FEATURE
Creating Multidisciplinary Research Opportunities A unifying framework model helps researchers to address the complexities of environmental problems. WILLIAM A. SUK, BETH E. A N D E R S O N , CLAUDIA L. T H O M P S O N , DAVID A. BENNETT, AND DANIEL C. VANDERMEER
lthough recent discussions of science policy support the concept of multidisciplinary and interdisciplinary research (i), science is ironically becoming more specialized as researchers continue to focus their expertise into narrower fields of inquiry. It is growing increasingly difficult to establish broad-based programs, necessary for addressing complex environmental problems, that combine scientific expertise from several fields. New models for fostering and implementing multidisciplinary environmental research are consequently needed, but governmental initiatives in general—save a few efforts at the National Institutes of Health and the National Science Foundation— have not brought this about; federal legislative mandates and most government-funded programs have historically encouraged research mainly within tight disciplinary bounds. One grants program, however, the Superfund Basic Research Program (SBRP), with a 12-year history of supporting such needed multidisciplinary research, provides such a model (2). Administered by the National Institute of Environmental Health Sciences (NIEHS), the SBRP has developed a unifying framework that conjoins a wide range of scientific and engineering research efforts to address problems found at the nation's hazardous waste sites. It serves as an excellent model for environmental health and science research generally and could be adapted to other scientific problem areas where a multiteam approach is being considered. Experience derived from implementing the framework suggests the program's utility. It has fostered
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research collaborations at national and international scales, contributing new research understanding, as well as helping to build the underlying multidisciplinary, investigatory infrastructure of environmental health sciences. The program's approach impacts how investigators participating in it conduct research and has beneficially expanded the research infrastructure, inclusive of partnerships, information transfer, and training elements, which are all considered critical components. Throughout the life of the SBRP, NIEHS has, for example, encouraged partnerships, whereby both those investigators conducting research and those affected by its findings have helped develop the program's framework. This is accomplished by forging research partnerships within and among universities, as well as collaborations with affected communities (those located near waste sites) and other program stakeholders. NIEHS encourages SBRP grantees to work with exposed communities, involving them in community-based research and its applications. Grantees are also encouraged to work with EPA, EPA regions, Agency for Toxic Substances and Disease Registry, and state agency professionals charged with protecting human health and the environment. Partnerships at these different levels allow researchers to learn what issues are important in real-life settings and facilitate technology transfer, providing opportunities for research to move from the laboratory to those who can use the results. The SBRP's application of the unifying framework is exemplified through results of programfunded research on transport and fate, bioavailability, biomarkers, and bioremediation. JUNE 1, 1999 /ENVIRONMENTAL SCIENCES TECHNOLOGY / NEWS • 2 4 1 A
Required relationships To be effective, multidisciplinary environmental and health-effects research programs concerned with the presence of hazardous substances must link together a wide range of traditional scientific and engineering disciplines, inclusive of their inherent concepts, models, and ways of thinking about problems. This requires careful planning, as well as a commitment by researchers to work at the "edges" of their disciplines—at the interfaces where there is the greatest potential for synergy. The chances for fullest benefit of such an approach are further heightened if investigators working within any particular discipline are made aware of all other research components (disciplines) and understand their interrelationships. The unifying framework (see figure below) satisfies these requirements. It provides a way to identify areas of research and create linkages having great potential to protect public health and enhance environmental quality. The model also allows researchers flexibility in designing studies and experimental approaches. The framework structure used by the program assures that vertical and horizontal collaborations are possible among disciplines in designing and conducting research. It also allows for systematic evaluation of the consequences (both beneficial and potentially harmful) of efforts to clean up environmental contaminants. Framework design emphasizes research col-
laborations that improve upon the data and methods needed for quantifying adverse effects of hazardous substances on human health and ecological systems. Moreover, it recognizes the barrier created by the high cost and the risk of conducting demonstration research. Most SBRP-supported research focuses on components to the left of the demonstration research barrier (see figure below). In seeking to work at the edges of their scientific fields, investigators participating in this program pursue either vertical or horizontal collaborations. Some of these efforts have now progressed to the point where research has led to successful demonstrations that ultimately have impacted medical monitoring, ecological restoration, and site remediation activities. Framework examples Transport and fate: Contaminants can migrate through soils, air, and water and can undergo physical and chemical changes over time. Their migration and dynamically changing properties— transport and fate—must be determined in order to accurately assess potential contaminant (and metabolite) impacts on human health and ecosystems. The study of transport and fate of contaminants demands the skills of many scientists, including geologists, hydrogeologists, atmospheric, organic and inorganic chemists, agronomists, biologists, health scientists, and ecologists.
