Reconsidering the need for gain-of-function research on enhanced potential pandemic pathogens in the post-COVID-19 era.

The dual-use risk of infectious disease research using enhanced potential pandemic pathogens (ePPP), particularly gain-of-function (GOF) research, has been debated since 2011. As of now, research is supported on the condition that the research plan is reviewed and the actual experiment is supervised. However, the kinds of research conducted and what benefits they have brought to our society have not been adequately verified. Nevertheless, due to the COVID-19 pandemic that began at the end of 2019 and caused numerous deaths and wide economic disruption, the importance of infectious disease control from an international perspective has been recognized. Although complete control of the pandemic is still far off, positive signs include generating epidemiological trends based on genome analysis, therapeutic drug and vaccine development, clinical patient management, and public health policy interventions. In this context, the time has come to reconsider the true significance of GOF research on ePPP and the state of research governance in the post-COVID-19 era. In particular, the risks of such research are clearer than before, whereas its benefits seem less apparent. In this paper, we summarize the history of discussions on such GOF research, its significance in the light of the current COVID-19 pandemic, and the direction we shall take in the future.

Strengthening biological security after COVID-19: Using cartoons for engaging life science stakeholders with the Biological and Toxin Weapons Convention (BTWC).

The devastating effects of the COVID-19 pandemic have acutely shown the need for maintaining robust international and national systems for biological security and ensuring that life sciences are used only for peaceful purposes. Life science stakeholders can play an important role in safeguarding scientific and technological advances in biology and related fields against accidental or deliberate misuse, not least because they are on the frontlines of driving innovation. In this paper, we argue that enhancing awareness and understanding of the risk of deliberate disease is essential for effective biological security. We first discuss the issue of 'dual use' in science and technology as it relates to disarmament and non-proliferation of weapons of mass destruction. Second, we review how scientist engagement with dual-use risks has been addressed in the context of the Biological and Toxin Weapons Convention (BTWC). Third, we report on the development of an innovative awareness-raising tool, a cartoon series, that can be used for engaging life science stakeholders with BTWC issues. Finally, we outline a set of practical considerations for promoting sustainable life science engagement with the BTWC.

The vital importance of a web of prevention for effective biosafety and biosecurity in the twenty-first century.

Biological threats are complex and multifaceted, as evidenced by the ongoing COVID-19 pandemic. Their effective prevention and countering require multiple lines of collaborative action and sustained cross-sectorial coordination. This paper reviews the conclusions of Graham Pearson's 1997 JAMA article titled 'The Complementary Role of Environmental and Security Biological Control Regimes in the 21st Century', taking into account the international policy developments that have occurred over the past two decades. The paper underscores the utility of the concept of a 'web of prevention' for elucidating the need for continuous interaction between the international biosafety and international biosecurity regimes, in order to ensure that the life sciences are used only for peaceful purposes. The terms 'biosafety' and 'biosecurity' are used to denote the primary purpose of the two regimes: the international biosafety regime seeks to prevent the unintentional (accidental) release of pathogens and toxins, including naturally occurring disease, whereas the biosecurity regime seeks to prevent the deliberate release and misuse of pathogens and toxins. The paper concludes by recommending practical steps for strengthening the implementation of all elements of the web of prevention and upholding the norms against the hostile misuse of life sciences.

80 questions for UK biological security.

