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Nanotechnology
  & Defense

       Margaret E. Kosal
                  Assistant Professor
                 Sam Nunn School of
                  International Affairs
       Georgia Institute of Technology
                 nerdgirl@gatech.edu
“Military applications of molecular
                 y pp
     manufacturing have even greater potential
     than nuclear weapons to radically change
               the balance of power.”
                 Admiral (Ret) David E. Jeremiah,
            former vice chairman of Joint Chiefs of Staff *



* “Nanotechnology and Global Security,” (Palo Alto, CA; Fourth Foresight
   Conference on Molecular Nanotechnology), November 1995.
Security Puzzles
•    Does nanotechnology have unique strategic value?
      – Security, economic, political, &/or scientific
•    Disambiguate
     Disambig ate potential for unique capabilities from enabling
                                  niq e
     previous capabilities
•    Perception or ideation vs technical reality
      – “Hope” & “Horror” hype
      – Rhetorical equivalence with nuclear technology
      – (Pseudo)-technical assessments
        (       )
          E.g., “New technologies (at risk for terrorist appropriation) include biotechnology,
          nanotechnology, single nucleotide polymorphisms (SNPs), and Bose-Einstein
          condensates.”*
      – Influencing factors: institutional
•    International regimes for emerging technology
      – Adequacy of traditional arms control treaties
            q    y
      – Role of NGOs

* "WMD Terrorism Research: Where to From Here?” International Studies Review, March 2005, vol. 7, p. 140
Current Discourse
• Innovation
• Ethics, Legal & Social Issues (ELSI)
       – H lth and environmental i
         Health d     i      t l impacts
                                      t
           NSF, EPA, NIOSH, NIH-NIEHS, DOD R&D (~$38M/year)
           NNI EHS Research Needs
           OECD Working Group on Safety of Nanomanufactured Materials
       – Privacy and legal implications
       – Uncontrolled replication (“nano-assemblers”) and artificial
         intelligence

• Security is rarely in the dialogue
   Cou d there
   Could t e e be an “AQ Khan” of nanotechnology?
                    a      Q    a o a otec o ogy
      – Literature: limited & emphasizes “nano-assemblers”
      – How to build a framework to assess analytically?
      – Reconcile with theories?
           Balance of Power     Deterrence            Constructivist
           Offense-Defense      Arms Control Regime
       – What policy can be implemented to limit proliferation scenarios?
Changing Strategic Environment
• Post-Cold War international security environment
• T h l
  Technology no l
                longer guarantees security
                             t         it
• Globalization and information revolution as drivers
   – Enable spread and accessibility
• Dual-use conundrum
• Changing nature of warfare
   – Asymmetric warfare
   – Interest in unconventional weapons
• Relationship between science and security
             p                            y
• Disruptive technologies
Technology: An Operators Perspective
   CDR Mike Penny, MD
   Senior Medical Officer
   Chemical Biological Incident
   Response Force (CBIRF)
   USMC MEF II
                                             …To close with and save




What Do They Think of Technology?
Requires too much training
Requires too much maintenance
Too delicate
Too
T expensive.i
Then… it lets you down when you need it the most
A Warfighter’s Perspective on Possible
Nanotechnology Applications for
CBRNE/WMD Operations
   COL Barry Lowe
   Chief of Staff
   20th Support Command (CBRNE)

Individual Protection
• Applications to make uniform material capable of providing
  protection against chemical and biological agents, as well
  as other toxic materials
• Applications to make uniform material react instantly to
    pp                                                 y
  become armor in the event of a bullet or fragment impact
• Applications for prophylaxis against inhalation or ingestion
  of chemical or biological agents and toxic materials
                            agents,
• Applications for use as antidotes (this may be more
  feasible in the near term)
U.S. Overview                              DOD
Federal                                     2009 $431M PBR
• 21st Century Nanotech Act (2003-               $464 appropriated
  2008) $3.7B/5years (planned)              2011 $349M PBR
                                                 $
• NNI (2001-08) $8.3B (actual)
                                            DoD highly fractured by service &
• US federal nanotech                         program
   ( 000) $710M
   (2000) $ 0                               – DARPA
    (2011 PBR) $1.7B                        – Air Force: electronics,
                                              computing, communication, &
NNI Strategic Plan (Dec 07)                   sensors (AFOSR)
– E l D t ti of Lif Th t i
  Early Detection f Life Threatening        – A
                                              Army: energetics, b lli ti
                                                            ti   ballistic
  Diseases                                    protective materials, & power
– Engineered Nanoscale Materials              (ARO)
– Nanobiotechnology
                                            – Navy: electronics, materials,
                                              sensors (ONR)
– Nanotechnology-Based Water Purification   – CBDP: passive defense (by
  & Testing                                   law)
– Information Processing & Advanced
                        g                   – DDR&E
  Electronics                               – MDA
– Predictive Toxicology                     • OSD Emerging Contaminants
– Societal Dimensions of Nanotechnology       Working Group
Global Overview
•   China
     Estimated $300-400M per year over last 10
        years
•   Japan
    J                                             • Significant private investment
     $1B per year since 2002                             US: 3x times federal
•   Southeast Asia                                          investment in private sector
     Singapore Nanyang Technological
        g p         y g          g                       “guestimation” of $2T sales by
                                                          g                            y
        University (NTU) “NanoFrontier” >$200M              2015
     Malaysia
     Taiwan
•   Iran
     Majles Rep “America cannot tolerate Iran’s
       success in scientific fields such as
       nanotechnology and nuclear
                                                      A Nanotech
•
       technology,” Dec 2005
    Russia
                                                       Asilomar
     “nano-enabled thermobaric bomb”
     “nano-arms race”
                                                     Wouldn’t Work!
•   European Union
     $3.3B (2004-2005)
     30-100% increase over next 3 years
International Security Regimes
• Biological Weapons Convention (BWC)
• Chemical Weapons Convention (CWC)
• Export Controls
Case Study: Zyvex & Export Controls
– Richardson, Texas $10M revenues in 2005
– Nanoworks – nano tools electron
                    tools,
  microscopes & photovoltaic applications
– Kentara™ – CNT dispersions in resins
– Current market
     •   CNT-reinforced mountain bikes
     •   Easton baseball bats
–   Required to submit ITAR licenses for CNT-
    product exports to China
–   In response, founder suggests may relocate
    to SE Asia
Notional Nanotech Proliferation Pathway
                         Initially benign/
                          remain benign

