Some babies born from a new method used to treat a rare form of infertility have genes from three different people in their cells, researchers are reporting.

But the researchers emphasize that the added genes appear to be of no consequence. They are of a type that does not vary much from person to person and appear to have no effect on a child's characteristics, the researchers say. They say that their patients' babies who were born through use of the technique appear to be healthy.

The treatment has been used solely for a rare form of infertility occurring in only a small percentage of patients at fertility clinics. Women with this condition have eggs that can be fertilized, but the resulting embryos simply fall apart, dying before they can implant in the uterus.

Dr. Jacques Cohen, an infertility researcher at the Institute for Reproductive Medicine and Science at St. Barnabas Medical Center in Livingston, N.J., reasoned that the problem might be in the cytoplasm, the material that surrounds the nucleus of the egg and that directs its development after fertilization. So, in experiments that began a few years ago, Dr. Cohen and his colleagues began injecting cytoplasm from the eggs of fertile women into the eggs of these infertile women.

The group has treated 30 women, Dr. Cohen said, and they have given birth to 15 babies. About 30 babies have been born worldwide as a result of this technique, he added.

But the cytoplasm of an egg contains more than just proteins to help an embryo grow. It also contains mitochondria, which are self-contained tiny structures that use oxygen and nutrients to create energy for the cells. And mitochondria have their own genetic material.

That gave rise to a question. If the investigators injected cytoplasm containing mitochondria into an infertile woman's egg and then fertilized the egg and created a successful pregnancy, would the baby have genes from three people: the infertile woman, the man whose sperm fertilized the egg, and the woman whose egg was the source of the additional cytoplasm?

The answer, Dr. Cohen and his colleagues reported, was yes. In the March issue of a British journal, Human Reproduction, they described a genetic fingerprinting method they used to detect mitochondrial genes from the donor cytoplasm in blood cells of two 1-year-old babies born with this technique.

They tracked the one region of the mitochondrial genetic material that normally varies from person to person, a region, Dr. Cohen said, in which genes are inactive. "There are differences, but they are not meaningful," he said.

But in an editorial published in the journal Science on April 20, two ethicists, Erik Parens of the Hastings Center in Garrison, N.Y., and Eric Juengst of Case Western Reserve University in Cleveland, suggested that such treatments, because they result in permanent genetic alterations that in turn will be passed on to the babies' children, might not have been approved by a federal committee that oversees experiments that involve gene transfer. But, they explained, since the work was privately funded, the researchers had no obligation to ask the committee's permission to go ahead. The federal government does not pay for research related to human fertilization and early embryo development.

Dr. Cohen said: "We didn't come to them because they didn't give us federal funds. I would be happy to talk to them if they gave us funds."

Monday May 7, 2001 10:34 AM ET

Infertility Treatment Leaves Kids with Extra DNA

WASHINGTON (Reuter) - A treatment for infertility can leave the resulting babies with genetic material from two women and the father, a researcher said this weekend. The Institute for Reproductive Medicine and Science of St. Barnabas Medical Center in West Orange, New Jersey, has used the technique to produce 15 healthy babies, the oldest of whom turns 4 years old in a month, said Dr. Jacques Cohen, scientific director of assisted reproduction at the institute.

He said his institute was the first to use the technique called ooplasmic transfer, but other fertility specialists had followed. Another 15 babies had been born following the use of the technique at different facilities, Cohen said.

He dismissed criticism by some scientists who labeled as unethical a technique that in a sense leaves children genetically with two mothers.

``I don't think this is wrong at all,'' Cohen told Reuter Friday. ``And I think we have to look at the positive part here. I think this did work. These babies wouldn't have been born if we wouldn't have done this.''

In the technique, cytoplasm--the jelly-like material surrounding a cell's nucleus--is transferred from a donor egg into the egg of an infertile woman, and fertilized with sperm. The researchers believe the technique helps women conceive who had been unable to do so because of defects in their eggs.

While the nucleus contains the DNA that determines physical characteristics--eye color, hair color and thousands of other details--cytoplasm does contain small amounts of DNA contained within mitochondria, which are cellular ``power plants'' than generate energy for a cell.

This mitochondrial DNA is typically passed directly from mother to offspring, with no contribution from the father. The researchers found that children that result from the infertility technique have nuclear DNA from the previously infertile couple, as well as mitochondrial DNA from the two women.ONE CHILD, TWO MOTHERS

Tests confirmed that two of the 15 babies produced by the technique at the institute were carrying genetic material from the birth mother, the father and the woman who donated an egg, Cohen said.

The procedure, described in the British medical journal Human Reproduction, has raised ethics questions among some critics in the scientific community. Cohen and his colleagues wrote in the journal that this was ``the first case of human germline genetic modification resulting in normal health children.'' ``Germline'' refers to the genes that a person will pass on to his or her children.

