The NHS in the genomics era

1. The NHS in the genomics era Mark BaleDepartment of Health

2. 100,000 Genomes Project “It is crucial that we continue to push the boundaries and this new plan will mean we are the first country in the world to use DNA codes in the mainstream of the health service” The Rt Hon David Cameron MPThe Prime Minister 10 December 2012

3. Genetics White Paper

4. The rate of change Sequencing costs are dropping rapidly and new sequence data consequently rising Research is advancing at a rapid rate, but understanding of the role of genes in health and disease is still in its infancy Applications in some areas (such as cancer) are already here and the NHS must start to adapt for the advent of genomic medicine Benefits in reduced diagnostic time, better precision and possible savings from other (futile) treatment options Capacity challenges and bottlenecks in data storage and interpretation Concerns that investment unlikely piecemeal under current assumptions – industry and other private investment

5. The UK Strategy for Rare Disease • Launched November 2013 • 51 commitments across all 4 devolved administrations 5 themes: • Empowerment • Diagnosis • Prevention & early intervention • Better coordination of care • Research and development

6. Rare inherited diseases

7. Deciphering Developmental Disorders (DDD) https://decipher.sanger.ac.uk

8. NIHR Rare Diseases Translational Research Collaboration (RD-TRC) • >7,000 rare diseases (fewer than 5 in 10,000) have been identified • The UK is at the cutting edge of research in rare diseases internationally • ‘Deep’ phenotyping information combined with data on genomic abnormalities will increase research opportunities, enable faster diagnosis and support improved management and treatment of rare diseases • RD-TRC will provide world-class NHS research infrastructure as a key element to harness the unique strength of the NHS to support fundamental discoveries and translational research on rare diseases • Co-chaired by John Bradley (Cambridge BRC) and Patrick Chinnery (Newcastle BRC)

9. NIHR BioResource - Rare DiseasesSequencing Projects

10. Cancer • Disease of disordered genomes – over 200 drivers known • Stratified medicine and targeted therapy • Drug metabolism • Immunological targets • International Cancer Genomes Consortium- the Cancer Genome Atlas • Optimise Molecular Pathology Signal transduction pathways affected by mutations in human cancer Vogelstein et al. Science 339, 1546 (2013)

11. Incidence v survival at 5 years

12. Lung cancer before and after Gefitinib

13. BRAF inhibitors for Melanoma

14. Antimicrobial resistance

15. A vision for NHS genomics Human Genomics Strategy Group (2012) • By 2020, the NHS will be a world leader in the development and use of genomic technology in the areas of healthcare and public health. It will be seen as a first-choice partner for industry, academia and research, contributing substantially to the global genomics knowledge base by supporting and facilitating innovation and novel research. • Genomic information and clinical genetic testing will be used equitably across the NHS, improving diagnosis and treatment decisions by identifying the right therapies to maximise efficacy and reducing adverse effects. • Healthcare providers within the NHS will confidently use genomic information within their roles • Effective public engagement will increase awareness of the role of genomic information in healthcare; how it can inform health choices; and the need for consent to access, study and use genomic data for the greater good. • There will be a vibrant SME sector and large life sciences company investment in and around our best universities and genomics hubs.

16. CMO priorities for genomics in the NHS – 2012 • Reconfigure NHS laboratories around genomic technologies for single gene and gene panel diagnostic testing • Ensure fast, high quality testing services for high penetrance genetic variants of common diseases such as cardiac, eye and metabolic disorders • Develop a “discovery diagnostic” network of excellence for rapid translation into the clinic • Commission appropriate genome diagnostics on all children from specialist units where a diagnosis is unclear • Improve pathways for genetic testing or sequencing of cancers to build on current stratified medicines initiatives • Align standards and architecture to collect genomic data and phenotypes • Facilitate a network of clinical bioinformatics, with powerful computing and data analysis • Review the role of sequencing in antenatal and adult screening, for example new developments in fetal DNA testing and cervical screening WHOLE GENOME SEQUENCING

17. Genetic Services in the NHS: What is likely to change Genetic services in the NHS at present are primarily focused on testing for rare monogenic disorders, via specialist genetic service fundamental shift in approach *According to UKGTN second report (Nov 2010), between Apr 2008 and Mar 2010 the NHS Directory of Genetic Testing contained 503 diseases and 688 associated tests

18. Discovery Diagnostics Diagnosis from research studies using genomic technologies in a clinical translation research setting: DDD (UK) Analysed first 1,133 families, with a diagnostic rate of aprox 30%, discovered 12 new genes Gilissenetal (2014) – Nijmegen 42% diagnosis rate of 50 children with severe intellectual disability using WGS Beaulieu etal (2014) – FORGE Canada Consortium 45-95% diagnosis rate of 264 patients using whole exome sequencing

19. WGS500 Results • MENDELIAN • Of 95 families, to date • 23 families have new diagnosis • pre-screened for known genes • result will increase with follow-up • 74 families in follow up studies • Over 50% of these have strong lead • candidate • 7 Novel genes for disease • 6 Novel phenotypes for known genes • 2 pathogenic regulatory variants in or downstream of known candidate genes • 6 genes missed by prior Sanger Sequencing

20. Genomic medicine Specialist genetics, pathology and specialist clinical workforce in Genomic Medicine Increase in specialisedscientific training fellows funded over 3/5 years: • Molecular Pathology including Infections and Pathogens • Genetics / genomics • Bioinformatics Commission bioinformatics workshops in conjunction with partners Develop specialist on line on-line learning and an MSc in Genomic Medicine Develop an MSc in Genomic Medicine CPD access to MSc modules for specialist practitioners

21. Conclusion • Genomic Medicine is here • Time for translation is now • Prime therapies or repurpose treatments • It needs further optimisation • Together we can transform Genomic Medicine in the NHS