Scientists Splice Fluorescent Gene Into Monkey

Jan. 11, 2001 -- 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, 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.