Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015

Debate between Lord Patel and Lord Deben

Tuesday 24th February 2015 Lords Chamber

[The Deputy Speaker (Lord Geddes)]

I assume the noble Lord would like to move his amendment.

[Lord Deben]

I beg to move.

[Lord Patel]

My Lords, I am sorry for rushing in, but the noble Lord, Lord Deben, excited me so much with the comments he made that I have to answer some of his points, particularly on safety. I hope that noble Lords will have patience, because I need to go through each of the points he has made on safety, as I have no doubt that they will come back again in subsequent debate.

It is important that I put down some ground work. What are we talking about? We are talking about a mitochondrial DNA disease that commonly affects multiple different organs. Symptoms include severe muscle weakness, diabetes, heart problems, cardiac failure and sudden cardiac death, as well as central nervous system problems, which include dementia, epilepsy, stroke and such other horrible conditions. It results in death, which can occur early in childhood or after a prolonged period of incapacity and pain that can last for years.

It is important to have some facts about mitochondrial DNA genetics and inheritance. Mitochondrial DNA is strictly inherited maternally, via the egg. The mitochondrial DNA copy number and the number of mitochondria vary between cell types, with more than 200,000 in the egg and early embryo down to perhaps as few as 10 to 20 in many cells of the two to three-week old embryo, and hundreds to thousands in most cell types in adults, where the number tends to correlate with energy demand. Cells can have a mixture of two or more types of mitochondrial DNA sequence, a condition referred to as heteroplasmy, in contrast to homoplasmy, where each copy has the same sequence. More than 300 distinct mutations of mitochondrial DNA have been found in patients with mitochondrial disease. Although some mutations are far more common than others, if an individual is heteroplasmic, with a mixture of mutant and normal mitochondrial DNA, the proportion of the former determines whether they show symptoms of mitochondrial disease. Some women at risk of transmitting mitochondrial disease to their children are heteroplasmic and may have levels considerably below the disease threshold, but their eggs can have very high levels of mutant mitochondrial DNA or even be homoplasmic. This can be explained by the so-called bottleneck, which I will not go into in detail, but, during the development of the egg, only a certain number of mitochondria go into fertilisation, and that causes a bottleneck that sometimes results in only the mutant mitochondria getting through.

It is estimated that at least one in 200 children in the UK is born with some faulty mitochondrial DNA—so quite a lot of them may well have some faulty mitochondrial DNA. It is estimated that one in 6,500 babies goes on to develop serious mitochondrial disorders. The severity varies from mild to extremely debilitating and may result in early childhood death. Almost 2,500 women of child-bearing age in the UK are at risk of transmitting mitochondrial disease to their children. Estimates based on this figure suggest that between 100 and 150 births a year in the UK risk passing on mitochondrial disease to the child. If today we were discussing cancer or dementia, and how we could modify those diseases with some form of genetic or mitochondrial manipulation so that people would not get it, everybody would be in favour of it; but as mitochondrial disease affects 100 to 150 people a year, we do not take it so seriously—or so it seems.

I will now go on to what the noble Lord, Lord Deben, said about the two techniques that we are likely to be discussing—the maternal spindle transfer, which the noble Lord prefers, and pronuclear transfer—and I will say why I believe it is necessary that currently the HFEA, as a regulator, is allowed to decide which method might be appropriate for a given patient in a given centre. We do not know which technique is the more efficient and safer, despite what some others may believe. In fact, they may not be equally efficacious in every woman.

Pronuclear transfer has been used successfully in animals for more than 30 years with no evidence of adverse effects. On the other hand, maternal spindle transfer is a newer technique, which is likely to result in less carryover of mitochondria but has a higher risk of chromosomal abnormalities. That is an important point: pronuclear transfer may have more carryover of mitochondria but maternal spindle transfer has a higher risk of chromosomal abnormality. Maternal spindle transfers are very sensitive to manipulation. The embryo is less sensitive in its early stage to such manipulation.

Furthermore, both techniques have been found to be variable for avoiding mitochondrial disease. Which technique will be used for each individual patient will be a decision for the patient, based on their informed consent, their clinicians, the evidence from research and the safety aspects. In my view, it would be inappropriate for Parliament to make a scientific judgment as to which technique should be able to be used. One thing is certain: the scientists and the clinicians will go with whichever method is the safest and most efficacious. If it turns out, through research that is currently going on, that we can make maternal spindle transfer safer and less likely to lead to chromosomal abnormalities, that is the method that the scientists and the clinicians will choose. Research is going on to make that process safer. There are many ways of doing this. I am not being flippant when I say that one of the methods that has been tried is to use a small amount of caffeine to make the maternal spindle transfer more stable. Eventually, we will get that research right and whatever method is safest will be used. However, it would be wrong to opt now for one method which is not as successful as others.

Issues have been raised about the health and safety risks of some of the techniques. I agree with the noble Lord, Lord Deben, that it is never possible to be certain that new medical procedures will be 100% safe or effective. That applies to the whole of medicine—drugs, devices or surgery. Risks have been assessed in detail. As the Minister said, there have been three separate reviews of the scientific evidence on the technique’s safety by a specially convened independent panel of experts. It would be wrong to suggest that these experts might be biased when none of them has any financial interest in mitochondrial research or treatment, or that they might not have understood the issues and that we in this Parliament are more likely to understand the science which underpins this research, which has led to the point where it is now possible to use this technique to help women to have normal babies.

Decisions on safety and efficacy should be taken by the statutory regulatory authority created to do this—the HFEA. Risks must be balanced. Evidence suggests that any risks of mitochondrial donation are proportionately less than the significant risk that children will continue to be born who will develop severe mitochondrial disease if these techniques are not used. Ultimately, it will be up to affected families to judge the balance of these risks. They are the ones who will take the risks.

I would like to explore some of the health risks that the noble Lord, Lord Deben, mentioned, although he did not mention that of the potential effects of the donated mitochondrial DNA on the rest of the cell. I turn first to traits attributed to mitochondrial DNA. On variations in the 37 well studied genes, a whole mitochondrial genome has been sequenced for all these genes and they have all been found to have one function in expressing the protein that produces energy. No other trait has been identified from the sequencing of the whole mitochondrial genome. Therefore, the variations have been well studied. Although this is still contentious among mitochondrial experts, theoretically—I admit—it is possible that a child born after mitochondrial donation might have a slightly different energy metabolism compared with his or her female ancestors. However, none of this has resulted in devastating mitochondrial disease.

Evidence has also been cited that a mismatch between the DNA in the donor’s mitochondria and the mother’s nuclear DNA might have a negative impact, namely sterility and impaired growth—the noble Lord mentioned sterility—in the resulting child, as well as slow metabolism. This issue was considered in great detail by the HFEA scientific panel. In normal human populations the mixing of nuclear DNA during sexual reproduction means that there can be a complete exchange of nuclear and mitochondrial DNA type over a few generations—I calculate it to be about six generations. Given that I married an English lady, the mitochondria of my children have changed dramatically. My ancestors’ mitochondria are no longer in my children—they have English mitochondria. However, I am glad to say that they have produced terrific children. Evidence of mismatch between nucleus and mitochondrial genomes has come mostly from research where new combinations have been made experimentally across animal species that have been separated for many hundreds of thousands of years or longer—for example, rats and mice. Within species, such as in some experiments involving mice or fruit flies, evidence of mismatch is seen only when particular sub-strains of a species have been reproductively isolated from each other and each inbred. The one species, the human race, is the most outbred species there is. Some of us are examples of that.