DNA mutations in mitochondria (seen here in pink), can cause devastating diseases that are passed on from mother to child.

P. M. Motta, G. Macchiarelli, S.A. Nottola/Science Source

Singapore could become the second country to legalize mitochondrial replacement therapy

SINGAPORE—This small city state could become the second country—after the United Kingdom—to explicitly legalize mitochondrial replacement therapy (MRT), a controversial assisted reproduction technique that allows women who are carriers of some rare genetic disorders to give birth to healthy babies.

Members of the Singaporean public and religious groups have until 15 June to provide their feedback about MRT to the Bioethics Advisory Committee (BAC). Based on its findings, a 13-member BAC review committee will make formal recommendations to the government later this year about whether to legalize the technology.

“Our position is to keep a close watch on what happens in the U.K., to track the U.K. experience, and to learn from what they have done,” says Oi Lian Kon, who studies human genetics at the National Cancer Centre Singapore and is leading the BAC review group. 

MRT is used to address devastating genetic diseases that arise from abnormalities in the DNA in mitochondria, the cell’s power sources, and that commonly affect energy-intensive organs such as the brain and heart, as well as muscles. Children inherit mitochondria only from their mothers; replacing faulty mitochondria in an egg or embryo with normal ones from a donor can result in healthy babies. But it also means that offspring will bear DNA from three “parents,” which makes MRT a controversial procedure.

In 2015, the United Kingdom gave MRT the go-ahead, and the first two babies resulting from the technique are likely to be born there later this year. MRT has already been used in other countries that don’t explicitly legalize it, but have more relaxed laws on genetic modification. In 2016, a female carrier of Leigh syndrome, a severe neurological disorder, received treatment in Mexico and gave birth to a healthy boy. The following year, a Ukrainian team reported two successful births from MRT as well.

No other countries have adopted laws specifically about MRT. Many have a blanket ban on changing the human germline that includes the technique. Thailand is the only country that does not explicitly prohibit altering the human genome, whereas Italy and Israel permit it under certain conditions.

In Singapore, MRT is theoretically possible today, says BAC review panel member Tracey Evans Chan, who studies biomedical law and ethics at the National University of Singapore. The country does not allow human germline modification in the clinical setting, but it does—unlike the United States and many European countries—permit genetic tinkering for research purposes, so MRT could be done if it were formally part of a scientific study. “But in order for the therapy to be mainstreamed,” he says, the law needs to change.

Singapore’s BAC has held two public dialogue sessions in the past month; they are also soliciting written feedback. “The most common concern expressed among the lay public whom we have consulted is the issue of self-identity and the fact that children who are born from such a method would, in theory, have part of the genomes of three individuals,” Kon tells Science.

Two MRTs are now approved for use in the United Kingdom: maternal spindle transfer, in which the nucleus from the mother’s egg is placed inside a donor egg whose nuclear material has been removed, followed by fertilization; and pronuclear transfer, in which an egg is fertilized first, after which the nucleus of the embryo is transferred inside the enucleated donor egg cell.

Singapore is considering a third, newer method called polar body transfer (PBT), in which a tiny cell from the recipient called a “polar body”—which forms when an egg cell divides—is placed inside a donor egg cell, before or after fertilization. Polar bodies have very little cytoplasm and contain few, if any, mitochondria, which makes PBT potentially simpler and safer. That the United Kingdom has not approved PBT is “really a matter of timing,” says Andy Greenfield of the Medical Research Council's Harwell Institute in the United Kingdom, who led the country’s Human Fertilisation and Embryology Authority review of MRT. “The possibility of using PBT came rather too late in the process to permit its smooth introduction into law,” he says.