Genomics in Biosecurity: Principles and Applications of Genomic Technologies in Expanded Biosecurity Concepts

By Manousos E. Kambouris

Genomics in Biosecurity: Principles and Applications of Genomic Technologies in Expanded Biosecurity Concepts, in the Translational and Applied Genomics series, explains in definite and practical terms the applicability of genomic technologies in every aspect of biosecurity, from emergent diagnostics to bioterrorism, agroterrorism, next generation biowarfare, biosurveillance and risk assessment. This book offers an integrated discussion of genomics and GCBR (global catastrophic biological risks) events, considering both basic aspects of biosecurity genomics and application of genomic technologies to drive new solutions. Readers will find evidence-based strategies to apply genomics in disease and pathogen monitoring and diagnosis, and more.

Social aspects of GCBR events and genomic biosecurity, such as issues of terrorism, policy ethics, and practice, are also considered in-depth.

• Examines the use of genomics in pathogen monitoring and diagnosis, biosurveillance, and countermeasures for spontaneous and perpetrated events
• Discusses social, ethical, and policy aspects of GCBR events and the use of genomic technologies in biosecurity
• Empowers new solutions in biorestoration, biocrime, counterbioterrorism, disaster management, and humanitarian crisis response
• Features chapter contributions from a range of international specialists

• Language: English
• Publisher: Academic Press
• Release date: Nov 24, 2021
• ISBN: 9780323852371

Manousos E. Kambouris

Dr. Manousos E. Kambouris serves as a Scientific Advisor for the Golden Helix Foundation, Craven House, London, UK, an international non-profit research organization aiming to advance research and education in the area of genomic and personalized medicine and as a Post Doc Researcher in the Laboratory of Pharmacogenomics and Individualized Therapy, Department of Pharmacy, University of Patras. Dr. Kambouris has long participated in different aspects and applications of microbiology, human genomics, biosecurity and cancer research. In his own work, he pursues an integrative approach to microbiomics, employing various -omics-driven approaches and realizing their application in human health, selective and personalized medicine, and panbiosurveillance among other areas. He has published widely in such peer-reviewed journals as OMICS-JIB, Hemoglobin, Medical Mycology, FEMS Immunology & Medical Microbiology, Public Health Genomics, and Future Microbiology.

Book preview

Part I

The spontaneous risk: Microbes and bugs

Chapter 1: Exploring the concepts: Biosecurity, biodefense, and biovigilance

Manousos E. Kambouris    Laboratory of Pharmacogenomics and Individualized Therapy, Department of Pharmacy, University of Patras, Patras, Greece

The Golden Helix Foundation, Craven House, London, United Kingdom

Abstract

Biosecurity emerged as a concept of interest rather belatedly, as the combination of biotechnology-for-all, bioterrorism for many, and a surge in the emergence of pathogens for the globe created a very dystopic future at the onset of the 21st century. Its purpose has been anything but plain: first to introduce measures and practices taken from other security areas so as to integrate seamlessly this new area of concern to the establishment; then to build on the standard experience and long-time practice of contamination control inherent in this field from time immemorial, and, last but not least, to offer a less repulsive term for public use, which could associate with a multitude of surrogate terms in order to cover cognitive, actionable, and operational/technical aspects. Such terms, including biovigilance, bioresilience, bioassault, and biocrime, were sometimes familiar and existent, as was biowarfare, but usually they are produced by the prefix bio- being added to handy existing terms. The purpose of its introduction is to delignate such terms and, most importantly, concepts that sit in-between bioscience and security studies, so as to reduce confusions in the chapters that follow, but also in other works on the subject, where, unfortunately, similar terms are occasionally used by preference or even haphazardly but almost always without previous definition.

