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At least 19 records

BioSecure Digital Twin: Manufacturing Innovation and Cybersecurity Resilience

U.S. national security, prosperity, economy, and well-being require secure, flexible, and resilient Biopharmaceutical Manufacturing. The COVID-19 pandemic reaffirmed that the biomedical production value-chain is vulnerable to disruption and has been under attack from sophisticated nation-state adversaries. Current cyber defenses are inadequate, and the integrity of critical production systems and processes are inherently vulnerable to cyber-attacks, human error, and supply chain disruptions. The following chapter explores how a BioSecure Digital Twin will improve U.S. manufacturing resilience and preparedness to respond to these hazards by significantly improving monitoring, integrity, security, and agility of our manufacturing infrastructure and systems. The BioSecure Digital Twin combines a scalable manufacturing framework with a robust platform for monitoring and control to increase U.S. biopharma manufacturing resilience. Then, the chapter discusses some of the inherent vulnerabilities and challenges at the nexus of health and advanced manufacturing. Next, the chapter highlights that as the Pandemic evolves, we need agility and resilience to overcome significant obstacles. This section highlights an innovative application of Cyber Informed Engineering to developing and deploying a BioSecure Digital Twin to improve the resilience and security of the biopharma industrial supply chain and production processes. Finally, the chapter concludes with a process framework to complement the Digital Twin platform, called the Biopharma (Observe, Orient, Decide, Act) OODA Loop Framework (BOLF), a four-step approach to decision-making outputs from the Digital Twin. The BOLF will help end users leverage twin technology by distilling the available information, focusing the data on context, and rapidly making the best decision while remaining cognizant of changes that can be made as more data becomes available.

99 GENERAL AND MISCELLANEOUS↗

IMAGINE BioSecurity: Mesocosm-Based Methods to Evaluate Biocontainment Strategies and Impact of Industrial Microbes Upon Native Ecosystems

Project Goals: The Integrative Modeling and Genome-scale Engineering for Biosystems Security (IMAGINE BioSecurity) SFA project seeks to establish an understanding of the behavior of engineered microbes in controlled versus environmental conditions to predictively devise new strategies for responding to biological escape. To this end, the IMAGINE Team has established a plant-soil mesocosm platform to track and quantify the fate of industrial microbes in environmental systems and assess the efficacy of biocontainment constraints upon genetically engineered microbe escape frequency and the impact of industrial microbes upon native ecological microbiomes. Abstract Text: Genetically modified industrial production microbes and their associated bioproducts have emerged as an integral component of a sustainable bioeconomy. However, the rapid development of these innovative technologies raises biosecurity concerns, namely, the risk of environmental escape. Thus, the realization of a bioeconomy hinges not only on the development and deployment of microbial production hosts, but also on the development of secure biosystems and biocontainment designs. Current laboratory-based biocontainment testing systems do not accurately reflect complexities found in natural environments, necessitating an environmentally relevant analysis pipeline that allows for the detection of rare escapees, the effect of associated bio-products, and the impact on native ecologies. To this end, we have developed an approach that utilizes soil mesocosms and integrated systems analyses to evaluate the efficacy of novel biocontainment strategies and to assess the impact of production systems upon terrestrial microbiome dynamics. We demonstrate the utility of this approach by modeling a contamination with industrial microbial chasses versus their biocontained counterparts. Here we demonstrate the broad utility of this system by highlighting findings from both strains of Saccharomyces cerevisiae that are contained with an inducible toxin anti-toxin system, and stains of Escherichia coli that are contained via genomic recoding. The resultant data demonstrate that this system has broad utility across diverse microbial chassis and biocontainment strategies, enables us to track the fate of our contaminating microbe with high sensitivity in the soil, as well as monitor broader impacts of the perturbation on the underlying soil system. The findings presented here support the use of this mesocosm-based approach to assess the environmental impact of industrial microbes and to validate biocontainment strategies.

BASIC BIOLOGICAL SCIENCES,INORGANIC, ORGANIC, PHYS↗

Community Input on the Need, Scope, and Development Roadmap of a Proposed National Virtual Biosecurity for Bioenergy Crops Center (NVBBCC)

