Human eggs from two different women have for the first time been combined and then fertilised in a pioneering experiment designed to prevent devastating, inherited mitochondrial diseases.

About 4000 children are born each year in the US with mutations in their DNA that cause problems to their mitochondria – the energy powerhouses of living cells. This result is incurable and sometimes fatal diseases, often affecting the brain and muscles.

The potential to repair faulty mitochondrial DNA for the next generation arises from the fact that it exists not in the nucleus of an egg, but in the material surrounding it. To help women with the disorder have healthy children, scientists can take the nucleus from the would-be mother’s egg and put it into a donor egg that has healthy mitochondria and has had its own nucleus removed.

This technique was trialled in four monkeys in 2009. They all gave birth to healthy offspring which are still going strong.


My two mums

Now, Shoukhrat Mitalipov of the Oregon National Primate Research Center in Beaverton, and his colleagues have fused human eggs using a similar technique. Mitalipov extracted the nucleus from 65 eggs and replaced each one with the nucleus from another donor egg.

The team then fertilised the eggs and let them grow into a ball of about 100 cells called a blastocyst. This takes about five or six days and is normally around the time that such a fertilised egg would become implanted into the womb. Of the 65 donated eggs that were fertilised, 48 per cent grew into healthy-looking blastocysts. Their development was similar to that of 33 unaltered fertilised eggs.

In theory, babies born following the procedure would be genetically related to the woman who donated the nucleus, but would also have a tiny amount of genetic material from a second female.

Encouraging, but…

Just over half of the eggs in the study developed abnormally. This appears to be a result of faulty division, whereby a polar body – an immature cell that contains a set of chromosomes and is normally shed just after fertilisation – is retained, generating an abnormal embryo with one set of chromosomes too many.

Nevertheless, Mitalipov reckons the procedure is “efficient enough to move to clinical trials”.

“Overall, the findings are encouraging, but in contrast to previous findings using monkey oocytes, these researchers found that a high proportion of human eggs did not fertilise normally,” says Mary Herbert, a member of a team that in 2008 pioneered a similar technique at Newcastle University in the UK. “The data indicate that this is caused by failure of the eggs to properly halve their DNA content during fertilisation.”

Fertilise first

In their version of the technique, Herbert and the leader of the Newcastle team, Doug Turnbull, transferred the DNA of the mother after fertilisation, rather than before, in a procedure called pronuclear transfer. “This allows the egg to halve its DNA content and become packaged into a large, clearly visible pronucleus before being transplanted, so the risk of abnormal fertilisation is minimal,” says Herbert.

“Pronuclear transfer holds the advantage that any manipulation takes place after fertilisation, so the sorts of abnormalities seen in the current work are less likely,” says Peter Braude, professor of obstetrics at King’s College London.

It would not currently be legal to carry out clinical trials of the new technique in the US and the UK. The UK government is holding an open consultation to gauge public support for the procedure before deciding whether to change its law.

Journal refererence: Nature, doi.org/jk3