Washington Post Staff Writer
Tuesday, October 14, 2003; Page A10
A New York fertility doctor whose experimental technique for making babies ran afoul of the Food and Drug Administration a few years ago has now tried the approach in China, where a woman became pregnant with triplets but eventually lost all three fetuses.
The experiment, which the doctor is scheduled to describe today at a fertility meeting in San Antonio, raised alarms in medical ethics circles yesterday after being highlighted in the Wall Street Journal.
The technique involves a degree of genetic manipulation that some fear could harm children conceived this way. Others yesterday took aim at a long-standing federal ban on public funding of embryo research, saying it drove the work overseas -- where scientific and ethical oversight is often lacking.
The doctor, Jamie Grifo of New York University School of Medicine, first tried a variant of the technique in the United States about five years ago, when he transplanted a woman's genes from her own egg cells into the gutted egg cells of a younger woman.
The rationale is that some women may be infertile not because of defects in their DNA but because of problems with the fluid surrounding the DNA in their eggs. That fluid, called cytoplasm, contains the egg cells' energy powerhouses, or mitochondria, and chemicals that nurture the cell and its genes. The idea, in effect, is to construct new eggs that have the infertile woman's DNA but the cytoplasm of a young, healthy woman -- then fertilize that egg with sperm from the woman's husband.
When Grifo described those efforts in October 1998 at the annual meeting of the American Society for Reproductive Medicine (ASRM), the FDA took note and determined that the procedure fell under the same regulations as human cloning, because both involve transfers of DNA from one cell to another. The agency warned Grifo against trying it again without FDA permission.
Grifo openly chafed at that constraint, calling the FDA's regulatory stance heavy-handed. In an interview about two years ago with The Washington Post, he complained vehemently that the agency had wanted him to conduct experiments on animals before trying his approach again with women.
"It's like dealing with the IRS," he said then, asking why bureaucrats he said did not understand his work were empowered to tell him how to practice medicine. "These people have never sat in front of a bunch of patients who have failed multiple IVF attempts," he said, referring to in vitro fertilization, the standard treatment for infertility.
Sean Tipton, a spokesman for the ASRM at whose annual meeting Grifo is to report his new results today, said yesterday that Grifo was declining to speak to reporters. But the experiment is described on the society's Web site.
Working with colleagues from Sun Yat-Sen University of Medical Science in Guangzhou, China, Grifo fertilized an infertile woman's egg with her husband's sperm, creating a one-cell embryo or "zygote." He then transferred the "pronuclei" -- the combined set of maternal and paternal genes -- into the zygote of a fertile woman whose own pronuclei had been removed.
Five of those reconstructed zygotes were transferred to the infertile woman's womb, where three successfully implanted. After a month, heartbeats could be detected in all three, but one fetus was surgically killed to improve the odds of survival for the other two. At 24 weeks, one fetus was delivered prematurely because of ruptured membranes and died of "respiratory distress." The other was delivered dead at 29 weeks.
The fetuses' cells contained a mix of DNA from the infertile woman and the fertile woman who had donated her eggs. Specifically, the fetuses' cells contained "nuclear DNA" (the main batch of genes) from the infertile couple as planned, but also "mitochondrial genes" (which reside in the cytoplasm) from the fertile woman who donated the egg. Scientists are not sure whether such mixtures of genes from two mothers can cause developmental problems, but that possibility has been noted by the FDA as one reason to proceed cautiously with such techniques.
"The FDA's decision to go slow in this research is warranted because of the extensive work that can be done with non-human animals and in the lab to assure safety and efficacy before beginning with human subjects," said R. Alta Charo, a bioethicist and associate dean of law at the University of Wisconsin in Madison. Charo applauded the agency for what she described as an invigorated commitment to apply its authority to reproductive medicine, a specialty that for many years, she said, had a "Wild West" reputation.
Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University, said Grifo's approach posed "huge safety questions." But she criticized the FDA for never explaining the legal theory that underpins its claims of jurisdiction over reproductive techniques, given its lack of authority over the practice of medicine.
Tipton criticized the congressional ban on embryo research, in place since 1996: "This is cutting-edge science on a technique which might help infertile women, particularly older women, have children. It points out the perils of prohibiting rather than funding and regulating fertility research."
It remained unclear yesterday whether Grifo had proper permission from NYU, which insists that its faculty obtain its approval for medical experiments done anywhere in the world. The research summary says only that the protocol was approved by Sun Yat-Sen University.
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