February 14th, 1999

Transmission 762908: Agents Involved

January 11 12:53 PM EST output: ABCNEWS.com

Scientists Splice Fluorescent Gene Into Monkey

Scientists have modified the genetic make-up of one of man's closest
relatives: the monkey. Scientists say the procedure that gave a monkey
genes to glow could be a boon for research while others fear it
dangerously tinkers with nature.

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 the 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 glow - glow green, in fact - under black light.

A Close Human Model

By altering the genetic makeup of ANDi, researchers hope they have
demonstrated they will be able to introduce other genes into monkeys
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 biomedical researcher who studies
genetic links to alcoholism at Wake Forest University Baptist Medical
Center. "So then you have a close model to the human condition."

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 black 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

"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 black
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, 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

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.