Virology-the path forward.

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

COVID-19 and the gain of function debates: Improving biosafety measures requires a more precise definition of which experiments would raise safety concerns.

The COVID-19 pandemic has rekindled debates about gain-of-function experiments. This is an opportunity to clearly define safety risks and appropriate countermeasures.

Does Biotechnology Pose New Catastrophic Risks?

Advances in biotechnology in the twenty-first century, fueled in large part by the field of synthetic biology, have greatly accelerated capabilities to manipulate and re-program bacteria, viruses, and other organisms. These genetic engineering capabilities are driving innovation and progress in drug manufacturing, bioremediation, and tissue engineering, as well as biosecurity preparedness. However, biotechnology is largely dual use, holding the potential of misuse for deliberate harm along with positive applications; defenses against those threats need to be anticipated and prepared. This chapter describes the challenges of managing dual-use capabilities enabled by modern biotechnology and synthetic biology and highlights a framework tool developed by a National Academies committee to aid analysis of the security effects of new scientific discoveries and prioritization of concerns. The positive aspects of synthetic biology in preparedness are also detailed, and policy directions are highlighted for taking advantage of the positive aspects of these emerging technologies while minimizing risks.

CRISPR Cautions: Biosecurity Implications of Gene Editing.

CRISPR, a powerful gene-editing technology, is revolutionizing the life sciences and medical research. The technology has also become democratized. Costs to use CRISPR are low and decreasing, kits are available to make the use of CRISPR straightforward, and there is a rapidly growing scientific literature describing CRISPR methodologies and novel applications. However, like other powerful advances in the life sciences, CRISPR raises biosecurity concerns: it could be misused for harm, and it lowers technical barriers to biological weapons development. This essay describes the history and dissemination of CRISPR as genome-editing techniques have become widespread, outlines potential biosecurity concerns, and recommends actions governments and scientists may take to reduce biosecurity risks. While it is not possible to eliminate biosecurity risks from the misuse of biotechnologies, including CRISPR, steps can be taken to increase security while allowing this powerful technology to remain widely available for beneficent purposes.

Analysis of sectoral participation in the development of Joint External Evaluations.

BACKGROUND: The Joint External Evaluation Process (JEE), developed in response to the 2014 Global Health Security Agenda (GHSA), is a voluntary, independent process conducted by a team of external evaluators to assess a country's public health preparedness capabilities under the 2005 International Health Regulations (IHR) revision. Feedback from the JEE process is intended to aid in the development of national action plans by elucidating weaknesses in current preparedness and response capabilities. METHODS: To identify gaps in sector participation and the development of national action plans in response to public health emergencies, all English-language JEE reports available on March 31, 2018 (N = 47) were systematically reviewed to determine sectoral backgrounds of key host country participants. RESULTS: Overall, strong representation was seen in the health, agriculture, domestic security, and environment sectors, whereas the energy/nuclear and defense sectors were largely under-represented. CONCLUSIONS: While strong participation by more traditional sectors such as health and agriculture is common in the JEE development process, involvement by the defense and energy/nuclear sectors in the JEE process could be increased, potentially improving preparedness and response to widespread public health emergencies.

Information Hazards in Biotechnology.

With the advance of biotechnology, biological information, rather than biological materials, is increasingly the object of principal security concern. We argue that both in theory and in practice, existing security approaches in biology are poorly suited to manage hazardous biological information, and use the cases of Mousepox, H5N1 gain of function, and Botulinum toxin H to highlight these ongoing challenges. We suggest that mitigation of these hazards can be improved if one can: (1) anticipate hazard potential before scientific work is performed; (2) consider how much the new information would likely help both good and bad actors; and (3) aim to disclose information in the manner that maximally disadvantages bad actors versus good ones.

Safety, security, and serving the public interest in synthetic biology.

This article describes what may be done by scientists and by the biotechnology industry, generally, to address the safety and security challenges in synthetic biology. Given the technical expertise requirements for developing sound policy options, as well as the importance of these issues to the future of the industry, scientists who work in synthetic biology should be informed about these challenges and get involved in shaping policies relevant to the field.

The Model State Indoor Air Quality Act.

This Viewpoint discusses how poor indoor air quality can affect health and examines the Model State Indoor Air Quality Act, which provides science-based regulatory standards aimed at ensuring public indoor environments provide healthy air.

Expert Views on Biological Threat Characterization for the U.S. Government: A Delphi Study.

Biological threat characterization (BTC) involves laboratory research conducted for the purpose of biological defense. BTC research is important for improving biological risk assessment and informing resource prioritization. However, there are also risks involved in BTC work, including potential for escape from the laboratory or the misuse of research results. Using a modified Delphi study to gather opinions from U.S. experts in biosecurity and biodefense, this analysis explores what principles and safeguards can maximize the benefits of BTC research and ensure that it is conducted safely and securely. Delphi participants were asked to give their opinions about the need for BTC research by the U.S. government (USG); risks of conducting this research; rules or guidelines that should be in place to ensure that the work is safe and accurate; components of an effective review and prioritization process; rules for when characterization of a pathogen can be discontinued; and recommendations about who in the USG should be responsible for BTC prioritization decisions. The findings from this research reinforce the need for BTC research at the federal level as well as a need for continued review and oversight of this research to maximize its effectiveness and reduce the risks involved. It also demonstrates the need for further discussion of what would constitute a "red line" for biothreat characterization research-research that should not be performed for safety, ethical, or practical reasons-and guidelines for when there is sufficient research in a given topic area so that the research can be considered completed.

