NewsweekNovember 9, 1998
SCIENCE
Designer BabiesScientists say that, with gene therapy, they may soon be able to cure a child's inherited disease before he is even born. But should they be allowed to create kids with made-to-order traits?
By Sharon Begley
It is only a matter of time. One day--a day probably no more distant than the first wedding anniversary of a couple who are now teenage sweethearts--a man and a woman will walk into an in vitro fertilization clinic and make scientific history. Their problem won't be infertility, the reason couples now choose IVF. Rather, they will be desperate for a very special child, a child who will elude a family curse. To create their dream child, doctors will fertilize a few of the woman's eggs with her husband's sperm, as IVF clinics do today. But then they will inject an artificial human chromosome, carrying made-to-order genes like pearls on a string, into the fertilized egg. One of the genes will carry instructions ordering cells to commit suicide. Then the doctors will place the embryo into the woman's uterus. If her baby is a boy, when he becomes an old man he, like his father and grandfather before him, will develop prostate cancer. But the cell-suicide gene will make his prostate cells self-destruct. The man, unlike his ancestors, will not die of the cancer. And since the gene that the doctors gave him copied itself into every cell of his body, including his sperm, his sons will beat prostate cancer, too.
Genetic engineers are preparing to cross what has long been an ethical Rubicon. Since 1990, gene therapy has meant slipping a healthy gene into the cells of one organ of a patient suffering from a genetic disease. Soon, it may mean something much more momentous: altering a fertilized egg so that genes in all of a person's cells, including eggs or sperm, also carry a gene that scientists, not parents, bequeathed them. When the pioneers of gene therapy first requested government approval for their experiments in 1987, they vowed they would never alter patients' eggs or sperm. That was then. This is now. One of those pioneers, Dr. W. French Anderson of the University of Southern California, recently put the National Institutes of Health on notice. Within two or three years, he said, he would ask approval to use gene therapy on a fetus that has been diagnosed with a deadly inherited disease. The therapy would cure the fetus before it is born. But the introduced genes, though targeted at only blood or immune-system cells, might inadvertently slip into the child's egg (or sperm) cells, too. If that happens, the genetic change would affect that child's children unto the nth generation. "Life would enter a new phase," says biophysicist Gregory Stock of UCLA, "one in which we seize control of our own evolution."
Judging by the 70 pages of public comments NIH has received since Anderson submitted his proposal in September, the overwhelming majority of scientists and ethicists weighing in oppose gene therapy that changes the "germline" (eggs and sperm). But the opposition could be a boulevard wide and paper thin. "There is a great divide in the bioethics community over whether we should be opening up this Pandora's box," says science-policy scholar Sheldon Krimsky of Tufts University. Many bioethicists are sympathetic to using germline therapy to shield a child from a family disposition to cancer, or atherosclerosis or other illnesses with a strong genetic component. As James Watson, president of the Cold Spring Harbor Laboratory and codiscoverer of the double-helical structure of DNA, said at a recent UCLA conference, "We might as well do what we finally can to take the threat of Alzheimer's or breast cancer away from a family." But something else is suddenly making it OK to discuss the once forbidden possibility of germline engineering: molecular biologists now think they have clever ways to circumvent ethical concerns that engulf this sci-fi idea.
There may be ways, for instance, to design a baby's genes without violating the principle of informed consent. This is the belief that no one's genes--not even an embryo's--should be altered without his or her permission. Presumably few people would object to being spared a fatal disease. But what about genes for personality traits, like risk-taking or being neurotic? If you like today's blame game--it's Mom's fault that you inherited her temper--you'll love tomorrow's: she intentionally stuck you with that personality quirk. But the child of tomorrow might have the final word about his genes, says UCLA geneticist John Campbell. The designer gene for, say, patience could be paired with an on-off switch, he says. The child would have to take a drug to activate the patience gene. Free to accept or reject the drug, he retains informed consent over his genetic endowment.
There may also be ways to make an end run around the worry that it is wrong to monkey with human evolution. Researchers are experimenting with tricks to make the introduced gene self-destruct in cells that become eggs or sperm. That would confine the tinkering to one generation. Then, if it became clear that eliminating genes for, say, mental illness also erased genes for creativity, that loss would not become a permanent part of man's genetic blueprint. (Of course, preventing the new gene's transmission to future generations would also defeat the hope of permanently lopping off a diseased branch from a family tree.) In experiments with animals, geneticist Mario Capecchi of the University of Utah has designed a string of genes flanked by the molecular version of scissors. The scissors are activated by an enzyme that would be made only in the cells that become eggs or sperm. Once activated, the genetic scissors snip out the introduced gene and, presto, it is not passed along to future generations. "What I worry about," says Capecchi, "is that if we start messing around with [eggs and sperm], at some point--since this is a human enterprise--we're going to make a mistake. You want a way to undo that mistake. And since what may seem terrific now may seem naive in 20 years, you want a way to make the genetic change reversible."
There is no easy technological fix for another ethical worry, however: with germline engineering only society's "haves" will control their genetic traits. It isn't hard to foresee a day like that painted in last year's film "Gattaca," where only the wealthy can afford to genetically engineer their children with such "killer applications" as intelligence, beauty, long life or health. "If you are going to disadvantage even further those who are already disadvantaged," says bioethicist Ruth Macklin of Albert Einstein College of Medicine, "then that does raise serious concerns." But perhaps not enough to keep designer babies solely in Hollywood's imagination. For one thing, genetic therapy as done today (treating one organ of one child or adult) has been a bitter disappointment. "With the exception of a few anecdotal cases," says USC's Anderson, "there is no evidence of a gene-therapy protocol that helps." But germline therapy might actually be easier. Doctors would not have to insinuate the new gene into millions of lung cells in, say, a cystic fibrosis patient. They could manipulate only a single cell--the fertilized egg--and still have the gene reach every cell of the person who develops from that egg.
How soon might we design our children? The necessary pieces are quickly falling into place. The first artificial human chromosome was created last year. By 2003 the Human Genome Project will have decoded all 3 billion chemical letters that spell out our 70,000 or so genes. Animal experiments designed to show that the process will not create horrible mutants are underway. No law prohibits germline engineering. Although NIH now refuses to even consider funding proposals for it, the rules are being updated. And where there is a way, there will almost surely be a will: none of us, says USC's Anderson, "wants to pass on to our children lethal genes if we can prevent it--that's what's going to drive this." At the UCLA symposium on germline engineering, two thirds of the audience supported it. Few would argue against using the technique to eradicate a disease that has plagued a family for generations. As Tuft's Krimsky says, "We know where to start." The harder question is this: do we know where to stop?
Newsweek, November 9, 1998