Abstract
The World Health Organization (WHO) Global Guidance Framework for the Responsible Use of the Life Sciences addresses the governance of biorisks, including dual-use research, for countries. It emphasizes engaging multisectoral stakeholders such as governments, scientific bodies, health and research institutes, standard-setting organizations, funding bodies, and others. Ethics constitutes a key component of the framework. Given the high social impact of such research and the importance of trust, risk, and benefit, national ethics committees could make a valuable contribution by providing ethical guidance in the decisionmaking process. The purpose of this study was to examine the role of national ethics committees in the context of governance and oversight of dual-use research at the national level. We conducted a landscape analysis of the activities of ethics committees in dual-use research oversight. We also searched the WHO database on National Ethics Committees for publications related to dual-use research and/or misuse of life sciences research and gathered additional documentation from national ethics committees websites and through author contacts. Results showed that in the context of the wide range of oversight mechanisms for dual-use research in countries, national ethics committees have contributed to guiding policy and assessing dual-use research risks in only a limited number of countries. Recommendations from those countries include establishing a multistakeholder, coordinated oversight mechanism at the country level; strengthening international linkages to guide, harmonize, and reinforce national and international efforts; and involving ethics committees as an expert resource in the governance and oversight process.
Introduction
The 2022 World Health Organization (WHO) Global Guidance Framework for the Responsible Use of the Life Sciences 1 provides updated guidance on the governance and oversight of biorisks in countries. It echoes and amplifies efforts in countries to respond to the changing nature of risk over the past decade and the need to take into account new discoveries, capabilities, and technologies. While the guidance framework focuses on the life sciences, its core principles apply to other scientific fields as well. The framework proposes an integrated approach to “biorisk management” as an overarching structure to address the full spectrum of risks associated with the life sciences research enterprise. These may include, for example, risks caused by accidents, disclosure of information, inadvertent applications, and dual-use research (DUR)—that is, the deliberate misapplication of knowledge that poses a threat. In the context of the framework, dual-use research refers to “life sciences research that is conducted for peaceful and beneficial purposes but has the potential to produce knowledge, information, methods, products or technologies that could also be intentionally misused to endanger the health of humans, nonhuman animals, plants and agriculture, and the environment.” 1
WHO engagement with health security is not new. The organization has been concerned with biological and chemical risks since the late 1960s.2,3 A 2002 World Health Assembly resolution 4 condemned deliberate chemical and radionuclear attacks as a global public health threat and called on countries to contain and mitigate their effects. In 2005, a resolution on laboratory biosafety 5 led to WHO guidance emphasizing education and training, preparedness, risk assessment, development of instruments and tools, and biorisk mitigation. Over the next decade, initiatives such as the Joint External Evaluation of Biosafety and Biosecurity, intended to monitor national biosafety and biosecurity systems, 6 were launched. The World Health Report 2007 on health security elaborated a broad spectrum of risks and stressed the need for international cooperation to address them. 7 WHO guidance from 2010 8 recommended investing in ethics capacity development as 1 of the 3 pillars supporting public health, along with research excellence and biosafety and laboratory biosecurity. Ethics constitutes a key component of the WHO framework, as the application of ethical principles is integral to fully articulated positions on DUR.
The WHO framework on DUR also links with other WHO efforts, such as strengthening capacity and monitoring of the International Health Regulations (IHR) 2005. 9 However, effective management of biorisk in countries goes beyond biosafety and biosecurity measures as evaluated by a regular IHR assessment. It also entails ensuring ethical principles and protections at each level of the research lifecycle: research conception, funding, conduct, and sharing of data and results. The nature and uncertainty of risk and the potential for harm at any given point in the process require input and expertise beyond any one group. In the context of national approaches to biorisk management, broad stakeholder input from health agencies, research institutions, and other concerned bodies is essential. In this article, we examine the role of national ethics committees as a contributor to this complex process.
