Human Genomics, Precision Medicine, and Advancing Human Health. The Human Genome. The Origin of Genomics : 1987

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1 Human Genomics, Precision Medicine, and Advancing Human Health Eric Green, M.D., Ph.D. Director, NHGRI The Human Genome Cells Nucleus Chromosome DNA Human Genome: 3 Billion Bases (letters) The Origin of Genomics : 1987 Editorial A New Discipline, A New Name, A New Journal Genomics (1987) For the newly developing discipline of [genome] mapping/sequencing (including the analysis of the information), we have adopted the term GENOMICS. The new discipline is born from a marriage of molecular and cell biology with classical genetics and is fostered by computational science. Eric D. Green, MD, PhD 1

2 Human Genome Project: Myriad Applications of Genomics Health, Disease, & Medicine Genomic Medicine An emerging medical discipline that involves using genomic information about an individual as part of their clinical care (e.g., diagnostic or therapeutic decision making) and the other implications of that clinical use. Eric D. Green, MD, PhD 2

3 The Path to Genomic Medicine Human Genome Project Realization of Genomic Medicine Nature International weekly journal of science (2003) A vision for the future of genomics research (2011) Charting a course for genomic medicine from base pairs to bedside Bringing Genomic Medicine into Focus Interpreting the Human Genome Sequence Eric D. Green, MD, PhD 3

4 ~3,000 bp (0.0001%) of Human Genome Sequence ENCODE: Giving GPS Views of Genomes Bringing Genomic Medicine into Focus Interpreting the Human Genome Sequence Developing New Genome Sequencing Methods Eric D. Green, MD, PhD 4

5 A vision for the future of genomics research: A blueprint for the genomic era (2003) Nature technological leaps that seem so far off as to be almost fictional but which, if they could be achieved, would revolutionize biomedical research and clinical practice. [For example,] the ability to sequence DNA at costs that are lower by four to five orders of magnitude than the current cost, allowing a human genome to be sequenced for $1000 or less. The $1,000 genome (2014) Nature With a unique programme, the US government has managed to drive the cost of genome sequencing down towards a much anticipated target. Erika Check Hayden (2014) Nature Sequencing a Human Genome Human Genome Project (1 st Sequence) ~1B ~6 8 years Today ~$2 4K ~1 3 days Eric D. Green, MD, PhD 5

6 Bringing Genomic Medicine into Focus Interpreting the Human Genome Sequence Developing New Genome Sequencing Methods Cataloging Human Genomic Variation Human Genetic Variation Your Genome: By the Numbers ~6B nucleotides ~3 5M single nucleotide variants ~150K not in databases ~60 not in either parent ~ disruptive variants in genes ~20 completely inactivated genes (both copies) Eric D. Green, MD, PhD 6

7 Bringing Genomic Medicine into Focus Interpreting the Human Genome Sequence Developing New Genome Sequencing Methods Cataloging Human Genomic Variation Elucidating the Genomic Bases of Disease Genomic Architecture of Genetic Diseases Manolio et al., J Clin Invest (2008) Rare, Simple, Monogenic, Mendelian Common, Complex, Multigenic, Non Mendelian Bringing Genomic Medicine into Focus Interpreting the Human Genome Sequence Developing New Genome Sequencing Methods Cataloging Human Genomic Variation Elucidating the Genomic Bases of Disease Implementing Genomic Medicine Eric D. Green, MD, PhD 7

8 Hot Areas in Genomic Medicine Cancer Genomics Cancer is a Disease of the Genome It takes several mutations to make a cell malignant Routine Clinical Diagnostic Tools Radiographic Imaging Cancer Genome Sequencing Eric D. Green, MD, PhD 8

9 Genomics and Cancer: Here and Now Hot Areas in Genomic Medicine Cancer Genomics Pharmacogenomics Pharmacogenomics Drug toxic but beneficial Drug toxic but NOT beneficial Drug NOT toxic and NOT beneficial Drug Not toxic and beneficial Eric D. Green, MD, PhD 9

