Policy paper

Genome UK: 2021 to 2022 implementation plan

Published 19 May 2021

Ministerial foreword

The UK is a global leader in genetics and genomics, and this has never been more apparent than in the last 12 months. The strength of our genomics science base, our leading life sciences industry, and public sector funding has allowed us to truly lead the world in sequencing the COVID-19 virus. This achievement has provided critical data, allowing a more informed response to the pandemic and ultimately saved many lives, in the UK and globally. It has also brought the value of genomics into the eyes of the public.

The UK’s historic leadership in the field of genomics has been demonstrated multiple times, from seminal discoveries in fundamental science through to translation into clinical practice and improved patient outcomes. Our scientists discovered the structure of DNA, we were a fundamental partner in the Human Genome Project and, more recently, completed the 100,000 Genome Project, the largest study of its kind worldwide. We are also the proud home of infrastructure that supports genomics research, from the UK Biobank, established in 2006 and our first world-leading large scale biomedical research resource, to Genomics England, the NHS England and Improvement Genomic Medicine Service (GMS) and Our Future Health, which will be the UK’s largest ever health research programme, recruiting up to 5 million diverse participants. Alongside this scientific leadership sits a distinguished tradition of rigorous examination of ethical issues arising from developments in bioscience and health. This continues to inform clinical practice and governance of genomics research, and provides a solid base for a strong, developing ethical framework for genomic medicine.

As a tangible step towards achieving our ambition to be the world’s most advanced genomic healthcare ecosystem, we published the Genome UK Strategy in September 2020. This set out how we will transform genomic healthcare over the next 10 years with a compelling vision and clear aspirations. Through this strategy we committed to developing a better understanding of the genetic causes of disease and using this knowledge to prescribe more effective treatments to patients. We will use genomic technologies to diagnose disease at an earlier stage and, where possible, predict and intervene before disease even appears, while ensuring that we rigorously examine ethical issues as well as engage with patients and communities to take account of concerns regarding the use of these technologies. We will use our leadership as a springboard to grow the life sciences industry in the UK and attract additional investment from overseas. And we guarantee that we will promote principles of equity of access, data security and privacy, which is crucial in building public trust and ensuring they understand and benefit from such progress.

But we now need to translate the strategy into actions and into tangible improvements to the health and wellbeing of our country, for the benefit of patients across the UK and millions more worldwide. That is why we are publishing this first implementation plan, which sets out through a series of commitments how we will build towards the vision laid out in Genome UK. It will cover how we will make meaningful progress over the period of 2021 to 2022, and how our delivery partners will work together across the healthcare system.

Genomics is at the apex of healthcare and research, with revolutionary science driving improved treatments, and health programmes providing critical data to accelerate research. Collaboration between our researchers, clinicians and policy makers will therefore be key to achieving our collective goals, and we must continue to come together to drive forward progress and ensure we stay ahead of the field. There is also enormous potential for the UK government and devolved administrations to work alongside each other and deliver collectively on what we agreed together in Genome UK. I have seen first-hand the successes of such a UK-wide approach through the COVID-19 Genomics UK Consortium (COG-UK) in pathogen sequencing. But there are countless more opportunities where collaboration between our nations will reap mutual benefits.

I truly believe that the UK is in a fantastic position to take advantage of our heritage in genomic research and innovation to transform healthcare in this country, to benefit patients and drive our economic recovery. I look forward to seeing the successes of implementing our vision in the next year and into the future.

Lord Bethell of Romford

Parliamentary Under Secretary of State (Minister for Innovation)

Introduction

In September 2020, the government published Genome UK – the future of healthcare, which sets out our 10-year strategy to create the most advanced genomic healthcare system in the world, delivering better health outcomes at lower cost. The strategy also sets out a vision for the UK to be the best location globally to conduct genomics research and grow new genomics healthcare companies, with a goal to increase private sector investment.

We want to ensure that patients across the UK can benefit from the wide range of opportunities offered by genomic healthcare – more preventative healthcare, faster diagnosis, and personalised and better treatment – and that researchers and industry are supported and incentivised to ensure that the UK remains at the forefront of genomic research in the world.

To achieve this, Genome UK set out 24 commitments across the 3 pillars of the strategy – diagnosis and personalised medicine, prevention and early detection, and research. These are underpinned by a further 21 commitments in 5 cross-cutting themes covering patient and workforce engagement, workforce development, data and analytics, industrial growth, and ethical and regulatory frameworks.

