Tomorrow, the House of Commons will debate regulations that would make it possible for the Human Fertilisation and Embryology Authority (HFEA) to authorise, on a case by case basis, the use of promising techniques to overcome serious mitochondrial disease. The step that is proposed is measured and modest, but important. It is consistent with the recommendations made by the Nuffield Council on Bioethics in our report Novel techniques for the prevention of mitochondrial DNA disorders (2012).

We concluded that provided that the techniques were shown to be sufficiently safe and effective, and that families were appropriately informed and supported, it would be ethical for them to use them. The regulations are being proposed only after careful work reviewing safety and efficacy data. The team who would be permitted to use the techniques are working in close collaboration with the families. These pre-conditions have therefore been met.

Our report noted that the families affected by mitochondrial disorders are in a dark place. There are currently no cures and the inherited nature of the problems casts a long shadow through the generations.

An extended and transparent process

The potential of mitochondrial replacement has been publicly recognised since at least 2000, when the CMO's Expert Group on Stem Cell Research reported. In 2008 Parliament provided the HFEA with the power to license research to develop the technique, bringing the opportunity to understand the prospects for a safe and effective clinical application. Research began in 2010 under the HFEA's regulatory oversight. This included convening an expert panel to review safety issues, which has been updated periodically as new data has become available.

During 2012 and 2013, the HFEA engaged in a public consultation exercise, including extensive deliberative events. At the Nuffield Council on Bioethics, we established a working party on the ethical issues that techniques raised. Our report in June 2012 was informed by the responses to our own consultation exercise. Early in 2014, the Government indicated its desire to propose regulations to enable the HFEA to take the next step of reviewing applications to use the technology in treatment services. A consultation on draft regulations followed. Overall, this has been an extended and transparent process and the scientists have been commendably open to debate about the ethical and social significance of their work.

Germ-line therapy

The technologies involve us taking a step over one of the lines that has been previously drawn in the sand - that between somatic and germ-line gene therapies. This is a significant step, but the rationale for using the distinction in ethical debate needs to be considered.

Somatic therapies will alter the genetic make up of the person being treated in a way that would not be passed on to any offspring. Consequently, the possibility that treatments would have unanticipated harmful effects is confined to those who will receive the benefits. The risks and the gains therefore accrue to the same person. A decision to use germ-line gene therapies is more complex because it would be expected to affect the descendants of the person receiving the treatment. This additional complexity thus concerns the number of people whose interests need to be taken into account. Further, potential harms and benefits may be less predictable and unevenly distributed.

Mitochondrial replacement is a germ-line therapy and for this reason, the Nuffield Council has recommended that particular care should be taken to assess the safety and efficacy of techniques. This includes putting in place systems for follow up of those treated and their children so that the consequences can be assessed; not only how far the desired and expected outcomes come to pass and also any unknown and unwelcome results.

These complexities also have implications for consent processes. For those able to choose for themselves, we take reassurance from the giving of informed consent. This ensures that the patient has considered the potential risks and likelihood of achieving the hoped-for benefits and concluded that they wish to take the chance.

With germ-line therapies, the interests of people from generations to come cannot be protected through a consent process because we have no means of asking them whether they believe the risks are worth taking. In practice, however, this difference has proved less clear than one might imagine.

Gene therapies have already been important for children because they are offered to address health problems that manifest during childhood and dramatically impair or shorten their lives. So parents and clinicians have needed to take decisions in the child's interests without being able to ask them. The therapies that could be permitted under the proposed regulations are limited to those where the children (and their descendants) face serious health problems. The balance of risk and benefit is therefore similar to that facing parents and children deciding about somatic therapies - the problems are predictable and significant, meaning that the potential for benefit might seem a risk worth taking. We may be reassured by the fact that somatic therapies bring no risk of any adverse impact affecting others in the future, but this does not mean that the overall balance of risk always falls differently in germ-line therapies.

The moral questions around somatic and germ-line therapies are not fundamentally different, but working out the implications of actions is more complex. Germ-line therapies are no more, and no less, alterations to the human genome than are somatic ones. Those who object to all gene therapies will also object to mitochondrial replacement. The stakes around handling the uncertainties that are inevitable in scientific advances may seem higher because of the potentially wider-reaching effects of germ-line interventions. This is a reason for proceeding carefully, but it is not a reason for doing nothing in the face of clear and substantial problems.

Stepping forward, carefully

The step being proposed in the regulations is carefully constrained. First, there will remain a prohibition on making alterations of the genetic material. The regulations permit the transfer, but not alteration, of nuclear and mitochondrial DNA (reg. 3(c)). So, no manipulation of the DNA is permitted.

Second, the HFEA's powers to permit the procedure can only be exercised when it has determined (i) that there is a particular risk that the eggs of the woman who is to undergo the treatment may have mitochondrial abnormalities caused by mitochondrial DNA and that (ii) there is a significant risk that a person with those abnormalities will have or develop serious mitochondrial disease. The technique can, therefore, only be used in circumstances where there is a clearly established need to overcome serious health problems. The scientific step forward is limited to techniques, defined in the regulations, that have been established to be safe and effective in an expert review of available evidence (including unpublished data).

The Nuffield report concluded that it was ethical for families to use these techniques in such circumstances. If Parliament approves the Regulations, it will enable to us to take a small step towards providing hope to families affected by mitochondrial disease. Like all other steps in science we need to learn from it, and for that reason, our report recommended that there needed to be follow up with the families and careful evaluation. That will enable us to consider whether any further progress on this particular path of understanding are appropriate. Without this initial step, we might never know.

Our report report also recommended information and counselling from specialists should be available to parents before mitochondrial replacement techniques were used. In present circumstances, this almost seems superfluous. The families likely to use the treatment under the limited opportunities permitted under the proposed regulations are as informed as anybody could hope them to be. This small and precisely defined step forward would be taken with them as partners. This is the right time to take it.

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