Research Progress on Environmental, Health, and Safety Aspects of Engineered Nanomaterials (2013)

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5 Going Beyond Green INTRODUCTION: A VISION FOR THE FUTURE In the previous chapters of this report, the committee examined research and infrastructure developments related to environmental, health, and safety (EHS) aspects of engineered nanomaterials (ENMs). The committee assessed findings from recently released US and European Union reports that provide global perspectives on the needs for advancing EHS nanotechnology research (see discussion in Chapter 2). The committee examined trajectories of progress in the research and infrastructure priorities articulated in its first report (Chapter 3) and identified critical barriers to progress and steps that are needed to ensure that progress is made (that is, to get to green) (Chapter 4). The present chapter builds on Chapters 3 and 4 to address overarching issues that are relevant to ensuring timely progress in the committee’s research priorities. It amplifies is- sues included in the overall charge on the basis of the committee’s review of progress since the first report and provides a means to address the criteria for assessing research progress over the longer-term described in that first report. As part of this evaluation, the committee presents a construct (Figure 4-1) that pro- vides an overall vision of a comprehensive research enterprise on the potential EHS risks posed by ENMs, capturing the interrelated and interdependent re- search activities that are driven by the evolving production of ENMs. That con- struct highlights critical interactions among members of the research community and the wider group of stakeholders and the importance of a coordinated infra- structure to ensure that the efforts of the research community are optimized. These themes are reflected in the committee’s longer-term criteria for addressing research progress and address issues such as the level of interaction and collabo- ration among key stakeholders; the coordination and integration of the research strategy with regards to planning, budgeting, and management; accessibility of information to interested stakeholders; and the feasibility of conducting the re- search in a timely manner so that it is responsive to stakeholder and decision- maker needs. 115 

116 Research Progress on EHS Aspects of Engineered Nanomaterials In this chapter, the committee provides a broader perspective and sugges- tions for creating a successful portfolio of risk-related research. Both here and in the first report, the committee has highlighted that how a research strategy is implemented is just as central to its success as is its scientific or technical con- tent. A strategy for risk research should recognize the inherent technical and cultural obstacles that researchers and the broader community can face in build- ing knowledge about potential EHS risks. Such considerations are vital for creat- ing a robust global research community that can successfully identify the risks associated with emerging ENMs while providing strategies for minimizing the risks. A successful research enterprise, as shown in Figure 4-1, will provide findings of immediate relevance to the responsible development of nanotechnol- ogy, and sustaining that enterprise will be of interest to all its diverse stakehold- ers to ensure that risk is effectively managed. This chapter offers a vision of a global research enterprise that will be the vehicle for answering current and future questions about the potential risks posed to human health and the environment by ENMs. The overarching (or ul- timate) goal of the enterprise is to generate the information needed to design materials and processes to be safer from the outset—to reduce or eliminate haz- ards and risks to human health and the environment; for example, see Hutchison (2008) on “greener nanoscience” and NIOSH (2012) for a more general descrip- tion of “prevention through design”. In this chapter, the committee projects to a time beyond the domain of its current research recommendations to consider how questions about risk can be best approached in an adaptive and continuing manner so as to update priorities for research and identify concerns constantly. The chapter is aspirational and goes beyond setting out a prospective research portfolio to consider how future concerns can be anticipated and addressed. The general approach recommended by this committee is germane not on- ly to ENMs but more broadly to any emergent technology or class of materials that may be perceived to pose a risk. Prospective and continuing assessment of potential hazard clearly is vital, and Figure 4-1 incorporates three key elements of the approach that are the focus of this chapter and are discussed below:  A governance structure, including designation of an institutional lead with sufficient authority and accountability, clearly defined metrics for gauging research progress, coordinated communications with and engagement of all stakeholders, leveraged public–private partnerships, and principles that prevent conflicts between applications and implications of nanotechnology research.  Stable, long-term support and incentives for sustaining the research community and engaging interdisciplinary and international researchers.  An adaptive decision-making process that integrates the latest nano- technology EHS information from all over the world into a “knowledge com- mons” and provides sufficient funding and incentives, with input from multiple stakeholders, to illuminate the path toward ENM design, application, and high- priority risk research. 

