Why Gene Editors Like CRISPR/Cas May Be a Game-Changer for Neuroweapons.

This year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC). At the same time, ongoing international efforts to further and more deeply investigate the brain's complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion, and behavior. These advances have tremendous promise for human health, but the potential for their misuse has also been noted, with most discussions centering on research and development of agents that are addressed by existing BWC and Chemical Weapons Convention (CWC) proscriptions. In this article, we discuss the dual-use possibilities fostered by employing emergent biotechnologic techniques and tools-specifically, novel gene editors like clustered regular interspaced short palindromic repeats (CRISPR)-to produce neuroweapons. Based on our analyses, we posit the strong likelihood that development of genetically modified or created neurotropic substances will advance apace with other gene-based therapeutics, and we assert that this represents a novel-and realizable-path to creating potential neuroweapons. In light of this, we propose that it will be important to re-address current categorizations of weaponizable tools and substances, so as to better inform and generate tractable policy to enable improved surveillance and governance of novel neuroweapons.

[1]  J. Giordano,et al.  “NEURINT” and Neuroweapons: Neurotechnologies in National Intelligence and Defense , 2014 .

[2]  J. Giordano Neurotechnology in National Security and Defense : Practical Considerations, Neuroethical Concerns , 2014 .

[3]  David Cyranoski,et al.  CRISPR gene-editing tested in a person for the first time , 2016, Nature.

[4]  C. Harvard Applications of CRISPR-Cas systems in neuroscience , 2016 .

[5]  L. Galland The gut microbiome and the brain. , 2014, Journal of medicinal food.

[6]  D. Cyranoski,et al.  Embryo editing sparks epic debate , 2015, Nature.

[7]  Heidi Ledford,et al.  CRISPR: gene editing is just the beginning , 2016, Nature.

[8]  Henry Markram,et al.  The human brain project. , 2012, Scientific American.

[9]  G. Pearlson,et al.  Genetics of cognitive control: Implications for Nimh's research domain criteria initiative , 2016, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[10]  Xuesi Chen,et al.  Production and clinical development of nanoparticles for gene delivery , 2016, Molecular therapy. Methods & clinical development.

[11]  M. Kay,et al.  Science Journals — AAAS , 2016 .

[12]  Introduction-On the need for neurotechnology in the national intelligence and defense agenda: Scope and trajectory , 2011 .

[13]  S. Reardon Gut–brain link grabs neuroscientists , 2014, Nature.

[14]  Lei S. Qi,et al.  CRISPR/Cas9 in Genome Editing and Beyond. , 2016, Annual review of biochemistry.

[15]  M. Dando Advances in Neuroscience and the Biological and Toxin Weapons Convention , 2010, Biotechnology research international.

[16]  Franck Ramus,et al.  Genes, brain, and cognition: A roadmap for the cognitive scientist , 2006, Cognition.

[17]  M. Dando Neuroscience and the Future of Chemical-Biological Weapons , 2014 .

[18]  J. B. Cohen,et al.  Moving toward a gene therapy for Huntington’s disease , 2015, Gene Therapy.

[19]  X. Breakefield,et al.  Genetic therapy for the nervous system. , 2011, Human molecular genetics.

[20]  C. Gunderson,et al.  Chapter 5: Nerve Agents , 1996 .

[21]  G. Kaebnick,et al.  Precaution and governance of emerging technologies , 2016, Science.

[22]  James Giordano,et al.  Neurotechnologies as weapons in national intelligence and defense - An overview , 2011 .

[23]  X. Breakefield,et al.  Viral vectors for gene delivery to the nervous system , 2003, Nature Reviews Neuroscience.

[24]  Jeffry D. Sander,et al.  CRISPR-Cas systems for editing, regulating and targeting genomes , 2014, Nature Biotechnology.

[25]  Sripriya Ravindra Kumar,et al.  Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain , 2015, Nature Biotechnology.

[26]  M. Nesbit,et al.  CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting , 2015, Gene Therapy.

[27]  James R. Clapper Statement for the Record, Worldwide Threat Assessment of the US Intelligence Community, Senate Select Committee on Intelligence, James R. Clapper, Director of National Intelligence, March 12, 2013 , 2013 .

[28]  Jennifer Kuzma,et al.  Societal Risk Evaluation Scheme (SRES): Scenario-Based Multi-Criteria Evaluation of Synthetic Biology Applications , 2017, PloS one.

[29]  Alison G. Smith,et al.  Towards developing algal synthetic biology. , 2016, Biochemical Society transactions.

[30]  Molly Gale,et al.  An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting , 2016, Nucleic acids research.