Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-23T10:39:48.883Z Has data issue: false hasContentIssue false
  • English
  • Français

Dual-use nano-neurotechnology

An assessment of the implications of trends in science and technology

Published online by Cambridge University Press:  29 November 2018

Kathryn Nixdorff ,
Tatiana Borisova ,
Serhiy Komisarenko  and
Malcolm Dando
Kathryn Nixdorff
Affiliation:
Darmstadt University of Technology
Tatiana Borisova
Affiliation:
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine
Serhiy Komisarenko
Affiliation:
Palladin Institue of Biochemistry, National Academy of Sciences of Ukraine
Malcolm Dando*
Affiliation:
University of Bradford
*
Correspondence: Malcolm Dando, Department of Peace Studies and International Development, University of Bradford, West Yorkshire, Bradford BD7 1DP, UK. Email: M.R.Dando@bradford.ac.uk
Get access

Abstract

The chemical and biological nonproliferation regime stands at a watershed moment, when failure seems a real possibility. After the unsuccessful outcome of the 2016 Eighth Review Conference, the future of the Biological and Toxin Weapons Convention is uncertain. As the Chemical Weapons Convention (CWC) approaches its Fourth Review Conference in 2018, it has almost completed removing the huge stocks of chemical weapons, but it now faces the difficult organizational task of moving its focus to preventing the reemergence of chemical weapons at a time when the international security situation appears to be increasingly more difficult and dangerous. In this article, we assess the current and near-term state (5–10 years) and impact of three related areas of science and technology that could be of dual-use concern: targeted delivery of agents to the central nervous system (CNS), particularly by means of nanotechnology; direct impact of nanomaterials on synaptic functions in the CNS; and neuronal circuits in the brain that might be targeted by those with hostile intent. We attempt to assess the implications of our findings, particularly for the consideration of the problem of state-level interest in so-called nonlethal incapacitating chemical agents for law enforcement at the CWC Review Conference in 2018, but also more generally for the longer-term future of the chemical and biological nonproliferation regime.

Keywords

Nano-neurotechnologytargeted deliveryneurotoxicityneuronal circuitsbiochemical security
Type
Article
Information
Politics and the Life Sciences , Volume 37 , Issue 2 , Fall 2018 , pp. 180 - 202
Copyright
© Association for Politics and the Life Sciences 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Mamo, T., Moseman, E. A., Kolishetti, N., Salvador-Morales, C., Shi, J., Kuritzkes, D. R., Langer, R., von Andrian, U., and Farokhzad, O. C., “Emerging nanotechnology approaches for HIV/AIDS treatment and prevention,” Nanomedicine , 2010, 5(2): 269–285.Google Scholar
Altmann, J., “Military uses of nanotechnology: Perspectives and concerns,” Security Dialogue , 2004, 35(1): 61–79.Google Scholar
Kosal, M. E., Nanotechnology for Chemical and Biological Defense (Dordrecht, Netherlands: Springer, 2009).Google Scholar
United Nations Interregional Crime and Justice Research Institute (UNICRI), Security Implications of Synthetic Biology and Nanobiotechnology: A Risk and Response Assessment of Advances in Biotechnology(Turin, Italy: UNICRI, 2012).Google Scholar
Zukas, W., Cabrera, C., Harper, J., Kunz, R., Lyszczarz, T., Parameswaran, L., Rothschild, M., Sennett, M., Switkes, M., and Viswanath, H., “Assessment of nanotechnology for chemical and biological defense,” in Nanoscience and Nanotechnology for Chemical and Biological Defense, Nagarajan, R., Zukas, W., Hatton, T. A., and Lee, S., eds. (Oxford: Oxford University Press, 2010), chap. 2.Google Scholar
Leins, K., “Shining a regulatory spotlight on new lasers,” January 21, 2016, https://ssrn.com/abstract=2719986, accessed July 20, 2018.Google Scholar
Article 36, “Nanoweapons,” Discussion Paper for the Convention on Certain Conventional Weapons (CCW), November 2017, http://www.article36.org/wp-content/uploads/2017/11/Nano-Final-17Nov17.pdf, accessed July 20, 2018.Google Scholar
