Justification Narrative

FY 2008 Budget

Authorizing Legislation: Section 301 and Title IV of the Public Health Service Act, as amended.

Budget Authority:

This document provides justification for the Fiscal Year (FY) 2008 activities of the National Institute of Environmental Health Sciences (NIEHS), including HIV/AIDS activities.  Details of the FY 2008 HIV/AIDS activities are in the "Office of AIDS Research (OAR) section of the Overview.  Details on the Roadmap/Common Fund are located in the Overview, Volume One.
 
DIRECTOR'S OVERVIEW
The NIEHS supports research that focuses on preventing disease and improving human health by using environmental health sciences to understand human biology and human disease.  The field of environmental health sciences examines the total body in its fullest complexity to understand how environmental exposures interact with underlying susceptibilities related to genetics, age, and other factors to set in motion molecular events that initiate disease processes.  Defining the interplay of these multiple factors and how they affect human biology generates the knowledge that provides the ultimate payoff for environmental health science research – better health and longer lives for all citizens.
Due to recent advances in technology, NIEHS can pursue a more targeted research effort that employs integrated science teams to conduct disease-focused research with clinical and public health applications.  The NIEHS has implemented a new strategic plan, "New Frontiers in Environmental Sciences and Human Health" (available online at http://www.niehs.nih.gov/about/od/strategicplan/), to address this multifaceted, multidisciplinary approach to environmental health that will allow the institute to capitalize on new approaches to environmental health research.  The plan highlights our future challenges and goals, including ways to attract more physician-scientists to the field, encourage integrated research that spans multiple disciplines, and move the research enterprise to a greater emphasis on disease outcomes.

Many of the goals of the new strategic plan are coming to fruition.  The NIEHS launched the Disease Investigation through Specialized Clinically-Oriented Ventures in Environmental Research (DISCOVER) Program for the extramural community and the Director's Challenge for the intramural community.  These two programs focus on the interface between basic mechanistic and clinical research to unravel the complexity of environmentally-influenced diseases that pose a health burden to society. In FY 2007, NIEHS will invest $6 million in these programs.

The NIEHS is a lead on the new trans-NIH Genes, Environment and Health Initiative (GEI), to accelerate research discoveries on the role of genes and the environment in human disease.  Through this initiative, NIEHS has established the Exposure Biology Program, to promote the development and application of new technologies that will precisely measure human exposure to environmental toxins.  For more information see the program portrait on this initiative.

As a commitment to improving the health of American citizens, many NIEHS staff responded personally, and as a community, to the devastation caused by Hurricane Katrina.  The NIEHS has continued to show support to this hard-hit region by creating a partnership to support the Head-off Environmental Asthma in Louisiana (HEAL) program, designed after the Inner-City Asthma Study, to address the problem of childhood asthma resulting from excessive amounts of mold, microbial toxins and airway pollutants. These efforts have also provided the foundation for a new Global Health Initiative to address pressing environmental health problems worldwide.

The environmental science field is uniquely poised to benefit from the incredible pace of biomedical discovery that has resulted from new advances in genetics, molecular biology, computational sciences, and the physical sciences.  The NIEHS is working hard to meet this challenge through targeted investments in training the next generation of environmental health scientists.  Recently, NIEHS launched the new Outstanding New Environmental Scientists (ONES), an R01 program for new independent investigators, and the Short Term Educational Experiences for Research (STEER) programs to attract and support the "best and brightest" new researchers to the field of environmental health sciences.  The first eight recipients of the ONES awards have already been selected.

The NIEHS intramural and extramural scientists continue to unravel important biomedical problems.  In the past year, there have been several significant breakthroughs, including:

• The identification of predisposing genetic mutations for breast cancer.  This discovery has the potential to improve the detection and treatment of the disease in women that are at high risk, as well as providing new ways to study gene-environment interactions in this disease;
• The discovery of the role of endogenous airway relaxants that may be targeted in the treatment of chronic airway hyper-responsiveness and chronic airway inflammation caused by environmental agents as well as other sources;
• The discovery of anti-inflammatory effects of natural glucocorticoids that could one day be used in therapeutic regimens for environmental diseases such as asthma, autoimmune disease and sepsis;
• The discovery of mechanistic linkages between exposure to inhaled particulate matter in urban areas and susceptibility to cardiovascular disease;
• The elucidation of regulatory mechanisms for synaptic plasticity in the brain that impact learning and memory and that could provide objects of study for environmental effects on these pathways; and
• The identification of the structural basis for errors in DNA synthesis, due to strand misalignment, that may result from environmental stress and have profound impacts on human disease.

