Catching A Bad Gene

By Philip Elmer-DeWitt

PARENTS USED TO HAVE TO WAIT until babies were born to find out if they had tragic birth defects. Then came two breakthrough fetal tests: amniocentesis, which can identify abnormalities in the 15th week of pregnancy; and chorionic villus sampling, which can be performed as early as the tenth week. Neither procedure is without risk, however, and when either succeeds in pinpointing a genetic defect, it forces would-be parents to make a terrible choice: Do they raise a child who might have a serious congenital affliction? Or do they suffer the torment and pain that accompanies an abortion?

Now couples who are concerned about passing on defective genes may be spared that agonizing dilemma, thanks to a remarkable new procedure that allows doctors to test days-old embryos for genetic abnormalities outside the womb. The technique -- which begins with in vitro, or "test-tube," fertilization and then involves plucking a single cell from an embryo the size of a grain of sand -- has already produced a healthy baby girl for a British couple with a 1 in 4 chance of having a child with cystic fibrosis, according to a report in last week's New England Journal of Medicine. It is now being used to detect several inherited ailments, including hemophilia, Duchenne muscular dystrophy and Tay-Sachs disease.

But the test also takes society right into the brave new world of genetic screening, raising the specter of eugenically minded parents throwing out embryo after embryo in search of the "perfect" child. And while it promises to reduce the number of abortions later in pregnancy, it is already drawing fire from those who oppose the taking of any human life, no matter how small. "Once you've joined the male sperm with the female egg, it's a human being," says Robert Powell, vice president of the National Right to Life Committee. "You're killing the very youngest of human beings, and that decision is based on disability."

At the heart of the debate are the tiny four- and eight-cell spheres that represent human life at a very early stage -- three days after fertilization. Scientists have long known from animal studies that cells in these pre-embryos are totipotent (that is, capable of taking any subsequent form, from skin to bone marrow) and more or less expendable. A 16-cell bovine embryo can be divided into four equal groups of four cells each, cultured for a few more days, and then redivided to yield 16 identical cell clusters, each of which will grow into a genetically interchangeable cow.

Applying this knowledge to human embryos created by in vitro fertilization, doctors at London's Hammersmith Hospital, led by Alan Handyside and Robert Winston, perfected a technique for drawing cells into hair-thin pipettes one at a time. Then they teamed up with a group from Houston's Baylor College of Medicine and Methodist Hospital who had developed a procedure for rapidly spotting the cystic fibrosis defect in a single strand of DNA, using the gene- cloning technique called polymerase chain reaction. "It's like finding one typographical error in a book 180 times the size of the Encyclopaedia Britannica in about six hours," says Dr. Mark Hughes, director of Baylor's Prenatal Genetics Center.

The experiment reported last week involved an English husband and wife who already had a child with cystic fibrosis and were worried about having another. Doctors followed the standard in vitro fertilization protocol, using hormones to stimulate the production of extra eggs, which were then mixed with sperm in a Petri dish. Two of the resulting embryos tested positive for cystic fibrosis. The rest were O.K., and two of them were implanted in the mother's womb. One became Chloe O'Brien, a healthy child who will neither get cystic fibrosis nor pass it on to her offspring.

Scientists have identified about 5,000 inherited diseases that could, in theory, be spotted in young embryos, including Huntington's disease and sickle-cell anemia. But gene screening to catch these disorders is not likely to be widely available anytime soon -- at least in the U.S. For one thing, it requires couples to go through in vitro fertilization, a costly ($5,000 to $13,000) procedure with a success rate hovering around 10%. The gene-screening test adds an additional $2,000 for each in vitro cycle, a bill the U.S. insurance industry has already indicated it has little interest in footing. Moreover, there is still deep resistance among some Americans to the idea of disposing of embryos, "defective" or not. "It doesn't fit the definition of abortion," says Sister Marian Brady, a professor of philosophy at Catholic University in Washington. "But it's doing the same thing."

This is more than a philosophical debate. Under pressure from the powerful right-to-life lobby, the U.S. government quietly cut federal support for in vitro research in 1979 and later backed away from several related fields, including fetal-cell research. Although the U.S. is still a world leader in molecular genetics, a report by the congressional Office of Technology Assessment recently concluded that the country is now "less than well prepared" to put its scientific findings into clinical practice. "The U.S. government has withdrawn funding from this field," says Britain's Handyside, who is understandably proud of helping produce baby Chloe. "They wouldn't be able to do this work in Houston."

With reporting by Dick Thompson/Washington