Making Security Viral: Shifting Engineering Biology Culture and Publishing

Abstract

The ability to construct, synthesize, and edit genes and genomes at scale and with speed enables, in synergy with other tools of engineering biology, breakthrough applications with far-reaching implications for society. As SARS-CoV-2 spread around the world in early spring of 2020, researchers rapidly mobilized, using these tools in the development of diagnostics, therapeutics, and vaccines for COVID-19. The sharing of knowledge was crucial to making rapid progress. Several publications described the use of reverse genetics for the de novo construction of SARS-CoV-2 in the laboratory, one in the form of a protocol. Given the demonstrable harm caused by the virus, the unequal distribution of mitigating vaccines and therapeutics, their unknown efficacy against variants, and the interest in this research by laboratories unaccustomed to working with highly transmissible pandemic pathogens, there are risks associated with such publications, particularly as protocols. We describe considerations and offer suggestions for enhancing security in the publication of synthetic biology research and techniques. We recommend: (1) that protocol manuscripts for the de novo synthesis of certain pathogenic viruses undergo a mandatory safety and security review; (2) that if published, such papers include descriptions of the discussions or review processes that occurred regarding security considerations in the main text; and (3) the development of a governance framework for the inclusion of basic security screening during the publication process of engineering biology/synthetic biology manuscripts to build and support a safe and secure research enterprise that is able to maximize its positive impacts and minimize any negative outcomes.

Reinventing positive-strand RNA virus reverse genetics

“…Of course, as new technologies are developed to make it easier to create, modify, and rescue viral cDNAs, molecular virologists must be mindful of the biosafety and biosecurity risks of these new technologies ( Mackelprang et al, 2022 ). Synthetic biology may also be used to address these concerns by engineering unbreakable biocontainment mechanisms into cells harboring the viral cDNA.…”

Bottom-up assembly of viral replication cycles

“…Members of the Engineering Biology Research Consortium (EBRC) recommend that the review and publication process needs to implement control mechanism to deal more seriously with safety and security issues: “The outcomes of the author, reviewer, and editor surveys should be used as a basis for discussion on minimizing publication risks. In some cases, additional safety and/or security experts may need to be engaged, and it may be valuable for authors to discuss security concerns that may result from publication with research institutions, funders, and (rarely) appropriate governmental officials” 85 .…”

SynHEAL: Synthesis of Health Equity, Advancement, and Leadership

“…Second, I emphasize the importance of biosecurity and biosafety. As engineering live cells, DNA synthesis techniques, and gene editing technologies, including the construction of smart probiotics, engineered microbiotas, and CAR-T cells, COVID virus construction protocols, and CRISPR-based therapies, become popular and available in health research fields and clinics, we must consider the consequence of their dual-uses as well as their biosecurity and biosafety. − Genetically modified organisms (GMOs) are not only issues of public perception but also biosecurity and biosafety concerns. For example, researchers can and should implement biocontainment measures such as “kill-switches” to trigger self-destruct of genetically engineered microbes (GEMs), once smart probiotics accomplish their human-defined missions, such as curing gut diseases, and are released with feces into the environment. , Additionally, the current practice of genetic engineering and GEM disposal in the lab should be reconsidered to minimize antibiotic resistance spread via horizontal gene transfer.…”

“…This practice should be replaced by shifting the paradigm: using novel plasmids containing auxotrophic markers or plasmid addiction systems rather than ARG-containing plasmids . Dual use research of concern (DURC) is especially critical to consider, given the easy DNA synthesis, numerous protocol papers, including COVID virus construction protocols, and do-it-yourself (DIY) biology activities …”

“…10 Dual use research of concern (DURC) is especially critical to consider, given the easy DNA synthesis, numerous protocol papers, including COVID virus construction protocols, and do-ityourself (DIY) biology activities. 7 Third, I encourage the community to develop breakthrough technologies with careful assessment. The past decade has witnessed the tremendous advancement of biomedical research and clinical approaches thanks to the transformative technologies of CRISPR-based gene editing and its modifications.…”