Biological Weapons and Biotechnology:Briefing to the Out of the Box and Into the Future Conference: Biological Weapons and Biotechnology: Briefing to the Out of the Box and Into the Future Conference David W. Siegrist Potomac Institute for Policy Studies Arlington, VA 22209 siegrist@potomacinstitute.org June 27, 2000


Biological Weapons and Biotechnology: Biological Weapons and Biotechnology Will Advanced Biotechnology more Favor Offense or Defense against Biological Weapons? Currently, Offense Far Outpaces Defense in Bioweapons


DoD Questions Utility of Genetic Engineering of Weapons: DoD Questions Utility of Genetic Engineering of Weapons Despite Prodigious Soviet Efforts, “Current BW Agents Do Not Represent a Significant, or Even Incremental Improvement Over What Was Available Decades Ago. This Fact Suggests That Nations With Current Programs, and Especially New Entrants, Will Find the “Classic” BW Agents Difficult to Improve.” Biotechnology and Genetic Engineering:  Implications for the Development of New Warfare Agents


Slide4: Anthrax (from DoD Website) “There is no effective treatment for inhalational anthrax. Antibiotics will suppress infection only if administered early after exposure -- usually within the first 24 - 48 hours. By the time symptoms develop, it is highly likely death will occur despite the best efforts of modern medical science. 99% lethal to unprotected individuals.”


Anthrax Scenario: Anthrax Scenario Limited Antibiotics and Vaccines Numerous “Worried Well” Sensors Cannot Detect Previous Open Air Aerosol Passage Non-Specific, Flu-Like Symptoms Potential for Civil Unrest, Lack of Faith in Authorities Need for Rapid (Pre-symptomatic) Diagnostics Need for Actual Cure for Inhalational Anthrax


Some Possibilities to Disrupt Anthrax Pathogenesis: Some Possibilities to Disrupt Anthrax Pathogenesis Prevent Anthrax Spore Germination Block Protective Antigen Binding to Host Cells Prevent Protease of Bound PA Neutralize Lethal Factor and Edema Factor Prevent Septicemia and Toxic Shock Prevent Secondary Hemorrhage in Lung Capillaries


Some Possibilities to Disrupt Anthrax Pathogenesis: Some Possibilities to Disrupt Anthrax Pathogenesis Prevent Anthrax Spore Germination DARPA Defense Sciences Office Program Block Protective Antigen Binding to Host Cells Small Molecules to Block CHO-K1 Cells Anthrax Molecular Receptor Decoys in Lymphatic System Prevent Protease of Bound PA Protease Inhibitor Neutralize Lethal Factor and Edema Factor Monoclonal Antibodies Prevent Septicemia and Toxic Shock Nitric Oxide Scavenger; Modulate Cytokines/Inflammation Cascade Lilly Medication in Phase III Test Prevent Secondary Hemorrhage in Lung Capillaries Fibrin Vasopressors for Hypotension


Or, Back to the Future…?Bacteriophage Therapy: Or, Back to the Future…? Bacteriophage Therapy Bacteriophages are Viruses that Prey on Bacteria Theoretically, Bacteriophage against Anthrax Might be Given to Cure Victims Germans in WWII had a Product against Shigella Antibiotics Lessened Interest in Bacteriophage Therapy Bacteriophages Can Survive in Bloodstream and Penetrate some Fibrous Defenses Currently Being Developed for MDR TB, VRE, MRSA Advanced Biotech Making What’s Old New Again


Transition: Transition Advanced Biotechnology Is Vital to Improving Biological Weapon Defense Although There Are Multiple Pathogens, the Ways They Damage Hosts Have Some Commonalities Targeting Common Disease Pathways May Help Overcome Current Offense/Defense Mismatch Biotech Supports Move to More Active Defense However, Biotechnology May Also Be Used by Weapon Developers Might It Also Assist Offense?