Altmann, J., “Preventing hostile and malevolent use of nanotechnology: Military nanotechnology after 15 years of the US National Nanotechnology Initiative,” in Cyber and Chemical, Biological, Radiological, Nuclear, Explosives Challenges: Threats and Counter Efforts, Martellini, M. and Malizia, M., eds. (Cham, Switzerland: Springer International, 2017), pp. 49–72.Google Scholar
Nasu, H., “Nanotechnology and challenges to international humanitarian law: A preliminary legal assessment,” International Review of the Red Cross , 2012, 94(886): 653–672.Google Scholar
Wallach, E. J., “A tiny problem with huge implications—Nanotech agents as enablers or substitutes for banned chemical weapons: Is a new treaty needed?” Fordham International Law Journal , 2009, 33(3): Article 4.Google Scholar
Tam, V. H., Sosa, C., Liu, R., Yao, N., and Priestley, R. D., “Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier,” International Journal of Pharmaceutics , 2016, 515: 331–342.Google Scholar
Petro, J. B., Plasse, T. R., and McNulty, J. A., “Biotechnology: Impact on biological warfare and biodefense,” Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science , 2003, 1: 161–168.Google Scholar
Royal Society, “The Chemical Weapons Convention and convergent trends in science and technology,” 2013, https://royalsociety.org/∼/media/policy/projects/brain-waves/2013-08-04-chemical-weapons-convention-and-convergent-trends.pdf, accessed July 20, 2018.Google Scholar
Pitschmann, V. and Hon, Z., “Military importance of natural toxins and their analogs,” Molecules , 2016, 21: Article E556, https://doi.org/10.3390/molecules21050556.Google Scholar
Kagan, E., “Bioregulators as prototypic nontraditional threat agents,” Clinics in Laboratory Medicine , 2006, 26: 421–443.Google Scholar
Institute of Medicine and National Research Council, Globalization, Biosecurity, and the Future of the Life Sciences(Washington, DC: National Academies Press, 2006).Google Scholar
Dando, M., “Advances in neuroscience and the biological and toxin weapons convention,” Biotechnology Research International , 2011, Article ID 973851, https://doi.org/10.4061/2011/973851.Google Scholar
Germain, R. N., Meier-Schellersheim, M., Nita-Lazar, A., and Fraser, I. D. C., “Systems biology in immunology: A computational modeling perspective,” Annual Review of Immunology , 2011, 29: 527–585.Google Scholar
Kelle, A., Nixdorff, K., and Dando, M., Controlling Biochemical Weapons: Adapting Multilateral Arms Control for the 21st Century (New York: Palgrave Macmillan, 2006).Google Scholar
Jackson, R. J., Ramsay, A. J., Christensen, C. D., Beaton, S., Hall, D. F., and Ramshaw, I. A., “Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox,” Journal of Virology , 2001, 75: 1205–1210.Google Scholar
U.S. Department of Defense, “The Military Critical Technologies List, Part II. Weapons of Mass Destruction Technologies,” 1988, p. II-3-1, http://fas.org/irp/threat/mctl98-2/mctl98-2.pdf, accessed July 20, 2018.Google Scholar
Nagai, T., Tanaka, M., Hasui, K., Shirahama, H., Kitajima, S., Yonezawa, S., Xu, B., and Matsuyama, T., “Effect of an immunotoxin to folate receptor $\unicode[STIX]{x1D6FD}$ on bleomycin-induced experimental pulmonary fibrosis,” Clinical and Experimental Immunology , 2010, 161: 348–356.Google Scholar
Balmer, B., “The UK biological weapons program,” in Deadly Cultures: Biological Weapons since 1945, Wheelis, M., Rosza, L., and Dando, M., eds. (Cambridge, MA: Harvard University Press, 2006), pp. 47–83.Google Scholar
Cole, L. A., “Open-air biowarfare testing and the evolution of values,” Health Security , 2016, 14: 315–322.Google Scholar
Discussed in, Scheuch, G., Kohlhaeufl, M. J., Brand, P., and Siekmeier, R., “Clinical perspectives on pulmonary systemic and macromolecular delivery,” Advanced Drug Delivery Reviews , 2006, 58: 996–1008.Google Scholar
Reviewed in, Lochhead, J. J. and Thorne, R. G., “Intranasal delivery of biologics to the central nervous system,” Advanced Drug Delivery Reviews , 2012, 64: 614–628.Google Scholar