There has been tremendous growth in the power and sophistication of many of the technologies used in biomedical research, bioimaging, and bioinformatics.  The NIEHS will continue to implement its strategic plan and pursue ways to apply these novel tools to the understanding of how environmental exposures affect human biology and alter disease risk, especially for complex diseases such as asthma, cancer, and autism that are caused by multiple environmental and genetic factors.  By capturing this larger understanding of disease initiation and progression, the ultimate goals – to alleviate suffering and to improve human health, can be achieved.

JUSTIFICATION BY ACTIVITY

Overall Budget Policy

Investigator-initiated research projects and new investigator research and career development are high priorities.  The NIEHS carefully evaluates investigator-initiated projects over $500,000, which require NIEHS approval prior to submission.  The level of support provided for peer-reviewed solicited projects (e.g., Request for Applications) is also evaluated.  The NIEHS maintains a balance between solicitations issued to the extramural community in areas that need stimulation and funding made available to support investigator-initiated projects.  Funding plans are discussed with the NIEHS Advisory Council prior to making awards.

Clinical Research:  One of NIEHS' primary goals is expanding the role of clinical research that illuminates the relationship between environmental exposures and human disease.  Diseases for which environmental health sciences can provide important clinical insight include degenerative diseases, cardiovascular diseases, reproductive disorders, breast cancer, and lung diseases, especially asthma.  The goals of the clinical research program are: 1) to encourage clinical research that emphasizes understanding the environmental causes of common, complex diseases; 2) to develop improved research models for human disease using our knowledge of environmental sciences and human biology; and 3) to enhance the role of the clinical investigator in environmental health sciences.

Budget Policy:  The FY 2008 budget estimate for the Clinical Research program is $45.874 million, which represents a funding level of +$2.307 million and +5.3% over the FY 2007 estimate.  Resources will be used to continue activities critical to the long-term success of the Clinical Research program.  These include programs to identify windows of susceptibility to breast cancer development from the prenatal period to adulthood, as well as to continue the Sister Study, which has recruited about half its goal of 50,000 sisters of women diagnosed with breast cancer, to target environmental causes of breast cancer.  Another example of NIEHS' support of clinical research focusing on environment and human disease is a program grant for an ongoing cohort study of 6,000 children from 12 communities in Southern California examining genetics, air pollution, and children's respiratory health, with a goal of identifying environmental and host factors, and examining the genetic variation in oxidative stress pathways that modulate response to air pollution.

Basic Mechanisms in Human Biology:  Scientists can employ environmental toxicants as laboratory probes to help study the complex molecular pathways that lead to chronic disease.  These toxicants are able to interrupt normal processes in ways that can set in motion the events that ultimately lead to conditions such as cancer, birth defects, and neurological disorders, thus providing a controlled method for studying mechanistic events leading to clinical disease.  Because environmental agents often operate early in the disease process, they also provide a useful technique for identifying very early events in disease pathogenesis that can potentially be used both to identify methods to diagnose diseases before they are clinically evident and to develop early interventions that prevent progression to end-stage disease.

NIEHS' goal is to gain an improved understanding of the influence of gene-environment interactions and their effect on biological networks and pathways, which could ultimately lead both to ways of identifying very early, pre-clinical disease endpoints and to development of therapeutic interventions early in the disease process.

Budget Policy:  The FY 2008 budget estimate for the Basic Mechanisms in Human Biology program is $253.762 million, which represents a funding level of -$3.254 million and -1.3% below the FY 2007 estimate.  NIEHS anticipates that several initiatives in capacity building in environmental genomics will have essentially been completed, reducing resources required for this program.  While modest investments in these areas will continue, resources will primarily be directed to high-priority activities critical to the long-term success of the Basic Mechanisms in Human Biology program, and to address research questions and concerns with the highest priorities.  These include the FY 2006 NIEHS-initiated Request for Applications (RFA) entitled Comparative Biology Elucidation of Environmental Pathways and Susceptibility, which utilizes recently developed research tools that can be recruited to identify genetic and environmental factors in complex human diseases, particularly as they affect cellular pathways.  Environmental response genes and pathways are highly conserved across species.  Thus, genetic information being generated in multiple laboratory species can be used to understand the molecular underpinnings of human disease.  This project examines entire biological pathways comprised of multiple genes and influenced by multiple environmental factors.  Outgrowths of this research allow toxicological response studies in laboratory animals to be done in parallel with human studies in ways that could identify and predict human subgroups that are particularly susceptible to an adverse effect from an environmental agent.  Partners for this RFA include the National Institute on Alcohol Abuse and Alcoholism and the National Heart, Lung, and Blood Institute.