Methods
National ethics committees (NECs) shared information on ethics and research ethics through a now discontinued online database held by the WHO Health Ethics and Governance unit. A landscape analysis of NECs addressing dual-use research was conducted using documents available from the WHO database, which is typically updated every 2 years. Due to the COVID-19 pandemic, the latest information available for this study was collected through 2018. Documents with opinions or guidance provided by NECs were grouped into 6 categories—biosecurity, safety and precaution, emerging technologies, genome editing, synthetic biology, and neuroscience—according to the topic addressed (Table 1), as described by Hummel et al. 10 Relevant documents issued by NECs from 11 countries were identified. The documents were reviewed in English, French, German, and Spanish to assess their scope, how DUR/misuse was addressed, and the role of NECs, research ethics committees, and/or other bodies. There was no limit on the date of publication. The works of national bodies not included in the database were not reviewed.
Main Topics Related to Dual-Use Research Addressed by National Ethics Committees
Note: The grouping made by Hummel et al 10 was used.
Two documents that fall in this category were issued by Argentina.
The content was expanded through a systematic search of additional documentation available from the webpages of NECs and internet search engines. To be included, a document had to be related to dual use/misuse of research either in the title or the content. The overarching concept of “potential for misuse” was used to allow the incorporation of data beyond the variety of definitions found for DUR. The analysis was based on areas and activities that produce knowledge, information, methods, products, or technologies that could provide useful knowledge but also pose a threat if misapplied. To complement the information, discussions were held with country focal points to better understand the current status and local systems and procedures followed with regard to DUR. Focal points were identified through the available documentation, NEC websites, and author and network contacts.
Results
A total of 16 relevant documents from NECs in 11 countries were identified from the database (Table 2).11-26 Of these countries, 10 were high-income countries (Denmark, Germany, Italy, The Netherlands, Norway, Portugal, Spain, Switzerland, The United Kingdom, and The United States) and 1 was an upper middle-income country (Argentina), according to 2022 World Bank income classifications. Almost all of the 11 NECs are policy development bodies without a research focus, with the exception of Norway, where the committee is a research ethics committee.
Documents Produced by National Ethics Committees by Year, Country, and Body Type
The classifications described by Hummel et al 10 were used to categorize national research ethics review committees into 3 groups: (1) National Research Ethics Review Committee (protocol review): committee reviews research protocols and projects that are intended to be carried out in the country; (2) National Research Ethics Committee (policy development): committee develops policies and guidelines that frame research projects in the country; and (3) National Bioethics Committees (no research focus): committee does not have a dedicated focus on research or specific research projects, but works on bioethical issues more generally.
This column describes the context in which documents were produced. Italicized text indicates that they resulted in, or were highly influenced by, cases that raised international controversy from an ethical perspective.
The documents identified for this review were produced between 2001 and 2018. Eleven were presented as “reports” and the remainder as “opinion,” “reflection,” “discussion paper,” or “booklet” (Table 2). Six of the 16 publications were issued as a result of, or highly influenced by, cases that were the subject of international controversy (eg, mutated variants of the avian influenza virus H5N1, a self-replicating bacteria cell, techniques for targeted alterations to DNA sequences in living cells) and possible consequences (eg, misuse of research findings, restrictions to publication). Other documents provided advice on a particular issue or were part of the ongoing work of NECs.
Results show that in only a limited number of the 146 countries with NECs, they have contributed to guiding policy, research codes of conduct, and assessment of DUR risks as part of the wide range of oversight mechanisms for DUR in countries. Recommendations from those countries actively addressing biorisk matters (eg, biosafety, biosecurity, and in various scientific fields) stress that the precautionary principle is fundamental in research areas of high uncertainty, until further knowledge is available. A precautionary principle is “when an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically.” 27 The central components of the precautionary principle are: (1) taking preventive action in the face of uncertainty, (2) exploring a wide range of alternatives to possibly harmful actions, (3) shifting the burden of proof to the proponents of an activity, and (4) increasing public participation in decisionmaking. Four countries—Germany, the Netherlands, Portugal, and Spain—recommended establishing a multistakeholder, coordinated oversight body at the country level. They likewise suggested strengthening international linkages to further guide, harmonize, and reinforce national and international efforts in DUR oversight. In countries, such actions may require creating new mechanisms or bolstering existing mechanisms and identifying entities to take on this role. Several NECs also suggested that bodies, such as the EU, play a formal coordinating role. Five countries—Denmark, Germany, Italy, the Netherlands, and The United States—emphasized that the global nature of biorisk and that of specific fields examined by the NECs requires international collaboration, and that regulations, legal limitations, and restrictions must be implemented internationally. Key findings and recommendations from NEC publications related to DUR, including the role of NECs, are further described in this article.
