Recombination between coronaviruses and synthetic RNAs and biorisk implications motivated by a SARS-CoV-2 FCS origin controversy.

The urgent need for improved policy, regulation, and oversight of research with potential pandemic pathogens (PPPs) has been widely acknowledged. A 2022 article in Frontiers in Virology raises questions, reporting on a 100% sequence homology between the SARS-CoV-2 furin cleavage site (FCS) and the negative strand of a 2017 patented sequence. Even though Ambati and collaborators suspect a possible inadvertent or intentional cause leading to the FCS insert, the related underpinnings have not been studied from the perspective of potential biorisk policy gaps. A commentary on their article contests the low coincidence likelihood that was calculated by Ambati et al., arguing that the sequence match could have been a chance occurrence alone. Additionally, it has been suggested that the odds of the recombination event may be low. These considerations seem to have put many speculations related to any implied viral beginnings, notably from a research setting likely outside the Wuhan Institute of Virology, to rest. However, potential implications for future disasters in terms of biosafety and biosecurity have not been addressed. To demonstrate the feasibility of the Ambati et al. postulate, a theoretical framework is developed that substantially extends the research orientations implicated by these authors and the related patent. It is argued that specific experimental conditions, in combination, could significantly increase the implied recombination profile between coronaviruses and synthetic RNAs. Consequently, this article scrutinizes these largely unrecognized vulnerabilities to discuss implications across the spectrum of the biological risk landscape, with special attention to a potential "crime harvest." Focusing on insufficiently understood features of interaction between the natural and man-made world, vulnerabilities related to contaminants, camouflaging, and various misuse potentials fostered by the digitization and computerization of synthetic biology, it highlights novel biorisk gaps not covered by existing PPP policy. Even though this work does not aim to provide proof of the viral origin, it will make the point that, in theory, a convergence of under-appreciated lab experiments and technologies could have led to the SARS-CoV-2 FCS insert, which analogously could be exploited by various threat actors for the clandestine genesis of similar or even worse pathogens.

Rarely Recognized Antibody Diversification in Covid-19 Evolution to Counteract Advanced SARS-CoV-2 Evasion Strategies, and Implications for Prophylactic Treatment.

The ongoing Covid-19 pandemic underscores the importance of finding effective and safe ways to combat the virus, and to optimally understand the immune response elicited upon natural infection. This likely involves all components of the immune system, both innate and adaptive. The impetus for the rapid development of prophylactic treatment options has led to an intense focus on neutralizing antibodies (Abs), and many novel and specialized platforms have been designed to achieve that goal. B-cell immunity relies on the generation of a diverse repertoire of Abs. Their structural variation is defined in terms of amino acid composition that is encoded in the genome or acquired through somatic mutations. Yet, key examples of frequently neglected antibody diversification mechanisms involving post-translational modifications such as N- or O-linked glycosylation are present in significant portions of the population. During the last few years, these and other beyond gene sequence determined humoral immune response mechanisms have in some specific cases revealed their potent immunomodulatory effects. Nonetheless, such more unusual mechanisms have not received much attention in the context of SARS-CoV-2. Thus, with specific focus on the latter, this paper presents, (1) the rationale for considering beyond sequence determined strategies, (2) evidence for their possible involvement in Covid-19 disease evolution, (3) consequences for vaccine design exemplified by one of the vaccine candidates that is currently undergoing trial, and (4) more general implications. Based on a critical interpretation of published literature, the hypotheses developed in this study point to a crucial role of non-genetic antibody diversification mechanisms in disease evolution to counteract unique immunogenicity determinants of SARS-CoV-2 infection. The involvement of post translational mechanisms may also help explain the widely varied immune response observed, not only among different patient groups, but also in terms of their observed incompatibility with SARS-CoV-2 infection in several human cell types. The article highlights potentials and challenges of these refined humoral immune response mechanisms to most optimally target non-genetic viral evasion strategies.

Facing the 2020 pandemic: What does cyberbiosecurity want us to know to safeguard the future?

As the entire world is under the grip of the coronavirus disease 2019 (COVID-19), and as many are eagerly trying to explain the origins of the virus and cause of the pandemic, it is imperative to place more attention on related potential biosafety risks. Biology and biotechnology have changed dramatically during the last ten years or so. Their reliance on digitization, automation, and their cyber-overlaps have created new vulnerabilities for unintended consequences and potentials for intended exploitation that are mostly under-appreciated. This study summarizes and elaborates on these new cyberbiosecurity challenges, (1) in terms of comprehending the evolving threat landscape and determining new risk potentials, (2) in developing adequate safeguarding measures, their validation and implementation, and (3) specific critical risks and consequences, many of them unique to the life-sciences. Drawing other's expertise and my previous work, this article reviews and critically interprets our current bio-economy situation. The goal is not to attribute causative aspects of past biosafety or biosecurity events, but to highlight the fact that the bioeconomy harbors unique features that have to be more critically assessed for their potential to unintentionally cause harm to human health or environment, or to be re-tasked with an intention to cause harm. It is concluded with recommendations that will need to be considered to help ensure converging and emerging biorisk challenges, in order to minimize vulnerabilities to the life-science enterprise, public health, and national security.

Are paradoxes of amoeboid cognition, memristors, and memory mandating a re-conceptualization of actions and behaviors?

