In this genomic era, is whole genome sequencing of babies an imperative to maximise their future health – or a burden to be avoided?
Whole genome sequencing of newborns for the diagnosis of genetic disorders is now technologically possible, and is already being used in selected cases where a rare disorder (whether recognised or novel) is suspected in a seriously ill baby.
With genome sequencing costs continuing to fall, and plans for an NHS Genomic Medicine service to make access to both sequencing and interpretation of data feasible, some have suggested that this technology could be used to expand the current NHS newborn screening programme
Many more rare and serious diseases could be diagnosed earlier, beyond the nine conditions included in the standard heel prick test. In theory, a better understanding of risk factors that could affect the child later in life could also be used to guide more personalised disease prevention. Whilst this would fall outside NHS approaches to screening, new parents might consider commercial genome sequencing services a sensible investment in the future health prospects of their baby.
However, it remains to be seen whether genome sequencing at birth is in the best interests of apparently healthy babies. At the societal level, should we also be questioning whether a ‘technological imperative’ obliges us to use the most sophisticated form of technology available?
Ethical concerns
The Nuffield Council on Bioethics has released a briefing detailing these considerations. These include questions regarding the capacity of the NHS to implement and deliver an effective genomics service, when and how data should be stored and released to the parents or individual, and the wider societal implications of increased genome sequencing. Ethical concerns outlined include:
- How much genetic information should be shared with parents? There seems to be a consensus among health professionals and ethicists that only information about treatable, childhood onset diseases should be shared, but others argue parents are entitled to know more, irrespective of whether the health impact of genetic variants detected is uncertain, is known to take effect only in adulthood, or is likely to cause disease for which there is no current treatment. After all, it may reveal information relevant to their own health.
- How reliable or clinically useful is the genomic information? At present, findings from genomic sequencing vary widely as to how reliably they predict disease and the extent to which potential disease could be prevented or the effects lessened. The difficulty in interpreting genomic data means that parents could be presented with news that their child has genomic variants of unknown clinical significance, the health impacts of which, if any, is currently unclear – they might indicate a potential health problem, or they might not. Making sense of complex and incompletely understood genomic data is hard enough in adults with well-defined disease symptoms, let alone in babies without overt health problems. Ambiguous information from infant genome sequencing could be potentially harmful for parents and child, leading to confusion and anxiety.
All of these concerns are heightened when talking about babies, as they are unable to make a choice. Following Feinberg’s principle of a child’s right to an open future, genetic testing should be delayed until the individual is able to make an informed choice for themselves. What of the ‘right not to know’ genetic information?
Future directions
Despite these and other reservations, this seems to be the direction in which healthcare is headed. The US-based BabySeq project began in 2015 and is the first randomised, controlled trial to measure the harms and benefits of newborn genomic sequencing. Through offering the parents of 240 ill and 240 healthy babies the opportunity to have their baby’s genome sequenced, they hope to answer the questions: “is this scary or not? Is this useful? Is this likely to confuse the hell out of people or not?”.
Even in the UK, where there is less emphasis on parents’ right to know information about their children, there are signs of change. The Nuffield Council notes that parents of children with suspected rare diseases taking part in the 100,000 Genomes Project can choose to learn about selected genetic changes that can cause childhood disease in addition to any that are thought to relate to their condition. There is concern that the planned transition from NHS-linked research project to routine NHS practice could result in this approach becoming standard without due consideration of the potential consequences.
Additionally, in the future, parents may be able to bypass the NHS altogether and access whole genome and exome sequencing through commercial providers. In the absence of appropriate genetic counselling to understand the results and implications of a genetic test, the potential harms must be emphasised: anxiety, distress, misconstruing information, overtreatment. Many people enjoy good health despite the presence of potentially damaging, disease-associated genomic variants.
The benefits must be weighed carefully against the harms. If we have a practical and reliable means to detect and diagnose serious genetic conditions earlier – and reduce suffering through avoiding unnecessary clinical investigations, allowing early treatment or management of disease – then are we not obligated to do so? But rushing to sequence the genomes of babies could open a Pandora’s box. The Nuffield Council’s briefing raises some important caveats for consideration.
A 2013 PHG Foundation paper sets out some key ethical points around the issues of feedback of incidental and other findings from whole genome sequencing of 100,000 Genomes Project participants.