Brookhaven National Laboratory (BNL) was awarded a pilot project in FY22 under the U.S. Department of Energy (DOE) Office of Science Biopreparedness Research Virtual Environment (BRaVE) initiative, to define research priorities, needs, and requirements for a national virtual center devoted to the biosecurity of bioenergy crops. The mission of the proposed center, referred to as the National Virtual Biosecurity for Bioenergy Crop Center (NVBBCC), would be to provide the scientific basis and tools to detect, characterize, model, and mitigate biothreats to bioenergy crops. This function will be essential to ensure the projected increased US reliance over the next few decades on key plant-based energy products, such as biojet fuel. The NVBBCC is envisioned as a distributed, virtual center with multiple national laboratories at its core to maximize the use of existing unique facilities and expertise across the DOE complex. A major goal of the pilot project was to develop a roadmap for establishing NVBBCC through a series of meetings to gather community input. A total of about 150 individuals, drawn from DOE laboratories, the USDA, academia, NIH, DHS and the private sector participated in six planning meetings held in FY23. Four of the meetings were focused on specific research topics (disease detection, dispersion and disease propagation, biomolecular characterization of plant-pathogen interaction, and mitigation strategies). These four meetings were followed by a meeting that focused on computational needs to support collaborative, data-intensive research within a distributed center as well as workforce development. A final meeting focused on establishing and maintaining preparedness within NVBBCC to respond to an emerging disease within bioenergy crops and how it would collaborate and coordinate with USDA and DHS.

09 BIOMASS FUELS↗

Rethinking U.S. Biosecurity Strategy for the Decade Ahead (Workshop Summary)

The Center for Global Security Research (CGSR) at Lawrence Livermore National Laboratory (LLNL) hosted a workshop titled, “Rethinking U.S. Biosecurity Strategy for the Decade Ahead” on October 27-29, 2020. The workshop included participants from the policy, military, and technical communities in the United States as well as from U.S. allies. The workshop, convened virtually due to the ongoing global COVID-19 pandemic, was a close collaboration between CGSR and the Physical Life Sciences (PLS) Directorate at LLNL. While the scope of conference extended beyond current circumstances to include precedents and predictions for both public health and bioweapons, contemporary events weighed heavily on the discussion participants.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Digital Biosecurity Pilot Project

Security models for the bioeconomy have largely been developed on risk profiles borrowed from the financial industry and, in some cases, industrial control systems. The bioeconomy, however, has unique characteristics that require domain-specific knowledge of the risks to environmental, health and economic impact from directly targeted attacks. Key questions need to be assessed and answered for any facility engaged in bioproduction. These include: how much technical information must the attacker possess in order to target a specific process or facility? Which processes cause the largest economic impact if disrupted? Can an attacker lead companies down the wrong path of research, leading to irrecoverable losses of time, resources and capital? Can attackers disrupt venture capital strategies and affect financial returns? What are the resources required to attack key workflows, and subsequently what is the cost of defense? What strategies are effective against such attackers, and what are their cost? Can government provide an active role in assurance of material, process and results for critical bioeconomic infrastructure?

59 BASIC BIOLOGICAL SCIENCES↗

Protein Factory on a Chip for Rapid Therapeutics

The potential for new, re-emerging, or engineered pandemic threats could challenge our nation's biosecurity, requiring rapid and flexible countermeasure development platforms. In healthcare, one of the main hindrances to the timely development of protein-based therapeutics for cancer, infectious disease, and other diseases has been a slow and expensive quality-controlled production stage. We present a protein-based technology that has the potential to address these crucial problems in biosecurity and healthcare by maximizing protein production and system portability, while minimizing production latency and cost. Specifically, we have developed a reusable, portable first-generation platform that leverages the advantages of cell-free protein synthesis (CFPS) and flow cells to create practical amounts of clinically relevant therapeutics. We have demonstrated that this technology is reusable and programmable, enabling a single platform that can synthesize multiple dosages of various therapeutics and vaccine in the field. Implementing this technology could mitigate pandemic threats by providing a rapidly-deployable (just-in-time), versatile (precision medicine) production of biologic therapeutics to the infected patient’s locale (point-of-care). In drug development, once promising drug variations are identified, the platform can be scaled to quickly produce practical amounts of protein for patient testing in the matter of days (vs. months) at a fraction of the cost of existing technology.

59 BASIC BIOLOGICAL SCIENCES↗

Beyond sequence similarity: toward function-based screening of nucleic acid synthesis

Synthetic nucleic acids are a key input to modern biotechnology, yet they represent dual-use materials that require robust screening to mitigate biosecurity risks. The prevailing screening paradigm, which identifies sequences of concern (SoCs) through sequence similarity to controlled pathogens and toxins, may not fully capture risks posed by AI tools that can decouple biomolecular function from reliance on known sequences. Rapidly advancing biodesign capabilities enable the generation of genes and proteins that might evade sequence-based detection. We highlight the critical need for function-based screening approaches that can detect sequences capable of hazardous biological functions, regardless of similarity to known SoCs. We examine the feasibility of function-based screening with an initial focus on proteins, arguing that, while protein sequence space is vast, biologically functional proteins are significantly constrained by biophysical and biochemical requirements that can be learned and modeled. We propose a concrete implementation framework organized along a continuum of complexity, starting with toxins as the most tractable targets before expanding to more complex pathogenic functions. We then discuss open challenges and describe a research and development strategy to address them.

