Chris Hughes discusses the Autumn Budget 2021’s implications for a potential roll-out of Whole Genome Sequencing in the UK
In the 2021 Autumn Budget, Chancellor Rishi Sunak announced £20 billion of spending across a number of areas. The key themes of this Budget were innovation, long-term improvements to living standards and elevating the UK’s global reputation in diagnostics and life sciences. These focus areas overlapped in the £5 billion pledged towards health-related R&D, including money earmarked to fund the delivery of the ambitious Life Sciences Vision and Generation Genome, a pilot programme to detect over 200 rare diseases in newborns. The financial support is significant, as the Chancellor notes that every £1 of government R&D investment stimulates an average of £2 in private investment.
The UK is already known for its sequencing expertise. As of October 2021, the UK contributed almost a quarter (24%) of genome sequences uploaded to the international Global Initiative on Sharing Avian Influenza Data (GISAID) database, a platform used to inform the world’s pandemic response. However, the Budget showed the government recognised the diagnostic value of investing in sequencing, specifically whole genome sequencing (WGS), beyond the immediate concern of Covid-19.
To better understand the significance of the budget announcement, it’s essential to consider the history of WGS, interest in its diagnostic abilities, and the growing momentum of support for genomics research.
The UK’s newborn screening (NBS) programme and national screening procedures
The UK has a long history of testing newborns for disease. The process was introduced in the 1950s via the ‘nappy test’ to diagnose the rare inherited disorder phenylketonuria - and this is still used in UK hospitals today. Newborn bloodspot tests were rolled out in 1969 and are presently used to test for nine serious rare conditions in the first weeks after birth. Although NBS has been in place for decades, the process of introducing any new developments to national screening procedures is intensive and requires considerable due diligence. Significant changes to any public screening process do not happen overnight. As an example, in June 2021, non-invasive prenatal testing (NIPT) was introduced to the pregnancy screening pathway after five years of research and public consultation - it was first recommended by the UK National Screening Committee (UK NSC) in 2016.
It’s arguable that WGS is at a similar research and consideration stage as NIPT five years ago. To fully comprehend the benefits WGS could bring to our healthcare system, it’s essential to know how the sequencing process works - and the significance of its potential introduction in the future.
Genetic markers of disease
Medical genetics broadly revolves around two key areas: research to understand the cause and inheritance of genetic disorders, and their diagnosis and management. The staggering volume of information contained within human genomes, formed of billions of DNA base pairs, means the process of WGS was once the topic of science fiction. Thanks to academic research, advances in laboratory techniques and improvements in computer processing power it became a reality in 2003 when an accurate and complete human genome sequence was finished for the first time.
In 2019, the UK’s Health Secretary laid out ambitions for WGS to be rolled out for all children in the country as part of a “genomic revolution”, demonstrating the technology’s shift from fantasy concept to significant potential policy. Public opinion on NBS is also shifting, and Genomics England launched a public dialogue this year to gauge the levels of support for WGS and explore potential areas of concern. The results were positive: public support for WGS in the UK is at a level for the first time which could make it viable through the NHS. So, what hurdles stand in the way of its introduction?
The roadmap to widespread adoption of WGS in the UK
As with NIPT, WGS cannot be integrated into NHS care overnight and there are a number of factors that must be considered. Crucially, the clinical benefits of WGS for newborn screening are significant - both from a human and a health economics perspective. As an illustration of this, a pilot study in the US called Project Baby Bear provided rapid WGS for children in intensive care to better understand their illness and adapt treatment accordingly. The pilot sequenced 178 babies, provided diagnoses for 43%, resulted in a total of 513 fewer days in hospital and an estimated US$2.5 million in healthcare savings.
Sequencing doesn’t just support improved health outcomes at the time of diagnosis, it can result in significant financial savings over the course of an individual’s life. While WGS may be more costly at present than current screening processes, the long-term savings are significant. When WGS identifies a disease in a newborn that would not be picked up by the standard screening, the early treatment of the disease can prevent the need for long-term hospitalisations, expensive diagnostic tests and prevent life-altering, often irreversible side effects of the disease before they manifest.
However, public support is necessary should WGS ever be adopted broadly. Some have concerns over the utility of having such a depth of information on an individual’s DNA, as well as worries around data privacy and what information should be disclosed to families.
For reference, NBS in the UK currently only screens for diseases that have accompanying treatment pathways, such as sickle cell disease, cystic fibrosis and congenital hypothyroidism. There is a belief that screening for disorders that don’t have readily available clinical treatment causes families severe emotional and psychological distress. Should we have access to an individual's entire genome sequence, the same decision would need to be made around what we would look for, and what we would disclose after diagnosis.
In response to this year’s public dialogue from Genomics England, the initial public response to the WGS of newborns appears to be extremely positive. Although reasonable ethical concerns were raised, these were alleviated through a set of recommended key conditions which WGS should be performed under. This level of public engagement throughout the process will be critical to the NHS’ exploration of WGS for NBS and beyond.
Maximising WGS’ clinical results
Beyond public response, there must be the right diagnostic infrastructure in place to support a wider WGS rollout, including laboratories able to contend with the fast-paced development of innovative new technologies. To maximise clinical results, the standard of clinical excellence must be reviewed regularly. Some of the aspects worth taking into account include:
The time elapsed between first testing a sample and gathering results varies depending on the equipment used. At present, the turnaround period is typically around two months, time where critical treatment is not administered to the patient. However, the latest equipment can turn around genomes in 10-12 days.
Sample gathering can be a complex process and requires the right equipment to overcome any logistical and technical challenges. Ideally, testing equipment would have the capability to test multiple sample types, such as saliva swabs, dried blood spots and genomic DNA.
Once a genome is fully sequenced, specialist analytical tools and the expertise of clinical geneticists must be used in order to understand a patient’s genotypic and phenotypic data. The relationship between a patient’s genome and their condition is complex, and an expert understanding as well as the right technology is required to unravel the biological relevance of the mass of data uncovered by sequencing.
A WGS rollout will not be viable without smart, optimised and automated technology to support it. It’s important that there is investment in the technology supporting WGS, so that data can be collected, stored or shared in a rapid and secure manner. By eliminating the processing bottlenecks of today’s sequencing technology through optimisation and automation, we can ensure that the future of WGS as part of the UK’s NBS is viable.
The future of genomics
As acknowledged by the Autumn Budget, investing in medical R&D has the potential to situate the UK at the forefront of emerging technologies that will shape the medical landscape. The use cases for genome sequencing ar only going to increase as further pilot studies and research provide evidence of its usefulness, generating vast volumes of data in the process. The UK’s world-class genomic sequencing infrastructure (seen at scale during the pandemic) means the nation is in a great position to analyse and then maximise the potential diagnostic capabilities of this data. This should also help researchers develop new diagnostic pathways and treatments for future generations.
Genomics may greatly improve specialist medical care, enabling a higher degree of personalisation of medical treatments to be offered to patients, both improving care outcomes and delivering cost savings. With genomics deployed at scale, healthcare shifts from being reactive to predictive, catching disease and beginning treatment long before negative side-effects appear.
One of the most recent developments since the Budget was the 100,000 Genomes Project, which demonstrated the huge potential of WGS in saving the NHS millions of pounds whilst diagnosing patients and providing families with reassurance. The Budget is a hugely promising sign that this area of diagnostics is being treated as a priority in the UK, and we look forward to supporting and celebrating further developments in the sector.
Chris Hughes is managing director of PerkinElmer UK & Ireland