Portrait of a Program: Manufactured Nanomaterials

FY 2007 Level $2,000,000
FY 2008 Level   2,000,000
Change                             0

Nanoscale science and technology involve imaging, measuring, modeling, and manipulating matter on the scale of 1 to 100 nanometers - a scale at which novel physical, chemical, and biological properties enable novel applications. Nanoscale materials and devices frequently provide increased sensitivity and selectivity, and improved electrical and optical properties, that make nanoscale products useful for drug delivery systems, tissue engineering, biological and environmental sensor technology, and environmental remediation. Consumer products containing nanoscale materials, such as sunscreens and stain resistant fabrics, are commercially available, and by 2010, the nanoscale materials, tools, and devices industry is projected to exceed $10 billion. Emerging technologies should create innovation while minimizing risk of adverse health effects and health effects of exposure should be assessed prior to extensive use. The diversity of materials in constructing nanoparticles suggests that the universal safety of such systems cannot be taken for granted, and there will not be a single answer. NIEHS has released an RFA, Manufactured Nanomaterials: Physico-chemical Principles of Biocompatibility and Toxicity to support research that explores the systemic, cellular and molecular responses to manufactured nanoscale materials.  Because the physico-chemical properties of nanoscale materials may change across experimental timelines, the studies will include evaluation of the physical and chemical characteristics of nanoscale materials at multiple points in the exposure model and link these measurements to biological effects. This research will improve the understanding of  potential health impacts of these novel compounds, as well as help guide development of these products so as to reduce adverse impact to an increasingly exposed population.

Interdisciplinary, Integrative Research:  Interactive, team-based scientific research approaches help NIEHS optimize its ability to integrate research from all levels of investigation to contribute to overall health and to reduce the burden of complex, multifaceted diseases. Scientific contributions from epidemiology, toxicology, molecular and cellular biology, bioinformatics, clinical medicine, and many other fields need to be coordinated and integrated. By fostering such broad-based, collaborative research, NIEHS will increase the relevance of basic scientific discoveries in environmental health sciences to human disease, and rapidly and more effectively move this knowledge into clinical and public health applications, ultimately improving human health.

Budget Policy: The FY 2008 budget estimate for the Interdisciplinary, Integrative Research program is $56.989 million, which represents a funding level of -$2.089 million and -3.5% below the FY 2007 estimate. NIEHS will fund fewer Core Centers in FY08, which is part of a long-range strategy to redirect resources to other projects.  Resources for the Interdisciplinary, Integrative Research program will be used to continue high priority projects to optimize the Interdisciplinary and Integrative Research program.  These include grants awarded under the DISCOVER program, which fosters collaborations across teams of scientists with complementary skills and areas of expertise.  These projects bring together basic, clinical, and population-based scientists to conduct integrative research programs on (1) understanding the cause and development of human diseases influenced by environmental factors, (2) using exposure to understand the interplay between genetic and environmental factors, and (3) applying available state-of-the-art technologies and methods to improve human health.

Support is also provided for the Centers for Children's Environmental Health and Disease Prevention Research and the Coordinating Centers for Parkinson's Disease Environmental Research.  In addition, NIEHS will continue designing and implementing several new models for research that integrate clinical, epidemiological, and toxicological research with basic mechanistic studies to address disease cause, development, susceptibility, and progression.

Community-linked and Global Environmental Health Research:  Differences in the environment contribute substantially to the excess burden of disease in minority and disadvantaged communities, both in the U.S. and around the world.  Examples of health indicators for which these disparities exist include shorter life expectancies, higher cancer rates, more birth defects, greater infant mortality, and higher incidences of asthma, diabetes, and cardiovascular disease.  The ways in which poverty and other factors create these health disparities are still poorly understood. However, there is increasing evidence that poor and minority groups are burdened with a disproportionate share of residential and occupational exposure to hazardous substances such as metals, pesticides, wood dusts, and air pollutants. In order to better define how poverty and environmental factors create health disparities, NIEHS held a Global Environmental Health workshop in January 2007 to determine those research opportunities where high-exposure conditions could yield insight into diseases common to the U.S., as well as abroad.