Through implementing the vision set out in Genome UK, we will be supporting the virtuous circle of health and genomic data feeding into and accelerating research, generating new insights which would be evaluated and, if proven, adopted at pace to benefit patients. We have made great strides in delivering our vision already and our focus is now on enabling the UK to maintain and extend its global leadership in genomics.

With this implementation plan, we set out our priority actions for the financial year 2021 to 2022 which include the following key commitments:

• a major drive, led by Genomics England, to improve the diversity of genomic data, addressing the historic under-representation of data from ethnic minority groups in genomic datasets, which results in health inequalities. The work will include widespread community engagement alongside sequencing and analytic tool development

• the roll-out of whole genome sequencing to patients with a suspected rare disease and certain cancers in the NHS GMS, in partnership with Genomics England. This is a truly transformational milestone for patients, and for our overarching one million genomes commitment – our ambition to sequence 500,000 genomes in the NHS and 500,000 in UK Biobank, creating the most advanced genomic healthcare system in the world

• proof of concept work, led by Genomics England in partnership with the NHS, to deliver the first phase of a next-generation approach for the diagnosis and treatment of cancer, integrating multiple data sources and new technologies to support faster and more comprehensive genomic testing for cancer in line with the NHS Long Term Plan

• Our Future Health (formerly known as the Accelerating Detection of Disease challenge) will help drive developments in the next generation of diagnostics and clinical tools – including the evaluation of polygenic risk scores (PRS), drug discovery, and smart clinical trials. In 2021, Our Future Health will pilot participant recruitment processes to build towards their 5 million participant ambition. Our Future Health will conduct feedback pilot studies in 2022 to test approaches to deliver health-related information, including PRS, to participants

• the National Institute for Health Research (NIHR), the Medical Research Council (MRC) and Wellcome Trust will, over the next 5 years, provide funding to the Global Alliance for Genomics and Health (GA4GH) to develop standards and policies for sharing genomic and related health data. GA4GH aims to ensure its standards are easily accessible and ready for use by global genomic programs and data sharing initiatives. It will proactively engage stakeholders at national and organisational level to drive uptake of GA4GH standards

These commitments are the first important steps on the journey to realising our vision. However, achieving all our objectives will require new investment over the next decade, including funding partnerships with others in the life sciences sector. We plan to align future iterations of this plan with Spending Review cycles and will work closely with our partners to ensure that we deliver our objectives and provide value for money.

Since we published Genome UK, we have engaged with our delivery partners and key stakeholders to identify early priorities and new projects and programmes that can be commenced and delivered during 2021 to 2022. Given the 10-year timescale of the Genome UK vision, and the number and range of commitments – across 3 pillars and with 5 cross-cutting themes – it is right that implementation should be phased. Genomics is a fast-moving field, and a phased approach will allow us to review our commitments and take action to reflect emerging science and latest research findings.

This implementation plan has been written in close collaboration with the genomics community and our delivery partners. To ensure the actions across the Genome UK strategy remain well aligned we have established an overarching Implementation Coordination Group, led by the Office for Life Sciences, with UK-wide representation. This group will continue to meet on a regular basis to track delivery against the commitments made in this document and agree the ambitions for future publications.

We are committed to delivering on a strategy with a UK-wide reach, while recognising that health policy is devolved and the ownership each nation has on implementation. It is important to acknowledge the different approaches to the development of genomics in healthcare across the United Kingdom, but there have been many areas where collaboration has been critical, such as pathogen sequencing in response to the COVID-19 pandemic. There are also significant opportunities where concerted efforts across the UK may lead to enhanced benefits, such as improving the linkages of genomic health data.

While many commitments in this plan are therefore focussed on implementation in England, it is important that we ensure alignment across the UK. We will work with the devolved administrations, as part of the Implementation Coordination Group, the National Genomics Board and in other fora, to ensure all parts of the UK will benefit from the Genome UK vision.

To reflect their contribution to this implementation plan, the devolved administrations have set out their respective approaches to implementation:

Scotland

In Scotland, we continue to invest in the development of genomic medicine and research and see these emerging medical advances as important parts of our future healthcare strategies. Genome UK provides a useful statement of the current position of Genomics Medicine across the UK, along with potential benefits and a vision for further development over a 10-year period.

Currently, we are focussing our efforts on developing an implementation plan for the strategy which will accommodate the separate population needs, structures and NHS system we have here in Scotland.

To support our policy planning, we will be working closely across the UK to adopt a 4-nations approach to our delivery where possible, alongside seeking the advice and strategic direction from our Scottish Genomics Leadership Group. As part of or planning, we will be engaging with the patients, clinicians and researchers to ensure our policies truly reflect the needs of the user.

