Putting Baby Together
Chinese doctors use technique developed by NYU researchers

By Jamie Talan

October 14, 2003

Three years after the federal government put restrictions on two New York doctors developing a controversial fertility technique and the scientists shared their technology with Chinese doctors, the method has been used to achieve a pregnancy in a 30-year-old infertile Chinese woman.

But none of her three developing fetuses survived, and some question the ethics of such research.

"The gestational outcome was a disaster," said Dr. James Grifo, director of the division of reproductive endocrinology at New York University. Grifo and his NYU colleague, Dr. John Zhang, are listed on the abstract of a paper on the case to be delivered today at the American Society for Reproductive Medicine meeting in Texas. Grifo said they didn't have anything to do with the clinical research "beyond showing them how to do it."

"We laid all the foundation for them to do this, and we taught them how," Grifo said. Zhang will deliver the talk because his colleagues at the Sun Yat-Sen University of Medical Science in Guangzhou, China, did not get their visas in time, Grifo added.

This week, the Chinese government published guidelines forbidding the technique there as well.

Some call the technology controversial because one of the techniques used to fuse the genetic material from an infertile woman into an egg that has been cleared of DNA in its nucleus is also used in cloning. That technique is called nuclear transfer.

"It utilizes a similar technology but in no way resembles cloning," Grifo said in a telephone interview yesterday. Cloning is the science of copying an adult with its complete set of DNA.

With the NYU researchers's approach, the mother's nucleus is infused in the lab into the female donor's healthy cytoplasm and the high-tech egg is fertilized with the husband's sperm and then re-implanted in the infertile woman's womb. This allows the woman and her male partner to have a child that is genetically related to both of them, said Grifo. The child also inherits some mitochondrial DNA from the donated cytoplasm.

With normal in vitro procedures, Grifo said, an infertile woman often carries a donor egg that has none of her genetic characteristics.

Grifo and his colleagues stopped developing the technique in 1999 after the hospital received a letter from the Food and Drug Administration saying the scientists needed to file the equivalent of a New Drug Application to do these studies. Grifo said they didn't have the funds or the time to invest so they stopped testing it. Instead, they turned the technique over to Chinese colleagues.

In the China pregnancy, one of the three embryos was removed to cut the risk of the pregnancy, one fetus was delivered stillborn at 24 weeks and the last died at 29 weeks when the blood supply in utero was cut off. But even with the disastrous outcome, Grifo said, the Chinese team found that all three fetuses were genetically normal.

"The notion of rejuvenating an egg is interesting," said Arthur Caplan, head of bioethics at the University of Pennsylvania in Philadelphia. "It is certainly not cloning, but it is a form of genetic engineering. You are altering the genetic nature of the offspring. It shouldn't happen in the U.S., China or anywhere without a lot more research and a lot more debate."

"If you create one dying or dead baby, you could set back the effort for years," Caplan added.

Pregnancy Through Science

A Chinese experiment has created a human pregnancy through nuclear transfer, a process that combined DNA from a would-be mother with hollowed-out eggs from a donor.

1. DNA is removed from the egg of the donor.

2. The hollowed-out egg is fused with DNA taken from ther mother's egg.

3. The egg is then fertilized by the father's sperm.

4. Five such fertilized eggs, or zygotes, are implanted in the mother's womb.

Copyright (c) 2003, Newsday, Inc.


This article originally appeared at:,0,1010540.story


Pregnancy Created With Egg Nucleus of Infertile Woman

October 14, 2003

Doctors in China have become the first 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 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
placed in 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 twin fetuses she was carrying died. Although the process, nuclear transfer, 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 been done or even seriously tried. Those who oppose nuclear transfer also say it poses unknown
hazards to children who may be born as a result, and as evidence they cite the death of the fetuses in China.

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

A report on the experiment in China is to be presented today at a medical conference in San Antonio. It was
described yesterday in The Wall Street Journal.  Nuclear transfer is similar to a crucial step in cloning,
but it 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 nucleus from an adult animal, electrically stimulate the egg to start its development and
implant it in the prospective mother's womb. Any offspring will be a genetic copy, or clone, of the adult animal from
which the cell was taken.

Nuclear transfer and cloning are similar in that both involve 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 but 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," Dr. Grifo said in a telephone interview yesterday.
"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."

Dr. Grifo said the twin fetuses that died in the experiment 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.

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

He said the research was banned 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."

Dr. Grifo said he and his colleagues gave their findings to doctors in China because regulations imposed by the United
States 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 in Minneapolis, 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," Dr.
Kahn said. He pointed out that stem cell researchers had left California for England and that cloning experts had
left Scotland for Singapore to escape rules that they considered onerous.

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

Dr. Kahn also said that even though nuclear transfer was not the same as cloning, it helped demonstrate that cloning
might work. "It is effectively creating the path for other people to do that," he said.

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

Dr. 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.

He said his goal was to help women whose eggs became fertilized but then stopped developing, a problem mostly
traceable to defects in structures in their egg cells called mitochondria. The defects may appear with age but
they affect younger women in some cases.

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

But in 2001, the F.D.A. declared that it had jurisdiction  over nuclear transfer and related research, and that
experimenters would have to submit an Investigational New Drug Application.

That move put an end to nuclear transfer work in the United States, Dr. 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.

Dr. 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. Dr. Zhang visited the group at Sun Yat-sen University.

"We didn't perform the research, but we gave them the tools so they could do it," Dr. Grifo said.

Dr. Grifo and Dr. Zhang are named as co-authors on a summary of the research, and Dr. Zhang is presenting it
today in San Antonio.

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