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BIO-Defense Issues. Basic Premises. The Cat is out of the Bag Technology and Know-how too widely dispersed (Roger Breachy’s student) From Nations to: Nations Loose organizations/networks Garage Hackers (by 2010-2015) Impossible to distinguish beneficent from belligerent bioscience
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Basic Premises • The Cat is out of the Bag • Technology and Know-how too widely dispersed (Roger Breachy’s student) • From Nations to: • Nations • Loose organizations/networks • Garage Hackers (by 2010-2015) • Impossible to distinguish beneficent from belligerent bioscience • Everything is dual use (“not the needle, the hay”) • The Rate of change is exponential • By several measures > Moore’s law • E.g., genetic info fully sequenced, demand for specifically sequenced materials, pace of fundamental new discoveries (RNAi) etc. • And this is Manchester -- 1840 • Ability to synthesize and manipulate will increase radically over next decade • CAN NOT PREDICT > 5 Years Out (J. Watson) • Short window to set global norms of appropriate use
Choose a naturally occurring pathogen or toxin Weaponize it E.g., via aerosolizing Very recently: enhance through modification IMPLICATIONS: Limited number of agents of concern Largely, observable indicators for intelligence to track Containable Problem – ala Nukes -- i.e., Deterrence and non-proliferation more or less possible The Old Threats PLUS: Add new capabilities to a natural pathogen transgenically Add totally new capabilities not found in nature E.g., target to haplotypes or alleles New immune-suppressors or neuro modulators Bio time-bombs Design something totally new, UN-natural – designer bioweapons Engineered to exploit vulnerabilities (e.g. fear-inducing agent) Weapon does not have to be alive so long as it provokes a host response!!!! Biomolecules as the agents, with the organism as the delivery mechanism Further weaponize as necessary IMPLICATIONS: NO LONGER A CONTAINABLE PROBLEM No observable indicators in production Total Sequence Awareness??? Must shift to detection and rapid response: analysis and diagnosis, intervention, therapies Old vs. New BioDefense OLD World NEW World Dilemma: Don’t need real knowledge to design something bad, but need full knowledge to respond effectively.
Advanced Weaponization: Microencapsulation Biofilms Carrier Beads Nanoparticles/nano powders RNAi Virus-related: Viral reverse genetics Viral pseudotyping Engineered viral agents Prions and similar things Mycotics/Fungals Anti-materials applications Synthetic DNA/RNA Proliferated digitally DNA Shuffling Bioregulators – kinases, phosphates, peptides Immunoregulators – Cytokines, chemokines Multiple agents (e.g, influenza and pneumonococcus) Novel Toxins Transgenic Pathogens DNA Vaccines Ethnic Weapons Technologies of Concern
Points of Interest • Innate Immunity/defense -- Major revolution brewing – human and ag (why do most plants resist most pathogens???) • Antibiotic resistance (APUA) • MDRs (multidrug resistance organisms) increasing (now 2-6 antibotics, many no treatment at all) • Don’t know resevoirs of MDR • Some projects including getting big pharma to share databases on resistance to new drugs • Animal antibiotic use is a huge problem – no prescriptions and large quantities • Paratech – new paradigm from antibiotic resistance: Idea is to inhibit multiple pathogens to let the drugs do their work • Timing of prophylaxis is critical: Enfeeble the organism before it can colonize the host • MARA (bacterial protein) – this 1 protein appears to turn on/off 80 genes (lots of MARA homologues in other organisms) including those that enable colonization and reproduction • Small molecule to inhibit is goal
Broad Areas Germane to the Problem • Vaccines and Immunology • Antibiotics and antivirals • Toxicology and Pathogenicity • Epidemiology and Surveillance • Big emphasis on “a new epidemiology” in detection, prevention, mitigation • Detection, rapid diagnosis and sensors
Tentative Implications • Any response MUST fully leverage civilian bio, medical, agric., etc. capabilities • International Coalition against dark biology • BWC – Bush Administration has no credibility • In intelligence gathering • In research • In industry and technology
pharmaceuticals • Another story of vertical specialization: How & why? • The search for “blockbusters” through bulking up: So far, not so good. • The changing role of publicly funded research and universities: Be careful what you wish for. • Proteomics and genomics. • Foreign markets and IPR: The Doha Round of trade talks and developing-economy access to pharmaceuticals. • Creating incentives for development of drugs for developing-economy diseases. • Bio-defense and the pharma. Industry.