Our implementation plan will build on the success from The Bridge to a Scotland Genomics Strategy led by our delivery partners NHS Scotland National Services Division, along with our pioneering research efforts to support genomic medicine research in Scotland. We will look to continue to work in partnership with UK research funders and organisations on research initiatives and collaborative research activities to underpin further development of genomic medicine. Additionally, Genomics pathogen sequencing has been a key component of our response to COVID-19 and we will continue to use and expand our pathogen sequencing service to better understand the current pandemic and any future infectious disease outbreaks.

Wales

In Wales, we have a strong focus and commitment to harnessing genomics technologies in order that we improve the health and prosperity of the people of Wales. We are committed to the implementation of the UK National Genomic Healthcare Strategy ‘Genome UK – the Future of Healthcare’ and see ourselves as a key partner in the delivery of this ambitious and pioneering strategy.

In March 2016 we issued our Statement of Intent for Genomics and Precision Medicine in Wales. Building upon this, in July 2017 we launched the Genomics for Precision Medicine Strategy for Wales, outlining our plan to harness new genomics technologies to improve the health and prosperity of the people of Wales. The strategy was supported by funding to provide the infrastructure needed to develop world class genomic services for the people of Wales.

For example, we are proud of our fully established and accredited pathogen genomics service. It has been, and continues to be, world leading in genomics pathogen sequencing which is a key component of our response to COVID-19. We will continue to expand upon our pathogen sequencing service to ensure that Wales remains at the forefront of this global field.

To ensure that we are best placed to inform Wales’ contribution to the implementation of UK Genome, we are actively reviewing of our Genomics Precision Medicine Strategy for Wales. To support our policy planning, we will continue to work closely across the UK to adopt a truly 4-nations approach to our delivery where possible, alongside seeking the advice and strategic direction from Genomics Partnership Wales.

Pillar 1: diagnosis and personalised medicine

We will incorporate the latest advances in genomics into routine healthcare to improve the diagnosis, stratification, and treatment of disease. Our vision is to help people live longer, healthier lives using genomic technologies to identify the genetic causes of rare disease, early indicators of some common diseases, and cancer. This will enable us to offer personalised treatments, which are tailored to the patient’s or the cancer’s genetic makeup. Our world-leading response to tracking the spread of SARS-CoV-2 variants has successfully demonstrated that genome sequencing is also a vital tool in the control of infectious diseases.

NHS England and NHS Improvement has committed to sequence 500,000 whole genomes by 2023 to 2024, making the NHS the first healthcare service in the world to offer whole genome sequencing routinely and at scale to specific groups of patients. Since we published Genome UK, we have already reached an important milestone: from November 2020, the NHS GMS in England has started implementing the NHS Long Term Plan commitment of rolling out whole genome sequencing for seriously ill children and who are likely to have a rare genetic disorder, children with cancer, and adults with certain rare conditions or specific cancers.

In October 2019, the NHS GMS also introduced rapid whole exome sequencing in newborn and paediatric intensive care units (NICU/PICU), and in foetal medicine in October 2020. To date over 500 referrals have been received with a genetic diagnosis found in 37% of patients, allowing for diagnostic and prognostic information to inform patient management.

In January this year, the government published the UK Rare Diseases Framework – a high-level, community-led strategy document that outlines a coherent vision on how the UK will improve the lives of those living with rare diseases. Genome UK closely aligns with one of the Framework’s key priorities of helping patients get a final diagnosis faster. More than 80% of rare diseases are currently understood to have a genetic origin, and genomic healthcare provides a significant opportunity to reduce the ‘diagnostic odyssey’ for individuals living with these conditions. We will ensure that the mutual priorities of both Genome UK and the Rare Diseases Framework are achieved through effective implementation.

In 2021 to 2022 we commit to make progress on the following ambitions:

• the roll-out of whole genome sequencing to patients with a suspected rare disease and certain cancers in the NHS GMS, in partnership with Genomics England. This is a truly transformational milestone for patients, and for our overarching one million genomes commitment – our ambition to sequence 500,000 genomes in the NHS and 500,000 in UK Biobank, creating the most advanced genomic healthcare system in the world

• progress the NHS Long Term Plan commitment to offer more extensive genomic testing to patients who are newly diagnosed with cancer so that by 2023 over 100,000 people a year can access these tests, including progress on the NHS England and NHS Improvement implementation of pan-cancer panels which are already being rolled out more widely

• establish a proof-of-concept programme, led by Genomics England in partnership with the NHS, to explore next-generation approach for the diagnosis and treatment of cancer, integrating multiple data sources