A unifying framework for multidisciplinary research The unifying framework model accounts for how elements of environmental health and sciences are interrelated. The model indicates the influence of health and ecological findings on the selection of a remediation design. Demonstration research involves proving the applicability of laboratory findings to large field settings and moving the results of laboratory science into public health and medical practice. As depicted, success at this level will lead to improved medical monitoring and treatment and ecological restoration. The box (right side of figure) lists desired societal outcomes and outlines how progression through different research components contributes to achieving these outcomes.
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To understand nonaqueous phase liquids (NAPLs), for example, investigators Linda Abriola and Scott Bradford, of the University of Michigan-Ann Arbor, are exploring the entrapment and interphase mass transfer of NAPLs (3). Understanding and quantifying these parameters are necessary requirements for predicting organic contaminant persistence as well as the effectiveness of remediation technologies. Other investigators, such as Richard Stemberger and Celia Chen at Dartmouth College, N.H., are developing methods to study the underlying mechanism of metal transfer in aquatic food webs (4). Because metals can be toxic at high concentrations, this knowledge is crucial for preventing human exposures to harmful levels of metals that may be present in lake fish. The SBRP undertaking routinely combines researchers with diverse disciplines in projects and supporting technical core areas to address the complexity of contaminants, conditions, and properties that are found at hazardous waste sites. Composite information developed by the teams of scientists provides data for engineers, health and ecological risk assessors, and health and environmental protection officials, whose jobs are to make decisions about the impacts of contaminated sites on people and the surrounding environment, as well as cleanup methods, cleanup levels, and the efficacy of remedial actions. Bioavailability research: Although transport and fate research describes the movement and transformation of chemicals through the environmental media, it does not describe the uptake of a contaminant from the medium (e.g., soil) to an organism. Bioavailability research focuses on characterizing uptake—determining what fraction of a contaminant is available to an organism—and involves multidisciplinary studies that conceptually include moving both left to right and up and down within the framework (see figure on previous page). The research, which encompasses a wide spectrum of biological, chemical, and physical science disciplines, investigates amounts of hazardous substances migrating from hazardous waste sites and their bioavailability for ingestion, inhalation, or absorption through the skin. Characterizing the bioavailability of contaminants to various microorganisms is important in developing remediation strategies. Studies indicate that only some of the contaminant present in soil components (sand, sediment, or water) is available to plants and animals. For example, research performed by Martin Alexander, of Cornell University in Ithaca, N.Y., and other researchers (5, 6) has shown that microorganisms, which otherwise readily metabolize individual contaminants in laboratory settings, are only able to metabolize a fraction of the contaminant when present in soil under natural conditions. Soil contact time and soil type significantly influence the a m o u n t of contaminant that microbes can metabolize. The amount of contaminant not metabolized is sequestered in the soil's microstructure. Understanding sequestration is therefore important in determining actual contaminant uptake and dose to plants, animals, and humans.
