The announcement by the Secretary of State for Health and Social Care did not receive the fanfare or focus it deserved. There has not been a press release from the Department of Health and Social Care, and it was only picked up by the papers on Wednesday 6 November, just before the government and the civil service entered the pre-election purdah period.
The Sun, and the Times welcomed the news, sharing that 'around 3000 of the 660,000 babies born a year in England and Wales are thought to have a treatable, early-onset disease', while other coverage (Futurism, New Scientist) raised ethical challenges and privacy concerns.
It is not hyperbole to state that England will shortly lead the world in genomic diagnosis. The new NHS England Genomic Medicine service will offer all acutely ill children with a likely monogenic condition, and all children with cancer, a whole-genome sequence. The list of diagnostic grade genes on Genomics England's curated PanelApp which allows experts to review genes and the evidence for their relation to conditions, was at 3139 in August 2019 at PanelApp's fourth birthday, with 56,640 gene-disease curations.
In the UK we are in an unusual position. We are at the forefront of diagnosing people with rare diseases but are among the countries screening for fewest rare conditions at birth (see BioNews 1008). The announced pilot offers one route to bridge this disparity. We are behind most countries in Europe and other high-income countries when it comes to identification of babies at risk of genetic conditions at birth.
The UK National Screening Committee currently recommends that the NHS screens for nine conditions at birth – few enough to list here: phenylketonuria (first screened for in 1969), congenital hypothyroidism (1981), sickle cell disease (2006), cystic fibrosis (1983 in Northern Ireland, 1997 in Wales, 2003 in Scotland and 2007 in England), and four further metabolic conditions: medium-chain acyl-CoA dehydrogenase deficiency, maple syrup urine disease, isovaleric acidaemia, glutaric aciduria type 1 and homocystinuria (all began in 2015 in England and Wales, and 2017 in Scotland, with no screening in Northern Ireland).
For comparison, Italy screens for 43 conditions, the Netherlands 34, Australia 28, the Czech Republic 20, while Spain screens for seven, Ireland six, and France five.
Diagnosis of symptomatic individuals and screening at birth are two different things: clinical diagnoses are performed with a combination of genomic information from testing and phenotypic information from consultation and a screening approach is clearly not appropriate for all conditions listed in PanelApp. While the disparity between the UK's adoption of each is so great, it can appear to our community that the NHS is waiting for children to get ill instead of intervening sooner.
The benefits of diagnosis to families affected by rare conditions are accepted, but the benefits of screening to identify these families in advance of symptoms developing are ignored. For the affected child, screening can prevent a future lengthy diagnostic odyssey, provide access to treatments that are best delivered before symptoms develop, enable participation in clinical trials and ensure the best possible quality of life by beginning care pathways at the optimum moment.
To the family, screening can identify a risk to future births and enable reproductive decision-making, as well as giving time to prepare for the expected condition. More broadly, newborn screening can improve our knowledge of the incidence and nature of rare conditions and enable research.
In July 2019, Genetic Alliance UK launched our Patient Charter on Newborn Screening: Fixing the Present, Building for the Future. Our community recommended that a pilot of newborn screening using genome sequencing should go ahead as soon as possible for the key reason that the number of conditions that can be identified is much greater than when using traditional metabolic screening technology, which relies on early metabolic indications of the condition. Genomic screening can identify future risk before there are any symptoms. The US-based research project BabySeq labelled 885 gene-disease pairs as having 'definitive or strong evidence to cause a highly penetrant childhood-onset disorder'.
The community also identified the challenges that must be addressed in a pilot. Some of these were picked up in concerns aired in reporting of the announcement. Futurist raised that: 'It would also mean that kids' entire genetic sequence will be mapped out long before they can understand what that means or agree to having it done. As genomic science develops, dilemmas about personal privacy and what happens to the data after it’s collected are still far from being sorted out.'
Our workshop participants noted that we 'are struggling to adequately inform patients and families about the screening done now within the NHS' but felt that 'we should press on, but recognise that communication and standards need to improve'.
The concern about children's health data being examined before they gain the capacity to understand the implications was one of the many concerns around this initiative that have already been dealt with in some form. Parental choice and how it affects children as they grow up is not a new issue, and the approaches taken to explore this question in the past will be applicable to this pilot.
New Scientist's coverage focused on the challenge of dealing with a screening result for a late-onset condition, which raises the question as to which conditions should be screened for and how they should be selected. Again, this is a question that has been solved before in a different context. The means by which the 100,000 Genomes Project identified whether to report findings and which additional findings to offer can be adapted to address this question.
Other familiar questions will need to be examined again from a different perspective: how to manage a parallel health and research consenting process, the ethics of storing genome sequences, and how genetic information will be shared within families.
New questions that need to be addressed in the pilot include where this methodology fits alongside the current newborn screening programme, and whether this approach is a good use of NHS resources.
The key element of what little we know about this initiative so far is that it is a pilot. Genomics has vast potential to deliver benefit to the currently undeserved community of people living with rare, genetic and undiagnosed conditions. We need to take every opportunity to find answers to the challenges instead of letting them hold us back.