• deliver and analyse SARS-CoV2 viral genomes together with genomes from affected individuals to inform diagnostics, vaccines, prevention and containment strategies in response to the global pandemic

• expand viral genome sequencing and analysis capacity and capability to establish a world leading pathogen genomics system to detect and provide local, regional and national surveillance of infectious threats with strategies to provide this capability within the regional and national health and public health framework

Case study: viral genome sequencing to identify new variants

During 2020, the UK life sciences sector has been outstanding in its response to the coronavirus pandemic. One example of which has been our world-leading efforts to identify and track the genomic changes of the SARS-CoV-2 virus. There has also been significant progress made in linking this research to tangible public health interventions, such as how an individual’s genome can affect their immune response to COVID-19. This would not have been possible without our world-leading capability and expertise in genomic science and medicine.

In April 2020, COG-UK was set up to establish a COVID-19 genomics capacity. Since then, NHS Test and Trace provided additional funding and the Consortium has sequenced more than 270,000 SARS-CoV-2 genomes through its network of 16 sequencing labs including the public health agencies (PHAs) of the UK.

This work has provided open access data release of all genomes and developed an integrated national data flow for SARS-CoV2 genomes with standardised bioinformatics pipelines that generate virus phylogenies (family trees).

Early research focused on the fine-scale genetic lineage structure together with their transmission and introduction into the UK. This work exposed the history of SARS-CoV-2 importations into the UK – more than 1000 lineages were introduced in the first wave of infection in the UK, with lineage importation and regional lineage diversity declining after lockdown. A second study of introductions into Scotland during the first wave highlighted the role of European travel in COVID-19 emergence in the UK. Separate studies in Wales and Scotland of the first wave plus the early part of the second wave demonstrated that following the first lockdown, many SARS-CoV-2 lineages that were circulating in the population became extinct once the first wave had been supressed through interventions. The second wave was driven by numerous new importations into both countries, largely from other European countries.

COG-UK has also generated evidence on SARS-CoV-2 transmission in particular environments, including hospitals, long-term care facilities, schools, universities and work environments. The COG-UK HOCI (hospital-onset COVID-19 infection) study, a phase 3 prospective, interventional, cohort, superiority study was set up to evaluate the benefit of rapid COVID-19 genomic sequencing on infection control in preventing the spread of the virus in UK NHS settings.

COG-UK and others noted the emergence of the D614K mutation in the spike protein of the virus which mediates viral attachment and entry to the host cell where it can replicate. The mutation was not present when the virus first emerged but has now become almost ubiquitous.

Public Health England (PHE) used these methods for detecting D614K as part of the investigation of the epidemiology of high prevalence and rising incidence of cases in the South East. Using these tools, PHE detected the emergence and spread of lineage B.1.1.7. Further research with academic partners identified that this variant was more transmissible that others, with signals of increased severity and mortality compared to other variants in circulation.

Mutations will continue to arise that change the virus-human interaction over time. Genome sequencing is a vital tool to support PHAs to detect these, interpret their possible impact, and take appropriate public health actions.

This work is ensuring that genomics is delivered in all clinical trials and academic research and the data is open source and open platform to ensure that we reap the maximum benefit from the investment.

The UK Health Security Agency’s NHS Test and Trace with PHE are developing national sequencing capacity and data analytics to ensure that enhanced viral genome surveillance is available in 2021 to 2022 and to establish a framework for pathogen genomics in public health policies to control infectious diseases threats in the future.

Pillar 2: prevention and early detection

Preventing disease or detecting it as early as possible are vital ambitions for any healthcare system. Doing so brings the potential for improved health outcomes for patients while improving the cost effectiveness of interventions. As we highlight in Genome UK, genomic technologies have an enormous potential to accurately predict an individual’s risk of common disease as well as better identify at-risk populations in national screening programmes.

Through integrating genomic technologies into NHS pathways, there is the potential that individuals who are at higher risk of developing disease can be offered more frequent monitoring, or earlier intervention and be supported with adopting health behaviours. However, this is not entirely straightforward; the presence of genome-wide risk factors can increase the likelihood that an individual develops a given disease, but this increase in risk can range from very low to very high. Similarly, a genetic test can predict a high risk, or the early stages, of disease, but the individual may have many healthy years ahead of them or there may be no effective treatments available, for example in dementia. Consequently, there is a need to assess the implementation of these technologies between innovators, regulators, and clinicians before we see their true benefits realised. It is also important that, alongside technical assessments, there are meaningful opportunities to address any ethical and legal issues arising from the introduction of new technologies.

