Authorizing Legislation Section 301 of the Public Health Service Act, as amended.
FY 2005 Actual
FY 2006 Appropriation
FY 2007 Estimate
Increase or Decrease
FTEs
BA
FTEs
BA
FTEs
BA
FTEs
BA
651
$644,505,000
652
$641,132,000
655
$637,323,000
3
-$3,809,000
This document provides justification for the Fiscal Year 2007 activities of the National Institute of Environmental Health Sciences, including HIV/AIDS activities. A more detailed description of NIH-wide Fiscal Year 2007 HIV/AIDS activities can be found in the NIH section entitled "Office of AIDS Research (OAR)." Detailed information on the NIH Roadmap for Medical Research may be found in the Overview section.
Environmental exposures may adversely affect those who are vulnerable temporally (age, developmental stage), spatially (geographic location), or by unique circumstance (comorbid disease, nutritional status, socioeconomic status, genetics). Understanding the complex relationship between endogenous and exogenous risks within populations and affected individuals, how environmental exposures affect human biology, and how this knowledge can be used to reduce morbidity and extend longevity is precisely the opportunity and challenge that faces the National Institute of Environmental Health Sciences (NIEHS). The NIEHS mission is to improve human health by increasing this understanding through support of research and professional development in the environmental sciences (toxicology, relevant basic science), environmental medicine, and environmental public health. In addition to understanding how environmental exposures affect human biology, the NIEHS aims to understand how this knowledge can be used to reduce morbidity and extend longevity.
Because environmental exposures contribute substantially to the etiology of many common and complex human diseases, the NIEHS is in a unique position to focus on the interface between environmental exposures, vulnerable populations, human biology and genetics, and the common diseases that limit our longevity. In the postgenomic era of biomedical research, the NIEHS can take a leadership role in improving human health by using environmental exposures to understand how genes work in biological systems, how genetic variants contribute to the development of disease, and why individuals with the same disease have very different clinical outcomes. Moreover, because of its focus and concentrated expertise, the NIEHS is uniquely poised to:
develop sensitive preclinical markers of exposure and biological response,
develop strategies to prevent disease in exposed and biologically responsive individuals and populations,
establish population-based cohorts to understand the impact of environmental exposures on human health,
understand how environmental exposures affect the course and prognosis of a medical condition, and
stimulate dialogue to advance our understanding of environmental health policy and ethical issues of environmental concern.
To achieve this vision, NIEHS has developed individual and programmatic efforts to understand the role of environmental exposures on human health and disease. These goals will be achieved through the following broad strategies:
development of interdisciplinary research opportunities that will focus on common, complex diseases with a substantial environmental component;
efforts to define the epidemiological and clinical significance of environmental exposures in high-risk populations, including those in the international community;
efforts to understand how genes and genetic variants interact with environmental stimuli to either preserve health or cause disease;
programmatic integration of basic findings in the environmental health sciences with populations of diseased patients, communities at the extremes of exposure and vulnerability, other academic medical centers, and industry;
study of environmental toxicants to understand basic mechanisms in human biology;
use of eukaryotic model systems (yeast, worms, zebrafish, fruitflies, rodents) to accelerate understanding of how environmental exposures affect human health;
support of the development of high-throughput in vitro and in vivo bioassays to establish reliable toxicity screens for potential toxicants;
efforts to strengthen and expand the next generation of environmental health scientists by creating research incentives to encourage basic scientists, epidemiologists, and physician-scientists to develop research careers in the environmental health sciences;
fostering of an integrated scientific approach that supports partnerships between the NIEHS and other NIH institutes, national and international research agencies, academia, industry, and community organizations to improve human health; and
support of programs for environmental scientists to work with ethicists and policy makers to fully consider the regulatory implications of our scientific advances in environmental health.
The NIEHS is a complex institute with a distinguished history, a clear purpose, and a dedicated constituency. To develop a plan for fulfilling its mission of improving human health, the Institute recently engaged the scientific and public community in a process of strategic planning that will culminate in a formal Strategic Plan published in February, 2006. A number of initiatives have been developed in response to specific strategic needs, including: 1) interdisciplinary research centers that will more efficiently use environmental sciences to understand complex human diseases; 2) an Exposure Biology Initiative to develop biomarkers of exposure and biologic effect that are critically needed to move the field forward; 3) programs designed to develop physician-scientists and support young investigators; and 4) a Global Health Initiative that will better coordinate our international research efforts that examine unique exposures that occur throughout the world and substantially impair human health.
Environmental health sciences is like no other field of biomedical research. It is not limited by a biological system, a disease process, or an organ system. In fact, this scientific discipline represents the critical link between exposure and disease for many other fields of biomedical research. Through the efforts of NIEHS, the field of environmental health science will be shaped so as to fulfill its critical role in understanding human disease, reducing morbidity, and extending longevity. The Institute's success will be measured in the disease and suffering that is prevented.
