New Vision for NIEHS and NTP

1. New Vision for NIEHS and NTP Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S Director National Institute of Environmental Health SciencesNational Toxicology Program Collaborative on Health and the EnvironmentMarch 15, 2010

2. National Institute of Environmental Health Sciences • NOT in Bethesda area • Research Triangle Park, NC • Wide variety of programs supporting our mission of environmental health: • National Toxicology Program • Intramural laboratories • Extramural funding programs • Funding from 3 Congressional Committees • Health – Regular NIH appropriation • Interior - Superfund Research Program and Worker Training • Energy - Worker Training Program

3. Our Commitment : Translating Bench Science into Environmental Public Health

4. Conceptual Shift for Environmental Health Sciences OLD…chemicals act by overwhelming the body’s defenses by brute force at very high doses NEW… chemicals can act like hormones and drugs to disrupt the control of development and function at very low doses to which the average person is exposed

5. A Confounding Problem… • Humans are always exposed to multiple environmental agents • It is difficult to decipher how exposure to many agents will influence the effects of each one – both in time and space • Linking exposure and disease has to take multiple exposures into account

6. What is “Low Dose”? • The "dose makes the poison" … • Different effects occur at different doses • “Low” Dose may just mean “lower” than usually studied • The most common definition: Below previously identified “adverse” dose level; environmental exposure levels; in the physiological range…

7. “New” Types of Toxicity Endocrine Disruptors Exogenous agents that interfere with the production, release, transport, metabolism, binding, action, or elimination of the natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes Engineered Nanomaterials Three dimensional particulates with one dimension less that 100nm and possessing novel optical, magnetic, or electrical properties that emerge at the nanoscale and have unknown biological consequence.

8. Environmental Health Research: Poised toAdvance Research and Protect Public Health The Challenge • How do we come together to think strategically about the breadth, scope, participants, and goals for Environmental Health Research, a multi-science discipline primed for significant impact on human health in the 21st Century? • How do we create an Environmental Health Research Strategy that provides the data and information needed by the multiple audiences who use EHS data? • Do we have the right tools and methods to do Environmental Health Research in the 21st Century? • How can we integrate better new methods and technologies into science policy?

9. Early Markers of Disease Environmental Exposure External Contact Internal Dose Biological Response Clinical Disease Adapted from the National Research Council, 1987 Advance the Research Framework… Toxicity Testing Toxicology, Claussen, ed. Integrating Exposure into the Continuum of Health to Disease

10. Environmental Factors Health Genetic and Molecular Expression Life in Utero Disease Age Build on EHS Scientific Developments • Expanded definition of environmental exposures to include environmental stressors (nutrition, psychosocial stress, physical activity, behavior, noise, light) • More holistic approach to human health and disease • Relationship of perinatal exposures to adult onset disease • Windows of exposure • Increased sensitivity with life-long physical consequences

11. …and Close the Loop Fundamental Research in Mechanistic Toxicology Epidemiology Exposure Assessment Exposure- Disease Relationships Genetic Susceptibility Public Education and Involvement Policy and Regulation Prevention Research Prevention and Improved Public Health

12. Potential Outcomes from Closing the Loop • Change how we think about environmental health; how we formulate hypotheses • Improve translation of basic science into human health protection • Encourage a new paradigm for parallel tracks in material/product design/development and hazard assessment Photo courtesy of Environmental Health Perspectives

13. Expand Partnerships in Environmental Health Research and Public Health • More inclusionary definition of Partner • Congress, public stakeholders, general public, health professionals, other governments, other Federal agencies whose decisions impact public health (e.g., NASA, DOT, DOE, DOI, USGS) • New mechanisms & fora for dialogue • Evaluate program contributions to the advancement of environmental public health

14. The Environmental Polymorphisms Registry Linked DNA Biobank • N=15,000 subjects in central North Carolina • GIS coding allows for link to environmental exposure information • Racial/ethnic diversity (30% minority population) • Collection of DNA and personal information – contact information, demographics Recruit by genotype resource • Screen DNAs to identify subjects with specific genotypes of interest • Recruit subjects for phenotypic studies based on their genotype • Examine gene-environment interactions with respect to phenotypes of interest • Potential to be adult parallel of the National Children’s Study Phase I • Establish EPR consortium -- 25 DIR investigators • 110 environmental response genes nominated for initial study • Genotyping of functional SNPs underway in N=4000 nested cohort • Phenotyping studies to begin in early 2010

15. The Genes, Environment, and Health Initiative Genetic Susceptibility - Linking Exposure to Disease Exposure Biology Program Human Genetics Program Genetics/Epigenetics Environment GxE Identify genetic variants in animal models, develop technology and biomarkers Time Identify genetic variants • Diet • Physical Activity • Environmental Exposures • Psychosocial Stress and Addictive Substances • GWA Studies • Data Analysis • Replication • Sequencing • Database • Function • Translation

16. Breast Cancer and the Environment Program • Define how environmental agents affect lifelong risk of breast cancer • Identify potential windows of susceptibility • Apply GxE approach using direct measures of exposures & diet, polymorphism analysis, & comparison with animal models • Address concerns of communities / advocates in the research arena • Provide education and messages to enable informed lifestyle choices through outreach activities, forums, mentor activitieswww.bcerc.org