Keywords

Biodefense; Biosecurity; Biovigilance; Bioprotection; Bioterrorism; Biocrime; Agroterrorism; Biowarfare; Biooffense

The natural aversion to the concept of disease and especially the prospect of human-perpetrated disease, for gain or for power has resulted in a weird set of reflexes within the academia and the general population. From the neglect of the past years, before 9/11, to the great awakening just after the Anthrax attacks of 2002 to the overscrutiny on the morrow of Covid-19, the wider scope of biosecurity, under different names and guises, seems to reflect onto a terminology deficiency. Said terminology is sparsely and arbitrarily used, with little consistency and even less regard for correct linguistics and semantics. Any worthwhile advance of the wider biosecurity field, an undeniable necessity due to the regular incidence of pandemics in the 21st century, requires cognitive efficiency. This need is indirectly admitted by the emergence and then increase of publication platforms, especially journals, which specifically tackle bioterrorism and then biosecurity in a more inclusive context, which sat better with the different and militant activist platforms promoting civil and every other kind of rights, actual, factual, or fictional. Despite the rich tradition of the Westerners in biowarfare, from the blankets carrying Variola major and being presented as gifts to the native Americans back in the 18th century by agents of the Crown to the ideas of the British to use bioagents to starve Nazi Germany (and the rest of the occupied Europe) and the Agent Orange (Croddy, 2005), the biowarfare resided in a black realm to the fringe of science. The events of 9/11 and the 2001 Anthrax attacks in the United States (ibid) brought the issue, in the guise of bioterrorism, into the vogue. The White House has acknowledged the bioagents as a threat early, but the interest was to prove rather brief. Full comprehension seems to have occurred during the last decade. The development of the health sector to a central player in national and international security because of the repeated pandemics (bird flu, swine flu, H1N1, Ebola) but mostly due to Covid-19 accelerates and propagates such platforms and the underlying interest; but this is hardly adequate.

To understand, analyze, communicate, and synthesize novel concepts and ideas in a coherent and effective manner, one has to use linguistic and cognitive tools of appropriate specificity; if not precise, at the very least accurate. For example, the addition of the prefix bio- to terms applicable in security studies is not the best course of action; the prime example is the hazy concept of bioprotection, with unclear reference of the bio- constituent. Does it refer to protecting biological entities, protecting from biological entities, or protecting through the use of biological entities? An effort to analyze the basic terminology at the conceptual level is thus considered the main aim of the very first chapter of a book on Genomics in Biosecurity, instead of the usual diversion to a short synopsis of the history of the field and perhaps a statement of goals.

Still, one has to draw attention to a patent asymmetry: genomics, suffering no such aversion enjoy a rich, descriptive, and of high consensus terminology, which supports adequately the development of the sector since the early 2000s and is used more or less consistently and cohesively throughout the world. This terminology is not without problems, especially due to generational gaps that shift the context of a term, as is the term haplotype. There are problems, discord, and heated discussions but at least there has been a functional basis. Not entirely satisfactory, but functional nonetheless.

Biosecurity is a collective term that includes all concepts and measures actively taken and passively implemented against natural and anthropogenic—both spontaneous and perpetrated (Connell, 2017; Koblentz, 2017)—biorisks before they materialize to bioevents. The concept of (bio)risk underlines the inherent possibility and probability of an adverse event to occur, spontaneously or not. This risk resides on a material factor as a bioagent (i.e., a virus) or an immaterial one, as a condition, i.e., the residual radiation in a radiologically compromised/contaminated environment. Such factors may, under given circumstances, produce adverse results (bioevents) of different magnitude and impact. Thus biorisk is the possibility and subsequent probability of the aforementioned circumstances to occur. (Bio)event, on the other hand, constitutes actuality or, seen from the opposite perspective, any materialization of the (bio)risk (Lipsitch, 2017).

A term similar to biorisk is biothreat, which however applies mainly to perpetrated events, at least sensu stricto. Furthermore, biothreat, both sensu stricto and sensu lato, entails the quality of immediacy; it is a biorisk evolving from possibility to probability and even prospect, usually by a cognitive component substantiating intention. Biohazard, on the other hand, is rather applicable to specific material—and potentially to immaterial—entities as a characteristic; it implies their inherent potential to cause (bio)risk or to be manipulated to present biothreats.