Argentina
The National Committee of Ethics in Science and Technology analyzed biosecurity practices in the use of biotechnology in agriculture, where the law enumerates the evaluations needed to authorize a genetically modified organism to enter the market. The ethical evaluation 11 considered the extent to which the law incorporates the principles of precaution, social responsibility, and justice. Limited implementation of codes, standards, and regulations was considered an obstacle to implementing measures at the international level to avoid dangers that have become global in nature. 13 The development of legislation, coordinated action in the region, and the creation of an international fund to support compliance with established guidelines was recommended.
Denmark
In 2011, the Danish Council of Ethics and the Danish Board of Technology addressed the directions and values that should underpin technological development. 18 As the exact risks and potential of synthetic biology cannot be predicted, a continual reassessment of risks was proposed. National laws and regulations align with the EU directive on The Contained Use of Genetically Modified Organisms (1990), 28 requiring researchers to notify authorities of genetic engineering research and production. Authorities assess the risks to biological systems (human safety and health, animals, plants, environment) to grant approval and “it is prohibited to work with an organism if safer, alternative organisms are available.” 18 Commercial products must document safety and risks, and genetically modified organisms are subject to import/export rules. Denmark recommended no new legislation, but it recommends an ongoing assessment of regulations for new research as well as tools for the control and regulation of damages and risks from synthetic biology. The global nature of the field requires international implementation of regulations, legal limitations, and restrictions. The importance of avoiding the obstruction or constraint of scientific development is emphasized.
Germany
In 2014, the German Ethics Council analyzed biosecurity research from the scientific, ethical, and legal perspectives and issued recommendations for future research and funding requirements. 23 Classical risk assessment methods were deemed insufficient to assess research that could be misused. Recommendations included building biosecurity awareness in the scientific community and legally binding regulations on dual-use research of concern (DURC), with a central DURC Commission to work with the Central Committee on Biosecurity. The NEC recommended that an interdisciplinary commission be legislatively mandated, to “include life science and (bio)security experts as well as biosecurity expertise from civil society.” 29 Consequently, a Joint Committee—a cooperation between the German National Academy of Sciences (Leopoldina) and the German Research Foundation (DFG)—on the Handling of Security-Relevant Research was established. The creation of a DURC Commission at the European Union (EU) level was recommended, as well as unified legislation and standards in all member states.
Italy
The Italian Committee for Bioethics examined the precautionary principle from the perspective of environmental safety and health. 12 They stressed the engagement of the public in decisionmaking and when creating regulations. The committee highlighted the duty of the government regarding prevention of risks to the environment, calling for more cautious authorizations based on the precautionary principle where scientific information is incomplete.
The Netherlands
In 2013, the Biosecurity Committee of the Royal Netherlands Academy of Arts and Sciences asserted that all parties involved in knowledge generation (eg, funders, industry, academic institutions) are responsible for addressing the dual-use risks of life sciences research. Given the need for expertise in multiple areas, none of the existing bodies at the country level were considered equipped to advise on biosecurity aspects of research. The establishment of the Biosecurity Advisory Committee for Research in the Life Sciences was proposed, to include life scientists, security experts, and ad hoc experts. 21 The advisory report 21 and a code of conduct for biosecurity 30 also provide guidelines for scientists and organizations dealing with DUR.
Norway
The Norwegian National Ethics Committee for Research Ethics in Science and Technology (NENT) produced a booklet addressing articles 10 and 11 of the NENT Guidelines for Research Ethics in Science and Technology (2007). 15 Article 10 asks the researcher “to clarify the degree of certainty and precision that characterizes the research results. In particular, the researcher must take care to clarify the relative extent of the results' certainty and validity, as well as to indicate any elements of risk or uncertainty that may be significant for possible uses of the research results.” Article 11 states that “in cases where plausible, yet uncertain information exists that the use of technology or the development of a certain research field might lead to ethically unacceptable consequences for health, society or the environment, researchers within the given field must strive to provide information that is relevant for using the Precautionary Principle.” To facilitate the understanding of the articles, key concepts were addressed such as uncertainty (various types and methodologies for categorizing and addressing them), risk, precaution, and governance.
