UK-wide whole genome sequencing for newborns is feasible - but there are some key questions to answer first

Genomics England, the Department of Health and Social Care’s genome-sequencing hub, has this year announced that support for whole genome sequencing (WGS) has reached a level at which its national rollout on the NHS may someday become a reality.

The timing of this announcement is particularly opportune, as increasing knowledge and advances in WGS amongst scientists has resulted in the technology becoming increasingly affordable and effective, making its incorporation into the existing standardised newborn screening (NBS) procedures in the UK a possibility.

There remains a number of critical questions that must be considered before WGS can be deployed as standard practice in the NHS’s provision of neonatal care. What benefits will it bring? Are there any downsides or costs to its use? What potential ethical issues will it involve?

How NBS is currently conducted in the UK

The current standard practice for NBS in the UK is the blood spot tests, with four drops of blood being taken from the babies’ heel around 5 days after birth. Biochemical blood tests are performed on the dried blood sample to diagnose a number of serious disorders. Currently, these tests cover nine conditions, including sickle cell disease, congenital hypothyroidism and phenylketonuria. When identified in the early stages of a person’s life, these conditions can be treated effectively even before their first symptoms appear, leading to much better health outcomes for the individual. In the UK, babies are currently only screened for metabolic disorders that can be treated.

WGS would not act as a replacement for these biochemicals tests currently utilised for NBS. Instead, it would represent a support to the existing screening programme by offering a deeper level of information on the conditions that biochemical testing identifies. The introduction of WGS would provide an additional layer of screening for a wide range of genetic markers associated with rare disorders.  This enriched phenotypic data is enhancing our understanding of disease variants and delivering insights that can help to empower hospitals to provide the best possible early treatment and care decisions.

Boundaries to NBS’ scope

WGS opens up the capability to test for a wider range of conditions than presently tested for, but there are a number of considerations that must be taken into account before doing so. NBS in the UK is currently carried out according to the stipulations of the Wilson and Jungner criteria advocated by the World Health Organisation. These include:

• the condition screened for must be adequately understood
• facilities for the condition’s treatment must be available
• clinical management of the condition must be optimised in all healthcare providers

These boundaries are imposed taking into consideration the severe emotional and psychological distress that families can be exposed to upon receiving diagnosis of disorders that do not meet these criteria. This further underpins the importance of WGS to deepen our understanding of disorders that are identified by biochemical testing, rather than being viewed as a replacement diagnostic test.

The funding & resource benefits of WGS

Advances in genome-related laboratory technology have resulted in the cost of WGS decreasing considerably over the past few years – a trend that will continue in the future with even further technological developments. However, in spite of this, we are still a long way off WGS costs falling to a level equivalent to current biochemical tests. In a public health setting, it’s essential that any major changes to NBS are cost effective, making it vital that the cost and benefits are weighed up. So, if a country-wide rollout of WGS represents a significant jump in the cost of the UK’s NBS programme, how could it be justified?

The financial argument for WGS lies in the potential savings that it could bring to diagnostic processes overall. Treating the recurrent symptoms of a patient with an undiagnosed disorder over the years can cost the NHS hundreds of thousands of pounds. In contrast, if the disorder can be diagnosed early through WGS and the best possible treatment administered as soon as possible, the overall cost of doing so can be significantly lower.

This is also reflected in the resourcing required to treat an undiagnosed condition. When a condition is not known, treatment often necessitates specialist staff, hospital space and equipment. In the case of rare diseases, all of these may not be available in the location in which it is needed, presenting a logistical challenge. With the increased strain on NHS resources caused by Covid-19, any solutions that could potentially free up staff or space are an increasingly compelling argument.

As appealing as the financial advantages of WGS may be, these are insignificant in comparison to the positive impact that it could have on patients’ lives. In some cases, the early diagnosis of a disorder can allow for treatment long before the symptoms present, helping to avoid long-term damage to a patient’s health. This can result in the reduction of the physical and emotional cost of treatment and even prevent the emergence of lifelong symptoms of the condition.

Potential ethical hurdles to the rollout of WGS

Perhaps one of the most important ethical issues to overcome in the widespread rollout of WGS is the accuracy of tests for individuals of different ethnic backgrounds. Studies have previously demonstrated that the genetic markers for condition-causing variants are not necessarily identical across different ethnic groups, opening up the possibility for misdiagnosis under WGS for ethnic minority individuals.

The key to avoiding this is to ensure that the dataset used in WGS to determine what a ‘healthy’ genome looks like incorporates data of individuals from minority groups. The collecting of diverse data enables us to broaden our definition of a ‘normal’ variation beyond that of majority groups, providing individuals in these groups with the same quality of care as the rest of the population. Only when genomic databases are diverse can we ensure that we all benefit equally.

Will the NBS in future make use of WGS?

Both sides of the argument on whether or not WGS for NBS should be introduced on a national scale have compelling and complex reasoning behind. With WGS’ potential to unlock an incredibly positive impact on the health of future generations, the most important process in the immediate future is the education of the public, ensuring they’re well-informed on WGS and have the ability to engage in open discussions on its introduction.

The introduction of WGS for NBS will still be a lengthy process that has only just begun with widespread public support in the UK. To become a reality, there will be a need for continued consultation with both professionals and the wider public. Ultimately, regardless of how long this process may take, the implementation of WGS for newborns across the UK will help us to advance our ability to treat people affected by serious conditions and allow us to make substantial improvements to overall patient wellbeing.

About the author

Sukhvinder Nijhar Nicklen PhD is Market Development Leader, PerkinElmer

Sukhvinder is based in the UK and started her career in the laboratories doing post-doctoral research as a Virologist/Molecular Biologist. Sukhvinder moved into scientific sales 20 years ago.

Since 2015 Sukhvinder has been working in Reproductive Health with PerkinElmer. Now in this new COVID World she is using her experiences in public affairs and government advocacy to identify solutions to healthcare challenges and help influence policy in the UK and Ireland.