                         Initially benign/
                                 y     g /
                       convert to malfeasant
  Pursuit
  Decision              Initially malfeasant


                                                                                           Large
                                                                        Pilot                                     Maintain
             S&T Reqs                             Down-                                     Scale
                                                                                            S l
                                                                     Production                                   Weapons
                                                  select                                 Production
                                                                                                                  Capability

                                                  Review,                           Scale Up
                                               Evaluation, and                                                 Maintain Stockpile
                      Delivery                   (potential)                  Agent Weaponization
     Agents
                      Method                      revision                                                          ConOps
                                                                                 Incorporation

Literature Review    Literature Review                                            Field Testing                    Doctrine
                                             Technical   Programmatic                                            Promulgation
                                                                                Countermeasure
Experiment/Test
E    i   t/T t                                Factors       Factors
                     Experiment/Test
                     E    i    /T                                                Development

                                                                                   Deniability


     Synthesis
                                                  Envisioned
  Characterization                                 ConOps

     Reactivity


                            = major decision points              = major steps/activities           = optional steps/activities
                                                                                                                              11
Circumventing Vaccines
• Biothrax (AVA) & BioShield-funded                                        Anthrax
  recombinant vaccines based on                                             toxins
  protective antigen (PA)




                                                                                Academy of Sciences
                                                                                 Courtes National
• PA necessary to endocytose toxic
  proteins (the lethal and edema




                                                                                       sy
  factors (EF & LF)) t cytosol
  f t                  to t       l




                                                                                       y
                                                                         cell
• Functionalized single-walled carbon                                    wall

  nanotubes (f-SWNTs)
    cross mammalian cell walls &
                                                      AFM image of SWNT +
    release biologically active “cargos” -            Staphylococal Protein A (SpA)
       p
       proteins, p p
               , peptides, DNA, RNA,
                         ,      ,     ,
       small molecules




                                                                                          rtesy Hongjie
                                                                                        Da Stanford
                                                        f-SWNTs
• Motivated by medical applications                       inside
                                                         human
    drug delivery & gene therapy




                                                                                          ai,
                                                                                       Cour
                                                           cells
                                             100 nm


                                                                                                      12
Toxin Delivery
                             Applicable to other BW agents, e.g., Botulinum toxin
                             •    Difficult to produce in large quantities via traditional microbiological
                                  methods (Commercial Botox requires 30-275 vials to achieve one LD50, strain-dependent)
                             •    Current transgenic methods can only produce light chain (LC) of toxin
                                  from E. coli or yeast
                             •    Heavy chain (HC) necessary for toxin to cross cell wall
                             •    LC + carbons nanotubes could circumvent technical difficulties
Courtes Alberto Bianc CNRS




                                                                                          C) Human HeLa cells treated
                    co,




                                                                                          with functionalized multi-walled
                                                                                                              multi walled
                                                                                          carbon nanotubes (f-MWNTs) to
                                                                                          deliver DNA into cells.
                                                                                          D) A multi-walled carbon
                                                                                          nanotube crossing the cell
                                                                                                            g
      sy




                                                                                          membrane.


