, Inc., in San Diego, now attaches fluorescence to cancer
cells to trace their development in mice. He calls the fluorescent tags, "reporters" since they
inform the researcher of their location from inside a living animal.

"If you can have reporters that tell you something is wrong or right in the genes of interest —
that's a terribly important tool," he says.

But not everyone is pleased with the news of ANDi's conception. Animal rights activists claim
this is one more step toward exploiting animals for dubious research purposes.

Animals as Test Tubes?

"We condemn them for their philosophy that animals are nothing more than test tubes," says
Peter Wood, a research associate at People for the Ethical Treatment of Animals. "And we
believe this is another pipe dream of Frankenstein science."

Chang counters that improving the animal model as a way to study human disease could actually
reduce the number of animals used in laboratories. And Hoffman at Anticancer adds that using
fluorescent genes in laboratory animals allows scientists to glean more data from animals while
they're living and so less animals are needed for dissection.

Suzanne Roy, from the advocacy group In Defense of Animals, doesn't buy that claim.

"Within the context of their work, it may seem more humane," she says. "But the whole picture is
wrong to begin with."

Beyond the research claims and animal rights complaints that ANDi brings, the creation of this
young monkey also raises other issues that touch upon people's very sense of self. That's
because by altering the genetic make-up of a rhesus monkey, scientists have actually altered the
gene pool of the species.

Tinkering With Gene Pools
Even though ANDi will be confined to living with a group of other rhesus monkeys at the Oregon
laboratory for the rest of his life, his altered genetic presence could theoretically alter future
species. If ever applied to people, this technology could similarly forever alter the genetic pool of
humans.

"This gives great hope for genetic therapies," says Harold Garner of the McDermott Center for
Human Growth and Development at the University of Texas Southwestern Medical Center. "But it
also introduces ethical dilemmas such as modifying the gene pool [forever]."

Someday scientists hope to compound the technology used to create ANDi with another
controversial technology: cloning.

A year ago, scientists at the same Oregon research center reported they had cloned the first
monkey by embryo splitting. That monkey is named Tetra and, according to the lab's scientists,
remains healthy. As Grant says, "the real coup de grace will be to marry the two" methods and
clone modified monkeys for research.

The controversial ANDi was not created in one try. Chan and other researchers modified and
fertilized more than 200 rhesus monkey eggs. Of those eggs, 40 embryos were produced that
led to five pregnancies and three live births. Of the three baby monkeys, only ANDi was born
with the modified genes.

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