A U.S. fertility specialist, foiled by U.S. regulations, took his tools to Mexico to tweak human cells into developing into the world’s first three-parent baby, an infant born in April 2016 who carries DNA from two mothers and one father.
New Scientist broke the story, reporting that the parents are Jordanian Muslims who had already lost two children to Leigh syndrome, a fatal disease that involves the gradual deterioration of the nervous system, along with pain, gastric distress and, ultimately, respiratory failure, usually in the first years of life.
Unlike many human genetic conditions, though, the gene variants associated with Leigh disease don’t exist in the nuclear DNA. Instead, they are DNA sequences from our mitochondria, the organelles responsible for packaging nutrient energy into a readily accessible form.
We all inherit mitochondria only from our mothers, who pass them along to us as part of the cytoplasmic component of the egg. The children that the Jordanian couple lost thus inherited the disease-causing variants from their mother.
Through quirks of how mitochondria are allotted as an egg is produced, the mother in this case has a relatively small proportion of mitochondria with the gene variants and does not have the disease. But the two children she had ended up receiving a larger proportion that carried the disease-related variant and thus had Leigh syndrome. The mother had undergone four pregnancy losses, as well.
Seeking to do a runaround on passing along a fatal disease to their children, the couple sought help from a U.S. fertility specialist, John Zhang at New Hope Fertility Center in New York. They consulted with Zhang about a procedure that would result in an embryo containing an allotment of nuclear DNA from each parent, as any typical embryo does, but with the mitochondria replaced by those from another woman, presumably not a carrier of the Leigh-related gene variants.
The obstacle for Zhang and the couple was that the U.S. has not approved this mitochondrial replacement procedure. Indeed, only the UK currently has approved mitochondrial replacement. The sanctioned method in the UK involves using two eggs, one from the mother and the other from a donor, both fertilized by the father’s sperm. The nucleus from the donor egg is removed and replaced by the nucleus from the mother’s fertilized egg. The resulting cell has nuclear DNA from the two intended parents but mitochondrial DNA from the donor.
This approach was a no-go for the Jordanian couple, whose religious beliefs precluded the creation of the fertilized donor nucleus to be discarded. So Zhang went at the three-parent approach using a different configuration: he replaced an unfertilized donor egg nucleus with a nucleus from the intended mother and then fertilized the resulting egg, which contained nuclear DNA from the mother but mitochondria from the donor. It’s not gene editing, like CRISPR, but organelle editing.
Zhang made headlines 13 years ago by announcing the“three-parent baby” technique, although the paper from that announcement was published only this year.
Because the U.S. has yet to approve any three-parent embryo approaches, Zhang went to Mexico to do the work. He and his team have an abstract published that describes the process, which they plan to present at the American Society for Reproductive Medicine meeting in October.
According to that abstract, of five embryos processed in this way, only one ended up progressing through typical human development. The abstract says that tests of various tissue samples from the infant boy show that his cells contain an average of 1.6% of the mother’s mitochondrial DNA, meaning that the rest are presumably from the unaffected donor parent.
Zhang’s decision to get around the lack of U.S. approval by taking the work to Mexico has raised eyebrows, at the least. The abstract says that the team had an institutional review board-approved protocol and appropriate consents for the procedure, but that has by no means been sufficient information for some groups. The Center for Genetics and Society released a statement calling the development “troubling” and the procedure “biologically extreme.” They say:
We urge intended parents who might consider undergoing this biologically extreme procedure to carefully investigate the risks, as well as the areas where evidence of safety is lacking… And we urge scientists and policy makers to condemn rogue experimentation that takes advantage of families’ misplaced trust in people who wear white coats.
The BBC quotes a representative, David King, from “the pro-choice group Human Genetics Alert,” as calling the tactic “outrageous.”
New Scientist, however, quotes UK professor Sian Harding as saying that Zhang’s team seems to have taken “an ethical approach”:
The team avoided destroying embryos, and used a male embryo, so that the resulting child wouldn’t pass on any inherited mitochondrial DNA. “It’s as good as or better than what we’ll do in the UK,” says Harding.
The response meter to this news is, in other words, swinging wildly from one extreme (it "heralds a new era" and it’s “revolutionary” to another “ it’s ‘playing God‘”).
According to Science magazine, some scientists have questions about both the ethics and the biological validity of the claims that this is, indeed, the world’s first three-parent baby. The boy himself, according to the abstract, is “doing well.”
Emily Willingham is a journalist and biologist. Her book, The Informed Parent, with co-author Tara Haelle, is available now. Twitter.
Image via Wikimedia
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