Spain and Portugal
A 2011 joint report from Spain and Portugal 19 noted that synthetic biology raises ethical issues similar to issues raised in other emerging areas (eg, nanotechnology, neuroimaging, genetics). The same ethical principles, rules, and guidelines on biosecurity and the precautionary principle apply, and current evidence does not justify imposing additional restrictions. The countries recommend creating national, regional, and/or local commissions charged with the control, supervision, and follow-up of activities related to emergent biotechnologies.
Switzerland
The Swiss Commission fédérale d'éthique pour la biotechnologie dans le domaine non humain (CENH) concluded that according to Swiss jurisprudence, the fundamental right to freedom of research encompasses the publication of results and their potential misuse, as “only one aspect of the tension between freedom of research and security.” 24 Most topics addressed by the commission are also applicable to other domains of research that entail high risks. Thus, decisionmaking regarding DUR projects should consider the project as a whole; however, no reference is made to the body that should make such assessments. The importance of interdisciplinary expertise was highlighted in the analysis of risks, possible damage scenarios, and their probability. International institutions have a role to play in minimizing risks in DUR, and if legitimate restrictions are imposed to research freedom, they should also be applied at the international level.
The commission further examined the ethical requirements in the regulation of genomic editing, and the applications of these biotechnologies to the environment. 16 It also addressed the ethical significance of the concept of precaution and the obligations that may arise from it, 31 concluding that it should be used in the regulation of biotechnologies, anchored in environmental law, and used at the international level. Further recommendations concerned improving the reliability of risk assessments, strengthening the independence of scientific institutions, and ensuring the separation of roles (expert advisory bodies versus decisionmaking authorities and/or justice administration). Lastly, it recommended raising awareness about the political dimension of the use of technology and the management of uncertainties and to involve citizens given that value judgments influence decisionmaking. 31
United Kingdom
The UK Nuffield Council on Bioethics 2012 report offered “a set of principles by which our society may better think about, and discuss, the making of biotechnology choices.” 20 Debate on biosecurity and DUR in areas such as health, security, and academic freedom, and the framing of issues on biotechnology critically influence decisionmaking. Three distinctive characteristics of emerging biotechnologies are uncertainty, ambiguity, and transformative potential, because they can result in profound changes in environments (social, commercial, or physical) with implications for individuals and society. A “public ethics” approach to biotechnology governance was proposed and the limits to regulation reiterated: “regulation cannot provide all the answers to securing benefits or averting harms from emerging biotechnologies, not least because emerging biotechnologies do not fit into risk-based regulatory models but require instead an approach guided by the virtue of caution which, in turn, requires a continuous and reflective engagement with broader societal interests.” 20
The UK Nuffield Council on Bioethics report on genome editing, 25 a development that poses future risks for the Biological and Toxin Weapons Convention, 32 noted concerns about biosafety and environmental release and the ways in which knowledge is produced and innovation is managed have an impact on the public interest. Additional concerns relate to research with the potential for military or terrorist applications. The use of the precautionary principle is advised when consequences include highly undesirable and irreversible or catastrophic outcomes; however, the principle is difficult to define, interpret, and apply.
The council also identified ethical questions arising from neuroscience, uncertainties about the safety and long-term impact of therapies and technologies, the risk-benefit ratio, and the prospect for dual use. 22 The council called for continuous evaluation to ensure that innovations benefit the public and avoid dual-use applications. Concerns remain regarding the use of new technologies for military purposes as opposed to therapeutic ones: “The value of reflexive evaluation does not end at the point at which a neurotechnological application receives regulatory approval to enter the market, but endures with the responsibility to respond to unexpected adverse effects or emerging ‘off-label’ uses.” 22
United States
The US Presidential Commission for the Study of Bioethical Issues focused on synthetic biology to identify ethical boundaries that maximize public benefits and minimize risks. 17 The commission concluded that new agencies, offices, or authorities are not necessary, but recommended bringing together agencies involved to clarify oversight authority, ensure that the government is informed, and identify gaps in risk assessment related to the field release of synthetic organisms. Because synthetic biology is an international enterprise, oversight and regulation should be as well. Coordination with governments, WHO, and other partners including international bioethics organizations is considered essential for safety and security, as well as for the evaluation and update of regulations. The commission recommend strengthening the culture of responsibility among scientists and ethics education for researchers and student-investigators outside the medical setting, including in engineering and material science.