One way in which the UK is investing in the field of prevention and early detection is through the Our Future Health programme. Formerly known as the Accelerating Detection of Disease challenge, this will be the UK’s largest ever health research programme and will recruit up to 5 million diverse participants. Our Future Health will provide an unprecedented research resource which will help drive developments in the next generation of diagnostics and clinical tools – including the evaluation of PRS, drug discovery, and smart clinical trials.

Polygenic risk scores (PRS) will be calculated for at least 3 million Our Future Health participants – with the opportunity to offer results to participants, with their consent, and assess the outcomes. This will be essential for establishing the clinical utility of PRS. PRS could then be used in the future, in isolation or more likely in combination with other risk factors, to identify those at higher risk of certain chronic diseases, potentially enabling earlier clinical and risk-reducing lifestyle interventions.

The concept of PRS, including those that will be used in Our Future Health, derives from genetic analyses of UK Biobank participants. It combines the effects of very large numbers of genetic variants to identify people who are at particularly high risk of a particular disease (equivalent to single-gene disorders such as familial hypercholesterolaemia for heart disease or BRCA1/2 for breast cancer). With the launch of its innovative Research Analysis Platform, UK Biobank has recently enabled research access to much more complex and large-scale data, including by the end of 2022, whole genome sequencing data from all 500,000 participants.

Together UK Biobank, the 100,000 Genomes Project and Our Future Health are 3 pivotal examples of large-scale infrastructure investments into prevention and early detection in the UK. It proves that our ecosystem is able to build on past successes and continuously innovate into the future.

In 2021 to 2022 we commit to make progress on the following ambitions:

• in 2021, Our Future Health will pilot participant recruitment processes to build towards their 5 million participant ambition. There will be a number of pilot studies testing different recruitment routes to achieve the cohort goals of scale and diversity. Our Future Health will conduct feedback pilot studies in 2022 to test approaches to deliver health-related information, including PRS, to participants

• to progress their PRS commitments, Our Future Health will procure the supply of the genome arrays their Chip Committee has designed to calculate a wide range of disease- and condition-specific PRS. They will also develop the PRS delivery and follow-up procedures and partnerships to enable PRS results to be returned to pilot participants. Our Future Health will submit the protocols and materials to a Research Ethics Committee (REC) for ethics approval

• NHS England and NHS Improvement will continue to develop an evidence-based position on the wider introduction of PRS into routine care

• NHS England are partnering with GRAIL to pilot their Galleri blood test that has the potential to detect more than 50 types of cancer using high intensity sequencing of circulating tumour DNA (ctDNA). Up to 140,000 people between the ages of 50-79 will be involved in the study, which is due to start in mid-2021. Another 25,000 people with possible cancer symptoms will also be offered testing to speed up their diagnosis. Results of these studies would be expected by 2023, and if outcomes are positive, then they would be expanded to involve around one million participants across 2024 and 2025

• PHE in conjunction with NHS England and Improvement will start a 3-year evaluative roll-out of non-invasive prenatal testing (NIPT) for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome, with delivery by 3 NHS Genomic Laboratory Hubs. The roll-out will be monitored to ensure any changes to the pathway and screening processes can be made quickly and effectively

Pillar 3: research

The UK is world-leading in genomics research and has been at the forefront of discovery-led and translational genomics research for decades.

We led the way in 2006 when we established UK Biobank which, with 500,000 participants, is now the largest and most intensively genetically and phenotypically described cohort anywhere in the world, linking into the rich UK health record systems. UK Biobank is a prime example of how the public and private sector can come together to fund large scale genomic research initiatives. In addition to its original core funding from MRC and Wellcome Trust, UK Biobank now also receives core funding from NIHR, the British Heart Foundation and Cancer Research UK, and has attracted over £200 million of industry investment. There are over 20,000 researchers worldwide who use UK Biobank to study the genetic and other determinants of disease in over 2,000 diverse projects.

Genomics research in the UK takes place in our excellent academic institutions, the NHS, research institutes, as well as in industry. One example of this research is that we now know that an individual’s response to drug therapy is frequently determined by their genes, or by the specific genetic changes that are driving the disease process – such as in cancer. Pharmaceutical companies have started to use this knowledge to identify new drug targets and therapies that are more likely to demonstrate efficacy in clinical trials, and therefore more likely to result in the successful drug development programmes.