Chapman, C. D., Frey II, W. H., Craft, S., Danielyan, L., Hallschmid, M., Schiöth, H. B., and Benedict, C., “Intranasal treatment of central nervous system dysfunction in humans,” Pharmaceutical Research , 2013, 30: 2475–2484.Google Scholar
Singh, M. N., Hemant, K. S. Y., Ram, M., and Shivakumar, H. G., “Microencapsulation: a promising technique for controlled drug delivery,” Research in Pharmaceutical Sciences , 2010, 5: 65–77.Google Scholar
Zeng, Q., Han, J., Zhao, D., Gong, T., Zhang, Z., and Sun, X., “Protection of adenovirus from neutralizing antibody by cationic PEG derivative ionically linked to adenovirus,” International Journal of Nanomedicine , 2012, 7: 985–997.Google Scholar
Laube, B. L., “Aerosolized medications for gene and peptide therapy,” Respiratory Care , 2015, 60: 806–824, at p. 806.Google Scholar
Shoyele, S. A. and Slowey, A., “Prospects of formulating proteins/peptides as aerosols for pulmonary drug delivery,” International Journal of Pharmaceutics , 2006, 314: 1–8.Google Scholar
Karimi, M., Eslami, M., Sahandi-Zangabad, P., Mirab, F., Farajisafiloo, N., Shafaei, Z., Ghosh, D., Bozorgomid, M., Dashkhaneh, F., and Hamblin, M. R., “pH-sensitive stimulus-responsive nanocarriers for targeted delivery of therapeutic agents,” Nanomedicine and Nanobiotechnology , 2016, 8: 696–716.Google Scholar
Suri, S. S., Fenniri, H., and Singh, B., “Nanotechnology-based drug delivery systems,” Journal of Occupational Medicine and Toxicology , 2007, 2: Article 16, https://doi.org/10.1186/1745-6673-2-16.Google Scholar
Hoshyar, N., Gray, S., Han, H., and Bao, G., “The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction,” Nanomedicine , 2016, 11(6): 673–692.Google Scholar
Csaba, N., Garcia-Fuentes, M., and Alonso, M. J., “Nanoparticles for nasal vaccination,” Advanced Drug Delivery Reviews , 2009, 61: 140–157.Google Scholar
Rodriguez, P. L., Harada, T., Christian, D. A., Pantano, D. A., Tsai, R. K., and Discher, D. E., “Minimal ‘self’ peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles,” Science , 2013, 339: 971–975.Google Scholar
Sandy, P., Ventura, A., and Jacks, T., “Mammalian RNAi: a practical guide,” BioTechniques , 2005, 39: 215–224.Google Scholar
Discussed in, Merkel, O. M., Rubenstein, I., and Kissel, T., “siRNA delivery to the lung: What’s new?” Advanced Drug Delivery Reviews , 2014, 75: 112–128.Google Scholar
Merkel, Rubenstein, and Kissel, p. 116.Google Scholar
Gao, H., “Progress and perspectives on targeting nanoparticles for brain drug delivery,” Acta Pharmaceutica Sinica B , 2016, 6: 268–286.Google Scholar
Kosal, M. E., “Potential malfeasant cooption of nanotechnology,” in Nanotechnology for Chemical and Biological Defense (Dordrecht, Netherlands: Springer, 2009), chap. 4.Google Scholar
Ljubimova, J. Y., Sun, T., Mashouf, L., Ljubimov, A. V., Israel, L. L., Ljubimov, V. A., Falahatian, V., and Holler, E., “Covalent nanodelivery systems for selective imaging and treatment of brain tumors,” Advanced Drug Delivery Reviews , 2017, 113: 177–200, https://doi.org/10.1016/j.addr.2017.06.002.Google Scholar
Wong, H. L., Wu, X. Y., and Bendayan, R., “Nanotechnological advances for the delivery of CNS therapeutics,” Advanced Drug Delivery Reviews , 2012, 64: 686–700.Google Scholar
Gao, p. 269.Google Scholar
Gao, p. 270.Google Scholar
Douglas, K. L., “Toward development of artificial viruses for gene therapy: A comparative evaluation of viral and non-viral transfection,” Biotechnology Progress , 2008, 24: 871–883.Google Scholar
Laube, B. L., “Aerosolized medications for gene and peptide therapy,” Respiratory Care , 2015, 60: 806–824.Google Scholar
Doudna, J. A. and Charpentier, E., “The new frontier of genome engineering with CRISPR-Cas9,” Science , 2014, 346: 1258096-1–1258096-9, https://doi.org/10.1126/science.1258096.Google Scholar
Miller, J. B., Zhang, S., Kos, P., Xiong, H., Zhou, K., Perelman, S. S., Zhu, H., and Siegwart, D. J., “Non-viral CRISPR/Cas gene editing in vitro and in vivo enabled by synthetic nanoparticle co-delivery of Cas9 mRNA and sgRNA,” Angewandte Chemie, International Edition , 2017, 56: 1059–1063.Google Scholar
