DNA breakthrough may prevent inherited diseases

Devastating inherited diseases could be prevented using a pioneering fertility technique to swap DNA between eggs, scientists believe.

The British breakthrough opens up the possibility of avoiding mitochondrial disorders which can lead to early childhood death.

The diseases are caused by defective DNA in mitochondria - bean-shaped bodies in cells that act like batteries to generate energy.

Around one in 6,500 children in the UK is severely affected by the disorders, which can cause muscle weakness, blindness, heart and liver failure, diabetes and learning disabilities.

Mitochondria DNA is separate from that of the cell nucleus and contains far fewer genes. It is only passed from mothers to their children.

There are no treatments available which can cure mitochondrial diseases. Mothers with a family history of the disorders normally face the agonising choice of risking having an affected child or no child at all.

The new technique developed at the University of Newcastle raises the hope of ensuring a baby does not inherit malfunctioning mitochondrial DNA.

It involves transferring nuclear DNA inherited from a child's parents to a donor egg carrying its own, properly functioning, mitochondria.

"What we've done is like changing the battery on a laptop," said Professor Doug Turnbull, one of the study leaders. "The energy supply now works properly, but none of the information on the hard drive has been changed.

"A child born using this method would have correctly functioning mitochondria, but in every other respect would get all their genetic information from their father and mother."

Mitochondrial DNA only affects energy production, not all the characteristics that make a person a recognisable individual.

The mitochondria contain around 13 genes compared with an estimated 23,000 in the cell nucleus.

Members of the Newcastle team used a DNA-transfer technique similar to that employed in cloning.

A newly fertilised egg normally contains two "pronuclei" containing genetic material from the egg and sperm as well as mitochondrial DNA. Soon after fertilisation, the pronuclei fuse to form a single nucleus.

The scientists extracted the pronuclei from fertilised eggs in the laboratory, leaving behind the mitochondria.

They then implanted the pronuclei into fertilised donor eggs whose own pronuclei had been removed. The eggs were left with the transferred pronuclei plus working mitochondria from the women who donated them.

A total of 80 embryos were created using the technique. They were allowed to develop for six to eight days until they consisted of balls of around 100 cells called blastocysts.

In accordance with the research licence granted by the Human Fertility and Embryology Authority (HFEA), they were then destroyed. But blastocysts are often used in IVF (In-Vitro Fertilisation) treatment to help women have children.

In some cases, a very small amount of mitochondrial DNA was carried over to the new egg. However, the scientists believe it would not be enough to affect a child's health.

The research is published today in the journal Nature.

Prof Turnbull said: "This is a very exciting development with immense potential to help families at risk from mitochondrial diseases.

"We have no way of curing these diseases at the moment, but this technique could allow us to prevent the diseases occurring in the first place. It is important that we do all we can to help these families and give them the chance to have healthy children, something most of us take for granted."

Currently the law prevents fertility treatment embodying such techniques. However, the Human Fertility and Embryology Act is flexible enough to allow Government permission for them in the future.

Muscles require high levels of energy and are often most affected by mitochondrial disorders.

Philip Butcher, chief executive of the Muscular Dystrophy Campaign which represents people with the conditions, called mitochondrial myopathies, said: "These findings will be a ray of hope for people affected by mitochondrial diseases who can often be left with the heart-breaking decision of whether to have children who may be born with a serious illness.

"In the future this technique may give parents the choice to have a healthy child and end the tragic cycle that some families go through, passing on these conditions from generation to generation.

"I would urge the Human Fertility and Embryology Authority to permit fertility treatment using these techniques as soon as the method is proved to be effective and safe in humans."

The research was chiefly funded by the Muscular Dystrophy Campaign, the Medical Research Council and the Wellcome Trust.

Sir Leszek Borysiewicz, chief executive of the Medical Research Council (MRC), said: "This fantastic piece of research just goes to show how first class research can yield real results, unveiling new hope that a range of incurable diseases might be preventable in the future.

"Research such as this can only flourish where there is a robust regulatory framework and we are delighted to see UK researchers at the cutting edge of this developing field."

Sir Mark Walport, director of the Wellcome Trust, said: "This is exciting research that could lead to the major clinical advance of preventing devastating mitochondrial diseases by curing the disease in fertilised eggs."

The team used eggs which were unsuitable for fertility treatment such as those with one or three pronuclei instead of the normal two.

One in 10 fertilised eggs have to be discarded during IVF treatment because of this and other problems.

Speaking at a news conference in London, Prof Turnbull said there was no technical reason why the technique should not be available to patients within the next three years.

However there were significant legal and ethical challenges ahead.

Under the Human Fertilisation and Embryology Act it is illegal to create babies using embryos which have been manipulated in the laboratory. But this could be allowed if secondary legislation permitting carefully vetted procedures is brought into force.

Negotiations are now under way with the HFEA and an application has been made to extend the research.

One important step the scientists have yet to take is to repeat the experiments with "normal" cells instead of those with abnormal numbers of pronuclei.

They believe the DNA-swapping technique holds out the prospect of eradicating mitochondrial diseases from particular affected families.

The diseases will never disappear completely since new mitochondrial mutations are appearing randomly all the time.

Professor Alison Murdoch, head of the Newcastle Fertility Centre, whose patients donated eggs for the study, said: "I think it's realistic to say you could get rid of it (mitochondrial disease) in an individual family."

Mr Butcher said: "We have an honest prospect of taking these diseases out at the knees.

"These diseases are potentially devastating. They're extremely harsh and you wouldn't wish them on your worst enemy. It's a thrilling and exciting day."