The concept of perpetrated event needs also some clarification; it is usually considered identical in meaning to anthropogenic or, at the very least a subcase of the latter, as there are accidental anthropogenic events (which fall rather into the spontaneous category). But actually, it is neither and the two concepts partially overlap. Although current factuality lags behind, still the concept of perpetrated event makes allowance for any opposing/malevolent (this time sensu lato) mind. The latter may or may not be human; organic, inorganic, or completely alien. Thus, the notion of spontaneous includes natural and some anthropogenic events, but perpetrated includes, at least in theory, more than the balance of anthropogenic ones.

Biosafety should not be confused with biosecurity. It concerns measures taken to avert accidental and in some cases, other spontaneous events and refers to biorisks, not to biothreats. It can be understood as a version of biosecurity, or rather a concept equivalent to biosecurity but attuned to benign, spontaneous prospects; or as a subcase of biosecurity, simplified for implementation in more permissive environments.

Concerning the anthropogenic biorisks/events, some further distinction is warranted in terms of massiveness and objectives: Biological warfare/biowarfare is the most massive scale and can be understood as the use or threat of use of disruptive or destructive (but always in a negative sense and with malevolent intent) biological agents, be they bioorganisms or procedures and/or their products to pursue official political or military goals. This is a much wider concept than usually apperceived. Actually, the offensive concept of utilizing such agents constitutes, in a military and security context, bioattack as an instantaneous context describing an event, and bioagression as a coherent policy or SOP to implement bioattacks.

Biodefense is an extension of the biosecurity and refers to any actions taken, proactively or reactively, to directly nullify or alleviate the impact of a bioattack but not in a proactive manner. Raiding a bioterrorist depot and conflagrating the stack of bioagents is not biodefense; decontamination and medical countermeasures are.

The concept of biooffense (and bioassault) is proposed herein for reasons of symmetry, to help better define the bioagression/bioattack pair and in direct analogy to the latter. It denotes the targeting of biological, living entities, irrespective of the means used to effect such intentions. The use of living organisms or their products and procedures is not required to implement biooffense. As a result, biodefense does not apply by definition to this case, but only when the biooffensive procedure is a bioattack. To elucidate pervasive differences, an example might be helpful: shooting or stabbing a person is bioassault but not bioattack. Dispersing spores of Bacillus anthracis to cause health casualties and deaths in humans and livestock is both bioassault and bioattack. The use of microbes to degrade fuel, supplies, rubber parts, or to erode metals is bioattack, but not bioassault. Shooting or blowing a structure, a vehicle, or any other inanimate entity is neither bioattack nor bioassault. It must be stressed that in many cases the generic terms biooffense and bioaggression are used preferentially to simplify terminology.

Biocrime is qualitatively similar but quantitatively applicable to a limited context, in most cases regarding single person or entity (i.e., corporation, institution, organization) with main, but not sole, objective being the financial gain. Bioterrorism actually is the intersection of biowarfare and biocrime, as its scale may be massive, as in the former, or individual, as in the latter and its targeting political or financial.

There is an intriguing dimension in the core concept of biowarfare and the other forms of biothreat. It is usually surmised that in a bioattack the perpetrator uses a microbial or a biochemical agent (usually a biotoxin or a bioregulator, the former being a subcase of the latter in some interpretations); the first is represented in the clause of the definition referring to organisms, the second to the clause referring to the products. This is not necessarily so; the germ warfare and the biochemical warfare, which literally cover these cases, are a part of biowarfare. Even when interpreting narrowly the term use to denote an effector and an immediate causal relationship with the detrimental result, as opposed to facilitating or support functions, the sense and essence of biological far exceeds microbiology. Although the last decades have not witnessed any such examples, macroorgnisms have been frequently used as effectors in bioattacks, biooffensive or not. The trained dogs carrying antitank mines to counter and destroy enemy tanks or the use of falcons to intercept and destroy drones are cases of macrobiological, nonbiooffensive bioattack. The trained war dogs attacking troopers, and pack animals or cavalry mounts and falcons attacking messenger pigeons are historical examples of biooffensive bioattacks. A current one is the reported use of trained dolphins to intercept enemy divers along strategic waterborne facilities. The future will include enhanced organisms as main effectors, as an alternative to mechanically, genetically, or prosthetically enhanced human agents (bionic technologies). These contraptions though are not within the scope of this book.