Multiple national and international trends and drivers are radically changing what biological security means for the United Kingdom (UK). New technologies present novel opportunities and challenges, and globalisation has created new pathways and increased the speed, volume and routes by which organisms can spread. The UK Biological Security Strategy (2018) acknowledges the importance of research on biological security in the UK. Given the breadth of potential research, a targeted agenda identifying the questions most critical to effective and coordinated progress in different disciplines of biological security is required. We used expert elicitation to generate 80 policy-relevant research questions considered by participants to have the greatest impact on UK biological security. Drawing on a collaboratively-developed set of 450 questions, proposed by 41 experts from academia, industry and the UK government (consulting 168 additional experts) we subdivided the final 80 questions into six categories: bioengineering; communication and behaviour; disease threats (including pandemics); governance and policy; invasive alien species; and securing biological materials and securing against misuse. Initially, the questions were ranked through a voting process and then reduced and refined to 80 during a one-day workshop with 35 participants from a variety of disciplines. Consistently emerging themes included: the nature of current and potential biological security threats, the efficacy of existing management actions, and the most appropriate future options. The resulting questions offer a research agenda for biological security in the UK that can assist the targeting of research resources and inform the implementation of the UK Biological Security Strategy. These questions include research that could aid with the mitigation of Covid-19, and preparation for the next pandemic. We hope that our structured and rigorous approach to creating a biological security research agenda will be replicated in other countries and regions. The world, not just the UK, is in need of a thoughtful approach to directing biological security research to tackle the emerging issues.

Bioengineering horizon scan 2020.

Horizon scanning is intended to identify the opportunities and threats associated with technological, regulatory and social change. In 2017 some of the present authors conducted a horizon scan for bioengineering (Wintle et al., 2017). Here we report the results of a new horizon scan that is based on inputs from a larger and more international group of 38 participants. The final list of 20 issues includes topics spanning from the political (the regulation of genomic data, increased philanthropic funding and malicious uses of neurochemicals) to the environmental (crops for changing climates and agricultural gene drives). The early identification of such issues is relevant to researchers, policy-makers and the wider public.

Dual-use nano-neurotechnology.

The chemical and biological nonproliferation regime stands at a watershed moment, when failure seems a real possibility. After the unsuccessful outcome of the 2016 Eighth Review Conference, the future of the Biological and Toxin Weapons Convention is uncertain. As the Chemical Weapons Convention (CWC) approaches its Fourth Review Conference in 2018, it has almost completed removing the huge stocks of chemical weapons, but it now faces the difficult organizational task of moving its focus to preventing the reemergence of chemical weapons at a time when the international security situation appears to be increasingly more difficult and dangerous. In this article, we assess the current and near-term state (5-10 years) and impact of three related areas of science and technology that could be of dual-use concern: targeted delivery of agents to the central nervous system (CNS), particularly by means of nanotechnology; direct impact of nanomaterials on synaptic functions in the CNS; and neuronal circuits in the brain that might be targeted by those with hostile intent. We attempt to assess the implications of our findings, particularly for the consideration of the problem of state-level interest in so-called nonlethal incapacitating chemical agents for law enforcement at the CWC Review Conference in 2018, but also more generally for the longer-term future of the chemical and biological nonproliferation regime.

Dual-Use Nano-Neurotechnology: An assessment of the implications of trends in science and technology.

The chemical and biological nonproliferation regime stands at a watershed moment, when failure seems a real possibility. After the unsuccessful outcome of the 2016 Eighth Review Conference, the future of the Biological and Toxin Weapons Convention is uncertain. As the Chemical Weapons Convention (CWC) approaches its Fourth Review Conference in 2018, it has almost completed removing the huge stocks of chemical weapons, but it now faces the difficult organizational task of moving its focus to preventing the reemergence of chemical weapons at a time when the international security situation appears to be increasingly more difficult and dangerous. In this article, we assess the current and near-term state (5-10 years) and impact of three related areas of science and technology that could be of dual-use concern: targeted delivery of agents to the central nervous system (CNS), particularly by means of nanotechnology; direct impact of nanomaterials on synaptic functions in the CNS; and neuronal circuits in the brain that might be targeted by those with hostile intent. We attempt to assess the implications of our findings, particularly for the consideration of the problem of state-level interest in so-called nonlethal incapacitating chemical agents for law enforcement at the CWC Review Conference in 2018, but also more generally for the longer-term future of the chemical and biological nonproliferation regime.

