Scientists Create the First Genetically Modified Monkey

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Jan. 11, 2001 -- Scientists have turned science fiction into science by successfully inserting an extra gene into a monkey.

The "transgenic" rhesus monkey was developed from a genetically modified egg and born to a surrogate mother. The monkey, named ANDi, could lead to animal models that closely mimic human disease and bridge the current research gap between mice and men.

"This is the first transgenic monkey, and it shows that we're capable of creating a genetically modified nonhuman primate model for research," researcher Anthony W.S. Chan, DVM, PhD, tells WebMD. He is staff scientist with Oregon Health Sciences University in Portland. His paper appears in the Jan. 12 issue of Science.

To create ANDi, whose name means "inserted DNA" spelled backward, Chan's team placed a special "marker" gene directly into 224 mature eggs of adult female monkeys. These modified eggs were then fertilized with monkey sperm and implanted into 20 surrogate mother monkeys. The five resulting pregnancies ended in two miscarriages and three healthy male babies -- two that do not carry the genetic marker, and ANDi, who does.

This "marker" gene that was inserted into ANDi creates a harmless green glow under a special light. So does ANDi actually glow? No, Chan says. "But he might. He is only 3 months old, and certain genes take time to be expressed. We also don't exclude the possibility that there's already expression, but our tests are not powerful enough to detect it," he says. More extensive testing performed on tissue from the miscarried fetuses showed "that all tissues carry the gene, although it is not expressed in all tissues. The same might be true for ANDi."

ANDi is important because he provides a model from which "we can learn the details of genetic expression, how genes are regulated, and where exactly an inserted gene is integrated into the genome." By learning how, where, and when genes become activated or deactivated, ANDi and other genetically altered animal models can help researchers figure out what goes wrong in any number of diseases and conditions, from diabetes and breast cancer to Parkinson's and HIV.

According to David T. Curiel, MD, who reviewed the paper for WebMD, the researchers "show very convincingly that they've expressed the marker gene in these primates, and that's definitely a technical accomplishment." But, he says, ANDi is not the primate equivalent of a "knock-out mouse" -- an animal in which a gene is removed in order to determine its function in the body. Curiel is director of the division of human gene therapy and the Gene Therapy Center at The University of Alabama at Birmingham.

Chan admits that ANDi "is not the perfect model" and that "yes, a knock-out model is best." But ANDi does offer "very good opportunities for research." Much of the important mouse research, in fact, has been done using "random insertion" models like ANDi, he says.

There are some diseases where an animal's native genes will interfere with the function of any gene we try to insert, Chan says. In those cases, only a true knock-out model would do. "But in other diseases -- sickle cell and Alzheimer's for instance -- expression of an inserted gene will give symptoms or effects similar to the human disease. You can learn a lot and increase understanding of those diseases from models like ANDi."

The ultimate goal of gene therapy, Curiel says, "is precise genetic correction" where an inserted gene replaces a damaged or mutant native gene. "A primate knock-out model would be extremely useful for researching precise genetic correction in humans," he says, "and this work is a legitimate and logical first step to get there."

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