With annual costs of $12.7 billion a, asthma is a major public health problem in the U.S. It is the most common chronic disease of childhood and a leading cause of disability in children. Since 1980, asthma prevalence has increased dramatically in children. In addition to being a significant public health problem, asthma is an important health disparity problem because it is more common in poor, inner-city households. Over the past years, NIEHS has contributed to the following major findings:
Indoor Exposures
Discovered that cockroach allergens worsen asthma symptoms more than other common allergens. Interestingly, cat exposure, once thought to increase a child's asthma risk, appears to protect a child from developing asthma if the exposure to cat allergens occurred during infancy. If, however, a child's mother had asthma, the opposite effect was observed - exposure to a cat actually increased risk of asthma in these children. b
Identified simple interventions that, targeted to a child's individual sensitivities, noticeably reduced the severity and frequency of asthma attacks. Children were assessed for their sensitivity to six major irritants - dust mites, cockroaches, pet dander, rodents, passive smoking, and mold. Environmental interventions were tailored to reduce exposures for the sources for which the individual child was sensitive. Interventions included allergen-impermeable mattress and pillow covers, air purifiers with high efficiency particulate air (HEPA) filters, vacuum cleaners with HEPA filters, and professional pest control. Children who received the intervention had 19% fewer unscheduled clinic visits and a 13% reduction in use of asthma medication. b
In a nationwide assessment of allergen levels in U.S. homes c, discovered that:
100% of U.S. homes had detectable levels of cat and dog allergens, even though only 24% of homes had a resident cat and only 32% had a dog. Most homes had allergen levels that exceeded thresholds for allergic sensitization and one-third exceeded thresholds for asthma symptoms.
82% of U.S. homes had mouse allergens, with the highest level appearing in kitchens.
63% of homes had cockroach allergens.
Fungal allergens were found in 95% - 99% of homes.
Childcare facilities were also examined; seven allergens were assayed in 89 NC childcare facilities with each allergen being found in the majority of these facilities.
Outdoor Exposures
Beginning in 1974, NIEHS funded several long-term studies that established a relationship between polluted air and increases in the number of hospital admissions, asthma attacks, and deaths from all causes. The elderly, asthmatics, and children were identified as particularly susceptible subpopulations. Newer studies have validated these earlier findings.
Found that even levels of ozone below the federal standards posed risks to asthmatic children on maintenance medication. A 50-ppb (parts per billion) increase in 1-hour ozone was associated with increased likelihood of wheeze (by 35%) and chest tightness (by 47%) [Gent et al., JAMA 290:1859-1867, 2003].
Identified ozone as a cause of asthma, not just an irritant to existing disease states. In a study of symptom-free children engaged in outdoor sports, those who were athletically active in high-ozone environments were three times more likely to develop asthma than children who did not play sports. Moreover, other NIEHS-supported investigators have found that short-term exposure to ozone is independently associated with excess mortality rate.
Discovered that dietary supplements can reduce ozone-related asthma attacks, particularly in children with a particular genetic sensitivity. In this study asthmatic children living in high-ozone exposures of Mexico City were given vitamins C and E. These antioxidants were able to counteract the decreased lung function arising from ozone exposure, but the results were most significant in children who lacked an enzyme, glutathione S-transferase (GSTM1), that plays a major role in protecting cells against the oxidative damage caused by ozone. This genetic deficiency makes them more susceptible to the deleterious effects of ozone, so the antioxidant supplementation is of particular benefit.
Airway Sensitivities and Endotoxin Exposures
Another important airway toxin is endotoxin, derived from fragments of the outer coat of common bacteria. Endotoxin is widespread and can be found in household and grain dusts. Curiously, although high-dose exposure to endotoxin causes airway symptoms (wheeze and shortness of breath), early life exposure to endotoxin appears to protect against development of allergies. What, then, is its relationship to asthma? Recent resultsc have now definitively linked household endotoxin exposures with asthma symptoms, use of asthma medications, and wheezing. The protective effect of endotoxin observed for allergy sensitization was not found for asthma.
The molecular basis of endotoxin-induced airway sensitivity was elegantly assessed in studies using healthy human volunteers. People were exposed to increasing levels of endotoxin that represented typical occupational exposures and a marked difference in airway constriction was experienced by different people. It was found that the difference in response to endotoxin was related to mutations in the gene that encodes a specific receptor for endotoxin - the toll-like receptor-4 (TLR4) gene. Those with a normal TLR4 gene were sensitive to endotoxin-induced airway reactivity; those with a common polymorphism in this gene were much less affected by endotoxin. Thus the TLR4 gene was identified as having an important role in endotoxin-induced asthma. Taking the study of this gene further, researchers constructed mice lacking the TLR4 gene and again found that this gene was critical in the development of endotoxin-induced asthma.
