GRAND CHALLENGES AND GREAT OPPORTUNITIES FOR THE PUBLIC HEALTH SCIENCES and SCHOOLS OF PUBLIC HEALTH...
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Transcript of GRAND CHALLENGES AND GREAT OPPORTUNITIES FOR THE PUBLIC HEALTH SCIENCES and SCHOOLS OF PUBLIC HEALTH...
GRAND CHALLENGES AND GREAT OPPORTUNITIES FOR THE PUBLIC HEALTH SCIENCES and SCHOOLS
OF PUBLIC HEALTH
University of Pittsburgh GSPH Retreat, 15 March, 2004
Gilbert S. Omenn, MD, PhD
University of Michigan
GRAND CHALLENGES1. Public Health Genetics
2. Environmental Health Risk Assessment & Risk Management
3. Affordable Quality Health Care in the U.S., and globally
Engage the full range of the public health disciplines in academe and in practice
GRAND CHALLENGE #1:
Apply all of the public health sciences to the interpretation of variation in the genome in
full behavioral and environmental context
Our Genetic Future “Mapping the human genetic terrain may
rank with the great expeditions of Lewis and Clark, Sir Edmund Hillary, and the Apollo Program.”
--Francis Collins, Director
National Human Genome Research Institute, 1999
Next: -- Understand the dynamic proteomic
compartments
-- Elucidate genetic, environmental,
and behavioral interactions
APRIL 14, 2003:
THE 50th ANNIVERSARY OF THEPUBLICATION OF THE
WATSON-CRICK ARTICLE ON THE DOUBLE-HELIX STRUCTURE OF DNA
IT’S A NEW WORLD• New Biology---New Technology
• Genome Expression Microarrays
• Comparative Genomics
• Proteomics
• Bioinformatics & Computational Biology
• Evidence-Based Medicine: “What were you doing up to now?!”• Predictive, personalized, preventive healthcare and community health services
DEFINITIONS• Genetics is the scientific study of genes and their roles
in health and disease, physiology, and the evolution of human development.
• Genomics is the study of the sequence and functioning of the human genome---all the genetic material, the complete inheritance of a particular individual.
Genomics is a modern subset of the broader field of genetics, made feasible by remarkable advances in molecular biology, biotechnology, and computational sciences.
• Proteins are the action molecules of the cell and the leading candidates for biomarkers—in tissues and in the blood.
• The Genome is a blueprint, a parts list, of genes coding for proteins.
• Proteomics is the global analysis of proteins in cells or body fluids.
• Techniques for global analysis of proteins are advancing rapidly, especially for discovery of biomarkers for diagnosis, treatment, and prevention.
Protein DNA
PROTEOME: GENE PRODUCTS
Highly dynamic compartment: ideal for biomarkers
Regulated at the transcriptional and post- transcriptional levels, compartmentalized in cells
Numerous post-translational modifications: glycoproteins, phosphoproteins…
Protein subsets: secreted proteins, membrane proteins, antigenic proteins, auto-antibodies
COMING TECHNOLOGY• Nanotechnology for sensors• Microfluidics for miniaturization and automation--
DNA sequencing, protein analyses
--Leroy Hood: “In 10 years, we will be able to
sequence an individual’s genome for less than
$1000 in a fraction of a day.”• Microarrays for proteins (e.g., tumor antigens and
autoantibodies)• Nanocantilevers for detecting protein-protein
interactions, down to a single cell
PUBLIC HEALTH AND GENETICS• Epi and Biostat: Bring together the digital
code of inherited information with “environmental cues” from nutrition, metabolism, lifestyle behaviors, pharmaceuticals/nutraceuticals, and chemical, physical, and infectious exposures
• The result is “systems biology” at many levels from proteins to eco-systems…and health status for individuals and communities
• Recognize gene/drug interactions: efficacy and adverse effects (pharmacogenetics)
PUBLIC HEALTH GENETICS (2)• Infectious diseases: host-pathogen
interactions/clues for epidemiology and drug and vaccine development
• Nutrition: hyperlipidemias, high BP, high homocysteine, iron (hemochromatosis)…
• Unhealthful behaviors: smoking, alcohol, inactivity
• Chronic diseases:
--predisposing genes (variants, SNPs)
--genetic toxicology from exposures
PUBLIC HEALTH GENETICS (3)• Eco-genetics: environmental & occupational
exposures and variation in susceptibility --OSH Act: set standards to protect the most
susceptible worker over a lifetime at max exposure
--Clean Air Act: set criteria air pollution standards to protect “most susceptible subgroup”
• Training and continuing education in every public health discipline: preventive medicine, health services research, epidemiology, biostatistics, EOH, health behavior and health education, pathobiology (role for Supercourse)
“Harnessing Genetics to Prevent Disease & Improve Health: A State Policy Guide”
Partnership for Prevention
Washington DC, 2003
www.prevent.org
AIMS of the PfP REPORT
Help state policymakers to:
• Protect consumers
• Monitor the implications of genetics for health, social, and environmental goals
• Assure genetic advances will be tapped not only to treat medical conditions, but also to prevent disease and improve health before people become ill.
