Researchers at Columbia University in New York have created embryos containing genetic material from three people and are ready to use them to start pregnancies. But they’re at a legal impasse.
At a public forum at Harvard Law School on Wednesday, Dietrich Egli, assistant professor of developmental cell biology at Columbia, said his team has used a controversial technique called mitochondrial replacement therapy to make embryos for four female patients. The women are all carriers of genetic disorders that are passed down through maternal mitochondria, the energy-generating organelles inside cells.
The embryos cannot be transferred into a woman’s uterus because of a 2015 congressional amendment that forbids the Food and Drug Administration from considering human research applications “in which a human embryo is intentionally created or modified to include a heritable genetic modification.”
For now, Egli said, the embryos have been frozen. “They would be ready for transfer if a legal path could be found,” he said.
Wednesday’s event at Harvard was the first in a series of meetings meant to draft policy recommendations with the goal of persuading U.S. lawmakers to lift the prohibition on mitochondrial replacement therapy. In the U.K., the procedure is allowed but is strictly regulated.
The technique involves taking the nucleus from the mother’s egg and transferring it into a donor egg that has had its nucleus removed. In human cells, the nucleus is where the majority of DNA is located. But a tiny amount of DNA is also located in the mitochondria, which float around in the cytoplasm outside the nucleus. Mutations in mitochondrial DNA can cause serious genetic diseases. When the nucleus of the donor egg is taken out, it retains its healthy mitochondria. The donor egg with the mother’s nucleus is fertilized with the father’s sperm. Because a tiny amount of DNA comes from the donor, the resulting baby ends up with DNA from three people.
The 1996 Dickey-Wicker Amendment prohibits the use of federal funds for the creation of human embryos for research purposes, so Egli said that his group at Columbia, which includes neurologist Dr. Michio Hirano, is using philanthropic funds for their study.
Because of these restrictions, New York-based fertility specialist John Zhang went to Mexico in 2015 to skirt U.S. law. There, he transferred an embryo created with mitochondrial replacement therapy into a woman who’s a carrier of Leigh syndrome. She delivered a seemingly healthy baby in April 2016.
Egli and his colleagues previously studied the use of mitochondrial replacement in stem cells, but they have moved forward with creating viable embryos in hopes of being able to transfer them into women in the near future. “We want them to realize their dreams,” Egli said.
Shouhkrat Mitalipov, an embryologist at Oregon Health and Science University who was at the Harvard event, has also used mitochondrial replacement in human embryos but, according to a university spokesperson, those embryos were never intended to be transferred to establish a pregnancy, like Columbia is doing.
Marcy Darnovsky, executive director of the Center for Genetics and Society, in Berkeley, Calif., worries that allowing this kind of heritable alteration could open the door to genome editing in eggs, sperm or embryos. “I think it’s clearly a warmup to germline editing,” she said.
In separate experiments for research purposes only, Egli is using the genome-editing tool CRISPR in embryos in an effort to repair certain disease-causing genetic mutations.
Because of lingering safety concerns that a mismatch in mitochondria from the donor and intended mother could cause complications for a fetus or resulting baby, Egli said his group is using donor eggs with mitochondrial DNA from the same haplotype — essentially the same family of mitochondrial DNA — as the mother’s.
The women are a part of a study looking at female carriers of mitochondrial diseases. Out of 45 women of childbearing age, 78%, or 35 women, had thought about not having children because of the risk of transmitting mitochondrial disease to them, according to Egli’s presentation.
Clinics in Greece and Ukraine are currently using mitochondrial replacement therapy not to avoid serious genetic disease in babies but as an infertility treatment for women who haven’t been able to get pregnant with standard IVF. Egli said he and his team do not plan on transferring the embryos outside the U.S. though.
“We have no plans to move them abroad. We would like to advance the regulatory framework here,” he said.