References
Weiss KB and Sullivan SD: The health economics of asthma and rhinitis. I. Assessing the economic impact. J Allergy Clin Immunol 107:3-8, 2001.
This study was part of the Inner City Asthma Study, done in collaboration with the National Institute for Allergy and Infectious Diseases (NIAID).
This study was done in collaboration with the Department of Housing and Urban Development (HUD).
Bone Marrow Suppression in Workers Exposed to Very Low Concentrations of Benzene
Background: Benzene is known to have toxic effects on the blood and bone marrow, but its impact at levels below the U.S. occupational standard of 1 part per million (ppm) remains uncertain. Exposure to benzene occurs worldwide to workers in the oil, shipping, automobile repair, shoe manufacturing, and other industries.
Advance: Researchers found that white blood cell counts and platelet counts were significantly lower in benzene-exposed workers, even for exposures below 1 ppm. Cells that eventually become mature white blood cells (progenitor cells) also declined significantly with increasing benzene exposure. Because the enzymes involved in benzene metabolism are known, these investigators measured the influence of genetic variants of key detoxifying enzymes on the concentration of progenitor and mature white blood cells. Two genetic variants in key metabolizing enzymes, myeloperoxidase and NAD(P)H:quinine oxidoreductase, were found to influence susceptibility to benzene.
Implications: Toxicity of benzene in blood cells and bone marrow of exposed workers was evident even below the U.S. occupational standard of 1 ppm. Individuals with particular genetic variants in two key metabolizing enzymes may be especially susceptible to benzene toxicity.
Ozone Affects Mortality in U.S. Cities
Background: Ozone pollution is widespread in urban areas in the U.S. and in many other countries. Ozone exposure has been associated with various adverse health effects, including increased rates of hospital admissions and exacerbation of respiratory illnesses. Although numerous studies have estimated associations between day-to-day variation in ozone levels and measures of mortality, results have been inconclusive.
Advance: Using analytical methods and databases developed for the National Morbidity, Mortality, and Air Pollution Study, these investigators found that the mortality rate was increased in relation to short-term exposure to ozone. Specific models were used to adjust for confounders such as particulate matter, weather, and seasonality. After accounting for these factors, a 10-part per billion increase in the previous week's ozone was associated with a 0.52% increase in daily mortality and a 0.64% increase in cardiovascular and respiratory mortality (Bell et al., JAMA 292:2372-2378, 2004).
Implications: In addition to the other health effects that have been associated with ozone exposure, this report provides further evidence that ozone exposure in urban areas increases mortality.
Red Tide Toxin Research Yields Potential Therapies for Cystic Fibrosis
Background: "Red tide" is an algal bloom that results in toxin formation that can kill fish, contaminate shellfish, and lead to severe lung irritation and breathing problems in people who are exposed to this toxin when it is dispersed in the air. Coughing, shortness of breath, and other lung problems occur in normal people exposed to red tide toxins during bloom episodes, but seem particularly enhanced in people with preexisting airway diseases. For these reasons, researchers were interested in finding ways to neutralize the toxin. Unexpectedly, these same therapies might benefit people suffering from cystic fibrosis and other lung disorders characterized by excessive mucus secretion.
Advance: Researchers developed two anti-toxins to treat breathing problems caused by red tide and tested them in sheep. They found that not only did these compounds block the effect of red tide toxin, but that they sped up the clearance of mucus from the lungs. In fact, this ability of the anti-toxins mimicked the action of drugs used to treat cystic fibrosis, only at much lower doses than required by conventional therapies.
Cystic fibrosis is a genetic disease that causes the body to produce abnormally thick mucus in the lung and leads to life-threatening lung infections. On average, people with cystic fibrosis live only 30 years (US Department of Health and Human Services, NIH, NHLBI, NHLBI Listens and Responds. pp.13-14, 2004). These individuals are very dependent on drugs that help thin and clear the mucus from their lungs. The anti-toxins developed by these researchers appear to operate the same way, but at very safe doses (1 million times lower than current medications).
Implication: The anti-toxin compounds developed against red tide toxin offer new models for development of drug therapies to help sensitive individuals affected during episodes of red tide algal blooms. Interestingly, these same drugs may be useful for patients with cystic fibrosis. The potential is that a long-term therapy with these drugs may have fewer side effects than treatments currently available treatment for this disease.
Naturally Occurring Bronchodilator Protects
Against Asthma in Mice
Background: The incidence of asthma has been steadily growing over the past 30 years. Approximately 15 million people in the United States have asthma, leading to more than 500,000 hospitalizations and over 5,000 deaths annually (Weiss and Sullivan, J Allergy Clin Immunol 107:3-8, 2001. A variety of theories have been postulated for this rise including increased exposure to indoor allergens, air pollutants, and other inflammatory agents. Scientists and doctors have known about the effects of airway constriction on asthma exacerbation for some time, however, very little effort has been given to naturally occurring airway relaxants and the balance between constricting and relaxing agents.
