Monkey Business

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The next step is to give monkeys human genes and human diseases

At the end of an inconspicuous two-lane road near the city of Beaverton, Ore., a cluster of modest concrete-and-glass buildings nestles amid ponds, fields and magnificent groves of evergreens--an oasis of natural beauty standing firm against the encroaching suburbs. Only a pair of football-field-size enclosures surrounded by 9-ft.-high sheet-metal walls and monitored from a watchtower give the hint that this is something more than just an unusually idyllic office park. The huge pens suggest a dinosaur paddock from Jurassic Park--an image reinforced when whatever is inside inexplicably starts slamming violently against the metal walls.

But while the creatures housed at the Oregon Regional Primate Research Center are nothing more exotic than monkeys, one experiment performed here and reported in last week's Science had something in common with the Spielberg thriller: an animal, produced by genetic manipulation, like nothing else on Earth. Despite its utterly normal outward appearance, the Rhesus monkey known as ANDi bears an extra gene taken from, of all creatures, a jellyfish. And while so-called transgenic animals have been created before, this is the first time such a species-mixing experiment has been performed on a primate, the class of animals that includes human beings--a point driven eerily home by the monkey's uncannily humanlike hands, expressive features and big round eyes.

It's ANDi's close kinship to humans that makes this experiment at once so promising and so troubling. On one hand, the ability to manipulate the genes of a creature so similar to humans could give researchers an incredibly powerful tool for studying and perhaps someday curing human illnesses--introducing Alzheimer's genes, for example, to test new drugs and vaccines against the disease. For that reason, says Richard Weleber, a professor of ophthalmology at Oregon Health Sciences University who believes the research could help cure the form of blindness known as macular degeneration, "this is a revolutionary achievement."

But the experiment also raises disturbing questions not only about animal rights but also about how far genetic manipulation can be permitted to go. If ANDi's genome has indeed been altered, he'll pass the change on to his offspring, creating an entire line of transgenic descendants. And while this so-called germline gene engineering is routinely done in lower creatures, moving it up to primates brings the technique much closer to being done in humans--a step so troubling that nobody is ready to take it. Says Tom Murray, president of the Hastings Center for Bioethics in Garrison, N.Y.: "You could not morally justify attempting anything like this in humans for a very long time."

Doing it in monkeys, however, could save lives. For more than a decade, researchers have been working with so-called knock-out and knock-in mice--rodents that have had genes added or effectively subtracted from their genome. By observing these custom-made lab animals, researchers have gleaned invaluable information about the workings of hundreds of illnesses, including arteriosclerosis, sickle-cell anemia and nearly every variety of cancer that afflicts people.

But mice are different from people; they aren't perfect laboratory stand-ins. They don't age precisely the way people do, for example. They don't have monthly menstrual cycles, and their neurological and immune systems differ in important ways. Much better to have a more closely related animal with body systems that are more like ours--which is why primate center senior scientist Gerald Schatten and his colleagues decided to try manipulating the genes of the Rhesus monkey, a close cousin to humans and already the mainstay of many medical experiments.

Before they could try transferring a gene, the scientists had to master the technique of in vitro (that is, test-tube) fertilization, which isn't typically used with monkeys. Though the technique wasn't required to create ANDi, the Oregon team had already learned to clone the animals, which in the future will prove important since having identical copies of different monkey strains will be crucial for rigorous scientific experiments. That milestone--the first cloning of a primate by embryo splitting--was achieved by Schatten's group last year.

Finally, Schatten and his team were ready to try a DNA transfer (see diagram). This first effort was meant only to test the technique, so they decided to use a gene that occurs naturally in jellyfish, where it directs the production of a harmless protein that glows with a greenish light under the right illumination. Mice, rabbits and other creatures who have had the same gene inserted actually do shine dimly; while ANDi (his name is a backward acronym for "inserted DNA") does not, the scientists have detected traces of the gene in his muscle, hair, cheek and blood cells. The researchers suspect that the gene may not be expressing its protein--or at least not at detectable levels--and may turn on fully only as ANDi ages.

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