Discussion
This study presents several limitations, the first of which is related to the dates of the documents reviewed (2001-2018). The WHO NEC database was discontinued in 2020 due to the COVID-19 pandemic and we reviewed only the work of NECs included in the database as determined by countries. Committees may have produced documents that were not submitted to the database. It could be argued that, like influenza and other previous outbreaks, the pandemic might have prompted a reassessment of the role of NECs in the context of DUR. Yet, the ethical reasoning and its applicability to the different fields has not changed over time and is still applicable; issues discussed in 2001 in Argentina 11 are still pertinent in Switzerland. 33 And despite the timeframe, different committees addressed the topics using the same principles (eg, maximizing benefits while minimizing risks, applying the precautionary principle). A second limitation was the small number of countries (11) and documents (16) we reviewed. Third, we reviewed only those documents in English, French, German, and Spanish, and therefore NEC guidance in other languages was not represented. Despite these limitations, this study complements other studies addressing the role of ethics committees in raising awareness at national and institutional levels and reviewing DUR studies.34,35
In line with international guidelines,36,37 most documents reviewed refer to the importance of evaluating the risks and benefits of research within and beyond the life sciences. However, only 2 documents from Germany 23 and the Netherlands 14 called for the establishment of specific boards to oversee DUR studies. Germany proposed a DURC Commission affiliated with an existing institution to work with the Central Committee on Biosecurity, and the Netherlands recommended a Biosecurity Advisory Committee for Research in the Life Sciences, under the Dutch Health Council. The boards would comprise life sciences and security experts and would coordinate at the EU level. While Germany called for the establishment of a DURC Commission at the EU level, and unified legislation and standards to be established in all member states, the Netherlands prioritized “coordination at European level and, possibly, the eventual establishment of EU rules or institutions.” 21 The boards from Denmark, 18 Italy, 12 and the United States 17 called for the alignment of regulations within the EU and at the international level. Argentina also recommended coordination and harmonization on biosecurity among countries of the region. 11 The fact that the Argentinian document relates to a law project on biosecurity in the agricultural field indicates that countries may be at different stages with regard to biosafety, biosecurity, and DUR.
While laws and regulations were not modified in Germany, a high-level Joint Committee of DFG and Leopoldina was created to guide research institutions on setting up ethics committees, advising researchers, and developing competencies in DUR. 38 In the Netherlands, the governmental biosecurity office supports institutions working with high-risk biological material. A web-based Dual-Use Quickscan 39 allows researchers working with microorganisms to determine the dual-use potential of studies, as a basis for a biorisk mitigation plan or the involvement of the biorisk management committee. 40 Similarly, in the United States, researchers should notify the institutional review entity when planning to work with certain agents and toxins and, if necessary, develop risk mitigation measures. In Denmark, approval from authorities is needed to conduct research on genetic engineering.
In Germany, the establishment of ethics committees would serve to increase DUR awareness and capacity in research institutions. Establishing such committees requires institutional resources dedicated to a subject that may not often be present in certain disciplines. However, even if only a few existing ethics committees were used for DUR evaluation, an advantage would be that existing committees could expand their mandate to address DUR matters. Ad hoc experts could be called on as needed. Committees would benefit from established procedures, experience in evaluating ethical issues, and recognition as an authority by scientific and political bodies.
The German model allows for different structures; for example, several institutions might jointly operate a committee while others might assign ethics commissioners to research institutions. This approach may be particularly useful for low- and middle-income countries with limited resources and where existing infrastructures may be suitable. However, some research ethics committees may lack expertise in biosecurity and DUR. Results from a survey 38 by the Joint Committee of DFG and Leopoldina indicate that the role of research ethics committees has been limited to the evaluation of adherence to institutional and regulatory rules (ie, data security, export control) and that potential for assessing misuse was not identified in the majority of studies. This may reflect the fact that DUR is a dynamic area that requires expertise in a variety of complex subjects (eg, artificial intelligence, stem cell research, potential uses of population datasets), and the recent establishment of committees or new mandates for existing committees. Therefore, the onus is on countries to bring together the expertise needed to identify and address the DUR challenges at hand even as they continue to evolve and new ones emerge.