It remains always a possibility to expand the concept of use to include noneffector applications, such as support ones. These are to exclude by some clause or other the standing and unchanging uses of biological products and processes such as, but not limited to, food supplies for humans and animals and fabrics for clothing. Thus the use of biological entities for transportation (pack animals in the alpine environment), messaging/communications (messenger pigeons and dogs), production of materiel (biofuel, fabrics for body armor), or implementation of procedures (cell-based neuronic computers) may be included to some annex of biowarfare.

Biosecurity can be further divided into biodefence (or biological defense or defensive biological warfare), antibioterrorism, and antibiocrime functions (Millett and Snyder-Beattie, 2017a, 2017b), including a forensics component (Koblentz, 2017) that may apply to informing prophylaxis, treatment, and responses ranging from deterrence, through prevention (proactive but possibly also reactive in nature) to punitive measures. In the case of bioterrorism there is a subcase, agroterrorism, which refers to targeting the agricultural and, sensu lato, the environmental sector(s). At this point agrocrime is not relevant as a concept; but it may become in the near future, as the biotechnological components and the increasing importance of agriculture set a volatile stage prone to be used as leverage. On the other hand, the massive and diverse scale of biowarfare, by definition, makes any concept of agrowarfare redundant; agricultural dimensions have always been incorporated in biowarfare concepts and in most cases in conventional warfare as well.

Irrespective of causal status, all biorisks may be expanded, to include human, livestock, plants, and the environment (Hekim and Özdemir, 2017; Katara et al., 2012; Nuzzo, 2017; Schoch-Spana et al., 2017; Thelaus et al., 2017) thus defining the concept of total biothreat. The latter is innovative in the degree of integration it allows for; considering organisms beyond the humans as susceptible to bioattacks is perhaps as old as the history of massive warfare, especially as far as disruptive, not mere destructive effects are concerned (the Covid-19 being a prime example in this respect). But the idea that a single pathogen may implicate directly or indirectly a very wide range of hosts in wildly divergent kingdoms of life to result in global-scale events is novel indeed. The host-hopping of fungi that can travel over vast distances, propagate on crops to cause alimentary disease or famine and then sporulate to infect human and animal hosts with massive death tolls under some specific conditions is a prime example of such dynamics, which may apply to a not very distant future (Casadevall, 2017).

The Bioawareness refers to a cognitive status of understanding the issue of biothreats and biorisks and their evolution. An instrumental element of bioawareness is the cross-referencing of ongoing research and other data-producing procedures and processes to keep track of the horizon of events and potential. To produce actionable intelligence and information, though, further steps are required. This refers to the Bioresilience, which denotes the actual measures taken—a step after bioawareness—including, but not restricted to biopreparedness, biovigilance/biosurveillance, biodefence/biosecurity; it is, contrary to bioawareness, a hybrid, cognitive and interventional, entity.

The Biovigilance refers to a doctrinal framework that prioritizes, describes, and enables actions taken on a substrate of bioawareness by implementing biosurveillance, and other aspects of biopreparedness so as to remain current/relevant in understanding the evolution of the biorisk/biothreat and includes active research in relevant fields. Biosurveillance includes all the measures taken to become aware of any differentiation/divergence of an established horizon of events, including research but not focusing on research. It entails routines, planning, feedback, reaction but it is a cognitive, not interventional entity, an example of biovigilance is the document issued by the White House in 2002 (The White House, 2004).