Going Beyond Green 117 EFFECTIVE GOVERNANCE Throughout its deliberations, the committee has repeatedly concluded that stronger governance of nanotechnology EHS research is needed to manage, di- rect, and disseminate results of the numerous research activities. Achieving ef- fective governance is no small task. Considering the applications and implica- tions of nanotechnology requires enormous scale, input from diverse sectors, and a comprehensive systems-driven approach to science. Unlike some other “big science” research approaches, such as the Human Genome Project, the ap- plications of nanotechnology permeate virtually every sector of our society and economy. Such broad reach means that nanotechnology and related EHS issues span the missions and jurisdictions of many government agencies and intersect with the activities and interests of many stakeholders, including businesses, the academic community, consumers, workers, and myriad organizations that make up civil society. Governance should actively engage all those in the process of managing nanotechnology EHS research. Nanotechnology’s applications and its EHS implications are closely inter- twined. That is, the novel or enhanced physical and chemical characteristics of ENMs (such as greater reactivity or solubility than that of the larger “bulk” ma- terial of the same chemical composition) that are being exploited in new applica- tions may also lead to biologic behaviors of potential concern for environmental or human health. In addition, knowledge of the uncertainties in physical and chemical ENM characteristics is needed for estimation of design risk in the cas- es of materials, products, and applications and for estimation of EHS risks. Ap- plications research is often relevant to our understanding of potential EHS risks and vice versa, and this highlights the need for close collaboration of researchers in both fields and for an infrastructure that supports more efficient and facile information flow between and integration of the applications-research and im- plications-research communities. However, close researcher interaction does not necessarily imply that ap- plications research and implications research should be jointly managed. Many agencies conduct or fund both applications research and implications research in nanotechnology under the aegis of the National Nanotechnology Initiative (NNI). That coordinating body has as its mission both the development of nano- technology and ensuring that such development is socially and environmentally responsible. The dual mission contrasts with other big science initiatives that focus principally or exclusively on technology development and application, such as the aforementioned Human Genome Project and, more recently, the Na- tional Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) and the multiagency Toxicity Testing in the 21st Century (Tox21) Initiative. Separation of applications research and implications research in those fields naturally allays concerns that the drive to commercialize emerg- ing technologies could overshadow the fledgling understanding of possible risks. In nanotechnology, however, concerns regarding conflicts of interest between 

118 Research Progress on EHS Aspects of Engineered Nanomaterials the dual objectives, the disparities in resource allocations, and the differential rate of research progress are important to a number of stakeholders. Strong governance that separates the management of technology develop- ment from the management of EHS risk research is a potential solution. The risks associated with early-stage technology are intrinsically riddled with uncer- tainties; as this report alludes to in earlier chapters, the science needed to pro- vide definitive answers is highly complex and integrative. Conclusions are not revealed in a single study but develop from a laborious and consistent set of work that may span years. When faced with the nuances of risk research, an or- ganization that is in large measure evaluated by its success in technology devel- opment may not be perceived as able to set priorities effectively among either resources or topics for risk research. If the potential research synergies and cross-fertilization between applica- tions research and implications research are to be realized, concerns about the true equality of the dual objectives of “responsible development” must be ad- dressed. Only then can all stakeholders trust that there is an equitable allocation of resources and an appropriate focus on the most risk-relevant questions. One symptom of weak governance is the challenge of maintaining regular communication and coordination at all levels—between researchers in the Unit- ed States, foreign researchers, and relevant stakeholders. In the United States, many research activities on ENMs have been under way for some time and are supported through coordinated efforts that include conferences and workshops. But the level of information-sharing and communication among the participants and with other stakeholders remains primarily informal and in the committee’s judgment is insufficient. That is also true globally; effective alignment in nano- technology EHS research strategies could provide enormous leverage to many countries that have active nanotechnology-research portfolios. It is important to recognize that constructive collaborative initiatives between the United States and the European Union are already under way (Finnish Institute of Occupation- al Health 2012). With or without infusion of additional funds, the value of communication among investigators who are generating new nanomaterials and those who are studying EHS issues will need to be substantially improved. Improvements in collaboration and coordination among federal and nonfederal researchers would enhance the likelihood that research produces information that supports effective public-policy and private-sector decisions and ultimately protects the environ- ment and human health. An integrated and well-coordinated program on both national and global scales would help to ensure that research findings provide the evidence needed to inform decisions so as to effectively manage and, ideally, prevent EHS risks. The continued challenges of communication and coordina- tion, in spite of many good-faith efforts, are notable. There have been many ef- forts in the United States and abroad to identify and address research needs re- lated to the safe use of nanotechnology but little continuity and follow-through to ensure that the needs are being addressed. 

