Ralph S. Baric – University of North Carolina at Chapel Hill
Cite as: Baric RS. 2006. Synthetic Viral Genomics.
In: Working Papers for Synthetic Genomics
Risks and Benefits for Science and Society, pp. 35-81. Garfinkel MS, Endy D, Epstein GL, Friedman RM, editors. 2007
https://dspace.mit.edu/bitstream/handle/1721.1/39652/Baric%20Synthetic%20Viral%20Genomics.pdf
A. Viruses and Biological Warfare
Viral disease outbreaks have long inspired fear in human populations. Highly pathogenic infectious disease has shaped world history, primarily by impacting the outcome of wars and other global conflicts and precipitating human movement. Historic accounts have documented the catastrophic consequences and human suffering associated with widespread viral outbreaks like smallpox virus, yellow fever virus, measles virus, human immunodeficiency virus (HIV), the severe acute respiratory syndrome coronavirus (SARS-CoV), the 1918 influenza virus and others (51). News accounts and film have reinforced the serious threat posed by the emergence of new viral diseases as well as the catastrophic consequences of intentional release of highly pathogenic viruses in human populations. As illustrated by the SARS epidemic and the continuing evolution of the H5N1 avian influenza, global and national infectious disease outbreaks can overwhelm disaster medical response networks and medical facilities, disrupt global economies, and paralyze health and medical services by targeting health care workers and medical staff (21). This review focuses on viruses of humans, animals and plants that are viewed as potential weapons of mass disruption to human populations, critical plant and animal food sources, and national economies; and will consider whether and how the availability of synthetic genomics technologies will change this landscape.
Biological warfare (BW) agents are microorganisms or toxins that are intended to kill, injure or incapacitate the enemy, elicit fear and devastate national economies.
Because small amounts of microorganisms might cause high numbers of casualties, they are classified as weapons of mass destruction. A number of naturally occurring viruses have potential uses as BW agents, although the availability of these agents is oftentimes limited. This report discusses the potential use of recombinant and synthetic DNAs to resurrect recombinant BW viruses de novo and the potential for altering the pathogenic properties of viruses for nefarious purposes. Examples of weaponized viruses include Variola major (Smallpox), Venezuelan equine encephalitis virus (VEE), and the filoviruses Marburg and Ebola viruses, with the classic example being the use of smallpox virus-contaminated blankets against indigenous North American Indian populations (76). It is now clear that many viruses possess properties consistent with applications in biological warfare and bioterrorism.
B. Properties of Select BW Agents
Traditionally, biological warfare concerns have focused on a relatively limited, select group of naturally occurring pathogens viewed as having a set of desirable characteristics:
- highly pathogenic,
- readily available,
- easily produced,
- weaponizable,
- stable,
- infectious at a low dose,
- easily transmissible, and
- inspiring of fear (32).
Viruses of concern include pathogens that replicate and produce serious morbidity and mortality in humans to pathogens that target farm animals and plants of economic importance. Historically, weaponization of agents has been constrained by availability, the biological characteristics specified within the genome of these organisms, the ability to replicate and produce large quantities of the material, and by the lack of appropriate associated technologies. Culture (growth) and containment conditions for most of the virus agents of concern have been solved and are readily available in the literature. Natural hosts and reservoirs of many viral agents have been identified, providing a means of readily acquiring these pathogens in nature, although this is not always the case. Most recently, full length genome sequences have been solved for many important human, animal and plant pathogens, providing a genetic template for understanding the molecular mechanisms of pathogenesis and replication. Structural studies have identified contact points between the virus and the host receptors needed for docking and entry, providing the means to humanize animal pathogens (42). With the advent of synthetic biology, recombinant DNA technology, reverse genetic approaches (i.e. the development of molecular clones of infectious genomes) and the identification of virulence alleles, not only are new avenues available for obtaining these pathogens, but more ominously, tools exist for simultaneously modifying the genomes for increased virulence, immunogenicity, transmissibility, host range and pathogenesis (22, 59). Moreover, these approaches can be used to molecularly resurrect extinct human and animal pathogens, like the 1918 human influenza virus (81).
National biodefense strategies are focused on threats posed by this small group of plant, animal and human pathogens that occur in nature. However, counterterrorism think-tanks anticipate that these particular threats will ameliorate over the next decade because of medical countermeasures (e.g., drugs, vaccines, diagnostics), coupled with a limited set of pathogens that include all of the biological warfare characteristics. More important, the anticipated long-term threat in biological warfare is in recognizing and designing countermeasures to protect against genetically modified and designer pathogens, made possible by newly emerging technologies in recombinant DNA, synthetic biology, reverse genetics and directed evolution (59).
How will synthetic genomics effect future biological weapons development?
What are the risks and benefits of these new technologies and how serious a threat do they pose for human health and the global economy?
This paper builds upon earlier work and seeks to review the methodologies in isolating recombinant viruses in vitro and the application of these methods globally to biological warfare and biodefense (27).
II. Virus Classification and Reverse Genetic Approaches
A. Overview of Virus Classification and Reverse Genetics
From the genome, all viruses must generate a positive strand mRNA that is translated into proteins essential for genome replication and the assembly and formation of progeny virions. Depending upon the nature of the genome, all viruses can be clustered into seven fundamentally different groups, which utilize different strategies to synthesize mRNA from the input genome, a scheme called the Baltimore Classification (Figure 1).1
Because virus infectivity is dependent upon the ability to transcribe mRNAs, reverse genetic strategies are designed to insure expression of critical viral mRNAs that encode essential replicase proteins needed to “boot” (initiate) genome infectivity and initiate genome replication.
Unbelievable how clear the working on forbidden Biologic Warfare Technology to do warcrimes against nature and humanity is Apparent. And how unscrupulous such a mindset looks like…
This is absolutely shocking!
Please read the rest of this paper…
https://dspace.mit.edu/bitstream/handle/1721.1/39652/Baric%20Synthetic%20Viral%20Genomics.pdf
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