                                                                                                                             13
“Brain Fry”
                                                              NP that heats up A LOT
        Stealth coat – defeats                                upon absorption of EM –
       detection and optimizes                                maybe from a cell phone
           aerosolization

•   Coated Fe2O3 nanoparticles
•   Pass the blood brain barrier
•   EM-activatable
•   Specific combination of people, materials, &
    facilities:
    – Expertise in nanoparticle production (especially
      biological apps)
    – Directed energy experts who may have worked




                                                                                             versity of Rochester
      on ablation therapies




                                                                                            urtesy Hong Yang,
    – Engineers who have experience in battlefield
                                               f
      delivery of EM radiation
    – Vets to oversee animal testing
    – Aerosol drug delivery expert




                                                                                          Univ
                                                                                          Cou
• Current research motivated by need for
  targeted chemotherapeutics and diagnostic              Platinum-iron oxide core-shell
  imaging                                                        nanoparticles
Penetration of Bio-Nano Conjugates
                                                                                  •   Fullerenes conjugated to
                                 SU




                                                                                      cationic peptide show
Courtesy Nan Monteiro-Riviere, NCS




                                                                                      substantial uptake through skin
                                                                                  •   Mechanical stressed increased
                                                                                      penetration
                                                                                  •   Skin observed to be
                                                                                      surprisingly permeable to
           ncy




                                                                                      nanomaterials (fullerenes &
                                                                                      quantum dots) with diverse
                                                                                      physicochemical properties
                                                                                  •   Motivated by transdermal drug
C




                                                                                      delivery applications &
                                        Uptake of fullerene-lysine-FITC complex
                                       through intact stratum corneum (SC) and
                                                                                      nanoparticle safety
                                         underlying epidermal (E) and dermal          assess e ts
                                                                                      assessments
                                             layers (D). Scale bar = 50µm

                                                                                                                        15
Nanotoxicity: Range of Novelty
•   Some classes of nanoparticles not actually new
     – Liposomes
     – Ultrafine (<100 nm) particles
•   Toxicology of more familiar materials is better understood
     – Ultrafine “associated with exacerbations of airway disease” and implicated
       in enhanced inflammation
•   Carbon nanotubes (CNTs) – highly unusual aspect ratio and material
    properties
     – Focus of many early nanotoxicity studies




                                                                         Carbon nanotube
                                            nanoshell                or other nanowire (GaN)
liposome                    gold & silver
                dendrimer                                fullerene
                            nanoparticles
                                    ti l

       Familiar                                                        Novel
                                                                                        16
Research Underlying Threat Scenarios
•    CNTs Crossing Cell Walls: Nadine Wong et. al., “Carbon Nanotubes as Intracellular Protein Transporters: Generality and Biological Functionality,”
     J. Am. Chem. Soc., 2005, vol. 127, p. 6021; Alberto Bianco, et. al., “Cationic Carbon Nanotubes Bind to CpG Oligodeoxynucleotides and Enhance
     Immunostimulatory Properties,” J. Am. Chem. Soc. 2005, vol. 127, p. 58; Qi Lu, et. al., “RNA Polymer Translocation with Single-Walled Carbon
     Nanotubes," Nano Lett., 2004, vol. 4, p. 2473; and Davide Pantarotto, et. al., "Immunization with Peptide-functionalized Carbon Nanotubes
     Enhances Virus-specific Neutralizing Antibody Responses" Chem. Biol., 2003, vol. 10, pp. 961. D. Pantarotto; et. al., “Functionalized Carbon
     Nanotubes for Plasmid DNA Gene Delivery,” Angew. Chem., Int. Ed,. 2004, vol. 43, p. 5242.
                                                y,   g           ,         ,      ,      ,p
•    Vesicants: Sara Fernandez-Lopez, et. al., “Antibacterial Agents Based on the Cyclic d,l-alpha-peptide Architecture,” Nature, 2001, vol. 412, p. 452;
     W. Seth Horne, et. al., “Heterocyclic Peptide Backbone Modifications in an alpha-Helical Coiled Coil,” J. Am. Chem. Soc., 2004; vol.126, p. 15366;
     and Jorge Sánchez-Quesada, et. al., “Modulating Ion Channel Properties of Transmembrane Peptide Nanotubes through Heteromeric
     Supramolecular Assemblies,” J. Am. Chem. Soc., 2002, vol. 124, p. 10004.
•    Drug Delivery: D. Missirlis, N. Tirelli, J.A. Hubbell, “Amphiphilic hydrogel nanoparticles. Preparation, characterization, and preliminary assessment
     as new colloidal d
                ll id l drug carriers,” L
                                 i    ” Langmuir, 2005 vol. 21 p. 2605 H S Y
                                               i           l 21, 2605; H.S. Yoo, T G P k “F l t
                                                                                      T.G. Park, “Folate-receptor-targeted delivery of d
                                                                                                              t t      t d d li      f doxorubicin nano-
                                                                                                                                             bi i
     aggregates stabilized by doxorubicin-PEG-folate conjugate,” J. Control. Release, 2004, vol. 24, p. 247; C.Y. Huang, Y.D. Lee, “Core-shell type of
     nanoparticles composed of poly[(n-butyl cyanoacrylate)-co-(2-octyl cyanoacrylate)] copolymers for drug delivery application: Synthesis,
     characterization and in vitro degradation,” Int. J. Pharm., 2006 vol. 9, p. 345; R. M. Mainardes, et al., “Liposomes and micro/nanoparticles as
     colloidal carriers for nasal drug delivery,” Curr. Drug Deliv., 2006, vol. 3, p. 275; and Y. Zeng, W.G. Pitt, “A polymeric micelle system with a
     hydrolysable segment for drug delivery,” J. Biomater. Sci. Polym. Ed., 2006, vol. 17, p. 591.
•    Anti-Material Agents: S.L. Scott, C.M. Crudden, C.W. Jones, eds., Nanostructured Catalysts, (Plenum Publishing Corporation; New York), 2003;
     K.S. Suslick, et. al., "Nanostructured Materials Generated by High-Intensity Ultrasound: Sonochemical Synthesis and Catalytic Studies," Chemistry
     of Materials, 1996, vol. 8, p. 2172; N. Arul Dhas, et. al., “Sonochemical Preparation of Hollow Nanospheres and Hollow Nanocrystals J. Am. Chem.
     Soc. 2005, vol. 127, p. 2368; and A.J. Zarur, J.Y. Ying, "Reverse Microemulsion Synthesis of Nanostructured Complex Oxides for Catalytic
     Combustion," Nature, 2000, vol. 403, p. 65.
•    Brain Fry: Peter Varallyay, et al., “Comparison of Two Superparamagnetic Viral-sized Iron Oxide Particles Ferumoxides and Ferumoxtran-10 with a
                       Varallyay    al Comparison
     Gadolinum Chelate in Imaging Intracranial Tumors” American Society of Neuroradiology, 2002, vol. 23; Jun Sung Kin, et al., “Toxicity and Tissue
     Distribution of Magnetic Nanoparticles in Mice” Toxicological Sciences, 2006, vol. 89, p. 338; and K Hynynen, et al., “Focal Disruption of the Blood-
     Brain Barrier Due to 260-kHz Ultrasound Bursts: a Method for Molecular Imaging and Targeted Drug Delivery” Journal of Neuosurgery, 2006, vol.
     105, p. 455.
•    Self-Assembly: Jean-Marie Lehn, “Toward Complex Matter: Supramolecular Chemistry and Self-organization,” Proc. Natl. Acad. of Science, 2002,
     vol. 99 p. 763; G
       l 99,     63 George M Whi id and Mil B
                             M. Whitesides d Mila Boncheva, B
                                                           h       Beyond M l
                                                                            d Molecules: S lf A
                                                                                     l    Self-Assembly of M
                                                                                                     bl f Mesoscopic and M
                                                                                                                     i   d Macroscopic C
                                                                                                                                      i Components,” P
                                                                                                                                                     ” Proc.
     Natl. Acad. of Science, 2002, vol. 99, p. 769; C. P. Collier, et. al., “Electronically Configurable Molecular-Based Logic Gates,” Science, 1999, vol.
     285, pp. 391; and Kelly S. Chichak, et. al. “Molecular Borromean Rings,” Science, 2004, vol. 304, p. 1308.