Advance: Researchers at Duke University, supported by NIEHS and the Howard Hughes Medical Institute, have discovered a naturally occurring bronchodilator that relaxes the airway and helps keep it open. Asthmatic animals and humans are deficient in the compound, which is known as S-nitrosoglutathione (GSNO). In laboratory animal studies, mice exposed to allergens exhibited airway constriction and increased levels of GSNO reductase, an enzyme that breaks down GSNO and other S-nitrosothiols (SNOs) However, mice missing the gene for GSNO reductase, when exposed to allergens, showed increases in lung SNOs and didn't develop airway constriciton.
Implication: This study shows that GSNO reductase is very important in the regulation of the size of the airway under normal conditions and in response to allergen challenge. A deficiency of SNOs may make fundamental contributions to the development of asthma and GSNO repletion may prove to be a novel treatment for asthma.
Background: Despite significant reduction of environmental lead in the U.S., exposure has not been completely eliminated and most adults continue to have substantial body burdens of lead. Much of the lead taken up by the body is incorporated into bone; however, lead constantly exchanges from the bone to other tissues. Recent studies have revealed that long-term lead exposure is associated with a number of chronic disorders, including hypertension and cognitive decline. There have also been reports that lead may accumulate in the lens of the eye. These observations led to the question: "Does lead exposure play a role in increasing risk of cataracts?"
Advance: Researchers showed that lifetime lead exposure may cause an increase in the risk of developing cataracts, the leading cause of blindness. This study included over 600 men and found that participants with high levels of lead in the long bone of the leg (tibia) were more than 2.5 times as likely to develop cataracts as men with low levels of lead in the tibia. Blood lead levels, which are more indicative of short-term lead exposure, were not significantly associated with increased risk of cataract development.
Implication: This study suggests that accumulated lead exposure, common in the United States and other parts of the industrialized world, may be an important, but as yet unrecognized risk factor for cataract development. Reducing lead exposure may not only preserve the vision of many Americans as they age, it may also reduce the financial burden for cataract surgery and its attendant costs which for Medicare alone are approximately $4 billion/year (Steinberg, et al. Arch Opthalmol 111:1041-1049, 1993).
Sperm Motility Study Identifies Unique Target for Male Contraception
Background: The ability of sperm to move quickly is a primary determinant for successful fertilization of eggs. Several systems exist that could generate the energy needed for sperm motility. Researchers recently identified the energy system responsible for sperm motility and made a surprising discovery that could lead to a male contraceptive drug.
Advance: Two systems exist for energy production - oxidative phosphorylation and glycolysis. Glycolysis was of interest to these researchers because, although the enzymes that control this system are found throughout the body, a very specific version of an enzyme critical for glycolosis (glyceraldehydes 3-phosphate dehydrogenase-S or GAPDS) appears only in sperm.
Mice lacking this particular enzyme GAPDS were constructed and it was found that deficiency of this enzyme resulted in severely impaired sperm motility and infertility.
Significance: This study identifies an enzyme necessary for generating energy for sperm motility, an activity critical to successful fertilization of eggs. Although this study was done in mice, it is expected that the results may be applicable to humans which also have a sperm-specific form of this energy-producing enzyme that is found no where else in the body. Thus, it may be possible to develop a contraception scheme that would target this enzyme only, and leave all other similar energy-producing enzymes in the body unaffected.
Mouse Life-Span Increases 20% with Reduction of Oxidative Stress
Background: The free radical theory of aging refers to the role reactive oxygen species play in aging processes. Reactive oxygen molecules damage biological molecules and cause decline in the function of cells, tissues, and organ systems that eventually lead to death. The cumulative effect of oxidative damage is thought to play an important role in the physiological declines associated with aging as well as in a diversity of diseases associated with aging including cataracts, neurological diseases, atherosclerosis, and cancer. To test whether life-span in higher organisms can be extended by traducing oxidation, these investigators developed three genetically engineered (transgenic) strains of mice that overexpress the antioxidant enzyme, catalase, specifically targeted to key organelles in the cell such as mitochondria.
Advance: In the transgenic animals that have catalase (antioxidant enzyme) targeted to their mitochondria, life-span was extended by about 5 months or about 20%, and antioxidant activities were increased in the heart, skeletal muscle, and brain tissue. In fact, cardiac levels of antioxidant activity were 50 times higher in the transgenic animals than wild-type mice. The life-span extension in these animals was accomplished without deleterious side effects such as those seen in other studies using caloric restriction and other models of delayed aging. Cardiac disease and cataract development were delayed in these animals, and oxidative damage and the production of reactive oxygen molecules were reduced.
