Scientists at Newcastle University have developed a pioneering technique which enables them for the first time to successfully transfer DNA between two human eggs. The technique has the potential to help prevent the transmission of serious inherited disorders known as mitochondrial diseases.
The study, led by Dr Mary Herbert and Professor Doug Turnbull, and funded primarily by the Muscular Dystrophy Campaign, the Medical Research Council and the Wellcome Trust, is published today in the journal 'Nature'.
Every cell in our body needs energy to function. This energy is provided by mitochondria, often referred to as the cell's 'batteries'. Mitochondria are found in every cell, along with the cell nucleus, which contains the genes that determine our individual characteristics. The information required to create these 'batteries' - the mitochondrial DNA - is passed down the maternal line, from mother to child.
A mother's egg contains a copy of her own DNA - 23 chromosomes - as well as DNA for her mitochondria. The amount of genetic material contained in mitochondrial DNA is very small - 13 protein-producing genes, compared to an estimated 23,000 genes that we inherit from our parents - and this information is used solely to generate the energy produced by the 'batteries'.
Like all DNA, the DNA in mitochondria can mutate and mothers can pass these mutations onto their children. Around one in 200 children is born with mutations that in most cases cause only mild or asymptomatic forms of mitochondrial disease. However, around one in 6,500 children develops mitochondrial diseases including muscular weakness, blindness, fatal heart failure, liver failure, learning disability and diabetes. These can lead to death in early infancy.
There are no treatments available to cure these conditions and mothers often face the agonising choice of whether to risk having a child who may be affected by such a disease or not to have children at all.
Now, researchers at Newcastle University have developed a technique which allows them to replace these 'batteries'. This is the first time such a technique has been used in fertilised human eggs.
A fertilised egg usually contains two pronuclei - genetic material from the egg and sperm - as well as mitochondria. The technique developed by the Newcastle team involves extracting the pronuclei but leaving behind the mitochondria. The researchers then take a fertilised egg from a donor, remove its pronuclei and replace them with the extracted pronuclei. This new fertilised egg contains the DNA of the father and mother, and the mitochondria from the donor.
"What we've done is like changing the battery on a laptop. The energy supply now works properly, but none of the information on the hard drive has been changed," explains Professor Turnbull. "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."
The Newcastle team used their technique to create a total of 80 zygotes (fertilised eggs). These were cultured for six to eight days in the laboratory to monitor development as far as the blastocyst stage (the stage at which it has divided into a group of around one hundred cells) in line with the terms of the licence granted by the Human Fertilisation and Embryology Authority (HFEA) in 2005.
In some cases, a very small amount of the mother's mitochondrial DNA was carried over to the new egg. Since severe diseases only occur with large numbers of mutations, this would be very unlikely to affect a child's health.
The research is proof of a principle that researchers should be able to prevent transmission of mitochondrial diseases, thereby allowing the mother to give birth to a healthy child.
Professor Doug Turnbull and Professor Alison Murdoch explain the breakthrough - Running time: 3 min 2 s
The Newcastle team used eggs that were unsuitable for IVF - for example, eggs with one or three pronuclei rather than the normal two. This is common in the IVF process and affects around one in ten fertilised eggs. The eggs were donated by couples attending the Newcastle Fertility Centre at Life. The egg donation programme and the ethical and regulatory aspects of the project are led by Professor Alison Murdoch.
The team are now planning further studies that will provide further evidence of the safety of this procedure. The Human Fertilisation and Embryology (HFE) Act, as amended in 2009, currently prevents fertility treatment using these techniques. However, the HFE Act includes the provision for the Secretary of State to make provisions for this to be permitted in the future.
Support from the study's main funders
Muscle cells require especially high levels of energy, causing many people with mitochondrial diseases to experience severe muscle weakness. These conditions are called mitochondrial myopathies and are among the 60 different types of muscle disease affecting people supported by the Muscular Dystrophy Campaign.
Philip Butcher, Chief Executive of the Muscular Dystrophy Campaign: "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 Fertilisation and Embryology Authority to permit fertility treatment using these techniques as soon as the method is proved to be effective and safe in humans."
Sir Leszek Borysiewicz, Chief Executive at the Medical Research Council: "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: "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 research was made possible because of the sensible regulatory regime in the UK that enabled the Human Fertilisation and Embryology Authority to issue a licence for the research and thanks also to the donation of eggs by patients undergoing IVF treatment. We have every hope that the Newcastle team's work will lead to great clinical benefit for the families affected by severe mitochondrial diseases."
Case study: Sharon Bernardi, 44, Sunderland, UK
Sharon Bernardi has a form of mitochondrial disease. The condition has claimed the lives of six of her children, all of them dying within a few hours of being born. It was passed down to her from her mother, who lost three babies herself.
Her only living son, Edward, is now 20. He has Leigh's disease and needs constant care. He is wheelchair bound and has to be fed liquids as he struggles to digest solids. His life expectancy has been dramatically reduced.
The new technique developed in Newcastle could potentially prevent the complications and deaths caused by mitochondrial disease.
Sharon said: "I wasn't diagnosed until after my fifth baby had died, no one knew why it was happening, they had no answers. I would get pregnant again and just pray this time would be different.
"My mum sat me down and told me it had happened to her. The previous generation lost 11 children in total.
"It is just such a devastating thing to happen, but I feel lucky to have Edward. It will be too late for me but it would be an amazing thing if scientists and doctors can prevent this in the future."