Written Evidence Submitted by the Wellcome Sanger Institute (C190066) Introduction 1. The Wellcome Sanger Institute uses genomics to advance the understanding of human and pathogen biology to improve human health. We use science at scale to tackle the most challenging global health research questions. 2. The Wellcome Sanger Institute is based on the Wellcome Genome Campus: a world-leading hub for genomes and biodata research. The campus is also home to EMBL-EBI, Connecting Science, Genomics England and several spin-out and start-up companies. Key Messages 3. Thanks to an advanced national genomics sector, the UK was ideally placed to rapidly reposition to launch and deliver a genomic strategy to help combat COVID-19. Established practices of collaboration and transparency in genomics enabled the swift launch of the COVID-19 Genomics UK Consortium (COG- UK) and its subsequent speedy provision of real-world evidence to inform public health interventions. 4. Continued investment in scientific research and infrastructure by successive governments and UK research charities has enabled the development of invaluable scientific resources, such as the Human Cell Atlas, which have been rapidly utilised and repurposed to tackle COVID-19. 5. Medical research charities play an integral role in UK research, but have suffered financially during this global health crisis. Financial support for medical research charities is not only vital for mitigating the impacts of the pandemic but for protecting and maintaining the UK’s research sector which is reliant on the medical research charities. 6. Public-private partnerships can be an excellent vehicle for the advancement of basic science from the laboratory into healthcare. Opportunities to collaborate across the academic, commercial and healthcare sectors should be incentivised to accelerate the development of healthcare interventions. 7. The Health Research Authority’s (HRA) rigorous and efficient fast-track system for approving COVID-19 research studies was hugely beneficial and reflects the UK’s responsive and pragmatic approach to research regulation. 8. The free and unrestricted sharing of SARS-CoV-2 genomic data has been enormously important for public health efforts. It is vital that regulations to support access and benefit sharing, such as the Nagoya Protocol, do not hinder or prevent data sharing during pandemics. 9. Difficulties obtaining metadata and the use of different data standards are major challenges with the large-scale sequencing projects and can reduce the overall effectiveness of interpreting the SARS-CoV-2 genome and identifying localised outbreaks. Initiatives such as HDR-UK and use of recognised data standards, such as those created by the Global Alliance for Genomics and Health (GA4GH), can support the open sharing of data and knowledge to ensure fair and equitable access to scientific research. 10. Efficient and effective data connectivity is vital in creating a consolidated UK-wide COVID-19 dataset. Efforts to reduce data fragmentation and improve data connectivity will revolutionise our scientific understanding of human health and disease. The contribution of R&D in understanding SARS-CoV-2 transmission and epidemiology 11. Rapid scientific insights have been invaluable in tackling the global COVID-19 pandemic by guiding public health responses and driving the development of vaccines and therapeutics. The Sanger Institute is uniquely positioned within the UK research landscape to provide globally recognised expertise and infrastructure in pathogen surveillance and large-scale, high-throughput genome sequencing to strengthen COVID-19 research efforts. The Sanger Institute rapidly refocused its research towards understanding the biology and evolution of the SARS-CoV-2 virus, tracking its transmission and deciphering its interactions with human cells. 12. To identify SARS-CoV-2-infected individuals in large populations globally, diagnostic tests must be rapid, accurate, scalable, portable and available at a low-cost. In collaboration with UCL and the Universities of Oxford and Cambridge, the Bassett and Teichmann labs at the Sanger Institute have developed INSIGHT – a 2-stage COVID-19 testing strategy that is designed to detect SARS-CoV-2 in a highly specific manner from human saliva in 1-2 hours via fluorescence detection or a dipstick readout1. Unique barcodes can be added to samples to enable the monitoring of viral mutations and transmission among populations. COVID-19 Genomics UK Consortium (COG-UK) – coming together to tackle a public health challenge 13. COG-UK is an innovative partnership connecting leaders in genomics and public health across the interface of government, public health and academia2. Led by Prof Sharon Peacock, COG-UK brings together NHS organisations, the four UK Public Health Agencies, multiple university hubs and sequencing centres, including the Sanger Institute, to deliver rapid and large-scale sequencing of the SARS-CoV-2 virus. 