59 BASIC BIOLOGICAL SCIENCES↗

Ongoing Cooperative Engagement Facilitates Agile Pandemic and Outbreak Response: Lessons Learned Through Cooperative Engagement Between Uganda and the United States

Pathogens threaten human lives and disrupt economies around the world. This has been clearly illustrated by the current COVID-19 pandemic and outbreaks in livestock and food crops. Here, to manage pathogen emergence and spread, cooperative engagement programs develop and strengthen biosafety, biosecurity, and biosurveillance capabilities among local researchers to detect pathogens. In this case study, we describe the efforts of a collaboration between the Los Alamos National Laboratory and the Uganda Virus Research Institute, the primary viral diagnostic laboratory in Uganda, to implement and ensure the sustainability of sequencing for biosurveillance. We describe the process of establishing this capability along with the lessons learned from both sides of the partnership to inform future cooperative engagement efforts in low- and middle-income countries. We found that by strengthening sequencing capabilities at the Uganda Virus Research Institute before the COVID-19 pandemic, the institute was able to successfully sequence SARS-CoV-2 samples and provide data to the scientific community. We highlight the need to strengthen and sustain capabilities through in-country training, collaborative research projects, and trust.

59 BASIC BIOLOGICAL SCIENCES↗

Cyberbiosecurity and Public Health in the Age of COVID-19

Cyberbiosecurity, the aspect of biosecurity involving the digital representation of biological data, had already been emerging as a matter of public concern even prior to the onset of the COVID-19 pandemic. Key issues of concern include, among others, the privacy of patient data, the security of public health databases, the integrity of diagnostic test data, the integrity of public biological databases, the security implications of automated laboratory systems and the security of proprietary biological engineering advances. With the onset of the COVID-19 pandemic, and the importance of digital resources in combatting it, concern about the potential for cyber attacks by state-based or non-state actors has been elevated. To illuminate the challenges, we focus on the cyber vulnerabilities that need to be addressed in public health activities such as disease surveillance and outbreak management. In particular, we examine cyber issues raised by the accelerated pace of development for COVID mitigations, treatments, and vaccines.

cybersecurity, biosecurity↗

Agnostic capture of pathogens for the detection and diagnostics of emerging threats

The continued emergence of pathogens, whether novel, re-emerging, or engineered, poses a persistent global biosecurity and public health challenge. Recent outbreaks, including COVID-19, Lassa fever, Marburg virus, mpox, and avian influenza, underscore the urgent need for robust systems that enable rapid surveillance, early diagnosis, and timely countermeasures before widespread human transmission occurs. In this article, we focus on early detection technologies and systematically evaluate current diagnostic and sensing modalities. We highlight sequencing and spectroscopy as two complementary approaches capable of providing broad, agnostic detection and rich biological insight. Our analysis emphasizes that scientific innovation alone is insufficient: effective preparedness also requires improved data curation, integration, and sharing to build AI-ready resources that accelerate future responses. We argue for coordinated advances in both technological capabilities and supporting infrastructure to enable the rapid identification and characterization of emerging pathogens and to fully leverage modern science against evolving infectious threats.

Environmental health↗

Lyophilization of ASFV vaccine candidate ASFV-G-ΔI177L offers long term stability

Abstract For over a century African swine fever (ASF) has been causing outbreaks leading to devastating losses for the swine industry. The current pandemic of ASF has shown no signs of stopping and continues to spread causing outbreaks in additional countries. Currently control relies mostly on culling infected farms, and strict biosecurity procedures. Recently a vaccine, ASFV-G-ΔI177L was approved for use in Vietnam. In this study we evaluate the long-term stability of lyophilized ASFV-G-ΔI177L. Understanding the stability of different formulations of vaccines is information necessary for deployment of vaccines to ASF outbreak areas, particularly those that do not have a reliable well established cold chain to ensure conservation of vaccine quality. In this report, we determined that ASFV-G-ΔI177L, when lyophilized under specific conditions, is stable for up to one year at 4 °C, with similar vaccine titers after storage. Next-generation sequencing analysis also determined that lyophilization and long-term storage under these conditions had no effect on the genome of ASFV as the genome remained genetically identical to the original non-lyophilized form.

Science & Technology - Other Topics↗