Meet mama, papa and mama: how three-parent IVF works

Mitochondrial genes are inherited from our mothers’ eggs and passed on through her daughters to subsequent generations. Shutterstock

The UK government has announced its intention to draft proposals allowing carriers of mitochondrial disease to have babies using a controversial IVF treatment that’s currently prohibited. The procedure is controversial because the babies will inherit DNA from three genetic parents.

The draft proposals will detail the regulation of the procedure and need to be endorsed by public consultation and parliament before being put into practice.

The mighty mitochondria

Mitochondrial DNA diseases offer distinct challenges to scientists and clinicians because we inherit our mitochondrial DNA in a different manner to our chromosomal genes. Our mitochondrial genes are passed down from our mothers’ eggs and on through her daughters to subsequent generations.

Mitochondrial genes are located in very small bodies called mitochondria and not with the chromosomes in the nucleus of the cell, which determine characteristics such as hair and eye colour.

The mitochondria are the “powerhouses” of the cell as they generate energy. Our cells use this form of energy for their everyday functions; mitochondrial genes are essential to this process.

If one of these genes is mutated, the individual may suffer from very debilitating diseases that affect, for example, muscle and nerve function. There are an increasing number of diseases that are associated with these mutations including diseases we hear about everyday, such as diabetes and Alzheimer’s disease.

The dilemma for a woman who carries mitochondrial DNA disease is that she doesn’t know how much damaged mitochondrial DNA is present in each of her eggs; each of these eggs is likely to have a different amount of mutation. Also, there’s no simple genetic test that can be used to tell the carrier whether her child would be affected.

So, if she and her partner choose to have a family, they will have no idea of the outcome – for them, it’s simply a matter of chance.

Overcome mitochondrial disease

Scientists are now developing two approaches to try and prevent children from inheriting these diseases.

The first of these techniques will transfer the mother’s chromosomes from one of her eggs into an egg from a donor. The donor egg would have had its chromosomes removed but retains its healthy mitochondrial DNA.

Then, as with normal IVF treatment, the eggs are fertilised with her partner’s sperm and the resultant embryo can develop for a few days in the lab before being transferred to the chromosomal mother to implant into her womb.

The second technique is similar but would first allow the partner’s sperm to fertilise the egg and then transfer the mother’s and father’s chromosomes to a healthy (empty apart from mitochondria) donor egg.

The controversy around these approaches lies with the baby having three genetic parents. Shutterstock

The controversy around these approaches lies with the baby having three genetic parents. These are the chromosomes that the mother and father contribute, as is normal following fertilisation. And then there’s the “third parent” – the mitochondrial DNA mother who donated the egg.

Some things to consider

Some groups argue that scientists are entering the brave new world of designer babies and that these techniques are similar to cloning. For them, these procedures are unacceptable.

Others argue that the technologies offer significant benefits, such as the potential to eradicate mitochondrial diseases.

In many respects, UK scientists are at the forefront of convincing government to legalise these procedures under the control of the country’s fertility regulator, the Human Fertilisation and Embryology Authority.

In the last two years, there have been two significant reports supporting these procedures but they contained important reservations. In 2012, the UK’s Nuffield Council on Bioethics ruled:

If further research shows these techniques to be sufficiently safe and effective, we think it would be ethical for families to use them if they wished to, provided they receive an appropriate level of information and support.

The Human Fertilisation and Embryology Authority sought public views on behalf of the secretary of state for health and reported in late March, 2013. It noted:

… there is general support for permitting mitochondria replacement in the UK, so long as it is safe enough to offer in a treatment setting and is done so within a regulatory framework.

These reservations are important because they are directed to two key aspects of the procedures. The first is whether any of the mutant mitochondrial DNA accompanies the chromosomes as they are transferred into the donor egg.

This is very important as even a small amount of mutant mitochondrial DNA in the egg can become the dominant population in the baby and lead to mitochondrial disease. We are unsure why this happens but this is currently an area of intense research activity.

The second is whether these techniques would lead to the baby suffering from any harmful side effects.

While I fully embrace these new approaches to fight mitochondrial disease, we still need to make significant advances in determining their safety and effectiveness, and they require a considerable amount of validation.

If they pass these tests, these technologies offer ways to prevent mitochondrial genetic disease from being passed from a female to her descendants through one round of assisted reproduction.