    The Science is Real, the Scenarios are Notional!                                                                                                      17
Key Security Factors
•   Deniability
    Deniabilit & Lack of Transparenc
                         Transparency
     – Most of the dual-use concerns raised regarding biotechnology risks are potentially
       applicable to malfeasant co-option of nanotechnology *
          Except, biological agents require damp environments with moderate temperatures, moderate
             pressures and ambient oxygen
          * Nano-engineered materials do not replicate
     – Lack of explicit norms
     – Lack of explicit category for international arms control regimes
•   Vulnerability Perception
     – Perceived lack or limitation defensive countermeasures, e.g., limitations of stand-off biological (&
        to a lesser extent, chemical) detection
•   International prestige
                  p     g
•   No single discipline on which to focus
     – Chemistry to electrical engineering
     – Materials science to molecular biology
•   Overwhelmingly, a state-based proliferation concern
    O    h l i l       t t b    d    lif ti
     – Secondarily, rogue scientist scenario
•   Intent must be balanced with capability
     – Offensive versus defensive not transparent
•   Globalization
     – Private sector is major player global, e.g., sale or transfer of technology
Recommendations & Conclusions
• Strategic vision lacking
   We are currently attempting to limit the threat of “Biotechnology in an Age of Terrorism”
    • Serious threat anticipation with respect to nanotechnology should be
      initiated
      i iti t d now
    • Balance “hype” & hope
• Need to foster revolutionary technology
    •   Programmatic and institutional (intra- and inter-agency) challenges paramount
    •   Change in risk tolerance
• Response w/r/t international agreements & groups varies
    • CWC, BWTC, Australia Group
• Fostering pro-active international scientific cooperation as means to
  encourage beneficial use of technology
     • Pro-active “Nano” Cooperative Threat Reduction
     • T k 2 diplomacy
       Track di l
• Policy outcomes
     • JCS-JRO – Incorporation into Modernization Plan
     • DTRA-CB/JSTO – Incorporation into TCTI Strategy
       DTRA CB/JSTO
• Emerging framework and nascent theory to be tested against biotechnology,
   including synthetic biology; cognitive sciences, and nano-bio-info-cogno
   (NBIC) convergence
Contact information