14. Supported by £20 million funding from the Department of Health and Social Care, UK Research and Innovation (UKRI) and Wellcome, COG-UK is performing rapid and large-scale sequencing of SARS-CoV-2 to understand its transmission and epidemiology, the emergence of resistance mutations and to identify genetic markers associated with clinical severity. 15. The complex network of COG-UK was set up rapidly. With experts in pathogen surveillance and high- throughput genomics sequencing and a history of large-scale and rapid whole genome sequencing, the Sanger Institute was ideally placed to aid the UK government’s public health response to the COVID-19 epidemic. Viral samples were collected from the national testing centres and NHS and public health laboratories and then whole genome sequenced at regional laboratories and at the Sanger Institute. COG-UK delivered its first report to the UK government Scientific Advisory Group for Emergencies (SAGE) based on 260 SARS-CoV-2 genome sequences less than a fortnight after the initial COG-UK meeting. As of July 2020, COG-UK has sequenced 30,000 SARS-CoV-2 genomes, 9,000 of which were sequenced at the Sanger Institute. The Sanger Institute now has the capacity to receive 300,000 samples per week from the Lighthouse Laboratories and cherry pick the positive samples to sequence up to 1,000 SARS- CoV-2 genomes a day. 16. COG-UK data is made freely available to the research community as quickly as possible and according to the FAIR3 principles. COG-UK sequencing of SARS-CoV-2 has revealed there were 1356 sources of SARS- CoV-2 introductions into the UK during March 20204. Each of these viral introductions was transmitted onwards within the UK. 1 https://www.biorxiv.org/content/10.1101/2020.06.01.127019v1 2 https://www.cogconsortium.uk/ 3 https://www.nature.com/articles/sdata201618 Human Cell Atlas (HCA) – rapid repurposing of flagship science 17. HCA is a grass-roots international consortium creating a comprehensive reference map of all human cells to understand human health and disease5. Launched in 2016, HCA has already delivered projects to understand human biology including the immune system, nervous system, the gut and cancer. In response to the COVID-19 pandemic, the HCA community has rapidly refocused efforts to deepen our understanding of COVID-19 and transmission routes of SARS-CoV-2. 18. Existing HCA datasets were analysed to identify cells expressing key host proteins exploited by SARS- CoV-2 to enter human cells. Two types of cell in the nose were found to have the highest levels of these host proteins and are the likely infection route into the human body for the virus6. Over 1 million cells in nasal, airway and lung samples were then analysed to understand clinical outcomes and risk factors. A number of potential therapeutic targets were found and smokers and men were identified as being more susceptible to COVID-19 infection7. Open Targets – novel drug target identification for COVID-19 19. Open Targets is a precompetitive public-private partnership between the Sanger Institute, EMBL-EBI, GSK, Takeda, Celgene and Sanofi that uses genomics to identify and prioritise drug targets8. 20. Open Targets have developed a COVID-19 Target Prioritisation Tool, which has identified 261 potential host and virus drug targets associated with COVID-19. There are plans to integrate the tool with the EU COVID-19 Data Platform. The impact of COVID-19 on research funding 21. The Sanger Institute receives funding from Wellcome in the form of a core grant and is further supported by external grants from funders including UK Research Councils, charities and European and international funders. The Institute benefits from working in a well and diversely funded science ecosystem. 22. Half of publically funded medical research in the UK is funded by medical charities and during the COVID- 19 pandemic this sector has experienced a 38% loss in their fundraising income and charities have had to cut or cancel 18% of their spend on research in universities9. The immediate and long-term impact on medical research funding in the UK will be catastrophic and the sector has estimated that it will take approximately 4.5 years for their medical research spending to recover to normal levels. Reduced funding will stifle medical research, delay scientific breakthroughs and hinder the initiation and completion of clinical trials. This will negatively impact all parts of UK R&D whether funded directly by medical research charities or not. The flexibility of regulatory and ethical processes during the