New Fertility Technique Shakes Ethical Ground
Experiments Combine Genes From 2 Women
By Rick Weiss Washington Post Service
SAN FRANCISCO - Using a technique similar to the one that Scottish scientists used to clone Dolly the sheep, doctors in New
York have for the first time transferred genes from an infertile woman's egg into another egg, fertilized it with sperm, and placed the
resulting embryo in the womb in the hope of growing a baby.
The new approach, which could allow infertile women to have babies with some of their own genes, does not constitute cloning,
since any resulting child would have genes from a father as well as a mother. But it is similar enough to cloning to be illegal in
California and perhaps in other states where broadly worded anti-cloning legislation has been passed, said Dr. Jamie Grifo of New
York University, who is leading the experiments.
The work breaks new ethical ground by being the first to mix significant amounts of DNA from two women's eggs into a single egg.
That means any resulting child will have two genetic mothers - although one woman contributes vastly more than the other and so
will clearly be the dominant biological mother.
Dr. Grifo described the novel approach here Thursday at the annual meeting of the American Society for Reproductive Medicine.
Experts said the research offered evidence that in the fast-paced field of reproductive medicine the line between promising
therapeutic techniques and ethically questionable genetic manipulations is getting blurrier every day.
Until now, for example, most researchers have said they are adamantly opposed to making human genetic alterations that would be
passed on to future generations. By combining genes from two different women, however - albeit in a small degree - the new method
does exactly that.
''For the child and family, it raises questions of what bloodline means and what kinship means,'' said John Robertson, a professor of
law and bioethics at the University of Texas in Austin. ''I think in this case that's O.K.,'' but it shows that the line is ''not sacrosanct.''
Dr. Grifo said he and his colleagues, John Zhang and Hui Liu, had tried the method in two infertile women so far. The first one, a
47-year-old, failed to become pregnant. The second woman, 44, underwent the procedure just last week and is not scheduled to
have a pregnancy test until next week.
The team has permission from the university's scientific and ethics advisory board to try the technique in five women.
''There are a lot of concerns about this, a lot of issues,'' Dr. Grifo said. ''But it's not like we did this thoughtlessly.''
The goal, Dr. Grifo emphasized, is to provide an alternative to infertile women. Today, the only options for these women are adoption
or the creation of a baby through in vitro fertilization using a donated egg.
Many cases of female infertility are caused by an inability to produce eggs. But many others, including among most older
premenopausal women, involve eggs that are defective.
The method used by the New York team is based on scientists' growing recognition that in many of these cases the problem is not
with the DNA inside a woman's eggs but with the fluid, called cytoplasm, that surrounds that DNA. This suggests that their DNA
could be viable in reproduction if it could be drenched in healthier cytoplasm.
In the new work, the researchers removed the main mass of DNA, called the nucleus, from the infertile woman's egg and injected it
into the healthy donor's egg whose nucleus had already been removed. When the reconstituted egg was mixed with sperm in the
laboratory, it began to grow into an embryo that the doctors then placed in the infertile woman's womb.
By contrast, cloning involves the transfer of nuclear DNA not from an egg but from a body cell, such as a skin cell, and into an egg
in which the DNA has been removed. Body cells contain a full complement of DNA inherited from two parents, so no fertilization by
sperm is required. A jolt of electricity is enough to get such a reconstituted egg cell to divide as though it were an embryo.
Cloning has worked in sheep and mice but has not been attempted in people.
The ethical catch in Dr. Grifo's work is that there are also some genes, called mitochondrial genes, that reside in the cytoplasm of
every egg. Any baby born by his technique will have nuclear genes from the infertile woman and mitochondrial genes from the
healthy donor.
Mitochondrial genes are not generally considered to have an obvious impact on how a person looks or behaves. But they do play a
major role in various metabolic pathways in the body and, when mutated, are known to cause various inherited diseases. They may
play a role in such common ailments as Alzheimer's disease and Parkinson's disease.
Some experts at the meeting also questioned the ethics of conducting the experiments in women without first testing their safety in
monkeys.
''Animal colonies cost a fortune to maintain,'' Dr. Grifo replied. And because of a ban on federal grant money for embryo research, he
said, ''we have no research dollars.''
In the current studies, the women undergoing the experimental treatment paid part of the cost of the procedure; the rest was
absorbed by the NYU clinic.
It took two years for the scientists to get permission from NYU's research review board to conduct the studies. Dr. Grifo would not
elaborate on what aspects of the research troubled the board.
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