The ground-breaking 100,000 Genomes Project is a highly ambitious programme that has established the UK as the global leader in genomic medicine. Focussing on rare diseases and common cancers, the Project provided a proof of concept for establishing a fully integrated Genomic Medicine Service in the UK National Health Service, the first health service in the world to offer whole genome sequencing for some conditions.
Innovation Summary
Innovation Overview
Genomics is the study of the complete set of an organism’s genetic information. A spectacular leap in the speed and cost of technology has brought genomic medicine within reach of mainstream healthcare. The potential of genomics is huge, leading to more precise diagnostics for earlier diagnosis, new medical devices, faster clinical trials, new treatments and potentially, in time, new cures. The Project seized upon the unique opportunity in the UK – a combination of a single payer National Health Service (NHS) system able to collect samples of high quality DNA and longitudinal clinical data, coupled with a world class genomic science base.
In 2012, the then Prime Minister, David Cameron, set out an ambition for the UK to be the world leader in genomic medicine. The Department of Health and Social Care (DHSC) subsequently launched a moon-shot project to sequence 100,000 human genomes and bring the benefits of genomic medicine to NHS patients by laying the foundation for the introduction of a national Genomic Medicines Service (GMS). DHSC established a wholly-owned company – Genomics England Ltd– to develop a world leading sequencing and analysis pipeline. This involved partnerships with NHS Genomic Medicine Centres (GMCs), a commercial sequencing partner provider, and researchers in academia and industry.
Through the Project, a semi-automated bioinformatics analysis pipeline has been established, enabling the analysis of large clinical genomic datasets at the necessary speed and accuracy for Whole Genome Sequencing (WGS) at scale. The UK is now widely regarded as the global leader in genomics and holds the world’s largest whole genome dataset linked to lifelong health records. Unlike other global sequencing initiatives, the Project it is a health transformative programme, combining elements of research and clinical application in routine care - bringing genomics from ‘the bench to bedside’.
The Project has enabled a number of ambitions, including:
• to increase understanding of genetic variants leading to new treatments and diagnostics
• to accelerate the uptake of advanced genomic medicine integrated into the NHS
• to promote greater public understanding of the benefits of genomic medicine
• to stimulate the UK life sciences industry and commercial activity in genomics
The Project has laid the foundation for the use of WGS in the NHS. This required the establishment of a nationwide network of 13 NHS GMCs, improvements to cancer pathology and diagnostic services, one of the only semi-automated bioinformatics pipelines for analysis of genomic information in the world, as well as a £20m education programme by Health Education England to create a genomics literate workforce.
The 100,000 whole genomes sequenced were split approximately as 30,000 cancer and 70,000 rare disease genomes. Participants are receiving diagnoses of genetic conditions after years of uncertainty and unnecessary costs, and can now receive more personalised treatment leading to better outcomes. Public Health England has also established the world’s first service using WGS at scale to diagnose and treat tuberculosis.
Following on from the success of the Project, the GMS was launched in October 2018, providing comprehensive and equitable access to the latest in genomic testing and management for the whole country. The NHS has also become the first National health service to commission WGS as part of routine care. The GMS is underpinned by a new consolidated genomic laboratory infrastructure and facilitated by informatics, data and analytical platforms to enable the sequencing data generated to be integrated into clinical practice.
In 2018, the Secretary of State for Health and Social Care announced his bold ambition in to sequence 5 million genomes in an unprecedented five-year period, including 1 million whole genomes – an ambition made possible by the foundations laid by the Project. The NHS Long-Term Plan published in early 2019, lay out the strategic direction for the NHS over the next 10 years, and has a focus on utilising the genomic medicine expertise and infrastructure to improve early disease detection and more personalised treatments.
In response to the Chief Medical Officer’s Generation Genome report, a minister-chaired National Genomics Board (NGB) was established, which comprises of senior representatives from relevant organisations ensuring a joined up approach, to ensure that the UK remains the world’s leading centre for genomic medicine and research, and to leverage this position to deliver quantifiable benefits for NHS patients and for the UK life sciences sector. The Project has not only laid the foundation for genomic medicine in the UK, but around the world. The Prime Minister announced a Strategic Genomic Partnership with France at the UK France Summit in January, which aims to share expertise in order to embed a national GMS in both countries.
Innovation Description
What Makes Your Project Innovative?
The Project was integrated within a national health service. This has enabled the establishment of a nationwide network of Genomic Medicine Centres (GMCs)- each serving a population of 3-5 million people. Unlike other global sequencing initiatives, the Project combines elements of both research and clinical application in routine care.
Patient and public involvement has been an integral part of the Project. Views of potential participants on ethical issues raised by genomic medicine were sought from the start, and shaped patient literature. The Genomics Conversation was also launched to engage the general public and relevant stakeholders in genomic medicine.
The scale also sets the Project apart: 85,000 participants, 1,500 NHS staff and over 3,000 researchers are involved. The Project will generate over 21 petabytes of data, and has already led to the creation of the largest whole genome dataset linked to lifelong health records anywhere in the world.
What is the current status of your innovation?
The Project reached its 100,000 target in December 2018. Recruitment to the Project is completed and results will continue to be returned to participants throughout 2019. The Project has shown the benefits of a national approach to genomics and laid the foundation for the national GMS.
