The creation of babies with three biological parents has moved closer after a number of monkeys were conceived by a technique that could stop children from inheriting severe genetic diseases.
The birth of the four healthy macaque monkeys offers the strongest evidence yet that DNA can be transplanted safely from one egg to another, to correct genetic defects.
The experiment suggests that it should soon be possible to use the method to help women who carry certain genetic disorders to avoid passing them on to their children.
It should allow scientists to replace faulty cellular “batteries” called mitochondria, which affect about one in 6,500 births. While most genetic defects in mitochondria have mild effects, some can trigger severe brain, heart, muscle and liver conditions, as well as cancer, diabetes, blindness and deafness.
The technique is controversial, however, because the children it creates would inherit some genetic material from three parents. The mother and father being treated would contribute most of their child’s DNA, but some would come from a second woman donating healthy mitochondria.
Such children would also be the first produced by “germline” genetic engineering, by which altered genes would be passed down to successive generations.
Shoukhrat Mitalipov, of the Oregon National Primate Research Centre, who led the research, said this would be justified because it was the only viable approach to preventing mitochondrial disease.
“The only way to treat these defects is to replace the genes,” he said. “This is gene transfer involving the germline, which is a concern, but we are pursuing it not for general use but for patients with mutations they will pass to the next generation. We believe this technology will prevent that.”
Although more than 99 per cent of a cell’s DNA is carried in the nucleus, a small amount resides in the mitochondria — tiny energy-producing structures which are often likened to cellular batteries. These are always inherited from the mother, via her eggs, and mutations in mitochondrial DNA can cause disease. It is the inheritance of this type of disease that the Oregon team is seeking to prevent.
In the research, which is published in the journal Nature, the scientists took chromosomes from the nucleus of mature eggs from one monkey, and transferred them into the empty eggs of another monkey. An extract from a virus was then used to fuse the chromosomes into their new homes.
The modified eggs, containing chromosomes from one female monkey and mitochondria from another, were fertilised by injecting a sperm, and the resulting embryos were transferred to the wombs of surrogate mothers.
The first two monkeys to be born were twins called Mito and Tracker, after a dye called MitoTracker used in the experiments. Two more monkeys were born after later experiments, named Spindler and Spindly after a genetic structure called the spindle along which chromosomes divide.
Tests showed that none of the monkeys had any trace of mitochondrial DNA from the mother that provided their nuclear DNA, suggesting that the process was successful.
“We consider it a big achievement,” Dr Mitalipov said. “Anything we study and achieve in non-human primates can be translated much more easily to humans.”
He said the technology could be applied “pretty quickly” in humans, and that his team would soon apply to an internal ethics board and the US Food and Drug Adminstration for permission to try it with human eggs.
Clinical use will have to wait for the results of experiments with human embryos, and follow-up studies on the health of the four monkeys. “It may take a few more years,” Dr Mitalipov said.
Similar research is being carried out by a team from the University of Newcastle upon Tyne, which has already created three-parent human embryos using a slightly different technique. It involves switching DNA to an empty egg after fertilisation, rather than before as in the Oregon study. Members of the team would not comment on the new research when contacted by The Times.
Other scientists welcomed the Oregon research, which they said was the best demonstration yet that mitochondrial disease could be corrected.
Professor Robin Lovell-Badge, of the National Institute for Medical Research in London, said: “These are proof-of-principle experiments suggesting that transfer of the nuclear genetic material from one egg to another may be a valid way to avoid the devastating problems associated with the inheritance of abnormal mitochondria that are present in the eggs of some women.
“The authors have adopted methods that have given an impressive rate of success to give apparently normal offspring. Moreover, the monkeys they used are reasonably similar in their early embryology to suggest that similar methods may well work in humans.”
Professor Peter Braude, of King’s College London, said: “For the first time, proof of principle has been demonstrated that transmission of mitochondrial disease might be avoided. It is a first step toward pre-implantation correction of the serious medical disorders caused by defective DNA inherited maternally in the mitochondria.
“Mitochondrial disorders may manifest with sudden blindness, severe heart disease in children, muscle weakness, some forms of epilepsy and profound mental and physical disability.”
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