Oversight of Dual-Use Research: What Role for Ethics Committees?

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.

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.

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.

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.