KEY FINDINGS• The greatest opportunity of the genomic era:
personalized medicine and pharmacogenetics to prevent or better manage chronic diseases. Products and services will include vaccines, diagnostic tests, drug therapies, and drug monitoring protocols.
• Genetics programs should be integrated into existing health, social, and environmental policies, rather than establishing stand-alone genetics/genomics programs
THE CASE FOR INTEGRATION• All health conditions have a genetic basis.
• Most common diseases result from gene-environment interactions, so genetic advances are likely to extend and expand, not supplant, current practices in medicine, public health, environmental protection
• Some genetic variations are associated with greater health risks than others; covering this wide range with one-size-fits- all policies is inappropriate.
PfP CITED MICHIGAN
“At a time when many state policies were based on exceptionalism, the Michigan Governor’s Commission on Genetic Policy and Progress adopted an integration perspective and recommended that genetic issues be dealt with in the context of overall medical care values and principles”.
(p.11, PFP Report)
HEALTH POLICIES RECOMMENDED BY PfP
• Increase consumer knowledge of genetics
• Strengthen public health infrastructure to accommodate genetics developments
• Add genetic competencies to licensing requirements for all health professionals
• Increase supply of qualified genetic counselors
• Invest in genetics research agenda
Additional Sources of Information
• CDC Office of Genomics and Disease Prevention
• Assn of State and Territorial Health Officers (ASTHO): Genomics Impact Newsletter, monthly.
• National Conference of State Legislatures: Genetic Technologies Project;
www.ncsl.org
GRAND CHALLENGE #2:
Discover, quantify, and reduce environmental risks to health of individuals and
populations
“ I know no safe depository of the ultimate powers of society but the people themselves; if we think them not enlightened enough to exercise their control with a wholesome discretion, the remedy is not to take it away from them, but to inform their discretion.”
- Thomas Jefferson
Presidential/Congressional Commission on Risk Assessment and Risk Management
Risk assessment science & models
Risk-management framework
Communicating uncertainty
Peer review
Inter- and intra-agency consistency
“Bright lines”
Sensitive subpopulations
Ecologic risk assessment
Comparative risk assessment
Economic analysis
Judicial review
Objectives of Risk Assessment1. Balance risks and benefits
Drugs Pesticides
2. Set target levels of riskFood contaminantsWater pollutants
3. Set priorities for program activitiesRegulatory agenciesManufacturersEnvironmental/consumer organizations
4. Estimate residual risks and extent of risk
reduction after steps are taken to reduce risks
Major Hazardous Chemical Laws in the U.S.
EPA: Air Pollutants Clean Air Act 1970, 1977, 1990 Water Pollutants Fed WP Control Act 1972, 1977 Safe Drinking Water Safe DW Act 1974, 1996 Pesticides FIFRA 1972 Food Quality & Protection FQPA, 1996
Ocean Dumping Marine Protection Act, 1995 Toxic Chemicals TSCA 1976 Hazardous Wastes RCRA 1976 Hazardous Waste Cleanup CERCLA (Superfund) 1980,
1986
FDA: Foods, Drugs, Cosmetics FDC Acts, 1906, 1938, 1962, 1977, 1997
CEQ: Envtl Impacts NEPA, 1972
OSHA: Workplace OSH Act, 1970
CPSC: Dangerous Consumer Products CPS Act, 1972
DOT: Transport of Haz Materials THM Act, 1975-79, 1984, 1990
Framework for Regulatory Decision-Making
Epidemiology
Hazard Identification Lifetime rodent bioassays Short-term, in vitro/in vivo
tests Structure / activity
Potency (dose/response)
Risk Characterization Exposure analysis Variation in susceptibility
Information
Risk Reduction Substitution Regulation / Prohibition
Biological End-Points
Cancers
Mutations
Birth defects
Reproductive
toxicity
Immunological toxicity
Neurobehavioral toxicity
Organ-specific effects
Endocrine modulation /
disruption
Ecosystem effects
Context
Multiple sources of same agent
Multiple media/pathways of exposure
Multiple risks/effects of same agent
Multiple agents causing same effects
Public health: status / trends
Ecological health
Social, cultural, environmental justice
considerations
Move beyond one chemical, one environmental medium (air, water, soil, food), one health effect (cancer, birth defect…) at a time in risk assessment and risk management: requires comprehensive public health view
Change the Context
Data Gaps: “Toxic Ignorance”
Only 7% of high production volume
(HPV) chemicals had full set of studies
for 6 basic endpoints, while 43% of
HPV chemicals have no publicly
available studies for any of 6 basic
toxicity endpoints (EPA, 1998) Environmental Defense Fund report
“Toxic Ignorance” and OECD (SIDS)
stimulated new commitments to test
Eco-Genetics
• The interaction of environmental exposures and genetic variation
• Range of susceptibility for specific exposures
• Application of gene and protein expression methods to detect and clarify “molecular signatures” as biomarkers of exposure, early adverse effect, and susceptibility
Reducing risk by orders of magnitude is not equivalent to linear reductions
0
200
400
600
800
1000
1 x 10-3 1 x 10-4 1 x 10-5 1 x 10-6
Level of risk
Risk Commission, Final Report, 1997