Biodefense in the Age of Synthetic Biology (2018) / Chapter Skim
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6 Assessment of Concerns Related to Bioweapons that Alter the Human Host
6 Assessment of Concerns Related to Bioweapons that Alter the Human Host
Pages 71-84
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From page 71... ...
These populations of microbes are likely far easier to manipulate than the human host itself, making the microbiome a potentially accessible vector for attack. The human microbiome is the focus of a great deal of academic and commercial research, and microbiome manipulation is an area that is rapidly developing, as also discussed in Chapter 5.
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From page 72... ...
Synthetic biology methods could advance such a capability, for example, through the engineering of toxin:antitoxin couples that would help ensure retention of plasmids. It is also conceivable that microbes could one day be engineered to horizontally transfer genes directly to human cells.
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From page 73... ...
Achieving desired phenotypic results might require the introduction of particular bacterial species or strains and/ or particular genetic modifications of these species or strains. In most cases, microbiome engineering is likely to be further complicated by the need to make multiple genetic introductions or edits involving multiple symbiotic microbiome species.
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From page 74... ...
Once a successful microbiome engineering approach is established, subsequent production of bioweapons could likely be achieved with a relatively small organizational footprint. However, a high level of expertise would likely be needed to perform the engineering required.
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From page 75... ...
may provide a means of engineering biological threats that would trigger life-threatening IgE-mediated immune responses. The development and testing of new immunotherapies could also provide a roadmap for potentially engineering threats; for example, actors could learn from clinical studies in which anti-CD28 antibodies caused life-threatening cytokine storms (Suntharalingam et al., 2006)
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From page 76... ...
. Moreover, several of the approaches considered would require an actor to not only successfully develop and deploy the immunomodulatory weapon itself but to successfully plan and execute a multipronged attack in which the immunomodulatory weapon is combined with another biological attack (such as deploying a pathogen after an initial attack causing immunodeficiency)
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From page 77... ...
Even if good countermeasures could be crafted, their expense would likely be inordinate, especially for more general attacks on population immunity. MODIFYING THE HUMAN GENOME In addition to using synthetic genes to impact human physiology through pathogens or modifications to the microbiome, it may also be possible to insert engineered genes directly into the human genome via horizontal transfer, in other words, to use "genes as weapons." Recent improvements in the ability to deliver genetic information via horizontal transfer, for example, through tools such as CRISPR/Cas9, potentially open the way for synthetic or cross-species transfer of genetic information into human hosts.
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From page 78... ...
. However, the sequence-specific binding capabilities of Cas9 and other CRISPR elements may allow fusion proteins to carry out sequence-specific epigenetic modifications (Brocken et al., 2017)
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From page 79... ...
. Concerns related to the use of gene drives in human populations were assessed separately from other potential approaches involving horizontal gene transfer because fundamental differences in the mechanisms involved in these different types of activity engender significantly different levels of concern.
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From page 80... ...
However, there would be significant challenges to determining the right targets or edits, packaging the genetic cargo into viral vectors, and delivering it to appropriate host cells. CRISPR-based genome editing technologies are advancing rapidly and could be used to create genetic modifications propagated through engineered pathogenic vectors or horizontal transfer to human cells.
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From page 81... ...
The reduction or removal of key bottlenecks and barriers in the future could make some of the approaches discussed in this chapter more feasible. • As understanding of microbiomes increases, the possibility of misuse also increases, and it may become feasible to use synthetic biology to engineer the microbiome to transfer toxic genes, debilitate human immunity, improve pathogen entry or spread, or create dysbioses.
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From page 82... ...
. The current state of knowledge of the human microbiome is rapidly increasing, and it may be feasible to use synthetic biology to engineer the microbiome to transfer toxic genes, debilitate human immunity, improve pathogen entry or spread, or create dysbioses.
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From page 83... ...
ASSESSMENT OF CONCERNS RELATED TO BIOWEAPONS THAT ALTER THE HUMAN HOST 83 TABLE 6-1 Bottlenecks and Barriers That Currently Constrain the Capabilities Considered and Developments That Could Reduce These Constraintsa Capability Bottleneck or Barrier Relevant Developments to Monitor Modifying the human Limited understanding of Improvements in knowledge related to microbiome microbiome microbiome colonization of host, in situ horizontal transfer of genetic elements, and other relationships between microbiome organisms and host processes Modifying the human immune Engineering of delivery system Increased knowledge related to the potential for viruses or system microbes to deliver immunomodulatory factors Limited understanding of Knowledge related to how to manipulate the immune system, complex immune processes including how to cause autoimmunity and predictability across a population Modifying the human genome Means to engineer horizontal Increased knowledge of techniques to effectively alter transfer the human genome through horizontal transfer of genetic information Lack of knowledge about Increased knowledge related to regulation of human gene regulation of human gene expression expression aShading indicates developments that are likely to be propelled by commercial drivers. Some approaches, such as combinatorial approaches and directed evolution, may allow bottlenecks and barriers to be widened or overcome with less explicit knowledge or tools.
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