Cao, J., Wu, L., Zhang, S.-M., Lu, M., Cheung, W. K. C., Cai, W., Gale, M., Xu, Q., and Yan, Q., “An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting,” Nucleic Acids Research , 2016, 44(19): Article e149, https://doi.org/10.1093/nar/gkw660.Google Scholar
Maddalo, D., Manchado, E., Concepcion, C. P., Bonetti, C., Vidigal, J. A., Han, Y.-C., Ogrodowski, P., Crippa, A., Rekhtman, N., de Stanchina, E., Lowe, S. W., and Ventura, A., “ In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system,” Nature , 2014, 516: 423–427.Google Scholar
Chen, J., Guo, Z., Tian, H., and Chen, X., “Production and clinical development of nanoparticles for gene delivery,” Molecular Therapy: Methods and Clinical Development , 2016, 3: Article 16023, https://doi.org/10.1038/mtm.2016.23.Google Scholar
Hodge, R., Narayanavari, S. A., Izsvak, Z., and Ivics, Z., “Wide awake and ready to move: 20 years of non-viral therapeutic genome engineering with the Sleeping Beauty transposon system,” Human Gene Therapy , 2017, 28(10): 842–855.Google Scholar
Izsvak, Z., Hackett, P. B., Cooper, L. J. N., and Ivics, Z., “Translating Sleeping Beauty transposition into cellular therapies: Victories and challenges,” Bioessays , 2010, 32: 756–767.Google Scholar
Hudecek, M., Izsvak, Z., Johnen, S., Renner, M., Thumann, G., and Ivics, Z., “Going non-viral: The Sleeping Beauty transposon system breaks on through to the clinical side,” Critical Reviews in Biochemistry and Molecular Biology , 2017, 52(4): 355–380.Google Scholar
Hudecek et al., p. 355.Google Scholar
A. L. Clunan and K. Rodine-Hardy, with R. Hsueh, M. E. Kosal, and I. McManus, “Nanotechnology in a globalized world: Strategic assessments of an emerging technology,” Report 2014-006, NPS Institutional Archive DSpace Repository, June 2014.Google Scholar
Organisation for the Prohibition of Chemical Weapons (OPCW), “Report of the Scientific Advisory Board on Developments in Science and Technology for the Third Special Session of the Conference of the States Parties to Review the Operation of the Chemical Weapons Convention,” RC-3/DG.1, October 29, 2012, p. 14, https://www.opcw.org/fileadmin/OPCW/CSP/RC-3/en/rc3dg01_e_.pdf, accessed July 21, 2018.Google Scholar
Murashov, V. and Howard, J., “Biosafety, occupational health and nanotechnology,” Applied Biosafety , 2007, 12: 158–167.Google Scholar
Danbolt, N. C., “Glutamate uptake,” Progress in Neurobiology , 2001, 65: 1–105.Google Scholar
Borisova, T., “Permanent dynamic transporter-mediated turnover of glutamate across the plasma membrane of presynaptic nerve terminals: Arguments in favor and against,” Reviews in the Neurosciences , 2016, 27: 71–81.Google Scholar
Borisova, T. and Borysov, A., “Putative duality of presynaptic events,” Reviews in the Neurosciences , 2016, 27: 377–383.Google Scholar
Borisova, T., Nazarova, A., Dekaliuk, M., Krisanova, N., Pozdnyakova, N., Borysov, A., Sivko, R., and Demchenko, A. P., “Neuromodulatory properties of fluorescent carbon dots: Effect on exocytotic release, uptake and ambient level of glutamate and GABA in brain nerve terminals,” International Journal of Biochemistry and Cell Biology , 2015, 59: 203–215.Google Scholar
Borisova, T., Dekaliuk, M., Pozdnyakova, N., Pastukhov, A., Dudarenko, M., Borysov, A., Vari, S. G., and Demchenko, A. P., “Harmful impact on presynaptic glutamate and GABA transport by carbon dots synthesized from sulfur-containing carbohydrate precursor,” Environmental Science and Pollution Research , 2017, 24: 17688–17700.Google Scholar
Pozdnyakova, N., Pastukhov, A., Dudarenko, M., Galkin, M., Borysov, A., and Borisova, T., “Neuroactivity of detonation nanodiamonds: Dose-dependent changes in transporter-mediated uptake and ambient level of excitatory/inhibitory neurotransmitters in brain nerve terminals,” Journal of Nanobiotechnology , 2016, 14: Article 25, https://doi.org/10.1186/s12951-016-0176-y.Google Scholar
Pozdnyakova, N., Pastukhov, A., Dudarenko, M., Borysov, A., Krisanova, N., Nazarova, A., and Borisova, T., “Enrichment of inorganic martian dust simulant with carbon component can provoke neurotoxicity,” Microgravity Science and Technology , 2017, 29: 133–144.Google Scholar