COVID-19 Mitigation in a K-12 School Setting: A Case Study of Avenues: The World School in New York City.

In this case study, we describe a well-resourced private school in New York City that implemented COVID-19 mitigation measures based on public health expert guidance and the lessons learned from this process. Avenues opened in New York City in 2012 and has since expanded, becoming Avenues: The World School, with campuses in São Paulo, Brazil; Shenzhen, China; the Silicon Valley, California; and online. It offers education at 16 grade levels: 2 early learning years, followed by a prekindergarten through grade 12. We describe the mitigation measures that Avenues implemented on its New York campus. We compare COVID-19 case prevalence at the school with COVID-19 case positivity in New York City, as reported by the New York State Department of Health. We also compare the school's indoor air quality to ambient indoor air quality measures reported in the literature. The school's mitigation measures successfully reduced the prevalence of COVID-19 among its students, staff, and faculty. The school also established a consistently high level of indoor air quality safety through various ventilation mechanisms, designed to reduce common indoor air pollutants. The school received positive parent and community feedback on the policies and procedures it established, with many parents commenting on the high level of trust and quality of communication established by the school. The successful reopening provides useful data for school closure and reopening standards to prepare for future pandemic and epidemic events.

Integrating safety, security, sustainability, and social responsibility principles into the U.S. bioeconomy.

Bioindustrial manufacturing is undergoing rapid expansion and investment and is seen as integral to nations' economic progress. Ensuring that bioindustrial manufacturing benefits society as the field expands is of critical, urgent importance. To better understand the industry's ethical trajectory and to shape policy, we explored the views of biotechnology leaders on four aspects of ethical and social responsibility-safety, security, social responsibility, and sustainability-what we have termed "4S principles." We identified policy actions governments and other stakeholders may take to maximize societal benefits in industrial biotechnology. IMPORTANCE: We analyzed biotech leaders' views on safety, security, social responsibility, and sustainability to recommend policies to maximize benefits and economic growth.

Shaping the future US bioeconomy through safety, security, sustainability, and social responsibility.

Biomanufacturing practitioners and researchers describe the norms that should govern the growing, global field, to include safety, security, sustainability, and social responsibility. These '4S Principles' should be broadly adopted so that the future of the field may provide the greatest benefits to society.

Improving U.S. Biosafety and Biosecurity: Revisiting Recommendations from the Federal Experts Security Advisory Panel and the Fast Track Action Committee on Select Agent Regulations.

Introduction: In response to a series of biosafety incidents in 2014, the White House directed two high-level expert committees to analyze biosafety and biosecurity in U.S. laboratories and make recommendations for work with select agents and toxins. Overall, they recommended 33 actions to address areas related to national biosafety, including promoting a culture of responsibility, oversight, outreach and education, applied biosafety research, incident reporting, material accountability, inspection processes, regulations and guidelines, and determining the necessary number of high-containment laboratories in the United States. Methods: The recommendations were collected and grouped into categories previously defined by the Federal Experts Security Advisory Panel and the Fast Track Action Committee. Open-source materials were examined to determine what actions had been taken to address the recommendations. The actions taken were compared against the reasoning provided in the committee reports to determine if the concerns were sufficiently addressed. Results: In this study, we found that 6 recommendations were not addressed and 11 were insufficiently addressed out of 33 total recommended actions. Discussion and Conclusion: Further work is needed to strengthen biosafety and biosecurity in U.S. laboratories handling regulated pathogens (biological select agents and toxins [BSAT]). These carefully considered recommendations should now be enacted, including determining if there is sufficient high-containment laboratory space for response to a future pandemic, developing a sustained applied biosafety research program to improve our understanding of how high-containment research should be performed, bioethics training to educate the regulated community on the consequences of unsafe practices in BSAT research, and the creation of a no-fault incident reporting system for biological incidents, which may inform and improve biosafety training. Significance: The work presented in this study is significant because previous incidents that occurred in Federal laboratories highlighted shortcomings in the Federal Select Agent Program and the Select Agent Regulations. Progress was made on implementing recommendations to address the shortcomings, but efforts were lost or forgotten over time. The COVID-19 pandemic has provided a brief window of interest in biosafety and biosecurity, and an opportunity to address these shortcomings to increase readiness for future disease emergencies.

Proposal for a national diagnostics action plan for the United States.

Providing a definitive diagnostic test in a disease emergency is critical to limit pathogen spread, develop and deploy medical countermeasures, and mitigate the social and economic harms of a serious epidemic. While major accomplishments have accelerated test development, expanded laboratory testing capacity, and established widespread point-of-care testing, the United States does not have a plan to rapidly respond, to develop, manufacture, deploy, and sustain diagnostic testing at a national scale. To address this gap, we are proposing a National Diagnostics Action Plan that describes the steps that are urgently needed to prepare for future infectious disease emergencies, as well as the actions we must take at the first signs of such' events. These recommendations require substantial collaboration between the US government (USG) and the private sector to solve a series of challenges now, as well as to prepare for the massive and rapid scale-up of laboratory and point-of-care test development and testing capacity in future emergencies. The recommendations include establishing pre-event contracts; ensuring rapid access to clinical samples; creating a permanent public-private testing coordinating body to allow for rapid information sharing and improved cooperation among the USG, test developers, and clinical laboratories; and accelerating testing rollout at the beginning of an event-and thus, the effective public health management of a disease crisis.