The Biopreparedness represents the full spectrum of measures taken in advance to guard against biorisks, plus the support and logistics background (infrastructure, processes, awareness, training/drilling) needed to implement them promptly. It refers to cognitive and interventional dimensions. The biopreparedness is the holistic response to an alarm sound by bioawareness, which includes bioresilience and all other indirectly involved elements which may bolster the latter (Table 1.1).

Table 1.1

The genomic aspect of biosecurity is much more complex than originally thought. Pregenomic (i.e., molecular biological) and genomic (as in microbiomics) methodologies have always been features of different aspects of what is now brought under the umbrella of biosecurity, especially in diagnostics. Currently, though, genomics, sensu lato, which means the inclusion of postgenomics disciplines, seem to play a role in the creation of the problem (Gómez-Tatay and Hernández-Andreu, 2019; Wang and Zhang, 2019) at least as important as the one they claim within the context of prospective solutions. Additionally, genomics created the need for high-tech databases with massive access and automated querying. At least in terms of methodology, regarding the distributed implementation, the interconnection, the access to depositories, the proofing and mining tools, genomics might be the perfect example for all issues and things concerning biosecurity; additionally, such infrastructure developed and used through the genomics revolution may be expanded and used for biosecurity research, instead of copying and recreating the entire framework. It is true that the genomic base of the 21st-century biosecurity (Vinatzer et al., 2019) is by definition restrictive compared to the multifaceted procedures of conventional microbiology. But this needs not to be so. The postgenomics and integrated multiomics concepts can bridge the unidisciplinary issue into multidisciplinarity, while the very fabric of genomics might dissect levels of interactions hitherto simply imaginable. Such cases are indicatively but not restrictively:

(i)The correlation of genotypes between pathogens and hosts to establish maximum and minimum susceptibility compound genotypes, possibly with undefined multiploidy (a version of polyploidy without standardized multiples of some genomes or loci due to the existence of additional carriers, as are cell populations, of unrestricted proportions). The Covid-19 brought the issue to the vogue.

(ii)The biphasic, host-pathogen pharmacogenomics, where the efficacy is connected with one genome (the pathogen’s) and the safety with another (the host’s) (Aceti, 2016; Patrinos et al., 2020; Velegraki and Zerva, 2020). As has already become obvious, genomics could solve some intriguing biosecurity issues, but the course takes us through bioinformatics and Big Data. The genomic analysis of microbiotic virulence and host susceptibility genotypes has been or becomes standard (Griswold, 2008; Ellinghaus et al., 2020 respectively). Their paired analysis though into a highly integrated pathogen-host environment of interactions may become much more robust. Additional pathogens do not simply multiply the interactions to proportionately additional pairs; exponential dynamics seem more likely and networks emerge as the most suitable and handy operative model (Mandlik et al., 2017). There is, or at least there may be, any kind of associations; as a result some genotypes may interact within the host or among the diverse pathogens. The infectomic dimension would thus have to consider the possible transformation of parts of the residual microbiome and also to detect epigenetic differentiations, which might explain different tropisms of given pathogens, for specific tissues or organs. In a plainer context, nonpharmaceutical disinfection would depend on traits coded by specific genotypic combinations, and thus even at this level genomics is poised to interact with the effector constituent of biosecurity. But most importantly, the regular updates of projected risks, threats, and hazards lean heavily toward the processes of reviewing large genomics datasets under different aspects.