10 Hot Areas in Genomic Medicine Cancer Genomics Pharmacogenomics Ultra Rare Genetic Disease Diagnostics When Disease Strikes from Nowhere (2014) Nature Children born with disorders not readily explained by standard tests can sometimes be diagnosed through genome sequencing and analysis. NIH Undiagnosed Diseases Network: Seven clinical sites and a coordinating center Stanford Medicine UCLA Baylor College of Medicine National Institutes of Health Vanderbilt University Medical Center Harvard Teaching Hospitals Harvard Medical School Duke University Eric D. Green, MD, PhD 10

11 Hot Areas in Genomic Medicine Cancer Genomics Pharmacogenomics Ultra Rare Genetic Disease Diagnostics Genomic Medicine Test Drive Programs Clinical Sequencing Exploratory Research (CSER) Implementing Genomics into Clinical Practice Network (IGNITE) Eric D. Green, MD, PhD 11

12 Hot Areas in Genomic Medicine Cancer Genomics Pharmacogenomics Ultra Rare Genetic Disease Diagnostics Genomic Medicine Test Drive Programs Prenatal & Newborn Genomic Analysis Noninvasive Prenatal Genome Sequencing Newborn Sequencing in Genomic medicine and public Health (INSIGHT) Eric D. Green, MD, PhD 12

13 Hot Areas in Genomic Medicine Cancer Genomics Pharmacogenomics Ultra Rare Genetic Disease Diagnostics Genomic Medicine Test Drive Programs Prenatal & Newborn Genomic Analysis Clinical Genomics Information Systems Generating a Human Genome Sequence is (Almost) Trivial Clinical Genomics Information Systems Clinical Genome Resource (ClinGen) ClinGen: Sharing Data. Bluilding Knowledge. Improving Care. Eric D. Green, MD, PhD 13

14 The Relevance of Genomics Biomedical Researchers Healthcare Professionals Patients (and Friends & Relatives of Patients) Pervasive DNA & Genomic Imagery Genomics and Society Eric D. Green, MD, PhD 14

15 Genetic Genomic Competency Center (G2C2) Access resources to learn more about use of genomic information in your practice Education repository of resources for diverse healthcare professionals Global Genetics & Genomics Community (G3C) Role of Both the Genomics and other Factors in Human Disease Genome Analysis Technologies mhealth and Environmental Monitoring Technologies Eric D. Green, MD, PhD 15

16 Precision Medicine A broader context for individualizing medical care to advance human health Today: most medical care based on expected response of the average patient Tomorrow: medical care based on individual genomic, environmental, and lifestyle differences that enable more precise ways to prevent and treat disease Precision Medicine Concept is not entirely new: Prescription eyeglasses Blood transfusions What is needed now: Rigorous research program Multidisciplinary approach Audacious scale and scope President Barack Obama Jan 30, 2015 the budget I send this Congress on Monday will include a new Precision Medicine Initiative that brings America closer to curing diseases like cancer and diabetes, and gives all of us access, potentially, to the personalized information that we need to keep ourselves and our families healthier. Eric D. Green, MD, PhD 16

17 Precision Medicine Initiative: The Vision NEAR TERM: Cancer as a Model of Precision Medicine Cancer as leading edge of precision medicine, yet more to learn. Ramp up current efforts to include more cancer types LONGER TERM: Expanding the Model to Other Diseases Create national research cohort of >1 million volunteers. Generate knowledge base for precision medicine. POLICY CHANGES: Remove Barriers to Clinical Implementation Update federal rules protecting research participants. Advance FDA oversight of precision medicine products. Precision Medicine Initiative: Proposed Fiscal Year 2016 Funding National$200 Million FDA $10 Million Office of the National Coordinator for Health Information Technology $5 Million TOTAL $215 Million National Research Cohort >1 million U.S. volunteers Participants to share genomic data, lifestyle information, biological samples all linked to their EHRs Forge new model for doing science that emphasizes: Engaged participants Open, responsible data sharing Strong privacy protections Convert healthcare system into a learning system Eric D. Green, MD, PhD 17

18 Precision Medicine Initiative: Next Steps Working Group of Advisory Committee to the Director Additional meetings/workshops Implementation Trans NIH implementation model Fall 2015: Initial funding opportunities announced Fiscal Year 2016: Funding begins Emphasis on Transparency Planning a National Research Cohort Eric D. Green, MD, PhD 18