Mr. Chairman and Members of the Committee, I am pleased to appear before
you today to discuss the important work of the National Institute of Environmental
Health Sciences.
Virtually all diseases have both a genetic and an environmental component.
Thus both environmental health research and human genome research are vital for
fulfilling the public health mission of this Nation.
The opportunity to make a difference in the environmental health sciences has
never been greater. The discipline has undergone a rapid transition and, coupled with
advances made in genetic research, we are nearing a breakthrough in the "bottleneck"
currently encountered when we try to identify environmental hazards that contribute to
human illness. We are now poised to make enormous progress to prevent, diagnose,
and treat the environmental components of diseases. Although we cannot yet say which
environmental or genetic factor is the most important contributor to a specific disease,
nor which individual is most likely to develop a particular disease, that day is not far
off. When that day arrives, policy makers can more rationally determine the best, most
cost-efficient ways to protect public health without unnecessarily sacrificing economic
vitality.
Efforts to control environmentally-caused illness must be based on the
understanding of human-environment interaction at the molecular level. Many of the
common diseases such as cancer, Alzheimer's, Parkinson's, osteoporosis, and asthma
appear to arise from the complex interplay between inherited genetic alterations and the
environment. So, before we can prevent or improve the treatment of such diseases, we
need a better understanding of the individual function of genes involved in the growth
and development of humans and the ability of environmental agents to interact with,
and damage, these genes.
In considering future research needs and opportunities, we have focused on
areas of fundamental knowledge and practical issues relevant to understanding the role
of the environment in the etiology of human illness. The areas of emphasis represent
issues where major information gaps exist, where reasonable research questions can be
formulated, where technologies are available, and where understanding offers the
potential to significantly improve public health and regulatory policy.
Today, I would like to talk about some of the critical research needs and plans
for the upcoming year.
First, we need to continue our effort to develop new and better carcinogenicity
and toxicity test systems. While we have greatly improved test methods, they are still
too costly and too time consuming for use in screening the thousands of natural and
synthetic environmental chemicals requiring toxicity assessment. Opportunities now
exist to develop alternative testing methods by incorporating knowledge of molecular
and cellular mechanisms associated with the toxic or carcinogenic process.
Second, environmental health research can also capitalize on recent
developments in molecular and cell biology to develop a mechanistic understanding of
the toxic action of environmental agents. Under this scheme the actual biological
events that lead to toxicity will be determined. Insights into molecular mechanisms of
diseases will: 1) provide a more rational basis for assessing human risk based on data
obtained in animals; 2) suggest new laboratory procedures for use in epidemiologic
studies to more precisely identify the causes of human illnesses; 3) increase
understanding of the wide person-to-person variation in risk to disease; and 4) provide
the basis to develop molecular medicine strategies to prevent, detect, and treat various
diseases.
Third, knowledge of mechanisms is also a prerequisite for prevention/
intervention using molecular medicine approaches. The field of environmental
toxicology has historically limited its prevention efforts to eliminating or reducing
environmental exposures. While this remains the most pragmatic approach, behavioral
intervention is not possible in some cases because the causative agent cannot be readily
controlled. Although much progress is being made in the laboratory in defining the
environmental basis of disease and dysfunctions, this knowledge and technology is not
being effectively translated into the practice of medicine. The recent creation of the
clinical program within the NIEHS underscored the importance of translating
discoveries made in the laboratory to benefit individuals and populations in terms of
improved health status and reduced health care costs.
Fourth, research is needed to determine the genetic, behavioral, and
developmental basis for the wide variation in individual responsiveness to exposures to
environmental toxicants. There are indications that differences in responsiveness can
be related to age, gender, lifestyle, or genetic predisposition. These differences could
be important for human risk assessment.
NIEHS proposes to greatly expand its molecular genetics research on
susceptibility genes for environmentally-induced diseases through a new Environmental
Genome Project. This genome project, which makes use of technology developed by
the human genome research efforts, will acquire a population database on the sequence
diversity for the environmental disease susceptibility genes.
