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

GRAND CHALLENGE #3:

Drive progress toward affordable, quality health care.

Figure out what works and what doesn’t, what is safe and what is not, in personal health care and in community public health services.

Risks of Over-interpreting Epidemiological Associations

• Chemoprevention of cancers (and CVD) with beta-carotene and retinoids

Subjected to randomized large-scale prevention trials: no benefit (x7), major adverse effects (x2) with increased incidence of lung cancers and increased mortality from coronary heart disease

Stimulated new generation of lab work.

Risks of Over-interpreting Epidemiological Associations (2)

• Post-menopausal estrogens to prevent CHD, osteoporosis, and breast cancers—the Women’s Health Initiative

Stunning findings of net adverse impact Frustration and anger among women and gynecologists• Trials of high-fiber/low fat diets to prevent

polyp recurrence and colorectal CA—not supported

Positive Examples

• Folic acid: reduces neural tube closure defects (many RCTs) and is associated with lower CHD mortality (via HCy) and lower colorectal cancer incidence

• Statins: may have benefits on CHD mortality beyond cholesterol reduction

• Very low cost “polypill” (Nicholas Wald): beta-blocker, HCTZ, statin, folate, ASA

IOM SERIES ON HEALTH CARE QUALITY

• To Err is Human---Patient Safety

• The Health Care Quality Chasm—

6 attributes of quality care: safe, timely, patient-centered, effective, efficient, equitable

• Leadership by Example: The Role of Government in Enhancing Health Care Quality—policy ramifications of patient-centered care and coverage

Population-based efficacy

“The average patient seeing the average doctor for a typical condition finally has a better than average chance of benefitting from the encounter.”

---L.J. Henderson, 1913

Let’s be sure the odds are still good!

Mobilize to overcome major global health problems

High-quality, low-cost training, kudos to UP “Supercourse”Technological breakthroughs Remember our best example: the Salk vaccine from U Pitt

Gates Fdn/NIH Fdn “Grand Challenges”Varmus, Klausner, Zerhouni, et al, Science 2003;302:398-99

To Improve Childhood Vaccines: #1: Effective single-dose neonatal vaccines #2: Vaccines that do not require refrigeration #3: Needle-free delivery systemsTo Create New Vaccines: #4: Reliable model systems tests to evaluate

live attenuated vaccines #5: More effective antigens #6: Learn which immune responses are protective

To Deplete or Incapacitate Insects that Transmit Agents of Disease:

#7: Genetic strategies

#8: Chemical strategies

To Improve Nutrition to Promote Health:

#9: Optimal bioavailable nutrients in staple plant species

To Improve Drug Rx of Infectious Diseases:

#10: Drugs and delivery systems to minimize resistance

To Cure Latent and Chronic Infections #11: Therapies to cure latent infections #12: Immunological methods to cure chronic infections

To Measure Disease and Health Status Accurately & Economically #13: Technologies for quantitative assessment of health status #14: Point-of-care technologies for individuals with multiple conditions or pathogens

MUCH MORE THAN TECHNOLOGY IS REQUIRED

• Influence of income inequalities• Other causes of health disparities• Need to be alert to identify—and

demonstrate scientifically--unanticipated benefits: the story of Vitamin A in child survival, on top of blindness prevention

• Play a professional role in prevention of violence, from interpersonal to terrorism and war: UP leadership

PRINCIPLES OF COMMUNITY-BASED RESEARCH University of Washington

• Community partners should be involved from the earliest stages• Community partners should have real influence on project• Research processes and outcomes should benefit the community• Community members should be part of the analysis/interpretation• Productive partnerships should last beyond the project• Community members should be empowered to initiate projects

Building Broader Partnerships

• RWJF/WK Kellogg Fdn initiative “Turning Point, a new Century for Public Health”—state and local coalitions

• Take advantage of the Internet

Public Health INFO from CDC

Supercourse from U Pittsburgh GSPH

REMEMBER: Our Most Certain, Major Products are

People

Recognize Schools of Public Health as a national and international treasure!