Implication: These results support the theory that free radical and reactive oxygen molecules generated in the mitochondria are very important in aging processes. It is too early to say that human lives could be extended by the administration of antioxidant compounds; however, this study has produced exciting results with implications for longevity, possible new treatments for aging related illnesses, and healthier aging.
Standardizing Gene Expression Analysis Between Laboratories:
A Critical Step for Environmental Genomics
Background: The first papers describing the technique of DNA microarrays appeared in the scientific literature in the mid-1990s. Since that time, over 15,000 papers have been published in the peer-reviewed literature. Despite the growing popularity of the technique, the reproducibility of results between laboratories and across microarray platforms has not been adequately studied. Differences in techniques, platforms, instrumentation, and analytical software raise questions about the accuracy and reproducibility of results and possibly delay the full benefit of the technique.
Advance: The Toxicogenomics Research Consortium, a group of seven research centers, began a study in 2001 to determine the sources of variability in gene expression profiling done on microarrays by analyzing results collected across multiple labs using multiple technology platforms and techniques. The study was conducted in seven laboratories, in which two standardized samples were analyzed using twelve microarray platforms. Either laboratory or commercial microarrays were used in each laboratory. Data reproducibility was generally good within a single platform used in any one laboratory, but was poor between labs. When standardized protocols were used across all labs, reproducibility between the labs improved. The study found that commercially manufactured microarrays produced the most reproducible results.
Implication: The results from these studies indicate that microarray experiments can be comparable across multiple laboratories, especially when a common platform and set of procedures are used. These advances in microarray technology demonstrate to the scientific community how to obtain more consistent and reliable results. Standardizing microarray techniques can accelerate the pace of scientific discovery about biological responses to environmental stressors. Ultimately this could improve our ability to detect very early indicators of a biological response to an environmental agent that could eventually be used to prevent the development of a specific disease.
NIEHS participates in, and benefits from, a number of Roadmap initiatives. For example, since August 2005, the NIEHS, through the National Toxicology Program (NTP), has formally participated in the NIH Roadmap Molecular Libraries Initiative (MLI). This collaborative effort is aimed at assisting the MLI project leaders with development of their screening program by adding a toxicity testing capability to the MLI effort. In addition, this collaboration is allowing rapid implementation of the NTP's High Throughput Screening Assays program by providing the NTP access to established testing laboratories through inter-institute cooperation. This collaboration is useful for both the MLI and the NTP. Specifically, the NTP, through its association with the MLI, has the opportunity to generate information that links data on the biological activity of environment substances generated from high throughput screening assays with toxicity endpoints identified in NTP's toxicology testing program. The NTP can then use this information to identify mechanisms of action for further investigation, develop predictive models for biological response, and help prioritize substances for further toxicological evaluation. The NTP hopes to use this technology in the future as a means for screening large numbers of environmental substances as part of its testing program. Through its interaction with the NTP, the MLI components -National Chemical Genome Center (NCGC) and other Molecular Libraries Screening Center Network (MLSCN) laboratories- will obtain information on biological activity for a wide range of compounds for which their potential toxicity in laboratory animals and standard in vitro assays is known and will gain input on additional assays for adding to their screening battery. The NTP has currently provided approximately 1,400 chemicals to the NCGC and is working to identify commercially available high throughput screening assays that the NCGC will adapt to their current testing battery and run routinely. Eventually, the chemicals will be distributed to each of the MLSCN laboratories for screening. Data collected on chemical activity from the high throughput assays will be stored in a mutually accessible database for future analysis. In addition, the NTP held a public workshop on high throughput screening assays in December 2005 in Washington with the goal of gaining input on the selection of targets for these assays, assay design and chemical selection, and data storage, analysis, and interpretation.
NIH Blueprint
NIEHS research investment in environmental neurosciences has increased dramatically in the past decade, mirroring the growing understanding of the far-reaching effects of environmental influences on neurological development and disease. Many, if not most, of the NIEHS's investments have occurred in partnership with one or more of our sister Institutes in order to leverage resources and share expertise. In recognition of the benefits of these partnerships, NIEHS joined the group of Neuroscience Blueprint Institutes in FY2005. Our Blueprint membership gives NIEHS a chance to influence the development of research tools and infrastructure that will benefit the work of our environmental neuroscientists and contribute substantially to the success of our mission in environmental health.
