Search for: All records

Introduction: Rapid advances in biotechnologies and transdisciplinary research are enhancing the ability to perform full-scale engineering of biology, contributing to worldwide efforts to create bioengineered plants, medicines, and commodities, which promise sustainability and innovative properties. Objective: This rapidly evolving biotechnology landscape is prompting focused scrutiny on biosecurity frameworks in place to mitigate harmful exploitation of biotechnology by state and non-state actors. Concerns about biosafety and biosecurity of engineering biology research have existed for decades as views about how advances in this and associated fields might provide new capabilities to malicious actors. This article considers biosecurity concerns using examples of research advances in engineering biology. Methods: The authors explore risk assessment and mitigation of transdisciplinary biotechnology research and development, using the framework developed in the National Academies' study on Biodefense in an Age of Synthetic Biology. Results: The Synthetic Biology Assessment Framework focuses on risks of using advanced approaches and technologies to enhance or create novel pathogens and toxins. The field of engineering biology continues to advance at a pace that challenges current risk assessment frameworks. Conclusions: This framework likely is sufficient to assess new science and technology advances affecting conventional biological agents. However, the risk assessment framework may have limited applicability for technologies that are not usable with conventional biological agents and result in economic or broader national security concerns. Finally, the vast majority of discourse has been focused primarily on risks rather than benefits, and analyzing both in future evaluations is critical to balancing scientific progress with risk reduction. 

ABSTRACT Human polyomaviruses are emerging pathogens that infect a large percentage of the human population and are excreted in urine. Consequently, urine that is collected for fertilizer production often has high concentrations of polyomavirus genes. We studied the fate of infectious double-stranded DNA (dsDNA) BK human polyomavirus (BKPyV) in hydrolyzed source-separated urine with infectivity assays and quantitative PCR (qPCR). Although BKPyV genomes persisted in the hydrolyzed urine for long periods of time ( T 90 [time required for 90% reduction in infectivity or gene copies] of >3 weeks), the viruses were rapidly inactivated ( T 90 of 1.1 to 11 h) in most of the tested urine samples. Interestingly, the infectivity of dsDNA bacteriophage surrogate T3 ( T 90 of 24 to 46 days) was much more persistent than that of BKPyV, highlighting a major shortcoming of using bacteriophages as human virus surrogates. Pasteurization and filtration experiments suggest that BKPyV virus inactivation was due to microorganism activity in the source-separated urine, and SDS-PAGE Western blots showed that BKPyV protein capsid disassembly is concurrent with inactivation. Our results imply that stored urine does not pose a substantial risk of BKPyV transmission, that qPCR and infectivity of the dsDNA surrogate do not accurately depict BKPyV fate, and that microbial inactivation is driven by structural elements of the BKPyV capsid. IMPORTANCE We demonstrate that a common urinary tract virus has a high susceptibility to the conditions in hydrolyzed urine and consequently would not be a substantial exposure route to humans using urine-derived fertilizers. The results have significant implications for understanding virus fate. First, by demonstrating that the dsDNA (double-stranded DNA) genome of the polyomavirus lasts for weeks despite infectivity lasting for hours to days, our work highlights the shortcomings of using qPCR to estimate risks from unculturable viruses. Second, commonly used dsDNA surrogate viruses survived for weeks under the same conditions that BK polyomavirus survived for only hours, highlighting issues with using virus surrogates to predict how human viruses will behave in the environment. Finally, our mechanistic inactivation analysis provides strong evidence that microbial activity drives rapid virus inactivation, likely through capsid disassembly. Overall, our work underlines how subtle structural differences between viruses can greatly impact their environmental fate.