               Margaret E. Kosal, PhD
                   Assistant Professor
Sam Nunn School of International Affairs
       Georgia Institute of Technology
                             Atlanta GA
                          phone: 404-894-9664
                margaret.kosal@inta.gatech.edu


                 www.cistp.gatech.edu
Technical Credibility Slide
  Prior experimental research includes:
  •    Nanoscale biochemical sensors
             mimic mammalian olfaction system

  •    Nanoporous porphyrin network
       materials
             size, shape and biochemical-selective
             molecular-scale ‘tinker toys’
                                       y

  •    Porphyrin-dendrimer nanotubes
             biocompatible encapsulation and
             delivery materials

  •    Polarized fluorescent Zn-porphyrin
       nanocrystals
             photovoltaic (solar cell) and light
             transduction materials
             photochromic recording media



Kosal, M.E.; Chou, J-H.; Wilson, S.R.; Suslick, K.S. “A Functional Zeolite Analogue Assembled From Metalloporphyrins,” Nature
Materials, 2002, 1, 118; Brunner, R.S.; Kosal, M.E.; Suslick, K.S.; Lamche, R.; Marti, O.; White, J.O. “Near-Field Scanning Optical
Microscopy (NSOM) of Zinc-Porphyrin Crystals,” Ultramicroscopy, 2000, 84, 149; and Kosal, M.E.; Brunner, R.S.; Suslick, K.S.;
White, J.O. Frederick Seitz Materials Research Laboratory Department of Energy (DOE) Program Review (cover), Urbana IL, June
1998, “Unusual Fluorescence Behavior of Zinc Porphyrin Crystals as Characterized by NSOM.”                                        21

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Kosal Nanotechnology & Defense 5 Feb10

