The announcement of the birth of the first child conceived using a technique to reduce the risk of inheriting a mitochondrial disease was unforeseen (1). The decision by the medical team from the New Hope Fertility Center in New York City to carry out the procedure in Mexico was deliberate as mitochondrial replacement therapy (MRT) is not prohibited or regulated there. This may change (2). Nonetheless, in any country regulation should be required to protect the interests of the child.
The US and the UK have debated at length the safety and potential risks of two of the MRT techniques being currently investigated – that of maternal spindle transfer (MST) and pro-nuclear transfer (PNT) (3).
Reproduction is regulated by state in the US, and so far none have given approval for MRT. In contrast, in February 2015 the UK became the first country in the world to pass legislation to regulate the procedure, and regulations came into force on 29 October 2015 (4).
Clinics that wish to carry out this treatment will be able to apply to the Human Fertilisation and Embryology Authority (HFEA) to update their existing treatment licence. Several conditions need to be satisfied, including the completion of a report by a scientific panel on the safety and efficacy of the techniques. Once granted a licence to carry out PNT or MST treatment, the clinic will then be able to seek authorisation to undertake the treatment in the case of a particular patient. The licence committee will need to be satisfied that the condition within the application meets the statutory requirement that 'there is a significant risk that a child born with that abnormality will have, or will develop, a serious physical or mental disability, a serious illness or any other serious medical condition'. There is no statutory definition of what would constitute 'serious' yet, although this lack of definition is not unique to MRT and is debated for reproductive screening technologies, for example.
The welfare of the child and the need for supportive parents
An FDA-commissioned report on the ethical, social and policy considerations of MRT was issued by the Institute of Medicine of the National Academies of Sciences, Engineering, and Medicine in February, and this placed the emphasis on the health of the child as paramount (5). In contrast, the emphasis in the UK at times seems to have focused on the needs of the parents to have a healthy child. However, one of the most important aspects of the regulation of IVF treatment in the UK, and which is not often included in the debate, is the statutory requirement by the clinic to consider the welfare of the child to be created and his or her need for supportive parenting (6). Although no licence will be granted until the HFEA is satisfied that the technique is 'safe', there is no certainty.
Concerns around risks to the child will remain, and the welfare of the child needs to be considered. For instance, it may be found that there is a mismatch between the DNA of the donated mitochondria and the DNA of the nucleus. Another concern is that the group focusing on PNT in the UK has shown that some of the mutated mitochondria are transferred to the new embryo (6). This means that the technique may not remove but rather reduces the risk of the child being affected by the condition. It is still possible that mutated mitochondria could replicate more successfully in the child compared to donated mitochondria, and the degree of risk is therefore uncertain. Mutated mitochondria could also be passed on to future generations to varying degrees. The technique of spindle transfer used by the scientists in Mexico may bring different risks such as aneuploidy (additional or loss of chromosomes during transfer.)
It will take a huge leap of faith for a clinic to offer the technique when it is unable to quantify the risks. The clinic will be sensitive to the possibility of unforeseen side effects of the treatment, and some of the side effects may not become evident until the child reaches adulthood. Subject to parental consent, until the child reaches the age of majority, the HFEA recommends that efforts be made to follow the child's progress after birth and monitor their health throughout life. If a clinic becomes aware that a child has been born with any disease, birth defect or genetic abnormality that may have been caused by the procedure, the clinic will be required by law to report this as an 'adverse incident'.
When the clinic is considering the welfare of the child, it is also required to consider the need of that child for supportive parenting. It should refuse treatment if it concludes that any future child or existing child of the family is at risk of significant harm or neglect. It also needs to take into account current circumstances that might impact on the ability to care for the child, for example the physical condition of one or either of the parents. Which brings us to the issue of the health of the mother.
The biological mother requiring MRT is trying to avoid passing on mitochondrial disease to future generations. She may have no symptoms or mild ones but, as mentioned above, the level of mutated mitochondria can change and symptoms can get significantly worse over a patient's lifetime. It needs to be considered whether the mother will still be capable of supporting the child as they grow. It would be regrettable if a healthy child born after the technique then had to support a mother with deteriorating health. As only a quarter of her mitochondria carried the mutation for Leigh syndrome, the mother of the child born in Mexico is well, but requests for help might come from those badly affected by mitochondrial disease or from those whose health will become progressively worse.