Going Beyond Green 119 The committee summarizes below several core aspects of effective gov- ernance that reinforce recommendations that it offered in its first report (NRC 2012). The suggestions help to address the challenges of coordination among researchers, communication with external stakeholders, and perceptions of con- flict of interest. Empowered leadership. If all agencies are responsible, to some degree, for nanotechnology EHS research, no agency can be held clearly accountable for its management and progress. Our nation needs empowered leadership for nano- technology risk research directed through a governance structure that clearly defines the metrics used to gauge progress and the roles and means of engage- ment of researchers and stakeholders. Without such leadership, efforts are likely to result in wasteful and duplicative efforts, fractured results, and knowledge gaps that could seriously dilute the science that underpins policy and regulatory decisions. Moreover, the gap in empowered leadership of nanotechnology EHS research at the federal level has made coordination and communication chal- lenging and left the enterprise open to perceptions of conflicts between technol- ogy development and risk research. Such leadership requires a stronger central convening authority than the NNI can now provide—one that has sufficient management and budgetary au- thority to direct implementation of a research strategy throughout all the NNI agencies and to ensure its integration with EHS research undertaken in the pri- vate sector, the academic community, and international organizations (NRC 2012, pp. 16-17). The committee recognizes that attaining that objective fully may require changes in the statute that established the NNI; as noted in our first report, such legislation was introduced but not adopted in the 111th Congress (NRC 2012, p. 166). Movement in the desired direction could be achieved through the designation of one of the NNI agencies whose mission includes EHS as the lead agency for directing EHS research throughout the federal govern- ment. Alternatively, it may be possible to establish a new entity to serve this function in analogy to the NIH NCATS. Metrics of research progress. Delineation and tracking of clearly identi- fied metrics of research progress are well suited to the capabilities of a central organization devoted to oversight of nanotechnology EHS research. Establish- ment of defined metrics that measure progress toward goals of a research strate- gy has been recommended by this committee (NRC 2012) and in other reviews of the NNI to increase the accountability of agencies and researchers. The spe- cific needs include development and implementation of performance metrics that can be used to track research progress against core objectives, establishment of a rigorous means of assessing whether funded programs are conducting risk research, and periodic estimation of the levels and identification of the sources of funding needed to meet the specific goals and priorities defined by the agen- cies and the broader community. As part of this activity, it is vital to strive for greater transparency in communicating the distribution of research in one’s portfolio. Agencies need 

120 Research Progress on EHS Aspects of Engineered Nanomaterials clearer guidance in differentiating between research directly relevant to EHS risk and applications-oriented research that has more indirect EHS implications. If research that centers on risk questions is clearly differentiated from research that develops applications with more distant EHS relevance, information on the relative amounts of funding allocated to the two will be viewed as more credible by many stakeholders. Sustained coordination and communication with all relevant stakeholders. In spite of good-faith efforts, the committee finds that more structured, reliable, and continuing forums are needed both for communication among researchers (in the United States and globally) and for stakeholder engagement. For exam- ple, as uses of ENMs extend globally, research on the potential EHS conse- quences of ENMs should be considered globally. The committee’s workshop that informed the present report provided a perspective on an extensive slate of research under way in Europe and elsewhere. The government should invest in such a way as to ensure that the research enterprise outlined in Figure 4-1 fully engages the global research community. Such engagement will widen the array of materials covered, provide analyses that address diverse and heterogeneous exposures and outcomes, and facilitate development of validated models. Another important audience that needs to be engaged is stakeholders who are not part of the nanotechnology EHS research community. With that in mind, the committee has identified a number of attributes of effective stakeholder en- gagement that are largely missing from the NNI’s efforts. It is especially im- portant to provide a process to continuously engage stakeholders and to receive their input on research progress and priorities. That could be accomplished through, for example, the establishment of standing advisory bodies that meet regularly to review strategy development, implementation, and priorities. Such stakeholder groups may be best formed around application-specific sectors of nanotechnology and nanomaterials and encompass each of the links in the value chain (for example, workers, consumers, environmental advocates, and produc- ers of raw materials, intermediates, and final products). As an initial step, the committee recommends that the National Nanotechnology Coordination Office (NNCO) establish its own stakeholder advisory council to develop best practices for this vital function and commit to funding regular workshops to bring togeth- er US and foreign researchers who are working on nanotechnology EHS re- search and other stakeholders. Public–private partnerships. Engagement with stakeholders is important for shaping research on nanotechnology-related risk, but it does not fully lever- age the opportunity to expand and enrich risk research through focused partner- ships with them. To implement the ambitious strategies outlined by the NNI effectively, this committee and others will require substantial leveraging of fed- eral funds, and the committee believes that public–private partnerships need to be more fully developed. Not only do such structures create the potential for greater resources, but direct stakeholder participation in partnerships that have defined research or communication goals is optimal for engagement. 