In 2007, the Blueprint will focus on neurodegeneration-the progressive death of nerve cells. Neurodegeneration occurs in classical neurodegenerative disorders such as Alzheimer's and Parkinson's disease, in macular degeneration and other disorders of sight and hearing, in drug and alcohol abuse, and perhaps in mental disorders and chronic pain. As our population ages, the already enormous impact of neurodegeneration on society will become even larger without better prevention and treatment. Developing strategies to prevent degeneration of neurons and to promote a healthy nervous system is thus critical to the missions of all Blueprint members. Following the successful model of the NIH Roadmap, the Blueprint will convene scientific workshops with leaders in research on neurodegeneration to identify barriers to progress and exceptional opportunities. The Blueprint will address these barriers and opportunities through initiatives targeted to provide resources, create tools, and answer key questions in neurodegeneration.
Exposure Biology Initiative: In order to be able to use environmental health sciences to understand human disease and improve human health, we need better tools to quantify both an individual's exposure and the characteristics that account for individualized responses to common exposures. This initiative will enhance exposure assessment tools so that researchers can, for certain exposures, have the same degree of individual-level precision in exposure measurement that is being achieved in genetics through the sequencing of the human genome. Technologies that could provide new exposure tools are medical imaging, nanotechnology, and sensor technology. They could potentially lead to development of research tools that quantitatively assess the temporal and biological response to multiple environmental exposures. Ideally, these new technologies will generate insight on exposures across the exposure-disease continuum, from the point of human contact to the internal dose to the early biological response. To the extent feasible, new technological developments should complement efforts that are ongoing in the public and private sectors, such as biodefense and national health surveillance. Our ability to develop and validate exposure-response indicators, and to correlate them with genetic variation, will be critical to our success in reducing the burden of human disease.
Environmental Genomics Initiative: In the postgenomic era of biomedical research, the NIEHS is moving to implement an Environmental Genomics Initiative using its leadership in investigating environmental toxicants to understand how genes work in biological systems, how genetic variants contribute to the development of disease, and why individuals with the same disease have very different clinical outcomes. This Initiative will feature new or redirected activities in multiple levels.
Epigenetics. There are mechanisms outside of normal inheritable mechanisms that are particularly relevant to environmental health sciences. A number of environmental and nutritional factors can substantially alter gene expression and generate developmental abnormalities or functional changes via alterations in genetic programming or control of gene expression. These changes in gene expression can cause or affect the risk of developing cancer, immunologic diseases and other complex diseases. NIEHS is proposing to develop a comprehensive program in epigenetics to specifically identify how gene expression is altered under different forms of environmental stress and how this alters the risk of developing disease.
Comparative Biology of Environmental Disease. The application of "omics" technologies and comparative biology approaches to the study of environmentally-responsive genes will allow the role of these genes in environmentally-relevant disease pathways to be further elucidated. These different sets of technologies and applications can be used to understand why people exposed to the same environmental stressors respond differently. The development of pathway analysis tools informed by comparative genomics will be instrumental to understanding toxicological mechanisms.
Training in Environmental Genomics. The existing T32 training grants program at NIEHS will be broadened to include other training opportunities in genetics and genomics. These will complement the existing areas of environmental health sciences which will continue to be covered.
Cohort and Case-Control Studies in Environmental Genomics. The initiatives described above will inform and complement ongoing epidemiology studies funded by NIEHS, both case-control and population-based, such as the Sister Study, which examines environmental factors in the risk of breast cancer, and the Carolina Lupus Study.
Human Health and Disease Initiative: Traditionally, NIEHS has focused on basic science and public health research. However, environmental sciences can be applied to research in human health and disease. In fact, we believe that environmental sciences are critical to understanding complex human diseases, like cancer, diabetes, heart disease, and lung disease. NIEHS is taking several approaches to integrate environmental health sciences with clinical and translational research that focuses on human health and disease.
DISCOVER. NIEHS is developing a new program called DISCOVER (Disease Investigation for Specialized Clinically Oriented Ventures in Environmental Research). It will bring together basic, clinical, and population-based scientists to conduct integrative research programs on: (1) understanding the etiology and pathogenesis 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.
Environmental Health Sciences Core Centers. New guidelines have been developed for the NIEHS Environmental Health Sciences Centers (EHS) programs. The next generation of EHS Core Centers is expected to bring their efforts to bear to a greater degree on translating environmental health research and related basic science results to public health and clinical arenas.
ONES. The Outstanding New Environmental Scientist Award, or ONES, is a first independent research grant designed to attract the most talented younger researchers into the field of environmental health sciences. NIEHS aims to identify a cadre of outstanding scientists in the early, formative stages of their careers who are interested in developing a career in environmental health sciences research and to provide a strong start for these individuals. These grants will assist young scientists in launching innovative research programs focusing on problems of environmental exposures and human biology, human pathophysiology, and human disease.
Physician Scientist Training. NIEHS is planning to expand its pool of qualified physician scientists who are engaged in environmental health sciences research. Several approaches will be taken to meet this objective, including: expansion of NIEHS' MD/PhD training awards; increasing our awards for clinical training (K awards); and reaching out to schools of medicine to let them know about the scientific opportunities for clinical research in environmental health and disease.