Our vision is to build on and extend this global leadership by developing an ecosystem of genomic datasets which is integrated, secure and of the highest quality. By integrating diverse genomic data with rich phenotypic data, as pioneered by UK Biobank, we can drive research into new prevention and early detection approaches and help researchers understand the pathways from genetic variation to disease. This in turn will enable earlier healthcare interventions, better diagnostics, and innovative therapies for patients from all backgrounds from across the UK.

Achieving this vision will require coordination, collaboration, and systematic sharing of insights by the many different organisations that currently generate and hold genomic data. Moreover, research is often coordinated and funded on a UK-wide basis and we will need to work together to build a comprehensive nationwide ecosystem which enables genomic research and provides access to innovative clinical trials regardless of geographic location. In the future this will be facilitated by the NHS Genomic Medicine Research Collaborative which seeks to maximise coordination of genomic research outputs for patient benefit.

The effective federation of and appropriate access to genomic and phenotypic data, will provide an important resource for commercial partners and the life sciences industry. The generation, curation and federation of high-quality genomic data has the potential to deliver wide-reaching benefits for both patients and the NHS and is crucial if the UK is to remain competitive in attracting high-value life sciences sector investment and the generation of high-quality life sciences sector employment across the UK.

We are committed to ensuring that patients and the public are at the heart of implementing the vision in Genome UK. Therefore, to enable this research, it is equally important that we harmonise patient choice and consent frameworks and data standards, so that patients and research participants across the UK can have trust in the safe, appropriate and responsible use of their data. More generally, an underlying principle of Genome UK is that all genomics research programmes will incorporate robust ethical frameworks and we will work with delivery partners and researchers to ensure ethics remains a central tenet in the design of research programmes. In 2021 to 2022 we commit to make progress on the following ambitions:

• a major drive led by Genomics England, to improve the diversity of genomic data, addressing the historic under-representation of data from ethnic minority groups in genomic datasets, which results in health inequalities. The work will include widespread community engagement alongside sequencing and analytic tool development

• by the end of 2021, all 500,000 participants in UK Biobank will have had their whole genomes sequenced (having already been genotyped and exome sequenced), funded by UK Research and Innovation (UKRI)-MRC, Wellcome Trust, Amgen, AstraZeneca, GSK, and Johnson & Johnson

• the UK Biobank Research Analysis Platform – a cloud-based research environment platform funded by the Wellcome Trust – will be made available for researchers to use from Q3 2021. They will be able to appropriately access whole genome sequencing data through the platform on about 200,000 participants in Q4 2021, and the whole genome sequence data on all 500,000 participants will be made securely available during 2022. This will enable study of the impact of genetic variation on disease in unprecedented detail and scale

• the newly established NHS Genomic Medicine Research Collaborative will bring together NHS England and NHS Improvement, Genomics England and NIHR to facilitate genomic research in the NHS GMS, with established processes for receiving research applications. The Collaborative will enable and support projects from academia and industry for patient and public benefit, with insights being rapidly adopted into the NHS

• the MRC will lead work with the sector to develop a detailed proposal for a UK Functional Genomics Initiative that will drive research and meets the needs of the sector; and has the potential to attract high-value investment in genomically-validated target discovery and drug development

• research into the genetics of symptom severity in COVID-19 infections, led by the European Bioinformatics Institute (EMBL-EBI) and funded through UKRI. This research looks at copy number variation (CNV), an important class of genetic variation and found in specific locations in the genome and their effect on symptom severity in COVID-19 infections

• consortia of UK scientific experts are funded by UKRI, NIHR and international programmes, including the ‘G2P-UK’ National Virology Consortium. COG-UK and PHE will work together to boost the UK’s capacity to study newly identified virus variants and inform government policy. These initiatives will build upon genomics research conducted by COG-UK, and study the effects of emerging variants on transmission, disease severity, and vaccine effectiveness

Case study: human genome sequencing to understand severity of response to COVID-19

Researchers at the GenOMICC consortium, led by the University of Edinburgh, and Genomics England are looking at why some people develop severe illness after being infected with coronavirus while others only develop mild symptoms, or even remain asymptomatic. The study is analysing the genomes of up to 20,000 patients with COVID-19 who were admitted to intensive care, and up to 15,000 people who have had mild or no symptoms. The aim of the study is to understand the biological differences that are involved in the wide range of COVID-19 patient outcomes in order to support the development of new drug therapies and other interventions (such as shielding guidance). The study will also generate a rich research asset to inform further research into drugs and vaccines as well as important research into the long-term, and sometimes multi-organ, effects of COVID-19. First results were published in Nature on 11 December (‘Genetic mechanisms of critical illness in COVID-19’) and already show new and highly plausible genetic associations with critical illness in COVID-19, some of which lead directly to potential therapeutic approaches.

