Doctors are a step closer to creating babies with DNA from three people after research on healthy embryos found the procedure was likely to produce normal pregnancies.
Studies on embryos made with extra DNA showed that the majority were indistinguishable from standard IVF embryos, although further tests hinted that the procedure still carried risks.
The work will be reviewed by the UK government’s fertility regulator, which is expected to make a recommendation on whether or not to approve the treatment under licence before the end of the year.
The experimental technique, known as mitochondrial donation, has been developed by researchers in Newcastle to prevent women from passing on devastating and often fatal genetic diseases to their children.
The illnesses, many of which affect the brain and muscles and worsen as children grow, are produced by genetic mutations in tiny structures called mitochondria that sit inside cells and provide them with energy. They are passed on exclusively from mother to child, but mothers can be carriers without having symptoms.
Using mitochondrial donation, doctors hope to block the transmission of faulty mitochondrial DNA by making IVF embryos that have the normal set of chromosomes from the parents, but healthy mitochondria from a donor.
In March last year, MPs voted to allow mitochondrial donation and handed responsibility for its use to the fertility regulator, the Human Fertilisation and Embryology Authority (HFEA). An expert scientific panel convened by the HFEA asked for more evidence of safety before it would consider issuing a licence for doctors to perform the procedure.
In research published in Nature on Wednesday, the Newcastle team led by Doug Turnbull and Mary Herbert describe a broad range of experiments on the safety of one particular form of mitochondrial donation, called pronuclear transfer (PNT). In PNT, the mother’s egg is fertilised with the father’s sperm using standard IVF procedures. Before the egg has a chance to divide into two cells, the parents’ chromosomes are plucked out and dropped into a fertilised egg from a healthy donor, which has had its own chromosomes removed.
The Newcastle team showed that by performing PNT about eight hours after insemination, they could create early-stage embryos with less than 5% mutated mitochondrial DNA. Most, some 80%, carried less than 2% mutated DNA. The small amount of faulty DNA is carried over from the mother’s egg when the parents’ chromosomes are removed.
The scientists next subjected embryos to a battery of tests and found no differences between them and normal IVF embryos. While that was a boost for the scientists, follow-up studies urged a note of caution. When cells were taken from PNT embryos and grown in the lab, some showed rising levels of mutated mitochondrial DNA. Though small amounts had been carried over, the faulty DNA came back.
The revival of mutant DNA in cells grown from the embryos is hard to interpret, but scientists suggest they could screen PNT embryos for high levels of mutated mitochondria before deciding which to implant. “It sounds a note of caution for us,” said Herbert.
A similar problem was reported by Dieter Egli at Columbia University in work reported from the New York Stem Cell Foundation Lab reported in the journal Cell Stem Cell earlier this month.
Egli said: “The question now is how do we make sure that such instability does not occur. Clearly it did occur after PNT, and one or two in five cell lines is not uncommon. Once we can show that mtDNA genotype instability can reliably be avoided, I don’t see any reasons not to use it clinically.”
“It is up to regulators to make the decisions on whether it a technique is ready to be used clinically, and many factors will play into that,” Egli continued. But he added that scientists do not yet know how such shifts in mitochondrial DNA will affect embryos, and ultimately babies. “I believe this is something regulators will certainly consider in their decisions,” he added. Herbert said her group was already working on ways to reduce the carryover of mutated DNA.
Turnbull said the procedure could potentially help 150 women who carry mitochondrial diseases in the UK each year, but added that many would probably choose alternatives to avoid passing the mutated DNA on, such as adoption or IVF with donor eggs.
“We are discussing this now with patients as a potential reproductive option. People are very positive about the technique. There are certainly patients who would move forward with this,” he said.
