Biosecurity Assessments for Emerging Transdisciplinary Biotechnologies: Revisiting Biodefense in an Age of Synthetic Biology.

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.

Safely balancing a double-edged blade: identifying and mitigating emerging biosecurity risks in precision medicine.

Tools and methods of precision medicine are developing rapidly, through both iterative discoveries enabled by innovations in biomedical research (e.g., genome editing, synthetic biology, bioengineered devices).

Perspective: The Rapidly Expanding Need for Biosecurity by Design.

Advancing biotechnologies are revolutionizing not only health and medicine, but also many different sectors such as agriculture, energy, chemistry, and textiles. As synthetic biology is leveraged as a programmable platform for the creation and biodesign of high-value biological medicines, foods, and commodities, the world is facing new territory in terms of ensuring the safety and security of both novel and engineered biological organisms, as well as the biological and digital platforms in which they are designed. Biosecurity practices and policies have traditionally revolved around preventing the misuse of biological pathogens, primarily through controlling access to pathogens.

The Need for Modernization of Biosecurity in the Post-COVID World.

At present, there are two hypotheses about the emergence of SARS-CoV-2; the first is that it was due to a naturally occurring zoonotic jump, and the second contends that it spread due to an accidental dispersion of a laboratory-acquired infection in Wuhan, China. While the pandemic's actual origins remain occluded, it is useful to examine the latter possibility as a paradigm for evaluating biosecurity policy in the post-COVID world. While the pandemic may not have emerged from a research lab, this is possible with research on dangerous pathogens and prompts questions for biosecurity.

Balancing Act: Precision Medicine and National Security.

Developments in genetics, pharmacology, biomarker identification, imaging, and interventional biotechnology are enabling medicine to become increasingly more precise in "personalized" approaches to assessing and treating individual patients. Here we describe current scientific and technological developments in precision medicine and elucidate the dual-use risks of employing these tools and capabilities to exert disruptive influence upon human health, economics, social structure, military capabilities, and global dimensions of power. We advocate continued enterprise toward more completely addressing nuances in the ethical systems and approaches that can-and should-be implemented (and communicated) to more effectively inform policy to guide and govern the biosecurity and use of current and emerging bioscience and technology on the rapidly shifting global stage.

Breaching the Department of Defense's Biotech Bottleneck.

The global biotechnology revolution offers a profusion of promising innovations for the US Department of Defense (DoD). As with other emerging technologies, the commercial market, rather than defense, is driving the evolution of biotechnology products, and the ability to harness biotechnology for defense benefits has been hampered by strategic confusion in DoD. Here we describe a set of high-level challenges and a set of potential solutions that could bring innovative biotechnology closer to reality for the warfighter and DoD writ large.

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.

Biodefense Policy Analysis-A Systems-based Approach.

Understanding the overall biosecurity and biodefense policy landscape, the relationships between policies and their effects on each other, and the mechanisms for leveraging advances in science and technology to enhance defensive capabilities is crucial for ensuring that policy strategies address long-standing gaps and challenges. To date, policy analyses have been conducted primarily on single issues, which limits analyses of broader effects of policies, particularly after implementation. Here we describe the first-ever systems-based analysis of the US biosecurity and biodefense policy landscape to analyze functional relationships between policies, including examination of the unintended positive or negative consequences of policy actions.

A Holistic Assessment of the Risks and Benefits of the Synthesis of Horsepox Virus.

The re-creation of horsepox virus, an extinct orthopoxvirus with similarity to smallpox virus, has caused concerns in the biosecurity and biodefense communities that the technical capabilities achieved could advance the re-creation of smallpox virus by nefarious actors. The work is now published. While the authors went through due biosecurity diligence at their research institution and with the proper Canadian federal authorities, now that the experiments have been published, there is an opportunity to discuss the dual use risks and benefits of the research itself, as well as those associated with publication of such research-all of which challenge current policies.

Biosecurity Implications for the Synthesis of Horsepox, an Orthopoxvirus.

This article examines the biosecurity and biodefense implications resulting from the recent creation of horsepox virus, a noncirculating (extinct) species of orthopoxvirus. Here we examine the technical aspects of the horsepox virus synthesis and conclude that orthopox synthesis experiments currently remain technically challenging-and will continue to be so, even once this work is published in the scientific literature. This limits potential misuse by some types of nefarious actors.

Options for Synthetic DNA Order Screening, Revisited.

Gene synthesis providers affiliated with the International Gene Synthesis Consortium (IGSC) voluntarily screen double-stranded DNA (dsDNA) synthesis orders over 200 bp to check for matches to regulated pathogens and to screen customers. Questions have been raised, however, about the continuing feasibility and effectiveness of screening. There are technical challenges (e.

Why Gene Editors Like CRISPR/Cas May Be a Game-Changer for Neuroweapons.

This year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC). At the same time, ongoing international efforts to further and more deeply investigate the brain's complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion, and behavior. These advances have tremendous promise for human health, but the potential for their misuse has also been noted, with most discussions centering on research and development of agents that are addressed by existing BWC and Chemical Weapons Convention (CWC) proscriptions.

The Department of Defense Chemical and Biological Defense Program: An Enabler of the Third Offset Strategy.

The US Department of Defense (DOD) established programs to defend against chemical and biological weapons 100 years ago because military leaders understood that the operational capability of the US military is diminished when service member health is compromised. These threats to operational readiness can be from an overt attack using chemical and biological threats but may also arise from natural exposures. In the current era of rapidly emerging technologies, adversaries are not only rediscovering chemical and biological weapons; they are also displaying an increased propensity to employ them to cause strategic instability among deployed forces or nations undergoing conflict.

The Role of Scientific Collections in Scientific Preparedness.

Building on the findings and recommendations of the Interagency Working Group on Scientific Collections, Scientific Collections International (SciColl) aims to improve the rapid access to science collections across disciplines within the federal government and globally, between government agencies and private research institutions. SciColl offered a novel opportunity for the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, to explore the value of scientific research collections under the science preparedness initiative and integrate it as a research resource at each stage in the emergence of the infectious diseases cycle. Under the leadership of SciColl’s executive secretariat at the Smithsonian Institution, and with multiple federal and international partners, a workshop during October 2014 fully explored the intersections of the infectious disease cycle and the role scientific collections could play as an evidentiary scientific resource to mitigate risks associated with emerging infectious diseases.

A practical approach to remote longitudinal follow-up of Parkinson's disease: the FOUND study.

The objective of this study was to examine a remote method for maintaining long-term contact with Parkinson's disease (PD) patients participating in clinical studies. Long-term follow-up of PD patients is needed to fill critical information gaps on progression, biomarkers, and treatment. Prospective in-person assessment can be costly and may be impossible for some patients.

A longitudinal program for biomarker development in Parkinson's disease: a feasibility study.

Long-term follow up is necessary to understand the natural history of treated Parkinson's disease (PD). The Longitudinal and Biomarker Study in PD (LABS-PD) is an observational study designed to prospectively measure the evolution of motor and non-motor features of PD and sample promising biomarkers from early to late stage illness. LABS-PD is organized on the premise that cohorts from completed clinical trials can be re-recruited for long-term follow up.

Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification.

Mitochondrial dysfunction plays a central role in the selective vulnerability of dopaminergic neurons in Parkinson's disease (PD) and is influenced by both environmental and genetic factors. Expression of the PD protein alpha-synuclein or its familial mutants often sensitizes neurons to oxidative stress and to damage by mitochondrial toxins. This effect is thought to be indirect, since little evidence physically linking alpha-synuclein to mitochondria has been reported.