Sojka, B., Kociolek, D., Banski, M., Borisova, T., Pozdnyakova, N., Pastukhov, A., Borysov, A., Dudarenko, M., and Podhorodecki, A., “Effects of surface functionalization of hydrophilic $\text{NaYF}_{4}$ nanocrystals doped with $\text{Eu}^{3+}$ on glutamate and GABA transport in brain synaptosomes,” Journal of Nanoparticle Research , 2017, 19: Article 275, https://doi.org/10.1007/s11051-017-3958-8.Google Scholar
Borisova, T., Krisanova, N., Borysov, A., Sivko, R., Ostapchenko, L., Babic, M., and Horak, D., “Manipulation of isolated brain nerve terminals by an external magnetic field using D-mannose-coated $\unicode[STIX]{x1D6FE}$ - $\text{Fe}_{2}\text{O}_{3}$ nano-sized particles and assessment of their effects on glutamate transport,” Beilstein Journal of Nanotechnology , 2014, 5: 778–788.Google Scholar
Horak, D., Benes, M., Prochazkova, Z., Trchova, M., Borysov, A., Pastukhov, A., Paliienko, K., and Borisova, T., “Effect of O-methyl- $\unicode[STIX]{x1D6FD}$ -cyclodextrin-modified magnetic nanoparticles on the uptake and extracellular level of l-glutamate in brain nerve terminals,” Colloids and Surfaces B: Biointerfaces , 2017, 149: 64–71.Google Scholar
Win-Shwe, T. T. and Fujimaki, H., “Nanoparticles and neurotoxicity,” International Journal of Molecular Sciences , 2011, 12: 6267–6280, https://doi.org/10.3390/ijms12096267.Google Scholar
Soenen, S. J., Rivera-Gil, P., Montenegro, J.-M., Parak, W. J., De Smedt, S. C., and Braeckmans, K., “Cellular toxicity of inorganic nanoparticles: Common aspects and guidelines for improved nanotoxicity evaluation,” Nano Today , 2011, 6: 446–465.Google Scholar
Soenen, S. J., Parak, W. J., Rejman, J., and Manshian, B., “(Intra)cellular stability of inorganic nanoparticles: Effects on cytotoxicity, particle functionality, and biomedical applications,” Chemical Reviews , 2015, 115: 2109–2135.Google Scholar
Organisation for the Prohibition of Chemical Weapons (OPCW).Google Scholar
Qiu, T., Liu, Y., Wang, L., Xu, L., Bai, R., Ji, Y., Wu, X., Zhao, Y., Li, Y., and Chen, C., “Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods,” Biomaterials , 2010, 31: 7606–7619.Google Scholar
Aaron, J. S., Greene, A. C., Kotula, P. G., Bachand, G. D., and Timlin, J. A., “Advanced optical imaging reveals the dependence of particle geometry on interactions between CdSe quantum dots and immune cells,” Small , 2011, 7: 334–341.Google Scholar
Tarantola, M., Pietuch, A., Schneider, D., Rother, J., Sunnick, E., Rosman, C., Pierrat, S., Sönnichsen, C., Wegener, J., and Janshoff, A., “Toxicity of gold-nanoparticles: Synergistic effects of shape and surface functionalization on micromotility of epithelial cells,” Nanotoxicology , 2011, 5: 254–268.Google Scholar
Singh, N., Manshian, B., Jenkins, G. J. S., Griffiths, S. M., Williams, P. M., Maffeis, T. G. G., Wright, C. J., and Doak, S. H., “NanoGenotoxicology: The DNA damaging potential of engineered nanomaterials,” Biomaterials , 2009, 30: 3891–3914.Google Scholar
Geys, J., Nemmar, A., Verbeken, E., Smolders, E., Ratoi, M., Hoylaerts, M. F., Nemery, B., and Hoet, P. H. M., “Acute toxicity and prothrombotic effects of quantum dots: Impact of surface charge,” Environmental Health Perspectives , 2008, 116: 1607–1613.Google Scholar
Fröhlich, E., “The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles,” International Journal of Nanomedicine , 2012, 7: 5577–5591.Google Scholar
Asati, A., Santra, S., Kaittanis, C., and Perez, J. M., “Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles,” ACS Nano , 2010, 4: 5321–5331.Google Scholar
Soenen, S. J. H., Baert, J., and De Cuyper, M., “Optimal conditions for labelling of 3T3 fibroblasts with magnetoliposomes without affecting cellular viability,” ChemBioChem , 2007, 8: 2067–2077.Google Scholar
“Occupational Safety and Health Act (OSHA) of 1970,” https://www.osha.gov/laws-regs/oshact/completeoshact.Google Scholar
Oberdorster, G., Kane, A. B., Klaper, R. D., and Hurt, R. H., “Nanotoxicology,” in Casarett and Doull’s Toxicology: The Basic Science of Poisons, Klaassen, C. D., ed. (New York: McGraw-Hill, 2013), pp. 1189–1229.Google Scholar