Global Environmental Health Initiative: NIEHS-supported scientists have long taken advantage of the fact that environmental exposures vary around the world and can offer fruitful avenues for defining the impact of the environment on human health. Other countries often have much higher levels of exposure to certain pollutants that can lead to insight into potential health effects from the lower levels of these pollutants found in the U.S. The combinations of environmental exposures around the globe can also offer unique "laboratories" for teasing apart different environmental contributors. Moreover, strategic interventions within these populations can have a profound effect on global health. One example is the discovery that liver cancer can arise from a dual combination of Hepatitis B infection and aflatoxin exposures arising from mold in food. Both these exposures are found in the U.S., but the levels of exposure are much greater in Africa and Asia. It was NIEHS-supported studies in these countries that led to significant milestones in aflatoxin research, culminating in preventive steps in the U.S. that greatly limit consumer exposure to aflatoxin. These research efforts continue as U.S. scientists investigate simple intervention techniques for reducing the risks of liver cancer arising from these environmental exposures.
As the nation's premier environmental health research institute, NIEHS has an opportunity and an obligation to address environmental health issues globally in a way analogous to how NIAID has addressed health crises of an infectious nature that extend beyond U.S. borders, such as AIDS, malaria, and bird flu. To enhance its ability to fulfill this obligation, the Institute will target global environmental health sciences as an area for greater focus. NIEHS is investigating a number of mechanisms to give greater focus and emphasis to this important area of research and is in the process of developing partnerships to better leverage resources in pursuit of new and emerging opportunities in global environmental research.
Public Health Response - Hurricane Katrina: Hurricane Katrina served to highlight the dedication and creativity of NIEHS staff in responding to an unexpected crisis. Recognizing that many of the health issues from Katrina would relate to environmental toxicants and clean-up, the NIEHS launched a new Web site(http://www.niehs.nih.gov/research/resources/hurricane/index.cfm) that used a Global Information System to assess environmental hazards caused by the storm. The Web site helps public health and safety workers identify contaminants in flood waters, provides infrastructure and industry maps, and gives demographic information on local populations. NIEHS is training workers in the Gulf Region and also helping its grantees to find new laboratory space where they can continue their research.
As the nation moves forward in repairing the damage from Katrina's flooding, it is expected that mold and microbial toxins will be significant environmental exposures. These exposures will be particularly devastating to people already at risk for airway disease. NIEHS is working with its federal partners, the Centers for Disease Control and Prevention (CDC) and the Environmental Protection Agency (EPA), to develop a coordinated response to monitor and ameliorate these anticipated adverse environmental effects in the aftermath of Hurricane Katrina. These efforts will complement the ongoing environmental sampling and prevention efforts already identified in the Environmental Health Needs and Habitability Assessment developed by EPA and CDC.
Breast Cancer and Environment Research Centers (BCERC): NIEHS and NCI are partnering to support a network of research centers in which multidisciplinary teams of scientists, clinicians, and breast cancer advocates work collaboratively on understanding the impact of early life exposures on breast cancer risk. The focus is on the interaction of chemical, physical, biological, and social factors in the environment with genetic factors on the process of mammary gland development. This period of time is a vulnerable one during which exposures may increase susceptibility to future breast cancer. The network is working towards integrating histological, pathological, cellular, and sub-cellular changes that occur in normal mammary gland tissue across the lifespan along with comparisons to exposure-induced changes.
The BCERC also has a working group of approximately ten scientists and advocates that provides input and advice on the progress of the program. Representatives from the National Environmental Health Advisory Council and the National Cancer Advisory Board are also included. Input and oversight of the working group have been used to monitor and improve many parts of the program The BCERC program has other ways of interacting with breast cancer advocacy groups and the public, including interactions with these groups during the BCERC's annual meetings. At the most recent meeting, approximately 150 participants were updated with the latest data, plans, and potential applications of the BCERC. In addition, invited speakers provided thoughtful perspectives on other studies with respect to environmental health and breast cancer. A complete report on the meeting is being prepared for distribution to interested communities, organizations, and policy makers.
Innovation in Management and Administration
Strategic Plan: To identify the emerging areas with greatest opportunities for understanding disease processes and contributing to public health, the NIEHS embarked on a strategic planning exercise in 2005. It was inaugurated with an initial outreach to the public to elicit input on what, in their opinion, the important issues are in environmental health sciences. Request for this input was advertised in the Federal Register, in Environmental Health Perspectives, in the NIH Guide, through the NIEHS Web site, and through outreach to environmental advocacy groups. People responding via mail or the internet included scientists, regulators, administrators, environmental advocates, public school teachers, and students.