The federally funded Recombinant DNA Advisory Committee (RAC) has banned any funding of gene research that could create changes in the human germline. However, potential changes to mitochondrial DNA are generally ignored, because they are thought to have little impact on the offspring, notes Erik Parens of The Hastings Center in Garrison, New York, and Eric Juengst of the Center for Biomedical Ethics at Case Western Reserve University in Cleveland in a commentary in the journal Science. Also, infertility treatments do not receive federal funding, so they aren't as affected by such bans.

However, the commentators note that there could possibly be unknown risks of tinkering with mitochondrial DNA, although, at this point, there are no known problems associated with the technique.

But Cohen countered: ``There are different levels of ethics. There are people who are saying, 'Why would you do something like this without maybe hard proof that it would work?' That's one level of ethics. The other one is, 'Well, you're tampering with nature,' which is the same question you get when you deal with any form of assisted reproduction.'' ``THE LITTLE THING THAT WE DID''

Cohen said the technique did not manipulate the genes, but merely added innocuous extra genetic material.

``We haven't changed any genes,'' he said. ``That's a huge step compared to the little thing that we did. But you could say there would have normally been mitochondria from only one source (the mother). Now there's mitochondria from two sources, and therefore there's two different types of mitochondria DNA there.''

Of the 15 babies produced by the technique used at the institute since 1997, 13 lived in the United States, one lived in Britain and another in France, Cohen said. He said the institute used the technique on 30 infertile women. Seventeen failed to become pregnant and one become pregnant but had a miscarriage, he said. The remaining 12 women delivered babies, with three of the women having twins.

``So far, from what we understand, they are doing OK,'' Cohen said of the babies. ``And those two that had the mixed mitochondria, they're doing OK, too.''

No government money was used in the research, Cohen said.

Source: http://dailynews.yahoo.com/h/nm/20010507/hl/dna.html

Saturday May 19, 2001 05:26 PM EDT

Scientists Say Stop Three-Parent Babies

By Robin Eisner ABCNEWS.com

Babies born with altered genes resulting from a fertility clinic technique have prompted scientists to call for the immediate regulation of such facilities.

Scientists are calling for the immediate regulation of fertility clinics to prevent the birth of any future gene-altered babies, the first of which was reported earlier this year.

In March, a team of fertility specialists at the Institute for Reproductive Medicine and Science of St. Barnabas, in West Orange, N.J., reported "the first case of human … genetic modification resulting in normal healthy children."

Fertility Method Creates Gene-Altered Babies

The group used a method that extracted cellular material from a donor woman's egg cell and transferred it into an infertile woman's egg. This material allowed the woman's egg to become fertile.

The donor egg contained DNA from mitochondria, little organs inside the cell that create the energy to do life's work. The group believes that problems with the mitochondria prevented the infertile women from becoming pregnant.

Mitochondria contain only about 0.03 percent of a cell's DNA, but that's enough that they can make copies of themselves when the cells divide. The other 99.97 percent of a cell's DNA comes from the nucleus and the 23 pairs of chromosomes.

The group says that transferring this mitochondrial DNA into the recipient eggs resulted in the birth of 30 babies, the first of which was born in 1997.

Extra Genes From Mitochondria

In March, the group reported for the first time in the medical journal Human Reproduction that genetic tests on two babies showed they had DNA from three parents: Two babies born with this method actually had mitochondrial genes from the donor mom, as well as chromosomal genes from the mother and father.

This extra-parental mitochondrial DNA could be transferred to the next generation.

Scientists in the latest issue of the journal Science are calling for the regulation of fertility clinics to prevent this practice from continuing.

"No research or clinical application involving humans should proceed that have the direct or indirect potential to cause inheritable genetic modification in either the public or private sector," unless it is reviewed by already existing federal regulators or a new body, wrote Mark S. Frankel and Audrey Chapman.

Both authors preside over public policy programs at the American Association for the Advance of Science, which publishes Science.

The two authors warn that efforts to modify genes transmitted to future generations could bring about both a medical and social revolution.

Social and Safety Consequences of Technology

"The dilemma is that inheritable genetic modification techniques developed for normal therapeutic purposes are also likely to be suitable for genetic alterations intended to improve what are already 'normal' genes," they write.

They warn that in a market economy the division between the haves and have-nots would increase if those who could pay could add "inherited advantage to the benefits of nurture and education already enjoyed by the affluent."

Safety concerns are also paramount, the authors say. It remains unclear how future generations with such genetic changes would fare.

"We have little experience and no evidence of long-term safety of inheritable genetic modification, whether intended or inadvertent," they write.

"There has not even been public consideration of how one would proceed in determining safety across generations. We should begin establishing an oversight process now so that we can make informed and reasoned choices about the future."

Source: http://dailynews.yahoo.com/h/abc/20010519/hl/genealteredbabies010518_1.html