  • 1. Nanotechnology & Defense Margaret E. Kosal Assistant Professor Sam Nunn School of International Affairs Georgia Institute of Technology nerdgirl@gatech.edu
  • 2. “Military applications of molecular y pp manufacturing have even greater potential than nuclear weapons to radically change the balance of power.” Admiral (Ret) David E. Jeremiah, former vice chairman of Joint Chiefs of Staff * * “Nanotechnology and Global Security,” (Palo Alto, CA; Fourth Foresight Conference on Molecular Nanotechnology), November 1995.
  • 3. Security Puzzles • Does nanotechnology have unique strategic value? – Security, economic, political, &/or scientific • Disambiguate Disambig ate potential for unique capabilities from enabling niq e previous capabilities • Perception or ideation vs technical reality – “Hope” & “Horror” hype – Rhetorical equivalence with nuclear technology – (Pseudo)-technical assessments ( ) E.g., “New technologies (at risk for terrorist appropriation) include biotechnology, nanotechnology, single nucleotide polymorphisms (SNPs), and Bose-Einstein condensates.”* – Influencing factors: institutional • International regimes for emerging technology – Adequacy of traditional arms control treaties q y – Role of NGOs * "WMD Terrorism Research: Where to From Here?” International Studies Review, March 2005, vol. 7, p. 140
  • 4. Current Discourse • Innovation • Ethics, Legal & Social Issues (ELSI) – H lth and environmental i Health d i t l impacts t NSF, EPA, NIOSH, NIH-NIEHS, DOD R&D (~$38M/year) NNI EHS Research Needs OECD Working Group on Safety of Nanomanufactured Materials – Privacy and legal implications – Uncontrolled replication (“nano-assemblers”) and artificial intelligence • Security is rarely in the dialogue Cou d there Could t e e be an “AQ Khan” of nanotechnology? a Q a o a otec o ogy – Literature: limited & emphasizes “nano-assemblers” – How to build a framework to assess analytically? – Reconcile with theories? Balance of Power Deterrence Constructivist Offense-Defense Arms Control Regime – What policy can be implemented to limit proliferation scenarios?
  • 5. Changing Strategic Environment • Post-Cold War international security environment • T h l Technology no l longer guarantees security t it • Globalization and information revolution as drivers – Enable spread and accessibility • Dual-use conundrum • Changing nature of warfare – Asymmetric warfare – Interest in unconventional weapons • Relationship between science and security p y • Disruptive technologies
  • 6. Technology: An Operators Perspective CDR Mike Penny, MD Senior Medical Officer Chemical Biological Incident Response Force (CBIRF) USMC MEF II …To close with and save What Do They Think of Technology? Requires too much training Requires too much maintenance Too delicate Too T expensive.i Then… it lets you down when you need it the most
  • 7. A Warfighter’s Perspective on Possible Nanotechnology Applications for CBRNE/WMD Operations COL Barry Lowe Chief of Staff 20th Support Command (CBRNE) Individual Protection • Applications to make uniform material capable of providing protection against chemical and biological agents, as well as other toxic materials • Applications to make uniform material react instantly to pp y become armor in the event of a bullet or fragment impact • Applications for prophylaxis against inhalation or ingestion of chemical or biological agents and toxic materials agents, • Applications for use as antidotes (this may be more feasible in the near term)
  • 8. U.S. Overview DOD Federal 2009 $431M PBR • 21st Century Nanotech Act (2003- $464 appropriated 2008) $3.7B/5years (planned) 2011 $349M PBR $ • NNI (2001-08) $8.3B (actual) DoD highly fractured by service & • US federal nanotech program ( 000) $710M (2000) $ 0 – DARPA (2011 PBR) $1.7B – Air Force: electronics, computing, communication, & NNI Strategic Plan (Dec 07) sensors (AFOSR) – E l D t ti of Lif Th t i Early Detection f Life Threatening – A Army: energetics, b lli ti ti ballistic Diseases protective materials, & power – Engineered Nanoscale Materials (ARO) – Nanobiotechnology – Navy: electronics, materials, sensors (ONR) – Nanotechnology-Based Water Purification – CBDP: passive defense (by & Testing law) – Information Processing & Advanced g – DDR&E Electronics – MDA – Predictive Toxicology • OSD Emerging Contaminants – Societal Dimensions of Nanotechnology Working Group
  • 9. Global Overview • China Estimated $300-400M per year over last 10 years • Japan J • Significant private investment $1B per year since 2002 US: 3x times federal • Southeast Asia investment in private sector Singapore Nanyang Technological g p y g g “guestimation” of $2T sales by g y University (NTU) “NanoFrontier” >$200M 2015 Malaysia Taiwan • Iran Majles Rep “America cannot tolerate Iran’s success in scientific fields such as nanotechnology and nuclear A Nanotech • technology,” Dec 2005 Russia Asilomar “nano-enabled thermobaric bomb” “nano-arms race” Wouldn’t Work! • European Union $3.3B (2004-2005) 30-100% increase over next 3 years
  • 10. International Security Regimes • Biological Weapons Convention (BWC) • Chemical Weapons Convention (CWC) • Export Controls Case Study: Zyvex & Export Controls – Richardson, Texas $10M revenues in 2005 – Nanoworks – nano tools electron tools, microscopes & photovoltaic applications – Kentara™ – CNT dispersions in resins – Current market • CNT-reinforced mountain bikes • Easton baseball bats – Required to submit ITAR licenses for CNT- product exports to China – In response, founder suggests may relocate to SE Asia