A transatlantic perspective on 20 emerging issues in biological engineering.

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.

The Creation of a Contagious H5N1 Influenza Virus: Implications for the Education of Life Scientists.

The paper contends that the ongoing controversy surrounding the creation of a contagious H5N1 influenza virus has already exposed the severe limitations of the possibility of preventing the hostile misuse of the life sciences by dint of oversight of proposals and publications. It further argues that in order to prevent the potential wholesale militarisation of the life sciences, it is essential that life scientists become aware of their responsibilities within the context of the Biological and Toxin Weapons Convention (BTWC) and actively contribute their expertise to strengthening the biological weapons non-proliferation regime .

Advances in neuroscience and the biological and toxin weapons convention.

This paper investigates the potential threat to the prohibition of the hostile misuse of the life sciences embodied in the Biological and Toxin Weapons Convention from the rapid advances in the field of neuroscience. The paper describes how the implications of advances in science and technology are considered at the Five Year Review Conferences of the Convention and how State Parties have developed their appreciations since the First Review Conference in 1980. The ongoing advances in neurosciences are then assessed and their implications for the Convention examined. It is concluded that State Parties should consider a much more regular and systematic review system for such relevant advances in science and technology when they meet at the Seventh Review Conference in late 2011, and that neuroscientists should be much more informed and engaged in these processes of protecting their work from malign misuse.

Biologists napping while work militarized.

As researchers discover more agents that alter mental states, the Chemical Weapons Convention needs modification to help ensure that the life sciences are not used for hostile purposes, says Malcolm Dando.

The dual-use dilemma for the life sciences: perspectives, conundrums, and global solutions.

The term "dual-use" traditionally has been used to describe technologies that could have both civilian and military usage, but this term has at least three different dimensions that pose a dilemma for modern biology and its possible misuse for hostile purposes: (1) ostensibly civilian facilities that are in fact intended for military or terrorist bioweapons development and production; (2) equipment and agents that could be misappropriated and misused for biological weapons development and production; and (3) the generation and dissemination of scientific knowledge that could be misapplied for biological weapons development and production. These three different aspects of the "dual-use dilemma" are frequently confused--each demands a distinct approach within a "web of prevention" in order to reduce the future risk of bioterrorism and biowarfare. This article discusses the nature of the different perspectives and divergent approaches as a contribution to finding a scientifically acceptable global solution to the problem posed by the dual-use dilemma. We propose that: (1) facilities that are intended for bioweapons development and production should be primarily prevented by a strengthened Biological and Toxin Weapons Convention (BTWC) effectively implemented in all nation states, one that includes provisions for adequate transparency to improve confidence and a mechanism for thorough inspections when there is sufficient cause, and enhanced law enforcement activities involving international cooperation and sharing of critical intelligence information; (2) potentially dual-use equipment and agents should be available to legitimate users for peaceful purposes, but strengthened national biosafety and physical and personnel biosecurity controls in all nations together with effective export controls should be implemented to limit the potential for the misappropriation of such equipment and materials; and (3) information should be openly accessible by the global scientific community, but a culture of responsible conduct involving the breadth of the international life sciences communities should be adopted to protect the ongoing revolution in the life sciences from being hijacked for hostile misuse of the knowledge generated and communicated by life scientists.

The potential for abuse of genetics in militarily significant biological weapons.

Concern has been expressed at successive Review Conferences of the Biological and Toxin Weapons Convention (BTWC) regarding the possible misuse of new biological knowledge; this article reviews some of these developments. Genetic manipulation, and genomics in particular, would modify existing pathogens and render previously harmless organisms pathogenic. Viruses could be modified as vectors to alter their pathogenicity in animals and man or act as carriers for genes or toxins. Plant pathogens, particularly fungi, could be modified as biological warfare agents against crops. An effective verification protocol for the BTWC is an essential part of the web of deterrence against these developments.