Still, there are some novelties and intricacies with terminology. Metagenome is a tricky term and actually implies a genome not retrieved from a purified single source but retrieved as a molecular methodology product. The term applies to both genomes compiled through metagenomics where algorithms annotate sequences of possibly diverse origin to different genomes assembled and characterized as a puzzle (Patrinos et al., 2020); and to synthetic biology context. In the latter, the additional concepts of undergenome, overgenome, and subgenome become handy. The metagenome in this case is a new genomic entity that results from such synthetic, combination, editing, fuzing, reshuffling, and any other procedure, while the other terms describe the nature of the participant genomic entities. The undergenome suggests minimal residual genomic entities incorporating the most basic and necessary housekeeping gene circuitry to maintain generic cell platforms (Gibson et al., 2010; Hutchison et al., 2016; Umenhoffer et al., 2010). An overgenome can thus be pasted (either transfer or transplant) on it to create a custom-built metagenome endowed with the desired characteristics. The overgenomes may be unitary, where a whole genome or, alternatively, a part of one specific genome is transplanted. The combined overgenome refers to the assembly of an overgenome from a number of subgenomes that have to integrate and function seamlessly with the undergenome and other subgenomes (Kambouris et al., 2018) of the overgenome. In reality, the notion of subgenome refers to one among a number of similar integrated genomic entities, a very plain example being the plasmids which may be added or subtracted from a bacterial genome.

Similarly, but more straightforwardly, the hologenome refers to the collective genome of a holobiont or, rather, to the sum of the genomes (understood as the entirety of the genomic sequences, be they DNA, RNA, chromosomal, episomatic, or exonuclear and viral) of a host and its symbionts, with the latter forming the respective microbiome (Kambouris and Velegraki, 2020). Some more intricacies are ingrained in spatial terms: the hologenome may refer to the combined genomes of the microbiome and the host as a total. For lack of better, more descriptive terminology to date (subhologenome really sounds weird), it may also refer to the combination of host-microbiome genomes in more specific and restrictive spatial terms. The obvious case is the different biocompartments, where the local/appendage microbiomes are expected to display considerable differences of both qualitative and quantitative nature among biocompartments of the same host. Additionally, some variability at the host genome, especially in biocompartments of intense procedures and high exposure and turnover, is natural, as well.

One last area where genomics will intersect with biosecurity is the realm of xenobiology. The mere term was always raising eyebrows and initially meant to describe extraterrestrial life with the notion of other planets and possibly, although not necessarily, of other biochemistries, beyond nucleic acids' or even carbon-based ones. These issues are now the realm of astrobiology, at least when referring to more Earth-like space biospheres (Budisa et al., 2020), after briefly being tackled by exobiology.

But nowadays xenobiology has expanded toward more mundane cases. The most current is the iteration of drastically expanded, synthetic life forms with analogues of the natural ingredients and procedures but in a more expansive nature; nucleic acid genetic code but with additional and/or different code letters instead of the well-known quartet (Acevedo-Rocha and Budisa, 2016; Leconte et al., 2008; Schmidt, 2010). It is not very clear and remains conjectural whether in such a context astrobiology is indeed a part of xenobiology, or altogether another realm. It has little to do with synthetic life-forms, but much to do with different biochemistry principles, despite sometimes being interpreted in a most narrow sense, for celestial bodies being like Earth in environment and thus able to support Earth-like life-forms of similar or identical biochemistry, although not of the same evolutionary pathways and forms.

At the same time, exobiology, which was initially used instead of Astrobiology, might find another use, once more as a subordinate to Xenobiology or as a completely independent field. There is a very large body of life-forms that are presently unaccounted for: the ones living or existing, even in a subviable stage (i.e., into dormancy) excluded or separated from the biosphere. This new concept adds possible extraterrestrial microflora, such as bacteria, which though might have migrated from the biosphere and remained, active or inactive, out of it. Such is the case of microbes in space garbage launched at a time from the surface, as are satellites, and then endlessly remaining in orbit or kicked to the infinite. But most importantly, it includes terrestrial locations isolated due to an event, usually of geological origin, which severed a (micro)ecosystem from the biosphere but the residual conditions made it sustainable, and thus evolution followed different pathways.

In such cases, entailing immense biosecurity (and biotechnological) interest, genomics and to a lesser degree postgenomic omics are indispensable as they allow the elucidation of wildly divergent contraptions if not prodigies with specs and details written in the standard code, along with some other, exciting possibilities to be applicable or grafted to the new realms. The field of xenogenomics, which is expected to follow should Xenobiology present an explosive growth, would be indispensable to describe and predict possible infringements of the two lines of evolution and thus initiate a novel spinoff of biosecurity.

