Screening State of Play: The Biosecurity Practices of Synthetic DNA Providers.

Introduction: Synthetic DNA technology is rapidly emerging as a key driver of innovation in the fields of medicine, biotechnology, and more. But it also poses significant risk, particularly in lowering barriers to the production of dangerous pathogens and toxins. At present, oversight of this technology is voluntarily coordinated among synthetic DNA providers and stakeholders, and detailed understanding of security processes, infrastructures, and insights from these providers is imperative to understand how to best mitigate the inherent risks of this technology. Objectives: In this study, we aimed to determine the trends, outliers, strengths, and gaps in current DNA provider security practices through a broad survey of the gene synthesis field. Methods: We interviewed synthetic DNA providers and stakeholders about their customer and sequence screening procedures. Respondents were divided into groups based on membership in the International Gene Synthesis Consortium, nationality, whether they were a new or established company, and whether they synthesize de novo DNA or not. We then performed meta-analysis and intergroup analysis to elucidate larger trends and points of variance. Results: In total, we interviewed 18 companies. We found that synthetic DNA providers and stakeholders tend to operate under a "zero-trust model" for screenings and utilize common governmental and private resources to navigate international import/export policies. Major variabilities were identified in the sensitivity of screening, monitoring and evaluation practices, screening pipelines, and approaches to synthetic oligonucleotide screening. In addition, we identified a significant vulnerability of lacking awareness among providers of formal law enforcement reporting procedures. Conclusion: Collectively, we observed significant heterogeneity in security practice throughout the field, reflective of the current lack of codified oversight for DNA synthesis. The results presented in this study provide insight into the specifics, strengths, and shortcomings of current DNA provider security practices, and are important considerations for the biosecurity community in ongoing deliberations of if, when, and how to approach oversight of synthetic DNA technology.

Chimeric Viruses Containing Select Agents: The Biology Behind Their Creation, Attenuation, and Exclusion From Regulation.

The US Centers for Disease Control and Prevention (CDC), as part of the Federal Select Agent Program, and under the purview of 42 CFR §73.3, has the ability to regulate chimeric viruses that contain portions of pathogens that are part of the select agents and toxins list. In addition, the CDC is responsible for excluding pathogens from regulation, including chimeric viruses, that are sufficiently attenuated. Since 2003, the CDC has excluded over 20 chimeric viruses that contain portions of select agents. But in late 2021, the CDC proposed a regulatory first-the addition of a chimeric virus to the select agents and toxins list. To better understand the importance and applicability of this action, we surveyed the landscape of previous exclusions from select agent regulation. First, we reviewed the exclusion criteria used by the Intragovernmental Select Agents and Toxins Technical Advisory Committee in their advisement of the Federal Select Agent Program. We then reviewed the literature on chimeric viruses that contain portions of select agents and that have been excluded from regulation due to sufficient attenuation, focusing on chimeric alphaviruses and chimeric avian influenza viruses. By analyzing biological commonalities and patterns in the structure and methodology of the development of previously excluded chimeric viruses, we provide insight into how the CDC has used exclusion criteria in the past to regulate chimeric viruses. We conclude by contrasting previous exclusions with the recent addition of SARS-CoV-1/SARS-CoV-2 chimeric viruses to the select agents and toxins list, demonstrating that this addition strays from established, effective regulatory processes, and is thus a regulatory misstep.

Regulating Select Agent Chimeras: Defining the Problem(s) Through the Lens of SARS-CoV-1/SARS-CoV-2 Chimeric Viruses.

In late 2021, the US Centers for Disease Control and Prevention (CDC) posted an interim final rule (86 FR 64075) to the federal register regulating the possession, use, and transfer of SARS-CoV-1/SARS-CoV-2 chimeric viruses. In doing so, the CDC provided the reasoning that viral chimeras combining the transmissibility of SARS-CoV-2 with the pathogenicity and lethality of SARS-CoV-1 pose a significant risk to public health and should thus be placed on the select agents and toxins list. However, 86 FR 64075 lacked clarity in its definitions and scope, some of which the CDC addressed in response to public comments in the final rule, 88 FR 13322, in early 2023. To evaluate these regulatory actions, we reviewed the existing select agent regulations to understand the landscape of chimeric virus regulation. Based on our findings, we first present clear definitions for the terms "chimeric virus," "viral chimera," and "virulence factor" and provide a list of SARS-CoV-1 virulence factors in an effort to aid researchers and federal rulemaking for these agents moving forward. We then provide suggestions for a combination of similarity and functional characteristic cutoffs that the government could use to enable researchers to distinguish between regulated and nonregulated chimeras. Finally, we discuss current select agent regulations and their overlaps with 86 FR 64075 and 88 FR 13322 and make suggestions for how to address chimera concerns within and/or without these regulations. Collectively, we believe that our findings fill important gaps in current federal regulations and provide forward-looking philosophical and practical analysis that can guide future decisionmaking.

Deployment of Engineered Microbes: Contributions to the Bioeconomy and Considerations for Biosecurity.