The new GMS became operational from October 2018 providing comprehensive access to the latest in genomic testing and management for the whole country. The first National Genomic Test Directory also became operational from October 2018, specifying which genomic tests can be commissioned for cancer and rare genetic conditions. Tests that are listed in the new Test Directory will be available to all patients nationwide bringing an end the so-called ‘postcode lottery’ that some patients have experienced in the past.
Innovation Development
Collaborations & Partnerships
DHSC used Civil Service convening and brokering skills to effectively collaborate with a wide range of partner organisations across UK Government and beyond, including NHS England and Genomics England partners, all Devolved Authorities, over 13 industry partners including GlaxoSmithKline and AstraZeneca, medical research charities, other government departments, as well as clinicians, patients and the public.
Users, Stakeholders & Beneficiaries
Project participants have already benefited through more effective treatment identification or receiving a diagnosis. Future beneficiaries will be the users of the Genomic Medicines Service. There are up to 300,000 new cancer diagnoses per year and up to 15,000 babies born with abnormalities that may benefit from genomic testing earlier than they are done now. 13 pharmaceutical companies came together on a non-competitive basis to create the Discovery Forum to optimise the programme for industry collaboration.
Innovation Reflections
Results, Outcomes & Impacts
The Project has provided the infrastructure to deliver the world’s first fully integrated GMS providing equitable access to genomic testing. This includes a nationwide network of 13 NHS GMCs, improvements to cancer pathology and diagnostic services, a semi-automated bioinformatics pipelines and a £20m education programme to create a genomics literate workforce. Through the Project the UK has created a unique dataset linking phenotypic and WGS data, enabling ground-breaking research.
Participants are receiving diagnoses of genetic conditions after years of uncertainty and unnecessary costs, and are receiving more personalised treatment leading to better outcomes. Many patients with a rare disease have found themselves on a “diagnostic odyssey” lasting for years. Taking part in the Project has meant that many of these patients have been given a diagnosis for the first time.
Challenges and Failures
Initially, cancer sequencing posed a significant challenge as it was established that using formalin fixing tissue damages DNA and is not compatible with WGS. An unplanned experimental phase to identify the optimum method for extracting DNA for successful sequencing was run, delaying recruitment to the main cancer phase of the Project. However, pathology and clinical experts worked to embed a new “genome friendly” fresh-frozen sample pipeline, and Genomics England ran a fast track cancer analysis pilot to return cancer reports with four weeks.
Appropriate participant consent was also a challenge. A national service evaluation of the consent materials was commissioned at the 10,000 participant mark, where the Project Participant Panel gained in-depth feedback from Project participants, patient groups and healthcare professionals. Patient materials were re-designed and improved to ensure they continued to meet needs.
Conditions for Success
Government commitment:
The project was announced by then Prime Minister David Cameron, and the commitment was reiterated in Theresa May’s 2017 Conservative party manifesto.
Leadership:
Having senior level champions - particularly in England’s Chief Medical Officer, Professor Dame Sally Davies - to raise the Project profile.
Agility:
Genomics England Ltd. was set up as a limited company, which allowed for the adaptable and agile ‘start-up’ mentality needed to ensure success.
Public willing:
Innovative engagement activities have been undertaken to raise the public awareness of genomic medicine, and address aspirations and concerns in dialogue with participants and the public, encouraging public awareness and the benefits of sharing genomic data.
Informed implementation:
Pilot sites were established prior to the Project start, and an evaluation was conducted to inform the delivery of the Project at scale.
Replication
The Project has established best practice in the collection and secure storage of large datasets: 21 Petabytes of data has been created and held in a secure private cloud environment with access for clinical research, and commercial R&D. Engaging and educating the public and the workforce has been a vital strand of the Project, involving collaboration between a wide range of stakeholders.
The Project has established the UK as world-leading in genomics, and the aim to integrate whole genome sequencing into a comprehensive health system is shared with other countries around the world. The UK and France have agreed to establish a strategic genomic medicine partnership, between Genomics England and France Genomique, to share knowledge and experience across the entire pipeline needed to embed a National GMS in both countries. The UK Government is providing funding of £2.7 million to the collaboration which is to be matched by the French.
Lessons Learned
The main challenge was to rapidly establish a new diagnostic pathway within a busy healthcare environment without precedent. This required high-level, dedicated and experienced leadership across the board, as well as rigorous project governance and monitoring. Establishing Genomics England provided a focus for rapid evaluation and procurement that involved sample handling, sequencing, data interpretation and storage. The Project has demonstrated the success of this approach in situations where an agile, ‘start-up’ mentality and drive is needed to ensure success.
Anything Else?
Generation Genome
Published on 4th July 2017, Chief Medical Officer Professor Dame Sally Davies's independent report explores how we currently utilise genomics in our health and care system and how its potential may be developed to improve health and prevent ill-health.
https://www.gov.uk/government/publications/chief-medical-officer-annual-report-2016-generation-genome
Genomics England website
Genomics England’s website provides an excellent, easily accessible multimedia gateway to the project and the science behind it.
https://www.genomicsengland.co.uk/
The Life Sciences Industrial Strategy
The report, written by Life Science’s Champion Professor Sir John Bell, provides recommendations to government on the long term success of the life sciences sector. It was written in collaboration with industry, academia, charity, and research organisations.
https://www.gov.uk/government/publications/life-sciences-industrial-strategy
Status:
- Diffusing Lessons - using what was learnt to inform other projects and understanding how the innovation can be applied in other ways
Innovation provided by:
Date Published:
10 January 2012