Salt Lake City, Utah

Replacing faulty DNA in a mother's egg is intended to prevent her offspring from inheriting some types of disease. Credit: KTSDESIGN/Science Photo Library

A baby boy conceived using a controversial technique that mixes DNA from three people seems to be healthy, according to a hotly anticipated talk by the leader of the team that created the child. John Zhang, a physician at New Hope Fertility Clinic in New York City, offered few other details during his presentation at the American Society for Reproductive Medicine’s annual meeting on 19 October.

But one thing is clear: that ‘three-parent’ baby may soon have company — if it does not already. Nature has learnt that a paper in review at an unnamed journal claims that a child conceived using the technique has been born in China. And on 13 October, researchers from Ukraine announced that two women are pregnant with fetuses created with DNA from three people.

Meanwhile, politicians in Mexico — where New Hope’s ‘three-parent’ baby was conceived in its Guadalajara clinic — are mulling over laws to restrict use of the technique. The circumstances of that birth, first reported last month by New Scientist, have also drawn criticism from scientists and bioethicists. They question why New Hope did its work in Mexico, where rules governing human-embryo modification are less stringent than those in the United States or the United Kingdom.

Techniques to create three-parent babies seek to prevent mothers from passing on metabolic diseases caused by faulty mitochondria, the structures that provide cells with energy. To do this, researchers exchange the diseased mitochondria of a prospective mother with those of a healthy, unrelated donor: the ‘third parent’.

Zhang’s team worked with a woman who carries a rare neurological disease called Leigh syndrome. The researchers transplanted the nucleus of one of the woman’s egg cells into a donor egg, leaving the donor’s healthy mitochondria intact. They then fertilized the modified egg with sperm from the woman’s husband, and implanted it in her uterus.

Questions remain

At the meeting in Salt Lake City, Utah, Zhang presented new data behind his team’s claims, which had initially drawn scepticism. Zhang told meeting attendees that nearly 100% of the mitochondrial DNA in the mother’s eggs contained the mutation that causes Leigh syndrome. But after the woman’s nucleus was transferred to the donor egg, the percentage of faulty mitochondria in the modified egg dropped to less than 5%, on average“I do believe the study is true,” says Dietrich Egli, a stem-cell scientist at the New York Stem Cell Foundation in New York City. “It’s good to hear the technique has resulted in an apparently healthy baby.”

But Egli says that there are still concerns about the safety and efficacy of the technique, called ‘mitochondrial-replacement therapy’ (MRT). These include whether the presence of mitochondria from two women will affect the resulting baby’s health, and whether the donated mitochondria will affect any of that baby’s eventual offspring. Zhang says that the group will soon perform a comprehensive medical examination of the baby, including testing whether the levels of diseased mitochondria hold steady.

Numerous scientific groups and government agencies are debating whether the procedure should be allowed in clinical use. Most conclude that mitochondrial replacement should be performed only under the auspices of a clinical trial and with independent oversight.

Many of these groups have also recommended that MRT be limited to male embryos. Because only mothers pass mitochondria to offspring, a male baby conceived using the technique would not be able to pass his modified mitochondria to any children. Alejandro Chavez-Badiola, New Hope’s medical director, says that his team implanted a male embryo because it was the only one that survived. Zhang says that the New Hope team will work with any future patients to determine whether implanting a female embryo would be ethical. And one of the two women treated in Ukraine is pregnant with a female fetus.

George Daley, a stem-cell researcher at Children’s Hospital Boston in Massachusetts, has led several efforts to examine the ethical and scientific aspects of MRT. He is concerned that Zhang and his colleagues at New Hope did not follow the recommendation of these advisory groups. “Going to Mexico is a way to evade the stricter regulatory regime in the US and UK,” Daley says. “The danger is to the families and the infants who are being born with this procedure. They’re taking all the risk before really being fully aware of the success rate and failure rate.”

Looking ahead

Daley worries that any substandard clinical research in this area could jeopardize approval for other groups that have been working within existing regulatory frameworks. In 2015, the UK government approved the use of MRT in limited cases, yet the technique remains controversial and has not been used in the clinic.

Chavez-Badiola says that the team worked in Mexico partly because no specific law there bans the procedure. But he notes that Mexico does have laws governing patient safety: New Hope’s Guadalajara clinic is inspected by Mexico’s regulatory agency, COFEPRIS, and the MRT work was approved by an ethics review board.

“I think this is scientific chauvinism,” Chavez-Badiola says of Daley’s criticism. “Why in the UK is it fine, why in Mexico is it morally questionable? We have the technology, we have the training, we have what it takes.” He adds that a paper describing the New Hope team’s procedure and outcomes is under consideration at a peer-reviewed journal.

And Valery Zukin, the Ukrainian team’s leader, notes that his work was approved by an ethical-review board of the Ukrainian Association of Reproductive Medicine. Unlike the woman that Zhang treated, Zukin’s patients did not carry mitochondrial disease. But they had been infertile for years, seemingly because of a mitochondrial defect that caused embryos to suddenly stop growing. Replacing the mother’s mitochondria with cellular components from a donor’s egg seems to have fixed the problem, and both babies are due early in 2017, Zukin said in a 13 October presentation at the ART World Congress in New York City.

But a surprise announcement, such as that of the New Hope baby, may be the only way to get regulators and scientists to make clear decisions about any limits on mitochondrial-replacement techniques. “I think the scientists and doctors showed a lot of courage exposing themselves to this type of criticism in doing this treatment,” Egli says. “I think there is an imbalance in regulation and oversight in some places, putting novel treatments on the long bench, and therefore it had to be done that way.”