Benzene biomarker research: The upper pathway of the unifying framework (see figure on previous page), leading from transport and fate focuses on the consequences of human exposure to environmental contaminants. As depicted, basic research (moving left to right) from exposure to disease, provides a mechanistic basis for understanding cellular and molecular changes that occur as a result of an organism's contaminant exposure. These observations can be used to develop biomarkers— tools that indicate contaminant uptake, effects of chemical exposures, and differences in susceptibility to disease among exposed individuals. Biomarkers used in this manner may have an important role in risk assessments, linking exposure to disease, and in formulating prevention and intervention strategies. The research and development of benzene biomarkers, supported by the SBRP, provide an example of how the unifying framework principles are leading to an improved understanding of the relationship between exposure and disease outcome. Preliminary studies performed by Stephen Rappaport, of the University of North Carolina-Chapel Hill and coworkers, using a simple, self-administered breath kit, have shown a significant correlation between the environmental benzene concentrations and exhaled, unmetabolized benzene. Translated as human dose of benzene-in-breath, this biomarker tool may be useful in understanding benzene bioavailability. As another biomarker, these researchers have also shown (7) that concentrations of hemoglobin and albumin adducts formed with the benzene-specific metabolite, benzene oxide, are directly related to benzene exposures in occupational and environmental settings. Other biomarkers that reflect specific cytogenetic changes in lymphocytes may be useful to assess early biological effects of benzene. For example, Martyn Smith of the University of CaliforniaBerkeley and coworkers found that lymphocytes from healthy individuals with known occupational exposure to benzene showed dose-dependent increases in deletions and losses of chromosomes 5 and 7 (8). These same cytogenetic changes are commonly observed in therapy- and chemical-related leukemia, which suggests the utility of this chromosomal change as a biomarker of effect. Exposure to similar levels of environmental contaminants does not necessarily pose the same level of risk to all individuals. Occupational and environmental epidemiological studies have shown that differences in the DNA sequences (genetic polymorphism) coding for xenobiotic-metabolizing enzymes affect risk, or susceptibility, to disease as a result of chemical exposure. In a population of benzeneexposed Chinese workers, research findings of Nathaniel Rothman, of the National Cancer Institute, Bethesda, Md., Martyn Smith, and coworkers suggest that the risk for benzene poisoning is related to certain genetic polymorphisms that alter the enzymatic activity of proteins important in benzene metabolism (9). These biomarkers reflect how the integration of multiple disciplines of science, as JUNE 1, 1999/ENVIRONMENTAL SCIENCE & TECHNOLOGY/ NEWS " 2 4 3 A
carried out by the SBRP using the unifying framework, can move research from basic laboratory findings to a more practical application in human epidemiological studies having the ultimate goal of improving health. Bioremediation: The lower pathway of the unifying framework (see figure on page 242A) recognizes the importance of remediation research in achieving the outcomes listed in the box on the right side of the illustration. Traditional cleanup options include engineered containment, pumping, treating contaminated aquifers, and incineration. The development of new techniques provides an opportunity for deployment of more rapid and costeffective remediation strategies. Contributions of biology and related sciences to remediation research have led to novel phytoremediation and bioremediation methods now being used for control and cleanup of hazardous substances. Experiments with hybrid poplar trees, a species that is particularly fast-growing and has a deep and extensive root system, have yielded a new approach to restoring groundwater contaminated by organic pesticides and solvents. Milton Gordon at the University of Washington-Seattle and other researchers have demonstrated that the poplar's metabolism reduces compounds, such as trichloroethylene, into innocuous gases and salts {10). Such low-tech remediation may lead to improved cleanup of chlorinated solvent-contaminated aquifers and prompt intervention studies to look for dose reductions within potentially exposed populations. Ian Pepper, of the University of Arizona-Tucson, and colleagues, in another SBRP-supported research project, are investigating the potential of bacterial gene