British physicians have for the first time screened embryos for genetic defects in the test tube and implanted healthy embryos in a woman who then gave birth to normal twins.
The new technique, the doctors say, eventually could make it possible to eliminate genetic defects in treated families, and in many cases also avoid the need for women to undergo a therapeutic abortion after the fetus is found to have a serious defect.
The twin girls were born nearly two weeks ago at Hammersmith Hospital in London to a mother who was the carrier of a gene for a fatal genetic defect that strikes only boys, Dr. Alan Handyside of the Royal Postgraduate Medical School at Hammersmith said Monday in a telephone interview.
Handyside and Dr. Norman Winston artificially fertilized eggs collected from the mother, Debbie Edwards, 29, and grew them in the laboratory until each egg had divided into eight cells--the smallest size from which a single cell can be removed without risk to the embryo. Using a newly developed procedure, they then removed one cell from each embryo and used it to determine its sex.
Male embryos were discarded and female embryos were implanted in the mother's womb. The newborn girls are apparently completely healthy, and three more similar births are expected over the next six weeks. The Hammersmith group plans to extend the work to 50 more couples over the next few months.
"It's a very exciting first step" in developing new ways to detect birth defects, said geneticist Yuri Verlinski of the Illinois Masonic Medical Center in Chicago.
"This . . . should have a huge social impact over the next two decades," Winston said.
Conventional prenatal analysis is now carried out in the 10th to the 16th week of pregnancy by collecting fetal cells from either the amniotic fluid that surrounds and cushions the fetus in the womb or from the chorionic villi, hair-like protrusions on the surface of the placenta.
When those tests reveal a serious genetic defect, many parents choose an abortion. But those abortions can be quite traumatic because the mother has already invested great energy in carrying the fetus and has often been able to feel it moving in the womb.
The technique "offers couples at risk an alternative that avoids some of the emotional distress caused by prenatal diagnosis later in pregnancy," said ethicist Kathleen Nolan of the Hastings Center in Briarcliff Manor, N.Y.
The researchers are also extending the technique so that it can be used to screen in the test tube for any genetic defect--not just those that affect only one sex.
Handyside said that within 12 months they will be able to screen embryos for specific genetic defects. That will require refining chemical techniques for multiplying the DNA--deoxyribonucleic acid, the blueprint of life--to large enough quantities for conventional screening.
Using those techniques, they would then be able to screen for any particular type of genetic defect and implant only the healthy embryos in the mother's womb. Because of the high cost of the procedure and the difficulties of test tube fertilization, however, it is likely that the technique would be used only for the most serious genetic defects, said Dr. Lawrence Platt of County-USC Medical Center. (Test tube fertilization now has a success rate of 20% to 30%.)
Thus far the British researchers have been working primarily with couples who have already had at least one therapeutic abortion because of a serious genetic defect such as Duchenne muscular dystrophy, Lesch-Nyhan syndrome, and adrenoleukodystrophy. All are so-called X-linked disorders in which females carry the genetic defect and each male child has a 50% chance of developing the disorder.
Edwards was drawn to the program when she learned that a nephew, then age 8, had developed adrenoleukodystrophy, a crippling disease that has left him blind and totally disabled. Tests showed that Edwards and her sister both carried the gene for adrenoleukodystrophy.
Coincidentally, Winston and Handyside were readying clinical trials with their new technique for diagnosing birth defects. Tests in animals had shown that one cell could be removed from the embryo at the eight-cell stage for genetic analysis without impairing normal development of the embryo, and the physicians were ready to try it in humans.
The Edwardses volunteered for the study because "the research was the only chance we had. We had to take it. . . . We couldn't risk having a boy," Delvin Edwards, 39, a baggage handler at Heathrow Airport, told the London Daily Mail.
Last fall, Handyside and Winston administered a fertility drug to Debbie Edwards and collected the batch of eggs that were released from the ovary. They fertilized them with Delvin Edwards' sperm and then checked the sex of each egg. Two female embryos were then implanted in Debbie Edwards' uterus to increase the chances of success.
To the researchers' surprise, both embryos "took" and Debbie Edwards became pregnant with twins. Conventional chorionic villus sampling at the 10th week of pregnancy indicated that both fetuses were girls and that both were genetically normal.
The twins were born five weeks prematurely, but both Natalie (5 pounds, 7 ounces) and Danielle (5 pounds, 6 ounces) apparently were healthy and normal in all ways.
Physicians will continue to monitor the children as they grow to watch for any problems. "But even Louise Brown (the first test tube baby) is only 10 years old, so long-term follow-up for in-vitro fertilization is going to take some time, and obviously the same is true for this technique," Handyside said.
Screening for specific defects would allow doctors to prevent the birth of not only infants with genetic defects, but also of infants that are carriers of the defect. "If we used the technique in that fashion," he said, "we could completely eliminate that genetic defect in that family."
But all those considerations are far from the Edwardses' minds. "To us, it doesn't matter that they're a world first," Delvin Edwards said. "They are the perfect family we have been longing for."