17. The Sister Study Prospective cohort study of 50,884 women aged 35-74 with a sister with breast cancer • Enrolled 2004-2009 • 2-3-fold risk of developing breast cancer Primary Aim - Study environmental and genetic risk factors for breast cancer • Create a framework to address current and future hypotheses • Address questions of public concern Secondary Aims • Study factors related to prognosis • Study other health outcomes

18. All Higher women norepinepherine 0-2 >2 0 1-2 3-5 6-7 8+ Stress Score Early Results from Sister Study Increased risk of uterine fibroids • Maternal diabetes and DES • Being fed soy formula • Lower childhood SES Shorter telomeres with • Higher perceived stress • Higher stress hormones • Lifelong obesity Longer telomeres with • Daily multivitamins • Ongoing case-cohort analysis • SNPs from breast cancer GWAS • telomere length • and methylation

19. NIEHS Asthma Research Asthma Severity in Children and Environmental Agents • Relates residential exposures (indoor allergens, mold, NO2, nicotine) to daily symptoms and medication use in children with asthma Dust Mite Allergen Reduction Study • Tests use of an in-home test kit to decrease dust mite allergen levels Mexico Childhood Asthma Study • Family study of genetic susceptibility to high-ozone in Mexico City Ozone and Rhinovirus-Induced Disease in Asthmatics • Tests whether exposure to ambient ozone levels directly enhances viral disease by increasing infectivity and intensifying virus-induced inflammation in allergic asthmatic subjects HEAL (Head-off Environmental Asthma in Louisiana) • Collaboration with Tulane and New Orleans Dept of Healthon effects of post-Katrina mold and indoor allergens on children with asthma

20. Evaluating the Safety of Engineered Nanomaterials:The NIEHS NanoHealth & Safety Initiative • To expand the base of knowledge on nanomaterials safety and how structural aspects affect biological activity • Extramural research: Biological interactions • Methods for exposure measurement • Linking physical/chemical properties to response • Capture results in database for meta-analysis • Intramural research: Impact on chronic disease • Carbon nanotubes and asthma • NTP: Nanotechnology toxicity research • Dermal penetration studies of nanoscale titanium dioxide • Pharmacokinetics of quantum dots • Toxicity studies of carbon fullerenes

21. Climate Change and Human Health • NIEHS is providing Departmental leadership on climate change and health • With FIC, heading trans-NIH workgroup • Leading interagency workgroup to develop white paper on research needs for health effects of climate change • Helping organize White House stakeholder briefing with HHS and EPA • Partnering with Wellcome Trust on a series of papers in Lancet • Worked with FIC on ARRA Challenge Grants initiative to: • Collect new and existing data on changes in ambient temperature, precipitation, humidity, and other climate variables and industrial pollutants • Identify related human health risks and vulnerabilities in the U.S. and around the world • Adds to ongoing NIEHS work on oceans and human health

22. NIEHS Superfund Program: Two Unique Roles Detect hazardous substances in the environment Evaluate the risk of hazardous substances on human health Develop basic biological, chemical, and physical methods to reduce the toxicity of hazardous substances Create state-of-the-art training programs for hazardous materials handlers, chemical emergency responders, and waste cleanup workers Integrate training with National Response Plan SRP Mandates WorkerTraining NIEHS Use environmental sciences to understand human biology and human disease EPA Regulate to protect human health and the environment ATSDR Prevent harmful exposures and diseases related to toxic substances

23. Biomedical projects: Identify health issues Evaluate risk Particulate and Metal Exposures: Mine Tailings in the Southwest Problem brought to SRP Mine tailings on a windy day Environmental projects : Mitigate risk Site characterization Develop/characterize remediation technologies Immunostaining shows As effects on lung Containing the tailings Measuring particulates

24. National Toxicology Program Interagency program Established in 1978 to coordinate toxicology research across the Department of Health and Human Services (DHHS) Headquartered at NIEHS Research on “nominations” Thousands of agents evaluated in comprehensive toxicology studies Results communicated through technical reports, scientific publications and the web Analysis activities Report on Carcinogens (RoC) Center for the Evaluation of Risks to Human Reproduction (CERHR) NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) Department of Health and Human Services (DHHS) NIH CDC FDA NIEHS NIOSH NCTR http://ntp.niehs.nih.gov

25. New and Renewed Areas of Emphasis for NTP • Better coordination across the Federal government • Develop new methods for efficient, thorough toxicological assessments • Increase understanding of exposure-response relationships and issues of dosimetry • Integrate results from new “data rich” techniques (i.e. genomics, high through-put screening) with traditional toxicology data to provide public health context • Toxicity for the 21st Century or “Tox21” • MOU between NTP, EPA and NHGRI • High throughput, robotic testing of toxic compounds in cell and molecular assays • Using knowledge of biological response to identify toxicity pathways • Prioritization for further testing

26. In Conclusion: A New Vision for NIEHS and NTP • A strong desire to partner with our sister institutes and other federal agencies: EPA, CDC, FDA, DOE…. • Health and Environment is a priority • New issues and technologies are emerging • We need the best individual and team science to address complex diseases and complex environmental impacts • We need to improve integration across research disciplines and with all partners • We need to improve our translation and communication of basic science findings into human health protection

27. Thank You