transfer to enhance remediation of contaminants in soil (11). In this example, indigenous microbes accepted genes from another bacterium and increased their biodegradation rate of an organic contaminant. The success of these two projects required collaboration among microbiologists, plant and soil scientists, and engineers. Lessons learned NIEHS has learned that it must assume the central role of information transfer agent in order to ensure that the research advances generated around the country by the program go beyond academic walls and are effectively communicated to the appropriate audiences. The SBRP plays a pivotal role in information transfer. In addition to traditional peerreviewed publication mechanisms, the program has sought other information transfer opportunities for research advances to reach all the partners and stakeholders of the program. Electronic information transfer has been pursued aggressively. The program currently supports an extensive Internet site (2) and distributes electronic Research Briefs every two weeks, which highlight important research findings from the program. Currently, there are more than 1300 subscribers from federal and state agencies, academia, and industry. In addition, Tech Focus articles are produced that describe specific research activities in greater detail and are available at the Internet site. These activities are effective and strengthen the program. 2 4 4 A • JUNE 1, 1999 / ENVIRONMENTAL SCIENCE & TECHNOLOGY / NEWS
The support of multidisciplinary science is also sustained through training activities. Training of predoctoral and postdoctoral candidates in a structured, multidisciplinary approach has produced a new generation of scientists and engineers having broad, interdisciplinary experience and an appreciation of multidisciplinary research efforts. Through sponsorship of interdisciplinary scientific conferences, the SBRP has successfully exposed research investigators to information outside their traditional scientific disciplines. Other conferences, focused on the application of research, have served to train professionals (such as risk assessors, site managers, and public health officials) working in related fields. NIEHS has found that these activities are important in providing a level of expertise, not available 5 to 10 years ago, to address the complex problems of environmental health and sciences. The concept of a unifying framework should be considered necessary whenever a multidisciplinary research program is pursued. In linking multidisciplinary research program components, the framework provides a context for basic research that is understandable by those who appropriate funds and by end users of program products; it helps demonstrate the relevance of the overall research program and program elements. The framework also enhances research planning and offers logical, consistent tools for setting priorities and for organizing information transfer efforts. Last, it displays the relationship of basic and applied environmental-health-science research studies to societal goals for protecting public health and preserving environmental quality. References (1} Metzger, N.; Zare, R. N. Science 1999, 283, 642-643. (2) Superfund Basic Research Program, http://www.mehs. nih.gov/sbrp/home.htm (accessed March 1999). (3) Abriola, L. M.; Bradford, S. A. Environ. Health Sci. 1998, 106 (suppl. 4), 1083-1095. (4) Stemberger, R. S.; Chen, C. Y. Can. J. Fish. Aquat. Sci. 1998, 55, 339-352. (5) Chung, N. H.; Alexander, M. Environ. Sci. Technol. 1998, 32, 855-860. (6) Robertson, B. K., Alexander, M. Environ. Toxicol. Chem. 1998, 17, 1034-1038. (7) Yeowell-O'Connell, K., et al. Carcinogenesis 1998,19,15651571. (8) Zhang, L.; Rothman, N.; Wang, Y; Hayes, R. B.; Li, G.; Dosemeci, M; Yin, S.; Kolachana, R; Titenko-Holland, N.; Smith, M. T. Carcinogenesis 1998, 19, 1955-1961. (9) Rothman, N., et al. Cancer Res. 1997, 57, 2839-2842. (10) Gordon, M., et al. In Phytoremediation of Soil and Water Contaminants, Kruger, E., Anderson, T. A., Coats, J. R., Eds.; ACS Symposium Series; American Chemical Society: Washington, DC, 1997; pp. 177-185. (11) DiGiovanni, G. D.; Neilson, I. W.; Pepper, I. L.; Sinclair, N. A. Appl. Environ. Microbiol. 1996, 62, 2521-2526.
William A. Suk is the director of the Office of Program Development, Division of Extramural Research & Training, National Institute of Environmental Health Sciences, Research Triangle Park, NC; at the same location, Beth E. Anderson is a program analyst; Claudia L. Thompson is a program administrator; and David A. Bennett is a program administrator on detailfromthe Office ofEmergency and Remedial Response, U.S. EPA, Washington DC. DanielC.VanderMeer is an environmental public health consultant in Chapel Hill, NC.