Budget Policy: The FY 2008 budget estimate for the Community-linked and Global Environmental Health (GEH) Research program is $39.594 million, which represents a funding level of -$.974 million and -2.4% from the FY 2007 estimate. Resources will be used to continue high priority projects to optimize the Community-linked and GEH program.  These include cultivating partnerships in Southeast Asia to better leverage resources in pursuit of new and emerging opportunities in global environmental research.  The NIEHS will also fund research on dietary aflatoxin (from mold in food), hepatitis B, and liver cancer.  Current research is focused on examining genetic alterations combined with aflatoxin-DNA adducts to predict liver cancer outcome and disease risk in populations in rural China and West Africa.

Exposure Biology/Exposure Measurement:  The methodologies for detection and measurement of the actual exposure sustained by a human or other organism are often weak and imprecise. This is in striking contrast to the robust tools we employ in the fields of genetics and genomics. In order to advance the field of environmental health sciences, personalized measures of environmental exposure must be developed that are equivalent to the ability to measure genetic variability between individuals. The increasing sophistication of our understanding of the biological pathways involved in host response to a given exposure points the way toward the use of that knowledge in the development of improved methods for detecting and measuring environmental exposures.

Budget Policy:  The FY 2008 budget estimate for the Exposure Biology/Exposure Measurement program is $22.565 million, which represents a funding level of +$67 thousand and .3% above the FY 2007 estimate. Resources will be used to continue high priority projects to optimize the Exposure Biology/Exposure Measurement program.  These include development of biomarkers that would 1) be accurate for the relevant timeframes (such as previous or historical exposures); 2) be mechanistically linked to diseases of interest; and 3) serve to link environmental exposures with biological effects.  Research areas with a critical need for specific biomarkers include common biological responses (inflammation, oxidative stress, apoptosis, and DNA damage), markers of gene and protein expression, and markers of organ dysfunction.

Portrait of a Program:  Exposure Biology Project

FY 2007 Level $6,684,000
FY 2008 Level   6,584,000
Change                -100,000

The Genes, Environment and Health Initiative (GEI),a new trans-NIH four-year program, aims to accelerate the understanding of genetic and environmental contributions to health and disease.  There are two components of the initiative – the Genetics Program, led by the National Human Genome Research Institute (NHGRI), which focuses on identifying major genetic susceptibility factors for diseases of substantial public health impact, and the Exposure Biology Program (EBP), led by NIEHS, which focuses on the development of innovative techniques to measure environmental exposures, diet, physical activity, psychosocial stress, and addictive substances that contribute to the development of disease.  New exposure assessment technologies and biomarkers/biosensors developed through the EBP will be applied, to the extent feasible, to the genome-wide association studies supported through the GEI.  The attempt will be to generate both exposure data and relevant biological response data at the level of the individual over multiple time points.  In addition to taking advantage of new molecular biology techniques that allow for the global analysis of gene expression and gene products, this program will encourage research that can capitalize on new capabilities in molecular imaging, nanotechnology, and remote sensing and data capture.  Optimally, personal monitors will be developed that can be used on individuals in large-scale studies and can provide information on multiple environmental exposures and stressors in a format that can be wirelessly transmitted for remote data capture.  Results from experiments such as these would provide information of very early events in environmentally caused diseases and would suggest successful early intervention strategies to prevent disease progression.  The Environmental Airway Disease Project was launched in FY 2006 as the initial research project under this program.  Additionally, five Requests for Applications (RFAs) were released in FY 2007 to recruit the extramural community into this effort.  By FY 2008 these efforts should be making progress in applying new technologies to assess an individual's real-world exposure and the internal or biological dose of this exposure, as well as incorporating information on factors that modify response to environmental agents.  The cost for the RFAs remains flat from 2007 to 2008.  The FY 2007 amount includes the cost of a workshop.