To maximise the value and impact of samples and data collected, Genomics England and GenOMICC have also joined forces with the REACT programme led by Imperial College London. This collaboration will enhance the REACT programme, with up to 8,000 REACT participants receiving whole genome sequences collected as part of the 15,000 ‘mild or no symptoms’ category in the GenOMICC study. In turn the REACT study is collecting multiple samples for analysis and measurements, providing a rich dataset for future study, including specific measures to enable improvements to our understanding of long COVID.

Cross-cutting themes: patient engagement and ethics

None of our success so far could have been realised without the involvement and participation of the wider UK population. As we expand on our ambitions into the future, and pursue our goal to be the most advanced genomic healthcare ecosystem in the world, we must redouble our engagement to ensure that patients are with us every step of the way.

Through working with our stakeholders, we will ensure that the voice of the patient is embedded throughout decision making, to ensure that new technological and clinical processes are met with trust.

We also recognise that while the use of genomic technology in disease prevention and detection has many benefits, it can also raise difficult ethical and societal questions for patients and their families as well as for healthcare staff. The UK has an excellent track record for inviting expert examination of ethical issues to inform public debate and policy making. For example, the Nuffield Council on Bioethics, an independent body established in 1991, was one of the first organisations in the world to examine and advise on ethical issues arising from developments in bioscience and health. We will build on this tradition as we work with experts and delivery partners to develop a strong ethical framework for genomic healthcare, including the use of and access to genomic data.

As set out in Genome UK, our vision is to build and maintain our trustworthiness by involving patients, the public, the NHS workforce and other experts in how we develop and implement genomic healthcare, including ethical and privacy considerations.

In 2021 to 2022 we commit to make progress on the following ambitions:

• significant public engagement, led by Genomics England, on a potential newborn sequencing initiative focussing in particular on ethics and public expectations

• further patient and community engagement through the People and Communities Forum, set up by NHS England and NHS Improvement with input from Genomics England, to help inform policies and strategies for the NHS GMS

• Genomics England will continue to engage its Participant Panel which was first set up to inform its work on the 100,000 Genomes Project

• Our Future Health will establish a governance structure that has public involvement and engagement embedded throughout. They are also setting up a Public Advisory Group for the next phase of the programme; a Participant Advisory Group will be set up once recruitment for the cohort is underway to build on its engagement programme to date

Cross-cutting theme: data

The government’s ambition is to create a health and care system that can harness the power of data to improve outcomes for people and patients. While genome sequencing data can pinpoint the genetic changes in a person’s genome, the real power of genomic healthcare is generated by analysing genomic data alongside other population-level health data, to identify relevant associations between changes in the genome and the development of disease. As the amount of genomic data, phenotypic data and other healthcare data continues to grow, artificial intelligence and other machine learning applications will become increasingly important for the analysis of these very large datasets.

In many cases, UK genomic assets are held by individual research bodies or initiatives, with a number of pockets of excellence, including leading national initiatives such as UK Biobank, Genomics England, Generation Scotland. We also have leading academic institutions such as the Wellcome Sanger Institute, the EMBL-EBI and the Wellcome Centre for Human Genetics. This is further boosted by local initiatives such as East London Genes & Health and Born in Bradford. Genomic data is also held by the private sector, often by start-ups working in the ‘omics’ space. We need to be able to bring together these rich data assets which collectively have the power to drive research of much larger cohorts.

Our long-term vision is to put in place a federated standards-led informatics infrastructure, spanning research and healthcare domains, to record and store genomic data. To do this, we must establish a clear agreed set of standards for genomic data and invest in the underlying infrastructure. This will facilitate genomic data analysis for both healthcare and research purposes and ensure that a patient’s genomic data record can inform their care throughout their life.

High-quality streamlined access to genomic data is critical to support timely clinical decision making and to inform genomically-enabled healthcare as well as to underpin the next wave of genomic research here in the UK. The NHS GMS approach to data will form a key part of this work and our commitment to progress the NHS GMS Research Collaborative will improve collaborative working in this space, especially on patient choice. The patient choice model adopted by the NHS GMS will enable an individual’s whole genome sequencing data to be included in the Genomics England Trusted Research Environment. Our aim is to ensure that a compatible patient choice approach is adopted by other research funders and studies.

As the government unit responsible for driving forward the digital transformation of care, NHSX will lead the implementation of this cross-cutting data workstream. This will ensure alignment with the implementation of the new Data Strategy for Health and Care, also led by NHSX, and will facilitate the coordination, collaboration and, in particular, capture of factors relevant to emerging ‘omics’ data.