Denmark, the Netherlands, and the United States propose a regulatory structure that supports closer follow-up of projects and better understanding of developments in the field. This could inform planning when taking additional preventive measures about DUR. The potential risks lie in DUR oversight being limited to certain pathogens, toxins, and categories of experiments. 41 The rapid advances in science and technology allow DUR to be identified in different domains and at later stages of the research process as new risks emerge. 42 Therefore, risk-based regulatory models may no longer suffice to govern biorisks because they relate to laws and regulations linked to particular fields.
This study presents a snapshot of ethics leadership in higher-income countries at a time when emerging global issues were beginning to drive the reconsideration of approaches to managing biorisk and dual-use research. In the intervening years (2019 to March 2024), the scientific world has seen even more rapid change as the COVID-19 pandemic spurred the adoption of new technologies and practices, such as broad scientific sharing of data and results and rapid publication of research. The ongoing political, scientific, and public debate seems to be prompting a reevaluation of approaches to risk and new ways of looking at DUR in countries.
The issues identified by the national ethics committees are still valid today, and their recommendations should be considered in light of the present situation and new developments. The engagement of the international community will be critical in continuing efforts to strengthen capacity, share knowledge, and support the independence of NECs, which will improve the capabilities and methods of the global ethics community and allow them to evolve together to meet the challenges to come.
Conclusion
The 2022 WHO framework on DUR calls for a mix of governance and oversight mechanisms to manage the risks posed by science and technology. 1 It calls for the involvement of multiple stakeholders in the governance of biorisks and the cooperation of different sectors nationally and internationally. Ethics represents a key component of the framework.
This study assessed the role of national ethics committees with regard to DUR. Based on the available documentation produced by NECs until 2018, relatively few national ethics committees have produced opinions and statements to raise awareness, reflect on DUR oversight at the country level, assess the potential risks of emerging fields and technologies, and propose alternatives to current practices to strengthen oversight. Only 1 country, Germany, has used institutional ethics mechanisms as a component of DUR oversight.
Given that DUR governance involves multiple partners and institutions and relies on practices and conduct of different actors, NECs would seem to have a fairly limited function within national structures and mechanisms. Nevertheless, they can play a fundamental role in analyzing ethical questions raised in various areas with regard to DUR, informing societal discussions relevant to shape the research agenda, and advising on policy and/or legislation. Their capacity to collaborate with other NECs is key to advancing discussions on societal challenges related to DUR.
The analyses made by NECs in the publications reviewed for this study reflected the importance of the precautionary principle, which seems to respond to the challenges of different fields. Accordingly, NECs can increase awareness among stakeholders (eg, research ethics committees, health safety institutions, security institutions, regulators) regarding the importance of applying the precautionary principle in areas that may raise dual-use concerns. In the absence of NECs, specialized research ethics committees are well positioned to alert stakeholders to those issues, as they are at the forefront of the ethical evaluation of research projects.
Governance of life sciences is intrinsically related to values and principles. While different bodies with diverse mandates looking at DUR may exist at the country level (ie, biosecurity/biosafety), NECs can inform decisionmaking based on the analysis of such values and principles, and they can provide valuable advice when building, strengthening, or modifying regulatory systems. This is particularly so in countries where other oversight mechanisms may not be fully established. The use of NEC expertise, however, is determined by the political context, their degree of independence, and the support they receive from different sectors and institutions. The role and contribution of NECs is likely to continue expanding as approaches and capabilities to manage biorisk continue to develop in countries and in the international bioethics community.
Footnotes
Acknowledgments
We thank Prof Dr Patrick Hummel (The Netherlands) for document retrieval, Dr Les Olson (Australia) for his valuable guidance and advice, Dr Soatiana Rajatonirina and Dr Emmanuelle Tuerlings for their thorough review. We certify that all persons named in the Acknowledgment have provided written permission to be named.