Going Beyond Green 121 The committee has identified five elements that are critical for effective public–private partnerships: a strong independent and accountable governance structure that provides transparency in selecting projects, conducting research, ensuring quality, and disseminating results; commitments of adequate and shared funding; open processes to develop priorities and specific goals; trans- parent sharing and peer review of research, including a commitment to release all research results and underlying data (NRC 2012, p. 173); and confidentiality agreements that balance the proprietary needs of industry participants with the public need to share information and make decision-making processes transpar- ent. Minimizing the potential for conflicts between applications research and implications research. The committee maintains that the NNI would benefit from a clearer separation of authority and accountability for its EHS research enterprise and its mandate to promote nanotechnology development and com- mercialization. The committee also acknowledges that, in the absence of a change in its statutory mandate, establishment of wholly separate management and budgetary structures and authorities for the NNI’s dual functions may not be realistic. Nonetheless, steps can be taken at both the agency level and across the initiative as a whole to address this concern. Agencies should create and adhere to strong scientific-integrity policies that govern both intramural and extramural research and should consider creat- ing an ombudsman position to receive, investigate, and resolve complaints or concerns about bias and conflicts of interest related to nanotechnology research. The NNCO should also develop and disseminate best practices for identi- fying, managing, and preventing conflicts of interest and bias in the planning, conduct, and reporting of research. Different offices and senior staff members that have parallel and comparable degrees of authority should be independently responsible for program management of the two lines of research within an agency. Moreover, agency scientists trained in the health or environmental sci- ences should be engaged in management of EHS risk-related research where possible. SUSTAINING AND NURTURING RESEARCH EXCELLENCE Whatever organization oversees the nanotechnology EHS research strate- gy, among its most important functions will be to secure and maintain adequate funding for the program. The research strategies outlined by the NNI and by this committee cannot be accomplished without a sustained commitment over at least the next decade. Such an investment will yield a more acceptable and ulti- mately more successful nanotechnology economy. It is only through a clear un- derstanding of the scientific data and uncertainties that possible EHS risks posed by ENMs can be reduced. Such information accelerates nanotechnology devel- opment, lowers barriers to the introduction of new nanotechnology-containing 

122 Research Progress on EHS Aspects of Engineered Nanomaterials products in the marketplace, and ensures public trust in the regulatory processes that protect the health of workers, the public, and the environment. Multiple sources of funding are needed to support the research strategy, but a sustained high level of management and funding through a single agency is needed if indeed the critical research on EHS is to be accomplished. A success- ful knowledge commons requires strong leadership. Such commitments of fund- ing will not be possible in the absence of a lead agency or organization that sees the issues as an essential part of its mission. Without such a lead organization to sustain support for the EHS agenda in the competition for government resources, the EHS nanotechnology research enterprise will falter, and we will not be able to achieve the ideal of responsible nanotechnology development. Funding is only part of the challenge, however; it is vital that the best re- searchers in this country and beyond remain interested in and willing to tackle this problem. Various cultures in government, academe, and industry both sup- port and sustain individual scientists and investigative teams. “Cultural and in- stitutional obstacles often discourage attempts to perform research across disci- plines, agencies, and institutions (including public and private organizations). Such obstacles can reflect historical tendencies to conduct research within par- ticular disciplinary or organizational boundaries—for example, toxicology vs epidemiology and government vs industry” (NRC 2001, p. 141). Moreover, a scientist’s career advancement requires attention to institutional, rather than na- tional, agendas. A role as coauthor of a multidisciplinary manuscript may do little to advance an academic career if recognition is attached only to first or senior authorship. Similarly, scientific journals typically focus on particular fields and are reluctant to publish outside of their own scopes. Meetings of pro- fessional societies often run parallel sessions with researchers partitioned into focused sessions on physical science or biologic science, and this limits oppor- tunities for cross-fertilization. All those factors taken together make it difficult to assemble the best teams to tackle the research outlined in Chapter 4. In recognizing such disincentives as they apply to multidisciplinary re- search on EHS aspects of ENMs, the committee recommends that incentives be established to foster joint planning and information exchange. Examples of such incentives are enhanced support to give higher priority to multidisciplinary, in- tegrated EHS aspects of ENMs; frequent multisponsor, multidisciplinary meet- ings to build a community of investigators addressing EHS aspects of ENMs; and a cross-agency budget for key multidisciplinary research initiatives. Such efforts might go a long way toward eliminating or at least decreasing the barriers that limit the broad perspective required in tackling the complex subject of EHS aspects of ENMs. ADAPTIVE DECISION-MAKING AND KNOWLEDGE-SHARING All stakeholders in nanotechnology EHS research, whether they are citi- zens or academic researchers, should have access to the growing body of 

