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A step towards three-parent babies?

February 6, 2008 By Erika ECH Check Hayden This article courtesy of Nature News.

Progress report shows clinical application of technique still far away.

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A predictable media circus followed a UK newspaper's report yesterday that scientists have created so-called 'three-parent embryos'. But some of the reports have misconstrued what the scientists have actually done thus far, and the scientists caution that their unpublished work, while promising, is still far from clinical use.

The scientists, based at the University of Newcastle upon Tyne in the UK, received a licence from the Human Fertilisation and Embryology Authority (HFEA) to perform 'three-parent embryo' experiments in September 2005. The experiments aim to replace genetically damaged structures called mitochondria, found in a woman's egg cells, with healthy mitochondria from unrelated eggs. The experiment has been mooted as a way to help women with diseased mitochondria have healthy babies.

Their work so far has reportedly created ten viable embryos containing genetic material from multiple 'parents'. But these resulted from transplants of DNA between embryos, rather than into a healthy egg as will be needed in future; it is not clear that the procedure will work in normally fertilized eggs.

The team says the progress confirms their hope that nuclear DNA can be taken out of embryos while leaving most, but not all, of the mitochondria behind — a step that will be needed in future for the procedure. "In that sense, it's reassuring that this offers great potential, and technically, the finding that we can allow these embryos to develop in vitro suggests that we should be able to continue," says neurogeneticist Patrick Chinnery, a neurogeneticist on the Newcastle team that performed the experiments.

Early days

The vast majority of our DNA is contained inside our cells in structures called nuclei. The mitochondria, in contrast, are found outside the nucleus and contain less than one hundredth as much DNA as in the nucleus. Healthy mitochondria provide energy to cells, and defective mitochondria passed down from mother to child can cause a variety of ailments, such as mental retardation.

The experiments described yesterday were not carried out on patients with diseased mitochondria, but instead on embryos left over from fertility treatments. The embryos were destroyed after six days of development in the lab so that scientists could analyse them, Chinnery said.

In the procedure that scientists envisage using in patients, doctors would first combine the genetic material from one woman's egg and her partner's sperm. The resulting egg would then contain the nuclear DNA from both parents, along with the woman's diseased mitochondria. Scientists would then remove the nuclear DNA from the fertilized egg, leaving the unhealthy mitochondria behind, and transplant it into a second woman's egg, which has been stripped of its own nuclear DNA but retains healthy mitochondria.

So far, Chinnery said, the Newcastle team has only exchanged the nuclear DNA of embryos that have failed fertility treatments. In other words, it has transplanted nuclear DNA from one failed embryo to another — not from one embryo into a healthy donor egg, as has been widely reported. These failed embryos contain abnormal doses of nuclear DNA.

The ten embryos in which the swaps succeeded were the result of experiments on numerous failed embryos — perhaps hundreds, Chinnery says, although he declined to give an exact number. A better efficiency would be needed for clinical application of the work, since scientists would not have access to hundreds of healthy donor eggs for every couple who wanted to undergo the procedure.

"There are still a number of scientific issues we've got to resolve, in terms of efficiency, and in terms of whether we can do this in eggs rather than in other embryos," Chinnery said.

Moving forwards

Other scientists have not yet had a chance to vet the work, because it has not been published. It was announced to Parliament by Lord Walton, a former dean of medicine at Newcastle. Walton hoped the news would convince his colleagues to allow the HFEA to green-light clinical use of the research, but his proposal was rejected on Monday, according to news reports.

Chinnery said he did not know how Walton had learned of the team's success, but said that the work was presented last week in a poster at a meeting convened by the UK Medical Research Council.

Chinnery said further that much scientific work and societal consultation should occur before the work is used in patients, because there are groups that object to the procedure on ethical grounds.

"I wouldn't feel comfortable doing it [in patients] now for a number of reasons," said Chinnery. "There are a number of scientific, legal and ethical issues — we've got to engage in a debate to ensure that society feels this is the right thing for us to do."

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