The ethical obstacles to an IVF breakthrough

Scientists in the UK say they have the expertise to remove the risk of mitochondrial diseases from IVF babies by substituting faulty genetic material with healthy DNA from a “third parent”.

But legislation currently precludes its use amid concerns over the implications of selective genetic procedures in the creation of babies outside the womb.

The Human Fertilisation and Embryology Authority (HFEA), which regulates IVF clinics and fertility research, is consulting the public before deciding whether to allow the mitochondrial replacement procedure – subject to parliamentary approval.

The public consultation ends on 7 December.

It is estimated that only between 10 and 20 badly affected women might qualify for such treatment each year.

However, their treatment would not only remove the risk of the baby developing mitochondrial diseases but would prevent future generations from inheriting the disorders.

Mitochondrial diseases

One in 200 children born each year in the UK has some form of mitochondrial disease. 
Not all suffer serious symptoms and not all the girls among them will pass the condition to their offspring.
But the defects in mitochondrial DNA can give rise to a range of serious and potentially life-threatening diseases, including a form of muscular dystrophy and conditions leading to the loss of hearing and vision, heart problems and intestinal disorders.

If parliament approves a change to the Human Fertilisation and Embryology Act, allowing the procedures, the authority would then decide whether to go ahead.

Scientists are considering two alternative methods of mitochondrial replacement: pronucleus transfer (PNT) and maternal spindle transfer (MST).

PNT involves transferring the nuclear DNA (the major genetic material that contains parents’ unique characteristic-forming chromosomes) from the mother’s fertilised egg into an embryo of a donor whose pro-nuclei have been removed, but whose mitochondrial DNA (containing non-faulty genetic material) is still present.

The donor embryo’s (unrequired) nuclear material would then be destroyed.

In MST the mother’s unfertilised nuclear DNA (the spindle) is implanted in the donor egg containing healthy mitochondria (but whose own spindle has been removed) before it is fertilised.

What remains of the mother’s egg is then destroyed.

The HFEA says the procedures raise a number of key issues which they want to explore with the public before taking the next step.

The comments below are among those offered by experts to the HFEA.

Slippery slope

Could the techniques required for medical reasons be used for more cosmetic purposes, perhaps to determine hair or eye colour or even intelligence, thereby creating a designer baby?

Dr Evan Harris, senior research associate at Queen Mary, University of London: “To actually get this made lawful… there has to be a vote in parliament. If it was ever going to change beyond that you would need to pass a new law. That isn’t slippery – it is extremely difficult.”

Dr David King, director of Human Genetics Alert: “You can have tight regulation, but regulation shifts. That is the slippery slope.”

Future generations

What would be the impact of genetic modifications on future generations further down the line?

Professor David Jones, director of The Anscombe Bioethics Centre: “Do we want to start treating these diseases by modifying the embryo? If we do, we should say yes now, but if we are worried about that kind of thing, then we should say no because this is the time that we make that decision.”

Dr Geoff Watts, science writer: “If this technique is introduced there should be a concerted effort to follow up not only the children that are born of this technique to find out if they really are as healthy as we hope they would be, but also the children’s children and the children’s children’s children. All follow-up studies are difficult to do. Following up over decades is even harder.”

Professor Jo Poulton, honorary consultant in mitochondrial genetics at the John Radcliffe Hospital, Oxford: “When they get to the age of 16 they are in charge of their own destiny, and nobody can make that child agree to carry on with this kind of follow-up.”

Identity

How will a child with DNA from three people perceive his/her identity?

Dr Watts: “Something like 25,000 genes come from the nuclear genetic material (from the natural parents) and about 37 genes come from the donor of the mitochondria. So you are talking about a genetic inheritance, a contribution from the donor, of 0.1 of one per cent. It is a vanishingly small amount of material. To suggest that (the donor is) a parent makes nonsense of the complete concept of parenthood.”

Professor Jones: “A small number of genes can have a huge effect, which is indeed why they are thinking of doing it “because the genes can have a devastating effect if they are faulty.”

Donor’s rights and responsibilities

People who currently donate sperm or eggs have to agree to be identifiable to any consequent child, who has a right to personal and medical information about the donor, and can contact them once they reach 18.

However, people who donate blood, bone marrow or other tissue can do so anonymously, largely because such donated material is not considered key to a person’s sense of identity.

The HFEA says it is recognised that people who receive certain types of organ transplants – such as face and heart – often have “identity issues” after the surgery.

As well as considering the rights of the child, experts would have to consider whether automatic identification could be a deterrent to would-be donors.

They will also explore the compromise of allowing the child to know how he/she was conceived, but not the identity of the donor.

And would the donor have any responsibilities herself?

Safety and regulation

At what stage can scientists be confident that the pioneering techniques are safe – and how can potential future impact be monitored and policed?

Professor Frances Flinter: “You can never prove that something is completely safe until it has been tried in human beings, and there will come a point where that leap of faith has to be made, just as it was when the first baby was conceived by IVF or when the first person had a heart transplant or a kidney transplant.”

Professor Poulton: “If scientific advance is going to go forward, the UK is a very good place for it because we have such excellent regulation, and I would be very upset if this was stopped in the UK and my patients.. were whisked off to somewhere like China or Russia, where there is no regulation and probably the genetic counselling would be very inferior to what it would be here.”

Professor Flinter: “If we make these treatments available here and they are not easily available elsewhere, some people might come here from other countries in order to be treated, and that could make it more difficult to follow up their children when they return home.”

Who is eligible?

The HFEA would decide how to monitor and regulate the use of mitochondria-replacement techniques, if they became legal.

It says it would allow clinics to offer the treatments only if they had the relevant expertise and equipment.

It might have to consider whether to offer the option that best suited the parties’ ethical preferences – for example, MST does not involve discarding an early embryo.

It might put more emphasis on safety and cost efficiency.

The HFEA might also decide which mitochondrial diseases were serious enough to qualify and leave it to the clinics and patients to decide whether their cases were appropriate – or make the decisions itself.