Going Beyond Green 123 knowledge surrounding nanotechnology-related EHS concerns. Such a resource would help to improve public understanding, inform policy-makers, offer data for future researchers, and shape the future focus of the research. As envisioned in Chapter 4, the diverse audiences would be served by the same resource— termed a knowledge commons—because it would provide information relevant to nanotechnology EHS research at multiple levels of detail. The resource would also provide an archival function: all data collected during the course of nano- technology EHS research would be available to future generations of research- ers. For researchers, the most important aspect of the knowledge commons is access to existing data. The knowledge commons would provide storage for raw data or links to data derived from the processed data and would offer some cura- tion, annotation, and linkages of datasets. Those features would make it possible to establish the provenance, reproducibility, and uncertainty of future data and in effect “bank” them for consideration by future researchers. The knowledge commons would provide a means of augmenting the current print literature digi- tally to access and compare raw data; evaluate their quality, uncertainty, and reproducibility; and augment collaboration to evaluate risk associated with both applications and implications of nanotechnology (Priem 2013). As presented in Chapter 4, research on nanotechnology-related risk is a highly multidisciplinary, systems-level scientific challenge; shared databases and knowledge commons are vital for rapid progress in that they permit the integration of information among material types, species, and exposure routes. For interested stakeholders (such as regulators, scientists, workers, and consumers) who are not actively engaged in the research, the knowledge com- mons could serve as an excellent resource for meta-analysis of multiple publica- tions, continuing research projects, and datasets. Summaries of research projects that lay out the key participants, goals, methods, models, underlying hypotheses, resource levels, schedules, and expected deliverables, and resulting publications or other avenues to access findings could be vital for adapting the priorities of nanotechnology EHS research in the United States. The availability of such in- formation on line and regularly updated would serve to stimulate interactions, identify gaps, and avoid unnecessary duplication by researchers. It would also facilitate oversight of the nanomaterial research program and provide greater accountability for research progress. It may be possible to engage researchers to offer snapshots or meta-analyses of the state of knowledge in their own fields, and this information could feed into an adaptive decision-making process that constantly evaluates the evolving consensus developing in the research commu- nity on such key issues as those presented in Chapter 4. Finally, the knowledge commons would provide context for addressing and satisfying the widely recognized need for improved terminology for ENM structures, experiments, characteristics, models, effects, and uses. It is vital that the terminology used in one study be compatible with that used in other studies. An ideal solution envisions a common taxonomy for all nanomaterials, methods, and risk-related data; however, attempts at even the simplest nomenclature have 