Genetic approaches used in the past have identified many susceptibility genes
for environmental diseases. An individual with a defect in such a gene has an elevated
risk of becoming ill after an environmental exposure. The molecular mechanisms of
susceptibility are not well understood; however, we are now able to categorize many of
the susceptibility genes into five broad classes: Genes controlling the distribution and
metabolism of toxicants; genes for the DNA repair pathways; genes for the cell cycle
control system; genes for metabolism of nucleic acid precursors; and genes for signal
transduction systems controlling expression of the genes in the other classes. The
NIEHS Environmental Genome Project will be a broad, multi-center effort to obtain
information about DNA sequence diversity for the U.S. population on all of the
environmental disease susceptibility genes now recognized, which number greater than
200. The Project will be expanded as additional susceptibility genes are discovered.
The availability of a population database on environmental disease gene
diversity will allow us to conduct more focused molecular epidemiology that relates
environmental exposures and disease to individual susceptibility genotype. Ultimately,
information from such medical genetic epidemiology will allow us to greatly enhance
public health through better prevention strategies for environmental diseases.
The Environmental Genome Project will provide information for future research
on molecular mechanisms of susceptibility gene products. The project will also foster
development of new high, through-put technology for the application of genetics in
medical epidemiology as a function of environmental exposure.
Fifth, investigation of the mechanisms and health effects of mixtures is another
area where lack of information is a serious problem. The data on exposure and
toxicology of mixtures is inadequate for assessing health risk. The current toxicologic
databases were developed using single chemicals in animal bioassays, whereas humans
are exposed at a variety of levels to large numbers of chemicals either concurrently or
sequentially via multiple pathways. Mixtures of chemicals are ubiquitous in ground
and surface water, and in air, food and soil. For example, 700 organic chemicals have
been identified in the drinking water supply of the U.S., 40 of which are possible
carcinogens; 320 toxic industrial chemicals are released into ambient air, of which 60
are possible carcinogens; and approximately 380 pesticides are applied to food sources,
66 of which have been identified as actual or potential carcinogens. Furthermore, the
problem of mixtures is not limited to chemical interactions since health outcome may
also be influenced by physical or biological agents. For example, risk of radon-induced
lung cancer is increased in cigarette smokers and people infected with hepatitis B virus
are more susceptible to aflatoxin-induced liver cancer. Thus, our inability to say
whether agents act in an additive, synergistic, or antagonistic fashion creates real
problems in health risk assessment.
Sixth, research is needed to develop methods for screening environmental
pollutants and natural products for endocrine-disrupting effects and for assessing the
health effects of these exposures. Although the possibility for human health effects of
these hormonally-active agents remains hypothetical, their pervasiveness and
persistence in the environment make this an area of significant public health concern.
These chemicals can potentially alter the balance of physiological systems whose
coordination is controlled by delicately balanced neuroendocrine mechanisms.
Animal studies have demonstrated that exposure of the fetus to endocrine-disrupting
chemicals can profoundly disturb organ development. Field studies have
shown an association between exposure to endocrine-disrupting chemicals in the
environment and developmental anomalies in fish, birds, reptiles and other wildlife
species. These anomalies include feminization of male fish, birds and mammals;
decrease in reproductive potential, and under-developed genitalia. Human exposure to
synthetic estrogen (e.g., diethylstilbestrol) during early development caused
reproductive organ dysfunction, abnormal pregnancies, cancers of the reproductive
tract, and decreased fertility in females.
Given the large numbers of hormonally-active chemicals released into the
environment over the past 50 years, more research is needed concerning the health
consequences associated with chronic exposure to low doses of mixtures of
endocrine-disrupting chemicals during the various stages of development. Exposure during the
development of the embryo, fetus, and neonates is of particular concern because the
consequences may be both more striking and permanent.
Lastly, a major challenge is to strengthen the links between fundamental
science, toxicology, epidemiology, and risk assessment. To make environmental health
research findings more applicable to human risk assessment, monitoring of human
exposure to specific chemicals must be undertaken using improved and highly sensitive
analytical procedures. NIEHS-supported scientists continue to generate novel and
innovative biomarkers of environmental exposure that could be incorporated into a
national survey to assess to what extent people absorb or retain the chemicals in their
environment. This more "real world" assessment would greatly strengthen our
capability to conduct risk assessment policy that reflects actual, rather than putative,
exposures. To be most useful, this survey would include information concerning the
nature of the exposure, estimated numbers of persons exposed, and demographic
information such as age, gender, socioeconomic status, race or ethnicity, and
geographic region.
In summary, environmental health policy decisions are only as good as the
scientific foundation upon which they are founded; that is, the data and models used in
assessing the risk, and the assumptions made in the absence of facts. The guiding
principal should be good science for good decisions. Health risk assessment policy
decisions affect millions of lives and involve hundreds of billions of dollars. Such an
investment is worth doing and worth doing well.
The budget request for FY1998 is $313,583,00. I would be pleased to answer
any questions.