Background From intelligent behaviors of individual molecules and primitive organisms to those with a nervous system and brain, nature displays a fascinating collective memory across time and space. Using certain electronic circuits called memristors, it has been possible to emulate several processes of memory and learning, including a predictive form of intelligence of simple amoebas. Purpose What is the core of such intelligent performances? Although memristors are able to effectively describe puzzling biologic behaviors, recent results challenge their very existence altogether. This paper asks what can be gleaned from the underlying controversy itself, which will be argued is analogous to the observer principle in quantum physics. It is hypothesized that the material phenomena of resonance and sync have a counterpart involving behavior and memory. This questions the prominent role of a causative agent, and which type of behavior or memory is being occasioned. Results Building on the theory of memristors, the challenge of their actualization, and puzzling behaviors of amoebas, this paper proposes that 'resonating actions' - that is, similar or interlinked behaviors beyond space and time - are enabled by an underlying field of potentiation or domain of influence, and not by a cause-effect relationship. Such linked behaviors resemble a form of 'action coherence.' Habituated actions, memory, and behavior may arise out of a similar field of consciousness (here, modeled as memristors). These principles may be at the core of many hitherto unexplained mysteries of collective learning and behavior beyond space and time. Although this study is based on amoebas, the key postulates are also of great relevance to human thinking, behavior, and performance (including the representation of illness), and have independently been confirmed in the fields of consciousness research and spirituality.

On DNA Signatures, Their Dual-Use Potential for GMO Counterfeiting, and a Cyber-Based Security Solution.

This study investigates the role and functionality of special nucleotide sequences ("DNA signatures") to detect the presence of an organism and to distinguish it from all others. After highlighting vulnerabilities of the prevalent DNA signature paradigm for the identification of agricultural genetically modified (GM) organisms it will be argued that these so-called signatures really are no signatures at all - when compared to the notion of traditional (handwritten) signatures and their generalizations in the modern (digital) world. It is suggested that a recent contamination event of an unauthorized GM Bacillus subtilis strain (Paracchini et al., 2017) in Europe could have been-or the same way could be - the consequence of exploiting gaps of prevailing DNA signatures. Moreover, a recent study (Mueller, 2019) proposes that such DNA signatures may intentionally be exploited to support the counterfeiting or even weaponization of GM organisms (GMOs). These concerns mandate a re-conceptualization of how DNA signatures need to be realized. After identifying central issues of the new vulnerabilities and overlying them with practical challenges that bio-cyber hackers would be facing, recommendations are made how DNA signatures may be enhanced. To overcome the core problem of signature transferability in bioengineered mediums, it is necessary that the identifier needs to remain secret during the entire verification process. On the other hand, however, the goal of DNA signatures is to enable public verifiability, leading to a paradoxical dilemma. It is shown that this can be addressed with ideas that underlie special cryptographic signatures, in particular those of "zero-knowledge" and "invisibility." This means more than mere signature hiding, but relies on a knowledge-based proof and differentiation of a secret (here, as assigned to specific clones) which can be realized without explicit demonstration of that secret. A re-conceptualization of these principles can be used in form of a combined (digital and physical) method to establish confidentiality and prevent un-impersonation of the manufacturer. As a result, this helps mitigate the circulation of possibly hazardous GMO counterfeits and also addresses the situation whereby attackers try to blame producers for deliberately implanting illicit adulterations hidden within authorized GMOs.

Are Market GM Plants an Unrecognized Platform for Bioterrorism and Biocrime?

This article discusses a previously unrecognized avenue for bioterrorism and biocrime. It is suggested that new gene editing technologies may have the potential to create plants that are genetically modified in harmful ways, either in terms of their effect on the plant itself or in terms of harming those who would consume foods produced by that plant. While several risk scenarios involving GMOs-such as antibiotic resistant pathogens, synthetic biology, or mixing of non-GMO seeds with GMO seeds-have previously have been recognized, the new vulnerability is rooted in a different paradigm-that of clandestinely manipulating GMOs to create damage. The ability to actively inflict diseases on plants would pose serious health hazards to both humans and animals, have detrimental consequences to the economy, and directly threaten the food supply. As this is the first study of this kind, the full scope and impact of suck attacks-especially those involving the intended misuse of technologies such as gene-drives-merits further investigation. Herein, the plausibility of some of the new risks will be analyzed by, (1) Highlighting ownership and origination issues (esp. of event-specific GM-plants) as unrecognized risk factors; (2) Investigating the unique role of GMOs, why-and how-certified GMOs could become a new venue for such attacks; (3) Analyzing possible dual-use potentials of modern technologies and research oriented toward the advancement of GMOs, plant breeding and crop improvement. The identification and analysis of harmful genetic manipulations to utilize (covertly modified) plants (GMOs and non-GMOs) as an attack vector show that these concerns need to be taken seriously, raising the prospect not only of direct harm, but of the more likely effects in generating public concern, reputational harm of agricultural biotechnology companies, law-suits, and increased import bans of certain plants or their derived products.

A covert authentication and security solution for GMOs.

BACKGROUND: Proliferation and expansion of security risks necessitates new measures to ensure authenticity and validation of GMOs. Watermarking and other cryptographic methods are available which conceal and recover the original signature, but in the process reveal the authentication information. In many scenarios watermarking and standard cryptographic methods are necessary but not sufficient and new, more advanced, cryptographic protocols are necessary. RESULTS: Herein, we present a new crypto protocol, that is applicable in broader settings, and embeds the authentication string indistinguishably from a random element in the signature space and the string is verified or denied without disclosing the actual signature. Results show that in a nucleotide string of 1000, the algorithm gives a correlation of 0.98 or higher between the distribution of the codon and that of E. coli, making the signature virtually invisible. CONCLUSIONS: This algorithm may be used to securely authenticate and validate GMOs without disclosing the actual signature. While this protocol uses watermarking, its novelty is in use of more complex cryptographic techniques based on zero knowledge proofs to encode information.