For first time in humans, fertility treatment succeeds

Doctors in China have successfully made an infertile woman pregnant

By DENISE GRADY 10/15/2003  New York Times

   Doctors in China have become the first in the world to make an infertile woman pregnant with an experimental technique devised in the United States for women who have healthy genes but defects in their eggs that prevent embryos from developing.

   The technique, called nuclear transfer, involves removing the nucleus, which contains the genetic material, from a woman's fertilized egg and transferring it to the egg of another woman that has had its nucleus removed. The resulting hybrid egg is then put back into the womb of the first woman. The idea is that the second woman's egg will provide a healthier environment for the genes.

   Although researchers at Sun Yat-sen University in Guangzhou succeeded last year in impregnating a 30-year-old woman with the technique, she gave birth prematurely and the fetuses died. Although the procedure was legal at the time in China, it was recently banned there.

   Critics say the technique is perilously close to human cloning, which has been widely condemned, although there is no proof it has ever been done or even seriously attempted. Those who oppose nuclear transfer also argue that it poses unknown hazards to any children who may be born as a result, and as evidence they cite the death of the Chinese woman's fetuses.

   Doctors involved in the research say it is not cloning, but is simply an attempt to give infertile women chances to have children that are genetically their own. They say that the technique has been studied extensively in mice and that it is safe and effective.

   A report on the experiment in China is to be presented on Tuesday at a medical conference in San Antonio. It was described in The Wall Street Journal on Monday.

   Nuclear transfer is quite similar to a crucial step in cloning, but it also differs in important ways.

   To make a clone like Dolly the sheep researchers start with a fertilized egg and remove its nucleus. Then, they replace the nucleus with a cell from an adult animal, electrically stimulate the egg to start its development and implant it in the prospective mother's womb. If it works, the offspring will be a genetic copy, or clone, of the adult animal that provided the cell.

   Nuclear transfer and cloning are similar in that each involves taking the nucleus from one cell and slipping it into an egg from a different individual.

   They differ in the goals of the procedure and in the kind of nuclei that are switched. In cloning, the goal is to make a copy of an adult, and the adult nucleus is transferred.

   In nuclear transfer for infertility, the nuclei transferred are not from adult cells; they are from the sperm and egg of the people who are trying to become parents. The offspring will be their child, not a clone.

   Dr. James Grifo, who developed the procedure at New York University and tried it in 1998 on several patients who did not become pregnant, said it was irresponsible to confuse it with cloning.

   "Cloning is making a copy of a human being who already exists," Grifo said Monday in a telephone interview. "This is nuclear transfer, one element of cloning. It allows a couple to have their genetic baby, not a clone. They shouldn't even be discussed in the same sentence."

   In China, Dr. Zhuang Guanglun, one of the researchers, said in an interview: "This isn't cloning. Cloning involves copying whole people."

   Grifo said the twin fetuses that died in the experiment were normal, had no evidence of genetic defects or other problems from the technique. He said the pregnancy ended because the mother's membranes ruptured and she went into labor early - one of the risks of carrying more than one fetus. The first fetus was born at 24 weeks and the second at 29 weeks. Between the births, the mother developed an infection.

   Guanglun said, "The problem was when an infection set in, but that doesn't negate the success of the initial experiment."

   He said the research had been would have to stop now; it was banned, he said, because it was thought to be too similar to cloning.

   He called China's regulations "nonsense for people who don't understand these techniques," and added, "When it's clear that something like this is to people's benefit, it should be allowed."

   Grifo said that he and his colleagues gave their findings to doctors in China because regulations imposed by the Food and Drug Administration in 2001 made it too difficult to continue the research in the United States.

   Dr. Jeffrey Kahn, director of the center for bioethics at the University of Minnesota, said he found the experiment in China troubling.

   "My concern is that people see this as an end run around oversight and restrictions within the United States," Kahn said. He pointed out that stem cell researchers had left California for England, and cloning experts had left Scotland for Singapore to escape rules that they considered onerous.

   "What's next?" Kahn asked. "A ship out in international waters?"

   Even though technically nuclear transfer is not the same as cloning, he added, it helps prove that cloning may work. "It is effectively creating the path for other people to do that."

   At the same time, Kahn said, stopping the research may well have the effect of penalizing infertile people who have no other hope of having their own biological children.

   Grifo said he had worked on the technique from 1995 to 1998 with consent from patients and the permission of New York University's ethics board. He said he had also studied it extensively in mice.

   His goal, he said, was to help women whose eggs became fertilized but then stopped developing, mostly likely because of defects in structures in their eggs cells called mitochondria. The defects may come on with age, but in some cases they affect younger women.

   Now, the only way such women can have children is to adopt or to become pregnant with an egg from a donor. Nuclear transfer, Grifo said, can give them a chance to have children that are genetically their own.

   But in 2001, the Food and Drug Administration declared that it had jurisdiction over nuclear transfer and related research, and that experimenters had to submit an Investigational New Drug Application to the drug agency to conduct their research.

   That move put an end to nuclear transfer work in the United States, Grifo said. He said the application process - normally followed by drug companies - would be too time consuming and expensive for most infertility researchers working in clinics and universities. In addition, he said, it seemed to him that the research was so frowned upon that his application would probably be rejected anyway.

   Grifo said that he and Dr. John Zhang, a graduate student from China studying with him, decided to give their research to doctors in China. Zhang visited the group at Sun Yat-sen University.

   "We knew patients would benefit, and we did not want to see the research die," Grifo said.

   Grifo and Zhang are named as co-authors on a summary of the research, and Zhang is presenting it in San Antonio. "We didn't perform the research," Grifo said, "but we gave them the tools so they could do it. We were included in this report because we did a lot of the foundation research."