Why it's time to define serious and significant genetic conditions

Rapid advances in the field of genetics give one a sense of needing to address the issue of what constitutes a 'serious and significant' genetic condition and to seek a broad definition. I will endeavour here to outline some scenarios to illustrate how a definition might help.

PGD and the transfer of an affected embryo

In the UK, application by a clinic for variation of its licence to offer preimplantation genetic diagnosis (PGD) for a specific condition is considered by the HFEA licence committee. The committee considers whether the condition is serious and significant in the absence of a definition.

The Human Fertilisation and Embryology Act allows for the transfer of an affected embryo if no unaffected embryo is available. This completely undermines the careful deliberations of the Licence Committee which deemed the condition serious and significant. This being so, then perhaps a definition of a serious and significant would be a condition that under no circumstance would an affected embryo be implanted, and the couple would prefer to remain childless. (This anomaly is recognised and addressed by Professor Julian Savalescu at the University of Oxford who suggests that there could be an obligation to edit the genome to correct the mutation before implantation.)

Genome editing

The discussion around making therapeutic changes to the human genome is blurred by fears of human enhancement. In December 2015, a US National Academies of Science, Engineering, and Medicine panel considered the medical, social and ethical aspects of this emerging technology, concluding that clinical trials using heritable genome editing should be permitted only for serious conditions within a robust and effective regulatory framework. A follow-up meeting will take place in Hong Kong in November 2018.

On 12 October 2017, the Parliamentary Assembly of the Council of Europe adopted a recommendation: 'The use of new genetic technologies in human beings', in which I participated as an expert witness. It proposed that the Committee of Ministers should foster a public debate on this issue; instruct the Council of Europe Committee on Bioethics to assess the ethical and legal challenges, and develop a common regulatory and legal framework.

A definition could focus the debate around genome editing as a prevention of harm rather than enhancement. At present, families carrying a known mutation have the option of PGD to prevent the birth of an affected child. Genome editing of gametes or the affected embryo would give families the opportunity of 'repairing' a mutation – a positive act of healing in contrast to the destruction of the embryo as in PGD.

Whole genome analysis and confidentiality

Whole genome analysis to uncover links between genetic variants and conditions – as proposed by the UK's 100,000 Genomes project – raises issues of patient confidentiality, as a mutation detected in an individual may have health implications for other members of the family. 

If so, the patient may be required to agree to reveal this information to their relatives. Should they refuse, there are GMC guidelines as to when a doctor can breach patient confidentiality but as highlighted in the case ABC v St. George's Healthcare NHS Trust this is difficult to follow. The doctor must feel vulnerable to the risk of prosecution for breaching patient confidentiality and also destroying the personal relationship with the patient. A definition of a serious and significant condition would aid in the doctor's decision-making, and also in legal defence. 

A potential definition can be found in the case of W v Edgell, where confidence can be breached if the risk to a clearly identified person (Palmer v Tees) is 'real, immediate and serious'. A genetic condition known to affect a child from birth or in early childhood may well pass this requirement, but conditions whose symptoms do not appear until adulthood may fail the requirement for immediacy.

Abortion law

The English Abortion Act of 1967 provides for a lawful termination of the pregnancy if 'there is a substantial risk that if the child were born it would suffer from such physical symptoms or mental abnormalities as to be seriously handicapped'.

The rise of genome analysis will likely extend the ability to diagnose genetic conditions, which could, if prenatal sequencing becomes commonplace, have an impact on decisions to terminate affected pregnancies. An application for judicial review on a decision to abort a pregnancy on the basis that the fetus had a cleft palate was rejected (see BioNews 300 and 361) but there may well be more to come. Again the debate might be more balanced with the existence of a definition.

I recognise that this issue has been addressed in the past with little progress. However, I suggest that a definition could be of assistance in all of the above scenarios. There is already a possibility that the definition of a genetic condition as serious and significant could include risk if it is 'real, immediate and serious' and the phenotype is so serious that there would be no desire to transfer an affected embryo under any circumstance. Whilst feeling some trepidation in writing this article, I also recognise that as with seeds that fail to germinate on fallow soil one has to try again as the environment can change. From little acorns…