Following web input and analysis, a Strategic Planning Forum was convened October 17 - 18, 2005. Ninety scientists and environmental advocates came to develop the best ideas in response to six broad issues that emerged from the public's input. These were:
Using environmental sciences and environmental exposures to understand human biology;
Using environmental sciences and environmental exposures to understand human diseases and improve human health;
Needs, opportunities, and challenges in exposure sciences;
Technological needs and applications for infrastructure investment;
Environmental health priorities and opportunities in the global health arena;
Training needs.
Participants selected for the Forum were well-respected representatives in their fields. Break-out groups were assigned to ensure that all fields were represented and that the participants were exposed to individuals and viewpoints outside of their own area or group. This dynamic approach was done in order to avoid the narrow vision that often occurs when people remain within the comfort zone of their own discipline. Participants were also repeatedly shuffled so that each topic had three separate working groups focused on it at various times. The format of the Forum greatly enhanced the synergy across disciplines, a synergy that is evident in the recently released 2006 Strategic Plan. This plan has already led to a number of significant new initiatives at the NIEHS and further change is expected as more of the ideas are integrated into the Institute's research and training portfolios. Outgrowths of this plan will be a greater initial focus on human disease, a more rapid transmission of environmental findings into clinical applications, improved exposure assessment methodologies, greater focus on insights from global environmental research, and development of a cadre of environmental health scientists with expertise in multiple, rather than single, disciplines. Ultimately, the 2006 NIEHS Strategic Plan is the Institute's blueprint for ensuring that environmental health sciences can fulfill its tremendous potential to improve public health across a wide spectrum of chronic complex diseases.
Management Initiative in Integrative Research: The NIEHS Division of Intramural Research (DIR) is planning to institute Centers for the Study of Complex Diseases (CSCD) which will integrate research efforts across the Institute's disciplines and use environmental sciences to understand disease and improve human health. These Centers will be virtual structures that will exist as an overlay to the existing Lab and Branch organization of the DIR.
Evaluation of Ongoing Programs: Environmental health sciences is a rapidly evolving field that requires regular assessments of current projects to ensure that the best science is pursued in the most efficient way possible. Two projects - the Mouse Genomics Research Centers and the Toxicogenomics Research Consortium - were discontinued in 2005.
The Fiscal Year 2007 budget request for the NIEHS is $637,323,000, a decrease of $3,809,000 and -0.9 percent from the FY 2006 Appropriation. Included in the FY 2007 request is NIEHS' support for the trans-NIH Roadmap initiatives, estimated at 1.2% of the FY 2007 budget request. A full description of this trans-NIH program may be found in the NIH Overview.
A five year history of FTEs and Funding Levels for NIEHS are shown in the graphs below. Note that as the result of several administrative restructurings in recent years, FTE data is non-comparable.
NIH's highest priority is the funding of medical research through research project grants (RPGs). Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated research while pursuing new research opportunities. We estimate that the average cost of competing RPGs will be $331,000 in FY 2007. While no inflationary increases are provided for direct recurring costs in noncompeting RPGs, where NIEHS has committed to a programmatic increase for an award, such increases will be provided.
NIH must nurture a vibrant, creative research workforce, including sufficient numbers of new investigators with new ideas and new skills. In the FY 2007 budget request for NIEHS, $900,000 will be used to support 10 awards for the new K/R "Pathway to Independence" award.
NIEHS will also support the Genes, Environment, and Health Initiative (GEHI) to: 1) accelerate discovery of the major genetic factors associated with diseases that have a substantial public health impact; and 2) accelerate the development of innovative technologies and tools to measure dietary intake, physical activity, and environmental exposures, and to determine an individual's biological response to those influences. The FY 2007 request includes $1,084,000 to support this project.
In the FY 2007 request, stipend levels for trainees supported through the Ruth L. Kirschstein National Research Service Awards will remain at the FY 2006 levels.
The FY 2007 request includes funding for 35 research centers, 107 other research grants, including 51 career awards, and 110 RStrategic Plan: D contracts. Intramural Research decreases by 0.5 percent. Research Management and Support increases by 1.5 percent.
Innovative information technology (IT) is required to support scientific research, to increase staff productivity, and to streamline administrative processes. However, to be most effective, the IT investments must be well managed and closely aligned with the goals of the Institute. To ensure that NIEHS IT is meeting the Institute's needs efficiently and effectively, NIEHS plans to conduct an assessment of its IT. Outside experts from government and academia will be asked to review resource levels, organization, governance, service levels and most important, effectiveness in facilitating the Institute's research programs. Recommendations will address improvements to collection and management of requirements, setting priorities, choosing appropriate technologies and setting service levels. Changes as a result of this assessment are expected to target IT investment to those activities that produce the greatest return for the NIEHS research program and to produce savings by eliminating expenditures that are no longer effective.
The mechanism distribution by dollars and percent change tables are shown below and on the following page.
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