Mitochondrial Transfer and “three-parent embryos”

Recent reports in the UK and Irish media have focused on a recently proposed change to the genetics laws in the UK to allow mitochondrial replacement. This new technique could provide an option for women with mitochondrial DNA mutations to enable them to give birth to healthy children.  The procedures use donated mitochondrial DNA whilst also allowing a woman to have babies that are genetically related to her.

This is extremely topical for Fighting Blindness, as a number of genetic eye conditions such as Leber hereditary optic neuropathy (LHON), and other rare forms of blindness and deaf/blindness can be caused by alterations in mitochondrial DNA.

Some forms of mitochondrial disease are linked to very severe syndromes that often strike in childhood and prove fatal before adulthood. There is no current cure for genetic diseases of the mitochondria.

What are mitochondria and what is mitochondrial transfer?

Mitochondria are found in the fluid surrounding the nucleus of our cells. They are tiny structures responsible for making energy within the cell, without which the cells would not survive. The vast majority of our DNA (over 99%) is found in the nucleus of the cell and we inherit this from our mother and father. However, the mitochondria contain only a very small amount of our total DNA (approx. 0.2% and known as mtDNA) which sits in its own genome and is only inherited from our mother. Any mutations in a mother’s mtDNA, which may cause mitochondrial disease, will be automatically inherited by her children.

Mitochondrial transfer works by removing the entire nuclear DNA, except for the mtDNA, from the egg of a woman carrying mitochondrial disease. The same procedure is also carried out on an egg that has been donated by a woman with healthy mtDNA. The nuclear DNA of the woman who wishes to have the child is transferred into that healthy egg. This results in an egg containing the nuclear DNA of the woman who wants to have the child but also containing healthy mtDNA from the donor. This egg is then implanted as per normal IVF procedures.

Why is this in the news?

Mitochondrial transfer has been in the news recently because of a historic House of Commons debate and vote in the UK, where UK members of parliament recently voted to permit mitochondrial transfer. The UK has become the first country in the world to permit this procedure.

In the media, mitochondrial transfer has sometimes sensationally been referred to as “three-parent embryos.”  However, women who donate their healthy mitochondria would remain anonymous and would have no rights over the child or its upbringing. At a genetic level all 23 pairs of chromosomes would come from the mother and father, and the donated mitochondria would contribute less than 0.2% of the total DNA.

What would this mean for families affected by mitochondrial disease?

Mitochondrial donation could allow women with abnormal mtDNA to give birth to healthy children and would potentially eliminate a large number of mitochondrial disease. This is because the genetic material is not only carried by the child that grows from the embryo, but is passed down the female line to all future generations. Mitochondrial transfer has the potential to alter this fate.

Why are there concerns about this procedure?

Both types of mitochondrial transfer procedures have been tested in animals and resulted in healthy offspring. Good results have also been seen in human cells, but embryos treated by these techniques have not been implanted into a woman to achieve a pregnancy. The long term generational effects of such a procedure are also unknown.

There are also concerns that mitochondrial transfer could open the door to a genetic “redesign” of future generations. However, there is strong and long standing international opposition to the alteration of inheritable traits such as eye colour and hair colour, and the ban on altering nuclear DNA remains in place.

Others have voiced strong ethical opposition to one of the methods used in mitochondrial transfer because a fertilised embryo from the mother is destroyed during the procedure.

How will this impact Ireland?

MPs in the UK have voted for a change in law and this decision will pass to the House of Lords for a vote at the end of February. If the House of Lords agree, clinics could be licensed to perform the procedure in the UK by autumn 2015, and the first babies could be born in 2016.

It is unclear how this legislation will affect Ireland, as one of the procedures involving the destruction of a fertilised egg would be a breach of our current constitution. Unlike other jurisdictions, Ireland essentially operates in a “legal vacuum” when it comes to IVF technology, and there is currently no statutory or legislative guidance when it comes to the practise of IVF.

For more information please contact Fighting Blindness at research@fightingblindness.ie or 01 6789 004, or the Genetic and Rare Disorders Organisation (GRDO) at info@grdo.ie.