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surrounding many NPI interventions and the adverse consequences that may follow them. Accidental Release and Biosafety Biosafety encompasses lab infrastructure, PPE, and laboratory protocols; these are the tools and practices designed to protect laboratory workers and the environment from infection escaping from the laboratory. Laboratory-acquired infections (LAIs) occur from occupational exposures to pathogens to those working in a laboratory. LAIs not only affect the health of the individual researcher but also pose a risk to the broader public health, as LAIs are a mechanism for accidental release of pathogens into the environment. This is especially troubling when the pathogen in question is not endemic to the area or when 59 there are few or no countermeasures or treatments. And it would be of potentially extraordinary consequence, even pandemic consequence, if a lab infection with a high-impact respiratory pathogen led to human spread outside the laboratory. Good biosafety practices substantially lower the risk of a pathogen escaping the laboratory via contaminated clothing, items, or skin, and they seek to ensure pathogens are contained during transportation. The 2 most widely used resources for biosafety are WHO’s Laboratory Biosafety Manual and the US CDC’s Biosafety in Microbiological and Biomedical Laboratories (BMBL) handbook.131,132 These documents outline how to categorize risk groups for pathogens, which then determines which biosafety precautions are necessary for working with that agent. The JEE tool also includes a section on biosafety and biosecurity, including minimum requirements of strong biosafety systems.66 These requirements primarily focus on training and a whole-government approach to handling biosafety and biosecurity. There are 2 different approaches to biosafety in laboratories, one relying primarily on infrastructure, such as biological safety cabinets, and the second primarily emphasizing PPE. Each national government is responsible for promoting a particular approach, which will determine both how resources are allocated for biosafety and what protocols are used in a laboratory in that nation. Many pathogens that spread via respiratory transmission or aerosols would be considered a Risk Group 3, which requires a Biosafety Level 3 laboratory. In a country that prioritizes engineering controls, laboratory staff may not be required to wear respirators while working in a laboratory that houses these easily aerosolized pathogens. When relying on engineering controls, regular maintenance of laboratory equipment, such as biological safety cabinets and venting systems, is vital to prevent the accidental release of a laboratory organism. In a country that emphasizes PPE, any personnel entering a laboratory space that works with such agents will have to wear respiratory protection and be trained regularly in appropriate biosafety procedures. Biosafety has often been perceived as not sufficiently important to afford resources necessary for training, oversight, equipment, standards, and other mechanisms to protect the laboratorians’ and the public’s health. This has happened in lower-income countries but also in high-income countries. It has been demonstrated repeatedly that accidents— whether in biomedical laboratories or in other highly technical spaces—can cause significant political and social problems, often with lasting consequences to research and operations. These events are believed to be considerably underreported due to lack of reporting mechanisms and potential consequences to the researchers or research institution. There are no widely accepted international biosafety norms or national model programs for countries that permit research labs to do experimental work on high-impact respiratory pathogens. There is a need to agree on and strengthen norms surrounding 60 oversight and approval of research around novel high-impact respiratory pathogens, laboratory accident reporting, biosafety instruction, accreditation, and requirements for biosafety oversight, and these steps require funding and political commitment. Deliberate Use and Biosecurity When considering the possibility of a deliberate release of a novel high-impact respiratory pathogen, the exact properties of the pathogen and its transmission dynamics would be uncertain, ranging from synthesis of a known virus to the creation of an engineered strain with highly unexpected properties. Deliberate release scenarios are more complex than natural epidemics because they would be initiated by an attacker who chose where and how to attack for a purpose.133 The objectives of such an attack would have an impact on the outcomes of the event above and beyond the properties of the pathogen itself in the sense of where and how the pathogen was disseminated. Deviation from a natural pattern would be expected even if no engineered or altered traits had been introduced into the pathogen. For example, its release might be coordinated across locations and timepoints, such that traditional outbreak response efforts could become misguided or overwhelmed. Risk would not be determined solely by epidemiology and exposure risks. Higher doses of pathogens could create more fulminant manifestations of a disease. Deliberate attacks might also target the emergency responses and critical services that a country would use to respond to the resulting epidemic. Countries and international organizations should not assume that preparedness for a naturally occurring outbreak equates to preparedness for a deliberate release event. Special attention should be given to plan and prepare for such deliberate events. Earlier national and international experience with biological weapons and bioterrorism predates the synthetic biology revolution. Over the past decade, technology has made it increasingly straightforward to alter the genetics of a pathogen. Some RNA viruses may particularly lend themselves to natural pandemic spread,15 but they are currently hard to engineer, particularly with trans genes.134 It is reasonable to predict that the barriers to such engineering will decrease in the future. Rapid advances in synthetic biology capabilities, such as