  • 11. Notional Nanotech Proliferation Pathway Initially benign/ remain benign Initially benign/ y g / convert to malfeasant Pursuit Decision Initially malfeasant Large Pilot Maintain S&T Reqs Down- Scale S l Production Weapons select Production Capability Review, Scale Up Evaluation, and Maintain Stockpile Delivery (potential) Agent Weaponization Agents Method revision ConOps Incorporation Literature Review Literature Review Field Testing Doctrine Technical Programmatic Promulgation Countermeasure Experiment/Test E i t/T t Factors Factors Experiment/Test E i /T Development Deniability Synthesis Envisioned Characterization ConOps Reactivity = major decision points = major steps/activities = optional steps/activities 11
  • 12. Circumventing Vaccines • Biothrax (AVA) & BioShield-funded Anthrax recombinant vaccines based on toxins protective antigen (PA) Academy of Sciences Courtes National • PA necessary to endocytose toxic proteins (the lethal and edema sy factors (EF & LF)) t cytosol f t to t l y cell • Functionalized single-walled carbon wall nanotubes (f-SWNTs) cross mammalian cell walls & AFM image of SWNT + release biologically active “cargos” - Staphylococal Protein A (SpA) p proteins, p p , peptides, DNA, RNA, , , , small molecules rtesy Hongjie Da Stanford f-SWNTs • Motivated by medical applications inside human drug delivery & gene therapy ai, Cour cells 100 nm 12
  • 13. Toxin Delivery Applicable to other BW agents, e.g., Botulinum toxin • Difficult to produce in large quantities via traditional microbiological methods (Commercial Botox requires 30-275 vials to achieve one LD50, strain-dependent) • Current transgenic methods can only produce light chain (LC) of toxin from E. coli or yeast • Heavy chain (HC) necessary for toxin to cross cell wall • LC + carbons nanotubes could circumvent technical difficulties Courtes Alberto Bianc CNRS C) Human HeLa cells treated co, with functionalized multi-walled multi walled carbon nanotubes (f-MWNTs) to deliver DNA into cells. D) A multi-walled carbon nanotube crossing the cell g sy membrane. 13
  • 14. “Brain Fry” NP that heats up A LOT Stealth coat – defeats upon absorption of EM – detection and optimizes maybe from a cell phone aerosolization • Coated Fe2O3 nanoparticles • Pass the blood brain barrier • EM-activatable • Specific combination of people, materials, & facilities: – Expertise in nanoparticle production (especially biological apps) – Directed energy experts who may have worked versity of Rochester on ablation therapies urtesy Hong Yang, – Engineers who have experience in battlefield f delivery of EM radiation – Vets to oversee animal testing – Aerosol drug delivery expert Univ Cou • Current research motivated by need for targeted chemotherapeutics and diagnostic Platinum-iron oxide core-shell imaging nanoparticles
  • 15. Penetration of Bio-Nano Conjugates • Fullerenes conjugated to SU cationic peptide show Courtesy Nan Monteiro-Riviere, NCS substantial uptake through skin • Mechanical stressed increased penetration • Skin observed to be surprisingly permeable to ncy nanomaterials (fullerenes & quantum dots) with diverse physicochemical properties • Motivated by transdermal drug C delivery applications & Uptake of fullerene-lysine-FITC complex through intact stratum corneum (SC) and nanoparticle safety underlying epidermal (E) and dermal assess e ts assessments layers (D). Scale bar = 50µm 15
  • 16. Nanotoxicity: Range of Novelty • Some classes of nanoparticles not actually new – Liposomes – Ultrafine (<100 nm) particles • Toxicology of more familiar materials is better understood – Ultrafine “associated with exacerbations of airway disease” and implicated in enhanced inflammation • Carbon nanotubes (CNTs) – highly unusual aspect ratio and material properties – Focus of many early nanotoxicity studies Carbon nanotube nanoshell or other nanowire (GaN) liposome gold & silver dendrimer fullerene nanoparticles ti l Familiar Novel 16
  • 17. Research Underlying Threat Scenarios • CNTs Crossing Cell Walls: Nadine Wong et. al., “Carbon Nanotubes as Intracellular Protein Transporters: Generality and Biological Functionality,” J. Am. Chem. Soc., 2005, vol. 127, p. 6021; Alberto Bianco, et. al., “Cationic Carbon Nanotubes Bind to CpG Oligodeoxynucleotides and Enhance Immunostimulatory Properties,” J. Am. Chem. Soc. 2005, vol. 127, p. 58; Qi Lu, et. al., “RNA Polymer Translocation with Single-Walled Carbon Nanotubes," Nano Lett., 2004, vol. 4, p. 2473; and Davide Pantarotto, et. al., "Immunization with Peptide-functionalized Carbon Nanotubes Enhances Virus-specific Neutralizing Antibody Responses" Chem. Biol., 2003, vol. 10, pp. 961. D. Pantarotto; et. al., “Functionalized Carbon Nanotubes for Plasmid DNA Gene Delivery,” Angew. Chem., Int. Ed,. 2004, vol. 43, p. 5242. y, g , , , ,p • Vesicants: Sara Fernandez-Lopez, et. al., “Antibacterial Agents Based on the Cyclic d,l-alpha-peptide Architecture,” Nature, 2001, vol. 412, p. 452; W. Seth Horne, et. al., “Heterocyclic Peptide Backbone Modifications in an alpha-Helical Coiled Coil,” J. Am. Chem. Soc., 2004; vol.126, p. 15366; and Jorge Sánchez-Quesada, et. al., “Modulating Ion Channel Properties of Transmembrane Peptide Nanotubes through Heteromeric Supramolecular Assemblies,” J. Am. Chem. Soc., 2002, vol. 124, p. 10004. • Drug Delivery: D. Missirlis, N. Tirelli, J.A. Hubbell, “Amphiphilic hydrogel nanoparticles. Preparation, characterization, and preliminary assessment as new colloidal d ll id l drug carriers,” L i ” Langmuir, 2005 vol. 21 p. 2605 H S Y i l 21, 2605; H.S. Yoo, T G P k “F l t T.G. Park, “Folate-receptor-targeted delivery of d t t t d d li f doxorubicin nano- bi i aggregates stabilized by doxorubicin-PEG-folate conjugate,” J. Control. Release, 2004, vol. 24, p. 247; C.Y. Huang, Y.D. Lee, “Core-shell type of nanoparticles composed of poly[(n-butyl