Genomic Medicine and NIH Francis S. Collins, M.D., Ph.D.

Director, National Institutes of Health Global Leaders in Genomic Medicine

January 8, 2014

“Science in pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce illness and disability.”

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NIH: Steward of Medical and Behavioral Research for the Nation

www.genome.gov/GWAStudies

Genetic Variants Associated with Disease Risk

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Cost of Sequencing a Human Genome September 2001–October 2013

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Disorders with Known Molecular Basis

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Source: Online Mendelian Inheritance in Man, Morbid Anatomy of the Human Genome

The Beery Twins

Mom questioned whether her twins’ symptoms were consistent with CP; sought new diagnosis

Tentative diagnosis of dystonia; began treatment with L-DOPA with some improvement

But by age 14 their health had deteriorated severely

Alexis and Noah diagnosed with cerebral palsy (CP) at age two

Sequencing found a new genetic disease; readily treated with the addition of an amino acid to diet

Undiagnosed Diseases Program (launched 2008) – Patients have longstanding medical conditions that have eluded

diagnosis; seen at NIH Clinical Center – Trans-NIH staff, led by Dr. William Gahl, has:

• Evaluated ~3,000 medical records • Accepted ~700 cases • Determined a diagnosis in ~25%

Undiagnosed Diseases Network (being implemented) – Expands Program, analysis, across U.S. (~$145M over 7 years)

• Harvard University named UDN Coordinating Center • 5-7 additional clinical sites to be added this summer

– Focus on patient phenotyping; gene function research; DNA sequencing; data sharing

Undiagnosed Diseases and NIH

Disorders with Known Molecular Basis

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Source: Online Mendelian Inheritance in Man, Morbid Anatomy of the Human Genome

<500 with therapy

NIH: Genomics and Drug Discovery

Therapeutics for Rare and Neglected Diseases (TRND) – Collaborations with expert outside labs to speed development

of new drugs for rare and neglected diseases

Discovering New Therapeutic Uses for Existing Molecules – Pharma partners have made 58 compounds, biologics, and

associated data available to select NIH grantees

High tech human biochips to test for toxicity – for all 10 major organ systems – Partnership with DARPA; FDA

Our laws and institutions must gohand-in-hand with progress of the human mind.

Thomas Jefferson

Major Legal Decision for Genomic Medicine: U.S. Supreme Court Ruling on Patenting Human Genes 1997/1998: U.S. patents result in exclusive rights for

diagnostic testing to Myriad for BRCA1 and BRCA2

2009: AMP/ACLU lawsuit filed asserting that patents on these genes should never have been allowed

2013: U.S. Supreme Court rules that genes in their natural state are not patentable

BRCA1 BRCA2

Chromosome 13 Chromosome 17

November 19, 2013: FDA announced first regulatory clearance of high-throughput DNA sequencing device Authorized broad clinical use of Illumina MiSeqDx

– Allows fast, full, accurate sequencing of patient’s genome

Potential applications include: – Assessing disease risk – Uncovering drivers of disease process – Determining possible responses to drugs

Regulatory Challenges: Preparing the Pathway to Effective Personalized Medicine

November 22, 2013: FDA warns 23andMe to discontinue marketing its Personal Genome Service until it receives clearance

Regulatory Challenges: Preparing the Pathway to Effective Personalized Medicine

GINA (Genetic Information Nondiscrimination Act, 2008) – Preceded by, expands on, HIPAA (Health Insurance Portability

and Accountability Act, 1996) – Extended by Affordable Care Act of 2010

Sharing data: expanded Genomic Data Sharing Policy – Promotes sharing of large-scale human, non-human data – Public has commented; final policy coming

Modernizing human subjects rules: revisions to the Common Rule are coming – Increase protections for participants; decrease

unnecessary burdens on research

Incidental findings: Presidential Commission reports

Critical Ethical and Policy Considerations for Genomic Medicine

Science knows no country, because knowledge belongs to humanity and is the torch which illuminates the world.

– Louis Pasteur

NIH… Turning Discovery Into Health