Engineering at microscopic scales has an immense effect on the modern bioeconomy. Microbes contribute to such disparate markets as chemical manufacturing, fuel production, crop optimization, and pharmaceutical synthesis, to name a few. Due to new and emerging synthetic biology technologies, and the sophistication and control afforded by them, we are on the brink of deploying engineered microbes to not only enhance traditional applications but also to introduce these microbes to sectors, contexts, and formats not previously attempted. In microbially managed medicine, microbial engineering holds promise for increasing efficacy, improving tissue penetration, and sustaining treatment. In the environment, the most effective areas for deployment are in the management of crops and protection of ecosystems. However, caution is warranted before introducing engineered organisms to new environments where they may proliferate without control and could cause unforeseen effects. We summarize ideas and data that can inform identification and assessment of the risks that these tools present to ensure that realistic hazards are described and unrealistic ones do not hinder advancement. Further, because modes of containment are crucial complements to deployment, we describe the state of the art in microbial biocontainment strategies, current gaps, and how these gaps might be addressed through technological advances in synthetic engineering. Collectively, this work highlights engineered microbes as a foundational and expanding facet of the bioeconomy, projects their utility in upcoming deployments outside the laboratory, and identifies knowns and unknowns that will be necessary considerations and points of focus in this endeavor.

Tuition reduction is the key factor determining tax burden of graduate students under the Tax Cuts and Job Act.

BACKGROUND: The proposed Tax Cuts and Jobs Act (H.R.1) has stirred significant public debate on the future of American economics.  While supporters of the plan have championed it as a necessity for economic revitalization, detractors have pointed out areas of serious concern, particularly for low- and middle-income Americans.  One particularly alarming facet of the plan is the radical change to education finance programs and taxation of students in higher education.  Methods:  By analyzing actual income and tuition of a public and a private university student, as well as the 'average' graduate student, we investigated the effect of both the House and Senate versions of H.R. 1 on taxation of students of various family structures.  Results:  Our findings indicate that taxable tuition would be the greatest contributor to graduate student tax burden across all four categories of filing status.  However, when tuition reduction is upheld or a student is on sustaining fees rather than full tuition, graduate students would realize decreases in taxation. CONCLUSIONS:   Overall, we conclude that removal of tuition reduction would result in enormous tax burdens for graduate students and their families and that these effects are dependent not only on the status of the student in their degree program but also on their tuition and stipend, and therefore the institution they attend.

An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery.

Recent advances in sequencing technologies have opened the door for the classification of the human virome. While taxonomic classification can be applied to the viruses identified in such studies, this gives no information as to the type of interaction the virus has with the host. As follow-up studies are performed to address these questions, the description of these virus-host interactions would be greatly enriched by applying a standard set of definitions that typify them. This paper describes a framework with which all members of the human virome can be classified based on principles of ecology. The scaffold not only enables categorization of the human virome, but can also inform research aimed at identifying novel virus-host interactions.

Comparative genomic and transcriptomic analysis of terpene synthases in Arabidopsis and Medicago.

This study provides a timely comparative genomic and transcriptomic analysis of the terpene synthase (TPS) gene family in Medicago truncatula (bears glandular and non-glandular trichomes) and Arabidopsis thaliana (bears non-glandular trichomes). The authors' efforts aimed to gain insight into TPS function, phylogenetic relationships and the role of trichomes in terpene biosynthesis and function. In silico analysis identified 33 and 23 putative full-length TPS genes in Arabidopsis and Medicago, respectively. All AtTPS and MtTPS fall into the five established angiosperm TPS subfamilies, with lineage-specific expansion of Subfamily A in Arabidopsis and Subfamily G in Medicago. Large amounts of tandem duplication have occurred in both species, but only one syntenic duplication seems to have occurred in Arabidopsis, with no such duplication apparent in Medicago. Expression analysis indicates that there is much more trichome-localised TPS expression in Medicago than in Arabidopsis. However, TPS genes were expressed in non-glandular trichomes in both species. One trichome-specific gene has been identified in each Medicago and Arabidopsis along with flower-, seed-, stem- and root-specific genes. Of these, MtTPS11 is a promising candidate for trichome-specific genetic engineering, a technology that may be possible for both plants according to the findings of this manuscript. These results suggest that non-glandular trichomes may play a role in plant chemical defense and/or ecological communication instead of only in physical defence. Finally, the general lack of correlation between expression patterns and phylogenetic relationships in both species suggests that phylogenetic analysis alone is insufficient to predict gene function even for phylogenetically close paralogs.

In the eyes of the beholder: National identification predicts differential reactions to ethnic identity expressions.

Two studies examined how perceivers' national identification influences their implicit and explicit attitudes toward White and non-White ethnic groups whose members express their ethnic identity overtly in public or discreetly in private spaces. Results revealed that at a conscious level, White American perceivers' national identification elicited more negative attitudes toward both White and non-White ethnic groups when members embraced their ethnic heritage in public rather than in private. However, at an unconscious level, White perceivers' identification with the national group led to less favorable attitudes toward non-White ethnic groups, but not White ethnic groups, when their group members embraced ethnic identity in public. By integrating research on national identification, ethnic identity expression, and prejudice, the present research highlights some conditions under which majority group members' national identification affects how they perceive ethnic subgroups within the nation.