It was a small study involving only four women carrying the pathogenic genes. The embryos were not implanted to create a pregnancy. But the work sets the stage, potentially, for human trials, pending approval by government regulatory agencies.
The technique used in swapping the genetic material was not immaculate: Some mutant DNA remained in the fertilized eggs and the ensuing replicating stem cell lines. In some of those stem cell lines the mitochondria reverted to the mother's disease-carrying genetic code. That happened in about 10 to 15 percent of the stem cells, which was a surprise, because that hadn't been seen in experiments with animal models. They concluded that, going forward, the donors of healthy mitochondrial DNA need to be carefully screened for compatibility with the mother's mitochondrial DNA.
This kind of genetic therapy “is more complex than we thought,” said the paper's senior author, Shoukhrat Mitalipov of Oregon Health & Science University, in a briefing Tuesday with reporters.
“The research is promising. It’s certainly not completed," said Alta Charo, a bioethicist at the University of Wisconsin who was not involved with the research but has tracked the field closely.
The mitochondria are organs within a human cell that live outside the cell nucleus. They're often described as the power plants of the cell. They also contain their own DNA, though not much. DNA in the cell nucleus carries something on the order of 20,000 human genes, while mitochondrial DNA codes for just 37 genes. That's why this kind of therapy, if it became implemented in humans, would not create “three parent” babies so much as a baby with two parents and a very small number of genes from a third person.
Despite that modest genetic contribution, mitochondrial DNA with mutant genes can cause serious and sometimes fatal diseases. The Nature paper reports that about 778 babies are born each year in the United States with diseases related to pathogenic mitochondrial DNA. These genes are passed only from mother to child, via the eggs; sperm do not contribute mitochondria to the fertilized egg.
“Currently there are no cures, and these diseases can be debilitating and often fatal,” said the paper's co-author, Paula Amato, also of the Oregon Health & Science University.
A small community of researchers is working on mitochondrial replacement therapy, navigating technical, ethical and legal obstacles. Bioethicists earlier this year gave their blessing to mitochondrial DNA replacement with some limitations (notably, that this go forward for now only in male embryos, which cannot pass along genetic changes via mitochondria and thereby potentially introduce permanent changes to the human genome). More problematic for researchers is a U.S. congressional ban on government agencies handling applications for genetic experiments on human embryos. Government approval would be required for human trials designed to result in pregnancies. The research so far has been funded by private donors and academic funds; the government by law cannot fund it.
One baby, at least, has been born using mitochondrial DNA replacement in Mexico, where there are no laws against such therapy. But the authors of the new report in Nature argue that this should go forward under close regulatory control by governments, with follow-up monitoring of the babies to ensure that they remain healthy.
A British agency, the Human Fertilisation & Embryology Authority, on Wednesday released a report from a panel of experts recommending the "cautious" clinical use of mitochondrial replacement therapy in carefully selected patients who have no other options and are made aware of the safety risks involved.