Bakand, S. and Hayes, A., “Toxicological considerations, toxicity assessment, and risk management of inhaled nanoparticles,” International Journal of Molecular Sciences , 2016, 17: Article 929, https://doi.org/10.3390/ijms17060929.Google Scholar
Hotze, E. M., Phenrat, T., and Lowry, G. V., “Nanoparticle aggregation: Challenges to understanding transport and reactivity in the environment,” Journal of Environmental Quality , 2010, 39: 1909–1924.Google Scholar
Maher, B. A., Ahmed, I. A. M., Karloukovski, V., MacLaren, D. A., Foulds, P. G., Allsop, D., Mann, D. M. A., Torres-Jardon, R., and Calderon-Garciduenas, L., “Magnetite pollution nanoparticles in the human brain,” Proceedings of the National Academy of Sciences, USA , 2016, 113: 10797–10801.Google Scholar
Ramos Guivar, J. A., Sadrollahi, E., Menzel, D., Ramos Fernandes, E. G., Lopez, E. O., Torres, M. M., Arsuaga, J. M., Arencibia, A., and Litterst, F. J., “Magnetic, structural and surface properties of functionalized maghemite nanoparticles for copper and lead adsorption,” RSC Advances , 2017, 7: 28763–28779.Google Scholar
Saptarshi, S. R., Duschl, A., and Lopata, A. L., “Interaction of nanoparticles with proteins: Relation to bio-reactivity of the nanoparticle,” Journal of Nanobiotechnology , 2013, 11: Article 26, https://doi.org/10.1186/1477-3155-11-26.Google Scholar
Shemetov, A. A., Nabiev, I., and Sukhanova, A., “Molecular interaction of proteins and peptides with nanoparticles,” ACS Nano , 2012, 6: 4585–4602.Google Scholar
Lin, S., Mortimer, M., Chen, R., Kakinen, A., Riviere, J. E., Davis, T. P., Ding, F., and Ke, P. C., “NanoEHS beyond toxicity—Focusing on biocorona,” Environmental Science: Nano , 2017, 4: 1433–1454.Google Scholar
Kirchner, C., Liedl, T., Kudera, S., Pellegrino, T., Munoz Javier, A., Gaug, H. E., Stölze, S., Fertig, N., and Parak, W. J., “Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles,” Nano Letters , 2005, 5: 331–338.Google Scholar
Lundqvist, M., Sethson, I., and Jonsson, B.-H., “Protein adsorption onto silica nanoparticles: Conformational changes depend on the particles’ curvature and the protein stability,” Langmuir , 2004, 20: 10639–10647.Google Scholar
Dutta, D., Sundaram, S. K., Teeguarden, J. G., Riley, B. J., Fifield, L. S., Jacobs, J. M., Addleman, S. R., Kaysen, G. A., Moudgil, B. M., and Weber, T. J., “Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials,” Toxicological Sciences , 2007, 100: 303–315.Google Scholar
Deng, Z. J., Mortimer, G., Schiller, T., Musumeci, A., Martin, D., and Minchin, R. F., “Differential plasma protein binding to metal oxide nanoparticles,” Nanotechnology , 2009, 20(45): Article 455101, https://doi.org/10.1088/0957-4484/20/45/455101.Google Scholar
Deng, Z. J., Liang, M., Toth, I., Monteiro, M., and Minchin, R. F., “Plasma protein binding of positively and negatively charged polymer-coated gold nanoparticles elicits different biological responses,” Nanotoxicology , 2013, 7: 314–322, https://doi.org/10.3109/17435390.2012.655342.Google Scholar
Fertsch-Gapp, S., Semmler-Behnke, M., Wenk, A., and Kreyling, W. G., “Binding of polystyrene and carbon black nanoparticles to blood serum proteins,” Inhalation Toxicology , 2011, 23: 468–475.Google Scholar
Linse, S., Cabaleiro-Lago, C., Xue, W.-F., Lynch, I., Lindman, S., Thulin, E., Radford, S. E., and Dawson, K. A., “Nucleation of protein fibrillation by nanoparticles,” Proceedings of the National Academy of Sciences, USA , 2007, 104: 8691–8696.Google Scholar
Vieira, D. B. and Gamarra, L. F., “Getting into the brain: Liposome-based strategies for effective drug delivery across the blood-brain barrier,” International Journal of Nanomedicine , 2016, 11: 5381–5414, https://doi.org/10.2147/IJN.S117210.Google Scholar
Wen, C.-J., Zhang, L.-W., Al-Suwayeh, S. A., Yen, T.-C., and Fang, J.-Y., “Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging,” International Journal of Nanomedicine , 2012, 7: 1599–1611, https://doi.org/10.2147/IJN.S29369.Google Scholar