In 2021 to 2022 we commit to make progress on the following ambitions:

• Genomics England will develop a new, next-generation Trusted Research Environment which provides improved, authorised access to genomic data and other linked data to researchers from across the sector (subject to patient consent, confidentiality and relevant data protection provisions)

• NIHR, MRC and Wellcome Trust will, over the next 5 years, provide funding to the GA4GH to develop standards and policies for sharing genomic and related health data. GA4GH aims to ensure its standards are easily accessible and ready for use by global genomic programs and data sharing initiatives. It will proactively engage stakeholders at national and organisational level to drive uptake of GA4GH standards

• the Office for Life Sciences will work closely with NHSX, UKRI and other partners to continue to build the investment case, as part of the Value of Data initiative, for building a federated data infrastructure for genomics data. This will include work on bringing together our rich and varied genomics data assets with other routinely collected health data and relevant registries, for example for cancer and rare diseases

• NHSX will engage with genomic incubators, start-ups and R&D initiatives, in particular those seeking to apply AI to genomics data, to understand their user needs and inform future data developments

Cross-cutting theme: workforce

We are increasingly dependent on a varied skills base to support and sustain innovation across the life sciences sector, including in the genomics industry. To deliver on our ambition to create the most advanced genomic healthcare system in the world, and position the UK as the global life sciences hub, the government, NHS, and industry are working together to develop a skilled workforce, including for jobs shaped by the next generation of technology.

In particular, we need a healthcare workforce with role-appropriate and up-to-date genomics knowledge. This includes having staff with highly specialist clinical and scientific expertise.

Healthcare staff must be empowered to know when a patient might benefit from genomic testing and feel confident that they have the skills to communicate complex results to patients and their families in a simple way. In addition to their technical and medical complexity, genomic and genetic test results often raise difficult ethical questions and dilemmas for both clinicians and patients. It is therefore important that clinicians are provided with a developing framework and guidance on how to navigate these issues with their patients, and empower patients to make informed decisions for themselves and their families.

Developing a workforce with these skills will require training and development of existing healthcare staff. We need to ensure that genomics knowledge and expertise is embedded in prospective education and training programmes.

We must also continue to recruit, retain and develop our specialist staff in areas that are in short supply, such as bioinformatics, by introducing innovative education and training models.

The Health Education England (HEE) Genomics Education Programme and the NHS England and NHS Improvement Genomics Unit have set up a joint Genomics Workforce Steering Group. This group works in partnership with a range of stakeholders with responsibility for NHS workforce education and training, and forms part of the HEE, NHS England, and NHS Improvement overall diagnostic workforce programme.

In England, the Genomics Workforce Steering Group will support workforce transformation and its underpinning pillars – education, training and workforce development – which are key to the development of the NHS GMS, as outlined in the NHS Long Term Plan and the NHS People Plan. The evolving NHS GMS will be supported by an underpinning education and training plan as detailed in the HEE mandate, inclusive of innovative clinical academic career models.

Every opportunity to work collaboratively across the United Kingdom, including in education and training arrangements, will be explored and opportunities for joint working introduced. The group will also work with PHE as it transitions into NIHP to ensure that the workforce needs of an enhanced pathogen genomics service are determined and supported.

In addition, UKRI’s Innovation Scholars data-science training programme, co-delivered by the Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, and Medical Research Council will drive enhanced data science skills, including in genomics, for researchers and healthcare professionals. The genomics training ranges from linking biomedical imaging and genomics, FAIR (findable, accessible, interoperable, reusable) data stewardship of genomics data, pathogen genomics and surveillance and genomics analyses through computational, statistical, and artificial intelligence methods.

In 2021 to 2022 we commit to make progress on the following ambitions:

• the Genomics Workforce Steering Group will:
  • implement a workforce survey to identify learning needs and preferences which will identify gaps and priorities for education and training and determine whether this would be appropriate to use in PHE
  • develop a clear picture of the current genomics workforce, to inform a genomics workforce plan and modelling
  • develop and implement evidence-based education and training plans
• there will progress on joint work between the Academy of Medical Royal Colleges (AoMRC) and HEE on improving genomic knowledge in the wider medical profession, including compulsory genomic medicine modules in the undergraduate medical curriculum and continuing to embed genomic medicine modules within the postgraduate education and training programmes. This will be coupled with collaborative work on developing the multi-professional workforce in clinical pathways where genomic tests and outcomes feature as part of the overall approach to embedding genomic medicine