The vertical so to say sequence of genomics/postgenomics is a linear and restrictive aspect of biosecurity. A horizontal one might be apperceived by the interaction or mating of different levels of some biome entity (genomics, postgenomics, etc.) with other, technical aspects; some of them already here, others incubating. For example, the cyberbiosecurity (Vinatzer et al., 2019) is to become of immense importance. As would be discussed later, the surveillance and especially the detection and identification functions depend on known attributes for the logical processes that output any kind of result, from binary to most descriptive ones. Similarly, the recorded genetic information is of the highest importance for biotechnology, as it provides ideas, applications, and occasionally ready-to-use bioproduction line blueprints, all within nucleic acid sequences. Using such resources in a malevolent manner, to produce aggressive agents, is the worst-case scenario of biosecurity; using it for illegitimate but benign, mundane purposes is just a very serious issue, as it encroaches with the sanctioned economic activity and the public health safety. The latter is occasionally difficult to apperceive, but the notion of black-market bioproducts, from cosmetics to food additives and supplements with unknown allergen context and profile usually sensitizes many indifferent folks.

The issue has many additional aspects: from compromising such resources to manipulating their use and users to acquiring actionable data, such as the allergy and reverse effect profile of individuals of interest to use in covert incapacitation attempts, all the way to the massive hacking of health-related databases for drafting personalized insurance contracts or the threat to delete such records, the cyberbiosecurity shows clearly the importance and potential impact of the horizontal dimension. The creation of biotechnidal organisms, using the biological blueprints with some modern manufacture twists, as in xenobiology and, more comprehensively and imminently with artificially enhanced organisms, with hybrid implants, is another iteration. Actually, only imagination is the limit once such crossovers begin to emerge. The technical dimension is just the tip of the iceberg. New extinction-level events and technoracism will appear, as the modified individuals would pursue the use of their restored or acquired abilities to the fullest, and the unmodified folk, neither able to afford nor eligible for a subsidy for upgrades, will sense a social, economic, and in a depth of 1–2 generations existential threat not only for individuals but also for the very fabric and nature of the society, a Matrix prospect.

Last, and extremely important, is the understanding of an important antithesis within the biosecurity context. All functions entailing a—security or—defense suffix suffer by definition from the friction between two different, if not opposing, tendencies: the first tendency is a drive to improvise, innovate, advance, and stay current. It is an existential need to outsmart and outpace the opponent and, preferably, to achieve surprise by quality of materiel and procedural improvisation, a concept very well known to military thinkers and decision makers (there the procedural is the tactics with or without a spatiotemporal spinoff—absolute and relative time, macrolocation-geography, microlocation-terrain). Even when the opponent is not a defined enemy mind, but something abstract (including a collective intelligence), the very event of differentiation, even stripped of its evolutionary context, may result in obsolescence or irrelevance of security/defense assets, both cognitive/procedural and technological/material ones.

This vital prerequisite for innovation and modernization is counteracted by the inherent propensity toward conservativeness of military/security organizations. Reluctant by definition to alter a working concept, since experimentation comes with a most heavy price possibly leading to extinction, and requiring a psychological background to infuse courage and moral stiffening in the face of both danger and hardship, the traditions and history are easy sources to tap. This net of a quest for continuity and minimization of risk results in the inclination toward conservatism. The latter may dull reflexes, actual, factual, and mental, sap awareness and undermine the very essence of vigilance. It is an age-old question of how to seamlessly integrate these two incompatible mindsets within a working scheme and within the mind, soul, and mentality of the implicated individuals. Technology offers some solutions for technical specs; still, for the foreseeable future the field of concepts, ideas, and impressions can only be approached by immaterial resources; if not training, then praying; if not praying, then educating, etc. Or, possibly, a wide and large combination of these three and possibly others, as seen and seem fit for different cases and subjects.