Casals, E., Pfaller, T., Duschl, A., Oostingh, G. J., and Puntes, V., “Time evolution of the nanoparticle protein corona,” ACS Nano , 2010, 4: 3623–3632.Google Scholar
Monopoli, M. P., Walczyk, D., Campbell, A., Elia, G., Lynch, I., Bombelli, F. B., and Dawson, K. A., “Physical-chemical aspects of protein corona: Relevance to in vitro and in vivo biological impacts of nanoparticles,” Journal of the American Chemical Society , 2011, 133: 2525–2534.Google Scholar
National Research Council, Committee on Military and Intelligence Methodology for Emergent Neurophysiological and Cognitive/Neural Science Research in the Next Two Decades, Emerging Cognitive Neuroscience and Related Technologies(Washington, DC: National Academies Press, 2008), p. 135.Google Scholar
Zupanc, G. K. H., Behavioral Neurobiology: An Integrative Approach 2nd ed. (Oxford: Oxford University Press, 2010).Google Scholar
Simmons, P. J. and Young, D., Nerve Cells and Animal Behaviour 3rd ed. (New York: Cambridge University Press, 2010).Google Scholar
Berkowitz, A., Governing Behavior: How Nerve Cell Dictatorships and Democracies Control Everything We Do (Cambridge, MA: Harvard University Press, 2016).Google Scholar
Dando, M., Neuroscience and the Future of Chemical-Biological Weapons (Basingstoke: Palgrave Macmillan, 2015).Google Scholar
Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Working Group Report to the Advisory Committee to the Director, NIH, BRAIN 2025: A Scientific Vision (Washington, DC: National Institutes of Health, 2014), p. 5.Google Scholar
See the contributions to the special issue of the journal Neuron, 2016, 92(3).Google Scholar
Grillner, S., Ip, N., Koch, C., Koroshetz, W., Okano, H., Polachek, M., Poo, M. M., and Sejnowski, T. J., “Worldwide initiatives to advance brain research,” Nature Neuroscience , 2016, 19(9): 1118–1122.Google Scholar
Adolphs, R., “The unsolved problems of neuroscience,” Trends in the Cognitive Sciences , 2015, 19(4): 173–175.Google Scholar
Lerner, T. N., Ye, L., and Deisseroth, K., “Communication in neural circuits: Tools, opportunities, and challenges,” Cell , 2016, 164: 1136–1150.Google Scholar
Yuste, R., “From the neuron doctrine to neural networks,” Nature Reviews: Neuroscience , 2015, 16: 487–497, at p. 487.Google Scholar
Marder, E., Goeritz, M. L., and Otopalik, A. G., “Robust circuit rhythms in small circuits arise from variable circuit components and mechanisms,” Current Opinion in Neurobiology , 2015, 31: 156–163, at p. 156.Google Scholar
Bucher, D. and Marder, E., “SnapShot: Neuromodulation,” Cell , 2013, 155:, 482–482.e1.Google Scholar
National Research Council, p. 135.Google Scholar
Doward, J., “The spice crisis: how the ‘zombie drug’ is devastating Britain,” The Observer, August 6 , 2017, 9.Google Scholar
National Research Council, p. 113.Google Scholar
Dando, M. R., “Advances in understanding targets in the central nervous system,” in Preventing Chemical Weapons: Arms Control and Disarmament as the Sciences Converge, Crowley, M., Dando, M. R., and Shang, L., eds. (London: Royal Society of Chemistry, 2018), chap. 8.Google Scholar
Doward, J., “Drug dealers target homeless with ‘spice,’ the 50p spliff more terrifying than crack,” The Observer, August 23 , 2017, 11.Google Scholar
Parker, L. A., Cannabinoids and the Brain (Cambridge, MA: MIT Press, 2017).Google Scholar
Mechoulam, R. and Parker, L. A., “The endocannabinoid system and the brain,” Annual Review of Psychology , 2013, 64: 21–47.Google Scholar
Lu, H.-C. and Mackie, K., “An introduction to the endogenous cannabinoid system,” Biological Psychiatry , 2016, 79: 516–525, at p. 519.Google Scholar
Volk, D. W. and Lewis, D. A., “The role of endocannabinoid signaling in cortical inhibitory neuron dysfunction in schizophrenia,” Biological Psychiatry , 2016, 79: 595–603, at p. 597.Google Scholar
Parker, p. 32.Google Scholar
Di Marzo, V. and Piscitelli, F., “The endocannabinoid system and its modulation by phytocannabinoids,” Neurotherapeutics , 2015, 12(4): 692–698.Google Scholar
Broyd, S. J., van Hell, H. H., Beale, C., Yücel, M., and Solowij, N., “Acute and chronic effects of cannabinoids on human cognition—A systematic review,” Biological Psychiatry , 2016, 79: 557–567.Google Scholar
