The Progress Educational Trust (PET)'s last event of 2021 continued its series of discussions about sequencing the genomes of newborn babies. A pilot project, the Newborn Genomes Programme, is planned as a collaboration between the NHS and Genomics England to gather evidence about whether this approach could be beneficial.
PET's director Sarah Norcross opened the event by outlining three key questions. What information will parents need to have before deciding whether to participate? How can information be made accessible and available? How should uncertainty about findings be communicated?
Four expert speakers discussed how these questions are being addressed. Amanda Pichini, consultant genetic counsellor at Genomics England, and a member of the screening programme's NHS Steering group, outlined three elements essential to legal consent. The consent has to be voluntary, has to be given by a person with sufficient mental capacity, and has to be sufficiently informed.
However, she explained, genomic testing presents unique difficulties. Screening could reveal unexpected results that might influence the clinical care a person needs in the future. Furthermore, most genetic counselling is offered to patients by specialist services, when there is reason to suspect that the patient has - or might develop - a genetic condition. By contrast, parents of newborns will not have this motivation.
Pichini emphasised that parents will need to understand the programme is at a research stage, and results may not be immediately usable in clinical care. The screening programme may allow newborns to be checked for hundreds of conditions, a drastic increase from the nine conditions currently screened for in the UK via heel pricks and blood spots.
However, informed consent will not require parents to be talked through every single condition. It will involve trust in the organisation generating, storing and interpreting the genomic data. Such trust can only be achieved through clarity about expectations and honesty about uncertainty.
The next speaker, Dr Simon Ramsden, consultant clinical scientist and lead scientist for rare disease at the North West Genomic Laboratory Hub, outlined the immense size of the human genome, and the small fraction that appears (at least initially) to be of interest. Around 1.5 percent of the genome codes for proteins, and perhaps a quarter of that may contain variants with known links to human diseases. Whole genome sequencing (WGS) can be carried out because we have the technology and capacity to do it affordably.
Dr Ramsden drew comparisons between the vast amount of information contained on the internet, and the human genome, to illustrate the issues we must consider. Can we infer reliable results from genetic information? How do we target the relevant information? Are we getting a balanced view?
He commented that there are parts of the genome that cannot yet be interrogated by WGS technology, and that studying whole genomes reveals new mutations and variants which we have yet to understand. We will need to know whether and how to interpret secondary findings, and what options and assurances are in place regarding privacy and data sharing.
Dr Ramsden concluded with a reminder that specific questions submitted to internet search engines can lead to specific answers, but wider questions can result in many bewildering and perhaps unreliable results - just like asking narrow and broad questions of the genome.
Waheeda Abbas, midwifery lead at the North West Genomic Medicine Service Alliance, stressed that communication must be personalised to parents. She explained that pregnant women already receive a large quantity of written information as a matter of course, and a better approach would be to let parents select their preferred mode and level of information. Digital technology could replace leaflets, while midwives will benefit from training in the rudiments and language of genomics, and knowing to whom cases should be referred. There will also be a need to accommodate interpreters, and provide information in different languages.
Abbas outlined how communication about the project could fit into the existing timetable of prenatal and postnatal appointments. The logistics and timing of blood sample collection have yet to be decided, and may influence when final information or consent can be given.
Abbas also pointed out that WGS has the potential to increase parents' negative feelings, due to distressing results. A personalised approach will be essential to alleviate this by considering the level of education, awareness of testing, language, religious influences, and expectations of parents. This is typically revealed to midwives and other health professionals through the oral rapport and relationship built with the new parents.
The final speaker, Anneke Lucassen, professor of genomic medicine at the University of Oxford, discussed the fact that the pilot project seems to be a hybrid research and clinical venture. She asked how consent can meaningfully be given in this context.
While media headlines have repeatedly stated how the Newborn Genomes Project will increase diagnoses at birth, Professor Lucassen warned that there are also potential downsides that need to be managed. There is a chance of false positives, especially as it is difficult to infer a diagnosis from genetic data alone, without physical symptoms. Each baby will have some 4-5 million variations in their genomes, several thousand of which will be deemed 'rare' or potentially 'suspicious'. We must be careful in our use of language and expectations, she warned - without wanting to discourage participation in the project, it is important to be transparent.
Professor Lucassen finished by saying that she would like to hear more about what can be done to improve consent, beyond adding more leaflets or boxes to be ticked.
Following the presentations it was time for questions, and the audience did not disappoint. Responding to a question, Dr Ramsden emphasised that genomic data may need to be revisited and investigated again in future, and genomes themselves may even need to be re-sequenced, to get more accurate results using updated technology and better knowledge. We are constantly learning more about how, for example, epigenetics provides a context in which to interpret genomic data.
Pichini considered whether the NHS will be thought to have a responsibility to re-contact individuals and reanalyse data, based on new scientific understanding, but this depends on if the service having the capacity to do so.
In response to a question about people who may change their minds about participation, the panellists explained that previous projects such as the 100,000 Genomes Project have already established mechanisms for individuals to withdraw consent at any stage, and similar mechanisms will exist here.
Asked whether discovering negative results at birth could affect parent-baby bonding, Abbas said that she had not observed any such events in her work as a midwife, but stressed that vulnerable patients in particular require supportive information and guidance. Pichini mentioned a study that had found no negative psychosocial effects from newborn screening, but acknowledged that this possibility must be planned for carefully nonetheless.
How is it possible to anonymise genomic data, when every individual has a unique genome? Pichini explained that genomic data needs to be deidentified rather than fully anonymised - guarded through checks and access committees, and by looking at data in the aggregate without collecting and copying individual data. However, genetic variations can be shared amongst families, and there are situations where it might be imperative for a discovery in one individual's genome to be discussed with that person's relatives.
Asked how anyone could give informed consent for an uncertain outcome, Professor Lucassen reiterated that consent for this project will mean consent to a broad set of principles, in a trusted environment. It's time to stop thinking of consent as the main component of ethics, she said.
PET is grateful to Genomics England and its Newborn Genomes Programme for supporting this event.