Biotechnology Assistance to Offense?(Note: US Stopped Its Offensive Program in 1969): Biotechnology Assistance to Offense? (Note: US Stopped Its Offensive Program in 1969) Improve Effectiveness of Existing Agents Create Different Kinds of Agents Proliferate Expertise and Tools The Population Capable of Creating Biological Agents Will Increase, Including “Bad Apples” Biotech Tools Will be Created to Routinize Complex Tasks


Biological Weapon CharacteristicsFrom DoD 1997 “Genetics” Report: Biological Weapon Characteristics From DoD 1997 “Genetics” Report


Different Types of Bio WeaponsThe Soviet Biopreparat Example: Different Types of Bio Weapons The Soviet Biopreparat Example Biopreparat: Up to 40K People Working for 20 Years Enhanced Anthrax “Super” Bubonic Plague Strategic Weapon for War with US Sought to Induce Its Resistance to Many Antibiotics Used Traditional Techniques (Vice Gene Splicing) “Chimera” Smallpox with Marburg/Ebola Virus Ken Alibek Contention Sought to Combine Stability and Infectivity of Smallpox with Lethality of Marburg/Ebola? Combination May Actually Reduce Lethality Behavior Modulators Endorphins. Others? Few Reported Results. Limited Results. Biotech Weapons Hard to Make.


One Successful Ongoing Biotechnology Weapon Application: One Successful Ongoing Biotechnology Weapon Application “’Advanced biological weapons techniques’ are already in use in agriculture with no restrictions - aerial spraying of recombinant baculoviruses containing the scorpion venom toxin gene” -- Floyd Horn, USDA


Possible New Agent Type: Neuropeptides/Bioregulators: Possible New Agent Type: Neuropeptides/Bioregulators Neuropeptides Mediate Many Bodily Functions May be Developed as Super Toxins or Behavior Modifiers They Regulate Reproduction, Metabolism, Growth, Temperature, Heart Rate, Eating, Drinking, Breathing, Behavior, Memory, Emotional State… May Act as Neurohormones, Neuromodulators, and/or Neurotransmittters Examples: Endorphins; Enkephalins; Tachykinins… Hard to Transit the Blood-Brain Barrier. Redundant Controls of Bodily Functions. Possibility to Change How People Are? “At Least Three of the Seven Deadly Sins Are Mediated by Neuropeptides” -- Charles F. Stevens


Utility of Genetically Engineered Weapons?: Utility of Genetically Engineered Weapons? Creating Bio Agents Just a First Step to a Weapon Actual Weaponization Requires Infrastructure, Extensive Testing Increases Organizational “Footprint” and Intelligence Signatures Increased Opportunities for Some Form of Intervention Attributability of a Biological Attack tends to Increase with Use of Advanced Biotechnology Relatively Few Have Capability for Sophisticated Attack Increase Traceability Back to State Sponsor, Other Presumptive Act of War Attributability Should Deter Potential State Sponsors


Example Approaches for Advanced Bio Defense Need to Leverage Common Pathways Among Diseases: Example Approaches for Advanced Bio Defense Need to Leverage Common Pathways Among Diseases Isis: Identified Several Common Pathogenic Portions of Bacteria and Small Molecule Lead Compounds to Bind Them May Be Useful Against Even Engineered Pathogens UVA: Heteropolymers to Link Red Cells and Decoy Receptors Developmental Antiviral Successful in Monkeys against Bio Agents Stanford U: Type 3 Secretion Pathway for Virulence Factors Inhibiting Pathway May Stop Transport of Toxic Proteins U Maine: Presymptomatic Diagnostics Through Nitric Oxide Exhaled NO Increases as Body Starts to Fight Disease U Texas: Monoclonal Antibodies with Immobilization Tails Create Hybrid “Immunoplastic” Biosensors Many Others. These Projects Are Listed as Examples of Possibilities. They Are Not Reduced to Practice.


Conclusion: Conclusion Defensive Advanced Biotechnology Is Critical to Mitigate Offense/Defense Mismatch in Biological Weapons High Utility also Against Emerging/Reemerging Diseases Biotech May Be Used by Some to Enhance Weapons Effects Note: US Offensive Program Stopped in 1969 Weapons Manufacture Harder than Many Think However, Risk of Their Use is Somewhat Mitigated by Operational Limitations to their Presumed Perceived Utility Net Benefit Accrues to Defense, Since It Is Already Far Behind The US and Its Allies Have an Asymmetric Advantage in Biotech We Need to Leverage to Overcome Asymmetric Biological Threats


Slide18: University of Virginia Heteropolymers