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This monkey's part jellyfish: Transgenic success a breakthrough

Friday, January 12, 2001

By Byron Spice, Science Editor, Post-Gazette

Just 3 months old, ANDi looks like any young, healthy rhesus monkey. Yet never has there been a monkey quite like him.

ANDi the monkey. (AP Photo)

ANDi -- a backward acronym for "inserted DNA" -- is the world's first transgenic monkey -- a monkey genetically altered to include a gene from another species, in this case a glowing jellyfish. Researchers in Oregon took a bit of jellyfish DNA and slipped it into the monkey egg that eventually became ANDi.

The jellyfish gene produces proteins that glow green, which isn't anything that's important to a monkey. In fact, ANDi doesn't glow, or at least not yet. What's important is simply that the gene is there, in every cell of his body.

The advance, reported in today's edition of the journal Science, is a first step toward genetically tailoring monkeys so that they can mimic devastating human diseases, such as Alzheimer's, diabetes and Parkinson's.

Transgenic lab mice have been used this way for years, but a transgenic monkey could prove especially valuable for developing and testing treatments because monkeys are close genetic relatives to humans.

"I think it's actually quite a big deal," said Dr. Ronald Herberman, director of the University of Pittsburgh Cancer Institute. A transgenic monkey with human genes that promote cancers, for instance, could provide insights that lead to new treatments and accelerate the evaluation of those treatments.

But the humanlike characteristics that make monkeys so valuable as disease models also raise ethical concerns. "It is hard to see what would ever justify genetically modifying monkeys to model human disease," said Donald Bruce, director of the Church of Scotland's Society, Religion and Technology Project. "Most people value large mammals and primates higher than small animals like mice and rats."

Anthony Chan, a senior scientist at the Oregon Regional Primate Research Center at the Oregon Health Sciences Center, sees it differently. By making monkeys that develop the same disease as humans, or perhaps develop it faster, scientists might be able to use fewer monkeys to get results.

The number of diseases in which monkeys are used may multiply, but the total number of research monkeys may not change much because fewer are used for each experiment, added Chan, who headed the transgenic monkey experiment with senior scientist Gerald Schatten.

Development of a transgenic monkey has lagged behind other transgenic species because researchers have tried to minimize the number of animals used, Chan said. Conventional gene transfer techniques are very inefficient -- injecting DNA into fertilized eggs might result in just one transgenic animal out of 100 births.

So Chan and Schatten used a technique similar to that used in many gene therapy trials. The jellyfish DNA was packaged inside a viral vector, a virus altered so that it cannot cause disease but will carry a gene inside a cell's nucleus. The vector was used to transfer the DNA into 224 monkey eggs, which were then fertilized. About half divided to become embryos and 40 of those were selected for implantation in monkey wombs.

The result was five pregnancies and three live births. Two of the three monkeys did not have the green fluorescence gene, but ANDi did.

The fluorescent gene was used, as it has been in many previous transgenic experiments, because it usually is easy to detect. Chan said genetic analysis shows that the gene has been activated, but has not yet produced fluorescent proteins, or at least not enough to detect.

It will be awhile before monkey-based disease models begin appearing in labs. "This is not entirely straightforward or safe technology," Herberman said, and experts such as Schatten and Chan are few. Pitt is ill-equipped to develop such animals, but Herberman said he hopes to develop a collaboration with Schatten, a friend of his.

Chan said the Oregon facility, home to 2,200 primates, is looking for that kind of input as the researchers try to decide which human disease should be transferred to monkeys first. He expects the first such disease models will be developed later this year or next year.

"We need to have a lot of input to make it right," Chan said.

The idea of redefining a species to accommodate human experiments "is sobering, at the very least," said Ronald Cole-Turner, an ethicist at the Pittsburgh Theological Seminary who specializes in science and technology issues. Scientists will be altering a species for a purpose other than what evolution or God intended.

"But we do things that are sobering because cancer is devastating," Cole-Turner said. "If it advances the science, then limited use, I think, is justified."

From a broader perspective, the Oregon experiment can be seen as a step toward so-called "germ-line" modification of humans, Cole-Turner said. Many moral and ethical questions remain to be answered before anyone should attempt to change the inheritable traits of humans, he emphasized, but the Oregon results underscore the fact that such modifications are "really very difficult."

"It shows how difficult it's going to be to cross the safety threshold," he said.

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