cyanoacrylate)-co-(2-octyl cyanoacrylate)] copolymers for drug delivery application: Synthesis, characterization and in vitro degradation,” Int. J. Pharm., 2006 vol. 9, p. 345; R. M. Mainardes, et al., “Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery,” Curr. Drug Deliv., 2006, vol. 3, p. 275; and Y. Zeng, W.G. Pitt, “A polymeric micelle system with a hydrolysable segment for drug delivery,” J. Biomater. Sci. Polym. Ed., 2006, vol. 17, p. 591. • Anti-Material Agents: S.L. Scott, C.M. Crudden, C.W. Jones, eds., Nanostructured Catalysts, (Plenum Publishing Corporation; New York), 2003; K.S. Suslick, et. al., "Nanostructured Materials Generated by High-Intensity Ultrasound: Sonochemical Synthesis and Catalytic Studies," Chemistry of Materials, 1996, vol. 8, p. 2172; N. Arul Dhas, et. al., “Sonochemical Preparation of Hollow Nanospheres and Hollow Nanocrystals J. Am. Chem. Soc. 2005, vol. 127, p. 2368; and A.J. Zarur, J.Y. Ying, "Reverse Microemulsion Synthesis of Nanostructured Complex Oxides for Catalytic Combustion," Nature, 2000, vol. 403, p. 65. • Brain Fry: Peter Varallyay, et al., “Comparison of Two Superparamagnetic Viral-sized Iron Oxide Particles Ferumoxides and Ferumoxtran-10 with a Varallyay al Comparison Gadolinum Chelate in Imaging Intracranial Tumors” American Society of Neuroradiology, 2002, vol. 23; Jun Sung Kin, et al., “Toxicity and Tissue Distribution of Magnetic Nanoparticles in Mice” Toxicological Sciences, 2006, vol. 89, p. 338; and K Hynynen, et al., “Focal Disruption of the Blood- Brain Barrier Due to 260-kHz Ultrasound Bursts: a Method for Molecular Imaging and Targeted Drug Delivery” Journal of Neuosurgery, 2006, vol. 105, p. 455. • Self-Assembly: Jean-Marie Lehn, “Toward Complex Matter: Supramolecular Chemistry and Self-organization,” Proc. Natl. Acad. of Science, 2002, vol. 99 p. 763; G l 99, 63 George M Whi id and Mil B M. Whitesides d Mila Boncheva, B h Beyond M l d Molecules: S lf A l Self-Assembly of M bl f Mesoscopic and M i d Macroscopic C i Components,” P ” Proc. Natl. Acad. of Science, 2002, vol. 99, p. 769; C. P. Collier, et. al., “Electronically Configurable Molecular-Based Logic Gates,” Science, 1999, vol. 285, pp. 391; and Kelly S. Chichak, et. al. “Molecular Borromean Rings,” Science, 2004, vol. 304, p. 1308. The Science is Real, the Scenarios are Notional! 17
  • 18. Key Security Factors • Deniability Deniabilit & Lack of Transparenc Transparency – Most of the dual-use concerns raised regarding biotechnology risks are potentially applicable to malfeasant co-option of nanotechnology * Except, biological agents require damp environments with moderate temperatures, moderate pressures and ambient oxygen * Nano-engineered materials do not replicate – Lack of explicit norms – Lack of explicit category for international arms control regimes • Vulnerability Perception – Perceived lack or limitation defensive countermeasures, e.g., limitations of stand-off biological (& to a lesser extent, chemical) detection • International prestige p g • No single discipline on which to focus – Chemistry to electrical engineering – Materials science to molecular biology • Overwhelmingly, a state-based proliferation concern O h l i l t t b d lif ti – Secondarily, rogue scientist scenario • Intent must be balanced with capability – Offensive versus defensive not transparent • Globalization – Private sector is major player global, e.g., sale or transfer of technology
  • 19. Recommendations & Conclusions • Strategic vision lacking We are currently attempting to limit the threat of “Biotechnology in an Age of Terrorism” • Serious threat anticipation with respect to nanotechnology should be initiated i iti t d now • Balance “hype” & hope • Need to foster revolutionary technology • Programmatic and institutional (intra- and inter-agency) challenges paramount • Change in risk tolerance • Response w/r/t international agreements & groups varies • CWC, BWTC, Australia Group • Fostering pro-active international scientific cooperation as means to encourage beneficial use of technology • Pro-active “Nano” Cooperative Threat Reduction • T k 2 diplomacy Track di l • Policy outcomes • JCS-JRO – Incorporation into Modernization Plan • DTRA-CB/JSTO – Incorporation into TCTI Strategy DTRA CB/JSTO • Emerging framework and nascent theory to be tested against biotechnology, including synthetic biology; cognitive sciences, and nano-bio-info-cogno (NBIC) convergence
  • 20. Contact information Margaret E. Kosal, PhD Assistant Professor Sam Nunn School of International Affairs Georgia Institute of Technology Atlanta GA phone: 404-894-9664 margaret.kosal@inta.gatech.edu www.cistp.gatech.edu
  • 21. Technical Credibility Slide Prior experimental research includes: • Nanoscale biochemical sensors mimic mammalian olfaction system • Nanoporous porphyrin network materials size, shape and biochemical-selective molecular-scale ‘tinker toys’ y • Porphyrin-dendrimer nanotubes biocompatible encapsulation and delivery materials • Polarized fluorescent Zn-porphyrin nanocrystals photovoltaic (solar cell) and light transduction materials photochromic recording media Kosal, M.E.; Chou, J-H.; Wilson, S.R.; Suslick, K.S. “A Functional Zeolite Analogue Assembled From Metalloporphyrins,” Nature Materials, 2002, 1, 118; Brunner, R.S.; Kosal, M.E.; Suslick, K.S.; Lamche, R.; Marti, O.; White, J.O. “Near-Field Scanning Optical Microscopy (NSOM) of Zinc-Porphyrin Crystals,” Ultramicroscopy, 2000, 84, 149; and Kosal, M.E.; Brunner, R.S.; Suslick, K.S.; White, J.O. Frederick Seitz Materials Research Laboratory Department of Energy (DOE) Program Review (cover), Urbana IL, June 1998, “Unusual Fluorescence Behavior of Zinc Porphyrin Crystals as Characterized by NSOM.” 21