124 Research Progress on EHS Aspects of Engineered Nanomaterials been under way for years and have yet to yield universally accepted definitions of even the most basic ENMs. A more pragmatic approach would be to develop ontologies and thesau- ruses that in effect map a given set of defined terms onto other commonly used sets to permit data to be fully shared even if researchers in different disciplines adopt different conventions for nomenclature formatting and reporting. Bioin- formatics provides relevant examples of what can be accomplished with these techniques; for example, the National Cancer Institute’s Metathesaurus provides synonyms that link cancer research and trial resources (NCI 2013) and linkages to hundreds of resources accessible through the National Library of Medicine (NLM 2013). There is far less controversy in defining ontologies for particular domains of knowledge and practice, but ontologies require the deep engagement of the research community in mapping terms among disciplines, conventions, and business practices. Without such tools, progress toward the ideal laid out in Chapter 4 and the NNI’s own research strategy will be severely compromised. Ultimately, the goal would be to encourage all researchers to label and or- ganize their materials by using one of several accepted and defined ontologies. There will need to be a working convention that describes target materials of interest and presents several options for their nomenclature. The terminology challenge extends to the description of the key characteristics and properties of ENMs at different levels of granularity—from atomistic and molecular through single particles, aggregates, structures, and systems for use in experiments, models, manufacture, and application. ENMs’ properties determine their novel or enhanced physical, chemical, and biologic behavior, and future definitions can incorporate readily measurable properties, such as particle diameter and size distribution. Decision-makers charged in the near term with inventorying or reg- istering ENMs have sometimes adopted definitions out of necessity, and these frameworks could be the basis of ontologies. If those approaches are coupled with the ability to adapt rapidly to new findings or growing consensus in the research community, they are likely to become widely adopted. Ontologies are tools for researchers and should not be used to generalize ENM properties or risks. As has been shown in multiple studies, the starting features of an ENM are only a few of the many attributes that define their ac- tions in biologic or environmental systems. As scientific understanding grows, the best terms for describing ENM properties will become clearer to the com- munity. Ontologies provide an excellent approach for capturing that evolution in that they will allow publications from the 1990s to be related to more recent literature. However, achieving such results will require continuing investment in not only the informatics infrastructure but the personnel required to maintain the enterprise: the data scientists, curators, and informaticists necessary to define terms authoritatively, evaluate the quality and reproducibility of experimental data and models, conduct validations, and aid users. Support of these activities by research scientists will be necessary, particularly in providing expert opinion and analyses. Equally important is the recognition that informatics specialists 

Going Beyond Green 125 provide crucial capabilities for planning, developing, and using the infrastruc- ture discussed here (Monastersky 2013). CONCLUSION Characterization of the risks posed by ENMs throughout their life cycle is a scientific challenge that requires integrated, quantitative, and systems-level ap- proaches. It is also an institutional challenge that stretches the conventional roles of agencies and researchers alike. Strong governance will be vital for ensuring effective, timely, and actionable research results. Ideally, empowered leadership at the federal level with oversight by a single agency would solve many of the organ- izational barriers perceived by the committee. Centralized attention to the argu- ments for sustained funding for this research and for the infrastructure needed to support data-sharing would be wise investments. The ideal of responsible devel- opment of nanotechnology is both daunting, but there is no doubt that it is attaina- ble if we plan well for the substance of the research and for the management infra- structure needed to shape and disseminate its findings. REFERENCES Finnish Institute of Occupational Health. 2012. EU-U.S. nanoEHS Community of Re- search (CORs) Flyer [online]. Available: http://www.nanosustain.eu/events/COR% 20flyer.pdf [accessed Feb. 1, 2013]. Hutchinson, J.E. 2008. Greener nanoscience: A proactive approach to advancing applica- tions and reducing implication of nanotechnology. ACS Nano 2(3):395-402. Monastersky, R. 2013. The library reboot. Nature. 495(7442):430-432. NCI (National Cancer Institute). 2013. NCI Metathesaurus (NClm). Biomedical Termi- nology Database. Version 2.2 [online]. Available: http://ncim.nci.nih.gov/ncimbr owser/ [accessed Mar. 29, 2013]. NIOSH (National Institute for Occupational Safety and Health). 2012. Prevention through Design. Workplace Safety and Health Topics [online]. Available: http://www.cdc. gov/niosh/topics/ptd/ [accessed Mar. 20, 2013]. NLM (National Library of Medicine). 2013. Databases, Resources, & APIs [online]. Avail- able: http://wwwcf2.nlm.nih.gov/nlm_eresources/eresources/search_database.cfm [accessed Mar. 29, 2013]. NRC (National Research Council). 2001. Research Priorities for Airborne Particulate Matter: III. Early Research Progress. Washington, DC: National Academy Press. NRC (National Research Council). 2012. A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials. Washington, DC: National Academies Press. Priem, J. 2013. Beyond the paper. Nature. 495(7442):437-440.