References

Aceti A. Pharmacogenomics for Infectious Diseases. 2016.doi:10.4172/2161-0703.1000223.

Acevedo-Rocha C.G., Budisa N. Xenomicrobiology: a roadmap for genetic code engineering. J. Microbial. Biotechnol. 2016;9:666–676. doi:10.1111/1751-7915.12398.

Budisa N., Kubyshkin V., Schmidt M. Xenobiology: a journey towards parallel life forms. ChemBioChem. 2020;doi:10.1002/cbic.202000141.

Casadevall A. Don’t forget the fungi when considering global catastrophic biorisks. Heal. Secur. 2017;15:341–342. doi:10.1089/hs.2017.0048.

Connell N.D. The challenge of global catastrophic biological risks. Heal. Secur. 2017;15:345–346. doi:10.1089/hs.2017.0056.

Croddy E.A. Introduction: chemical and biological weapons. In: Croddy E.A., ed. Weapons of Mass Destruction. Santa Barbara: ABC Clio; xxv–xxx. 2005;vol. I.

Ellinghaus D., Degenhardt F., Bujanda L., Buti M., Albillos A., Invernizzi P., Fernández J., Prati D., Baselli G., Asselta R., Grimsrud M.M., Milani C., Aziz F., Kässens J., May S., Wendorff M., Wienbrandt L., Uellendahl-Werth F., Zheng T., Yi X., de Pablo R., Chercoles A.G., Palom A., Garcia-Fernandez A.E., Rodriguez-Frias F., Zanella A., Bandera A., Protti A., Aghemo A., Lleo A., Biondi A., Caballero-Garralda A., Gori A., Tanck A., Carreras Nolla A., Latiano A., Fracanzani A.L., Peschuck A., Julià A., Pesenti A., Voza A., Jiménez D., Mateos B., Nafria Jimenez B., Quereda C., Paccapelo C., Gassner C., Angelini C., Cea C., Solier A., Pestaña D., Muñiz-Diaz E., Sandoval E., Paraboschi E.M., Navas E., García Sánchez F., Ceriotti F., Martinelli-Boneschi F., Peyvandi F., Blasi F., Téllez L., Blanco-Grau A., Hemmrich-Stanisak G., Grasselli G., Costantino G., Cardamone G., Foti G., Aneli S., Kurihara H., ElAbd H., My I., Galván-Femenia I., Martín J., Erdmann J., Ferrusquía-Acosta J., Garcia-Etxebarria K., Izquierdo-Sanchez L., Bettini L.R., Sumoy L., Terranova L., Moreira L., Santoro L., Scudeller L., Mesonero F., Roade L., Rühlemann M.C., Schaefer M., Carrabba M., Riveiro-Barciela M., Figuera Basso M.E., Valsecchi M.G., Hernandez-Tejero M., Acosta-Herrera M., D’Angiò M., Baldini M., Cazzaniga M., Schulzky M., Cecconi M., Wittig M., Ciccarelli M., Rodríguez-Gandía M., Bocciolone M., Miozzo M., Montano N., Braun N., Sacchi N., Martínez N., Özer O., Palmieri O., Faverio P., Preatoni P., Bonfanti P., Omodei P., Tentorio P., Castro P., Rodrigues P.M., Blandino Ortiz A., de Cid R., Ferrer R., Gualtierotti R., Nieto R., Goerg S., Badalamenti S., Marsal S., Matullo G., Pelusi S., Juzenas S., Aliberti S., Monzani V., Moreno V., Wesse T., Lenz T.L., Pumarola T., Rimoldi V., Bosari S., Albrecht W., Peter W., Romero-Gómez M., D’Amato M., Duga S., Banales J.M., Hov J.R., Folseraas T., Valenti L., Franke A., Karlsen T.H. Genomewide association study of severe Covid-19 with respiratory failure. N. Engl. J. Med.