BRAVE NEW MONKEY

He's a frisky little fellow, swinging from a ring in his doll-size white T shirt with the black belt, clambering over and through an elaborate cat-scratching post, sucking his thumb and ducking for cover when playmates Sandy and Sammy ambush him. To all appearances, ANDi (we'll explain soon) is an ordinary rhesus monkey. But appearances deceive. Born by cesarean section last October, ANDi is the first genetically altered primate ever created. If he were human, he'd be called a designer baby. And that makes him the embodiment of the greatest hopes as well as the worst nightmares here at the dawn of the age of genetics: that desirable genes will be inserted into human eggs, producing "genetically enhanced" children. Although that was not the purpose of the research that produced ANDi, the little guy with the soulful eyes is a landmark proof of concept. "At some point in the future," admits Anthony Chan of the Oregon Regional Primate Research Center, who performed the manipulations that created ANDi, "it is conceivable that others may attempt this technique to enhance humans."

The researchers say they had no such goal in creating ANDi. Instead, they hope to create primate models of human diseases, and they had to start simply. They first retrieved a well-studied gene, called the green fluorescent protein gene, from jellyfish. True to its name, the gene makes a protein that, in blue light, glows green. They then put copies of the gene into viruses, since (as anyone with the flu knows) viruses are adept at penetrating cells. Each virus dutifully carried the green gene into 224 rhesus-monkey eggs, where it slipped into the monkey genes like a foreign spy hiding in a crowd. The eggs were then fertilized through microinjection of sperm. After 126 of the fertilized eggs grew and divided beyond the four-cell stage, Chan selected what looked like the 40 best embryos and transferred them into 20 surrogate-mother monkeys. Five pregnancies resulted. One set of twins miscarried. One embryo failed to implant. Three monkeys were born. Sandy and Sammy show no sign of the green gene. But ANDi does. Hence his name: short for "inserted DNA," backward.

The next step is to give rhesus monkeys human genes that play a role in Alzheimer's disease, cancer, hereditary blindness, schizophrenia, Parkinson's or other scourges. A primate version of such a disease, scientists believe, should lead more quickly to vaccines or treatments than the mouse models that currently exist. In addition, genetically altered monkeys carrying a gene "for" Alzheimer's or prostate cancer, say, might show whether the suspect gene always causes the disease, or whether environmental factors like diet or activity can cheat genetic destiny.

The researchers chose the green gene because its presence is so easy to detect, not because they wanted glow-in-the-dark monkeys. In fact, ANDi looks nothing like a hairy green Lava lamp; the gene, although present in every tissue the Oregon scientists tested, seems to be dormant. That's actually a red flag. Since ANDi shows no sign of the trait that was supposedly engineered into him, viruses--which insert the foreign gene randomly--may not be the way to produce genetically altered animals. For genetic enhancement, and perhaps even for making a monkey model of a human disease, you have to get the gene to the spot in the chromosomes where it will be properly controlled.

Until ANDi, genetic engineering had meant slipping a bit of healthy DNA into cells of a patient who is suffering from a genetic disease such as cystic fibrosis. ANDi breaks that mold, bringing us a step closer to tinkering with an individual's genetic endowment before birth, and with the genetic legacy of generations unborn. The Oregon scientists don't know whether ANDi's sperm contains the green gene, and they won't know for four years, when the little guy reaches sexual maturity. But if ANDi's sperm does carry the green gene, he will pass it on to all his offspring. And then the first genetically altered primate will claim another title: father to a genetically altered race.

Although Oregon's Gerald Schatten is emphatic that "we don't support the extrapolation of this work to people for genetic enhancement," some regard that step as an act of medical humanitarianism. Engineering eggs so that a healthy gene replaces a disease-causing one should help both the child-to-be and his or her descendants, lifting a family curse of cancer, atherosclerosis, schizophrenia or another disease with a strong genetic component. "If you could prevent future generations from having grave genetic diseases, it would make the life of our species a little less terrible," says bioethicist Arthur Schafer of the University of Manitoba.

Even genetic enhancement for reasons that fall short of life and death has advocates. If parents want a tall, thin, hazel-eyed, athletic, brainy kid, whose business is it of anyone else's? Today's well-off parents hire tutors, music teachers, private sports coaches and SAT advisers for their children, if they can afford to. No one calls for banning SAT tutors in the interest of egalitarianism. "But genes are different," argues bioethicist Margaret Somerville of McGill University in Canada. The human genome--the collection of some 70,000 genes carried by every human--is "the patrimony of the entire species, held in trust for us by our ancestors and in trust by us for our descendants. It has taken millions of years to evolve; should we really be changing it in a generation or two?" And Schafer warns of new social divisions: in addition to haves and have-nots, we will have the gene-rich and the gene-poor.

At infertility clinics, couples are not clamoring to choose their would-be child's traits the way they choose options on a car. At least not yet. "Some request a particular gender, but no one has asked for a specific gene," says Dr. Paul Gindoff of the George Washington University in vitro fertilization clinic in Washington, D.C. "The traits that couples might care about--eye color, hair color, height, intelligence and personality--don't come from a single gene anyway, but from a complex combination. We are orders of magnitude away from being able to offer traits to order." The closest couples come to their own private eugenics is embryo selection, says Dr. Martin Keltz of St. Luke's-Roosevelt Hospital Center in Manhattan. In this process, clinics screen the embryos they create to determine whether any carries a deleterious gene that runs in either partner's family. If it does, that embryo is discarded; only healthy-seeming ones go into the woman's uterus. But if today's patients aren't asking for custom-made babies, tomorrow's might. When a March of Dimes poll asked people if they would "improve" their child's appearance or intelligence through genetic tinkering, 42 percent answered yes.

Whether society allows that will likely depend on what might be called the "ick" factor--a sense of repugnance at treating children as a product, at robbing life of its sacredness. Society emitted a collective "ick" at the first test-tube baby, the first surrogate mother, the first baby born to its biological grandmother. But "ick" tends to dissipate; more than 300,000 test-tube babies have been born. Science now has the power not merely to create, but to manipulate creation as never before. In a 1944 essay, novelist C. S. Lewis warned that "the final stage is come when Man by eugenics, by prenatal conditioning... has obtained full control over himself." That day is now a little closer.

Comments