Pathways for Future Environmental Health Scientists:  The NIEHS must develop innovative ways to attract some of the brightest young students and scientists into the environmental health sciences in order to have the right cadre for conducting the interdisciplinary research demanded by its strategic vision.  The NIEHS implemented the Outstanding New Environmental Scientist (ONES) Program, an exceptionally competitive program which is designed to identify and attract the most promising new investigators to environmental health sciences research.  Funds to encourage career development and start-up activities for these young investigators promote a long-term commitment to the field.

Budget Policy:  The FY 2008 budget estimate for the Pathways for the Future Environmental Health Scientists program is $27.971 million, which represents a funding level of +$.669 million and +2% over the FY 2007 estimate. Resources will be used to continue high priority projects to strengthen the Pathways for the Future Environmental Health Scientists program.  These include 1) the ONES program, an R01 program for new independent investigators; 2) re-engineering the NIEHS training grant program to increase participation of physician-scientists in environmental sciences research; 3) promoting the NIEHS MD/PhD program; 4) establishing a new Institutional Career Development Program (a program of K12 awards to support the early career development of patient-oriented researchers in the environmental health sciences); 5) continuing a joint training program in environmental genetics and genomics, co-sponsored with NHGRI; and 6) supporting the NIH Pathway to Independence program.

Intramural Research:  Scientists in the NIEHS Division of Intramural Research (DIR) investigate the role of environmental agents in human disease and dysfunction and define the important biological and chemical processes that these agents act upon. Intramural research studies are often long-term and high-risk in nature and involve unique components, such as the NIEHS contribution to the NTP, epidemiological studies of environmentally associated diseases, and intervention and prevention studies in humans to reduce the effects of exposures to hazardous environments.  DIR scientists interact with other laboratories regularly and are often engaged in interdisciplinary research. This encourages efficient testing of novel ideas, innovative hypotheses, and new paradigms. DIR scientists are also actively involved in translational research; new advances in cell and molecular biology are being extended not only into molecular medicine (from bench to bedside), but also into disease prevention (from bench to longer, healthier lives).

Budget Policy:  The FY 2008 budget estimate for the Intramural Research program is $165.076 million, which represents a funding level of -$1.128 million and -.7% below the FY 2007 estimate. Reductions to the Intramural Research program will result from routine staff attrition and retirements.  Available resources will be directed to high priority areas in the Intramural Research program, such as clinical studies and interdisciplinary research programs designed to understand human disease and improve human health under the Director's Challenge program.  The goal of this program is to create new research teams that integrate patient-oriented or public health research with basic biological and mechanistic studies to understand how environmental exposures modulate or regulate physiological processes that may lead to human disease.

Portrait of a Program:  Intramural Clinical Research Unit

FY 2007 Level $2,580,000
FY 2008 Level   3,550,000
Change    +970,000

The NIEHS campus is located in Research Triangle Park, North Carolina and does not have on-site clinical capacity, a fact that limits the ability of intramural investigators to translate their laboratory findings into more real-world applicability.  To correct this deficit, DIR has initiated construction of an on-site Clinical Research Unit (CRU) where physician-scientists can see patients.  By housing this unit on campus, NIEHS can improve opportunities to "put to practice" basic environmental health research discoveries of the NIEHS intramural program.  NIEHS plans to open the CRU, an 8,000-square foot structure, by the summer of 2007, with patients being seen by FY 2008.  The initial focus will be on important environmental components of pulmonary disorders, such as asthma.  In addition, we have instituted a new Office of Translational Research to accelerate global application of basic research discoveries to patient treatment and disease prevention.

Research Management and Support (RMS): NIEHS RMS provides administrative, budgetary, logistical, and scientific support in the review, award, and monitoring of research grants and training awards.  NIEHS plans to oversee over 600 research project grants and centers in FY 2008.  RMS functions encompass strategic planning, coordination, and evaluation of NIEHS programs, regulatory compliance, international coordination, and liaison with other federal agencies, Congress, and the public.  A major project in FY 2006 was the creation and implementation of the new NIEHS Strategic Plan (available online at http://www.niehs.nih.gov/about/od/strategicplan/ ), which took form through discussions with more than 400 scientific and public leaders from academia, government, medical professions, community advocacy groups, and the general public.

Budget Policy:  The FY 2008 budget estimate for RMS is $17.147 million, which represents a funding level of +$170 thousand and +1% above the FY 2007 estimate. Resources will be used to continue funding the important RMS activities mentioned above which support the infrastructure that allows NIEHS to pursue and achieve its mission.

 Back to top