Volk and Lewis, p. 595.Google Scholar
Skosnik, P. D., Cortes-Briones, J. A., and Hajos, M., “It’s all in the rhythm: The role of cannabinoids in neural oscillations and psychosis,” Biological Psychiatry , 2016, 79: 568–577.Google Scholar
Wiley, J. L., Marusich, J. A., Huffman, J. W., Balster, R. L., and Thomas, B. F., “Hijacking of basic research: The case of synthetic cannabinoids,” Methods Rep RTI Press , 2011, November, p. 22, doi:10.3768/rtipress.2011.op.007.1111.Google Scholar
Wiley, J. L., Marusich, J. A., and Huffman, J. W., “Moving around the molecule: Relationship between chemical structure and in vivo activity of synthetic cannabinoids,” Life Sciences , 2014, 97(1): 55–63.Google Scholar
Baumann, M. H., Solis, E. Jr., Watterson, L. R., Marusich, J. A., Fantegrossi, W. E., and Wiley, J. L., “Bath salts, spice, and related designer drugs: The science behind the headlines,” Journal of Neuroscience , 2014, 34(46): 15150–15158.Google Scholar
Tai, S. and Fantegrossi, W. E., “Synthetic cannabinoids: Pharmacology, behavioral effects and abuse potential,” Current Addiction Reports , 2014, 1(2): 129–136, at p. 129.Google Scholar
Rech, M. A., Donahey, E., Cappiello Dziedzic, J. M., Oh, L., and Greenhalgh, E., “New drugs of abuse,” Pharmacotheraphy , 2015, 35(2): 189–197.Google Scholar
Kemp, A. M., Clark, M. S., Dobbs, T., Galli, R., Sherman, J., and Cox, R., “Top 10 facts you need to know about synthetic cannabinoids: Not so nice spice,” American Journal of Medicine , 2016, 129(30): 241–244.Google Scholar
Miliano, C., Serpelloni, G., Rimondo, C., Mereu, M., Marti, M. M., and De Luca, M. A., “Neuropharmacology of new psychoactive substances (NPS): Focus on the rewarding properties of cannabimimetics and amphetamine-like stimulants,” Frontiers in Neuroscience , 2016, 10: Article 153, at p. 7, doi:10.3389/fnins.2016.00153.Google Scholar
Tai, S. and Fantegrossi, W. E., “Pharmacological and toxicological effects of synthetic cannabinoids and their metabolites,” Current Topics in Behavioral Neurosciences , 2017, 32: 249–262.Google Scholar
Kaneko, S., “Motor vehicle collisions caused by the ‘super-strength’ synthetic cannabinoids, MAM-2201, 5F-PB-22, 5F-AB-PINACA, 5F-AMB and 5F-ADB in Japan experienced from 2012 to 2014,” Forensic Toxicology , 2017, 35: 244–251, at p. 247.Google Scholar
Petro, Plasse, and McNulty, p. 161.Google Scholar
Zirlinger, M., “Editorial: Exciting times ahead,” Neuron , 2017, 96: 247.Google Scholar
Kim, C. K., Adhikari, A., and Deisseroth, K., “Integration of optogenetics with complementary methodologies in systems neuroscience,” Nature Reviews Neuroscience , 2017, 18: 222–235, at p. 222.Google Scholar
Misic, B. and Sporns, O., “From regions to connections and networks: New bridges between brain and behavior,” Current Opinion in Neurobiology , 2016, 40: 1–7, at p. 1.Google Scholar
OPCW, Scientific Advisory Board, “Report of the Temporary Working Group on Convergence of Chemistry and Biology,” June 2014, p. 26, https://www.opcw.org/fileadmin/OPCW/SAB/en/TWG_Scientific_Advsiory_Group_Final_Report.pdf, accessed July 21, 2018.Google Scholar
OPCW, “Note by the Director-General: The Impact of the Developments in Science and Technology in the Context of the Chemical Weapons Convention,” EC-85/DG.8, May 19, 2017, p. 3, https://www.opcw.org/fileadmin/OPCW/SAB/en/ec85dg08_e_.pdf, accessed July 21, 2018.Google Scholar
Crowley, M., Chemical Control: Regulation of Incapacitating Chemical Agent Weapons, Riot Control Agents and their Means of Delivery (Basingstoke: Palgrave Macmillan, 2016).Google Scholar
Crowley, M., Dando, M., and Shang, L., eds., Preventing Chemical Weapons: Arms Control and Disarmament as the Sciences Converge (London: Royal Society of Chemistry, 2018).Google Scholar
OPCW, “Aerosolisation of Central Nervous System-Acting Chemicals for Law Enforcement Purposes,” C-21/NAT.3/Rev.3, December 2, 2016, p. 1, https://www.opcw.org/fileadmin/OPCW/CSP/C-21/national_statements/c21nat03_e_.pdf, accessed July 21, 2018.Google Scholar