Synthetic Biology andEmerging ThreatsBy Dave Moorer
Six Emerging ThreatsBinary Biological WeaponsDesigner DiseasesDesigner GenesGene Therapy as a WeaponStealth VirusesHost-sw...
Six Emerging ThreatsBinary Biological WeaponsCombined can create                        e.coli bacteriaincreased virulence...
Six Emerging ThreatsDesigner diseasesCan turn off the immune systemCould initiate programmedcell death
Six Emerging ThreatsDesigner GenesVirtual Parts list:http://parts.mit.edu   red floursecent protein (RFP)“BioBricks”       ...
Six Emerging ThreatsGene therapy as a weaponRetroviruses i.e. HIV/AIDS                             Cross-section of AIDS v...
Six Emerging ThreatsStealth virusesFairly common in natureCovertly enter human cells andremain dormant                    ...
Six Emerging ThreatsHost-swapping diseasesDiseases sometimes “jump species”Ebola & HIV                            Bat link...
Trends in Terrorism Motivations changing in ways which lead to more indiscriminate and less concern for mass casualties Fo...
Trends in TerrorismRadical religious motivation:Local opposition to US hegemonyand military presence in areas withno histo...
Terrorist OrganizationsInclined to Use Bioterrorism Fundamentalist and religious groups Racist and anti-government groups ...
Benefits of DNA SynthesisCarbon-neutral energy sourcesConsolidated bioprocessing
Benefits of DNA SynthesisBio-based manufacturing“White Biotechnology”
Benefits of DNA SynthesisEngineering Specific PathwaysMetagenomics
Benefits of DNA SynthesisGenome Design and ConstructionMycoplasma genitaliumfirst genome completedsmallest known bacterial g...
Benefits of DNA SynthesisApplied Protein DesignAllows creation of protein-baseddrugs that can resist rapiddegradation in th...
Benefits of DNA SynthesisNatural Product SynthesisDecreased time to construct andmutate genesPlant: Artemesia annua        ...
Benefits of DNA SynthesisCreation of Standardized Biological Parts and Circuits167 basic parts, including sensors, actuator...
Research Obstacles andPotential RisksStandardization: M.I.T. Standard Parts RegistryDecoupling: “separate a complicated pr...
Research Obstacles andPotential RisksIncrease in BSL-3 and BSL-4 labssince 9/11U.S. Govt. unable to keep up withincreased ...
Research Obstacles andPotential RisksIncidents at different labsTexas A&M lab: Worker exposed to pathogenAtlanta lab: Powe...
Globalization andBiosecurity “Much has been written about the forces of globalization-the relentless expansion of market f...
Globalization andBiosecurity The U.S. strategy to reduce biological weapons threat comprises three tactics: Nonproliferati...
Globalization andBiosecurity  Of the top-six Class A biological threat agents identified by the HHS (anthrax, botulinum tox...
Biological and ToxinWeapons ConventionIn 2001, President George W. Bush’s administrationwithdrew support from efforts to s...
Vaccine Development andSupply ProblemsOf the 49 biological threat agents identified, the FederalDrug Administration (FDA) h...
Vaccine Development andSupply ProblemsProject Bioshield Act of 2004 (Project Bioshield)Allocates 5.6 billion over 10 years...
Policy Goals Enhancing biosecurity Fostering laboratory safety Protecting the environment
Policy Goals:17 options for GovernanceGene foundariesOligo manufacturersDNA synthesizersUsers and organizations
Gene Foundaries &Oligo ManufacturersRequire commercial firms to use approved software for screeningordersPeople who order s...
DNA SynthesizersOwners of DNA synthesizers must register theirmachinesOwners of DNA synthesizers must be licensedA license...
Users & OrganizationsIncorporate education about risks and best practices as part ofuniversity curriculaCompile a manual f...
ConclusionsWithout a reliable vaccine source, responses tobioterrorism or accidents will result in mass casualtiesPrograms...
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Synthetic Biology And Emerging Threats

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  • This area of research deals with the process of stitching together small pieces of DNA into large, gene or genome-sized pieces so that the DNA, for example of a medium sized virus can be constructed in a matter of weeks. This paper addresses the emerging DNA synthesis enterprise and what is being done within that community as DNA synthesis and other related processes continue to reveal new ways of integrating a wide array of agricultural, medical and scientific discoveries. \n
  • At least six potential biological threats exist, any of which could easily overwhelm a fragile emergency response system. A strong deterrent is one factor in preventing bioterrorism. One key factor in deterring would-be-terrorists from executing a biological attack is the existence of the current vaccines capable of counter-acting the effects of dangerous pathogens. Sadly, there is a severe lack of effective vaccines to many of the known biological agents. To complicate matters, numerous hurdles must be surmounted in order to design, produce, license, and stockpile current, effective vaccines.\n
  • To produce a binary biological weapon, a host bacteria and a virulent plasmid could be independently isolated and produced in the required quantities. Just before the bioweapon was deployed, the two components would be mixed together. The transformation of the host organism back into a pathogen could conceivably take place after a weapon is triggered and during transport/flight.\n
  • Designer diseases may work by turning off the immune system, by inducing specific cells to multiply and divide rapidly (like cancer), or possibly by causing the opposite effect, such as initiating programmed cell death (apoptosis). This futuristic biotechnology would clearly indicate an order-of-magnitude advancement in offensive biological warfare or terrorism capability.\n
  • For a bioweaponeer, the databases of increasing numbers of microbial genomes provide a virtual “parts list” of potentially useful genes for a genetic “erector set” to design and produce a new organism. It is possible to pick and choose the most lethal characteristics\n
  • One class of experimental vectors is the retroviruses which permanently integrate themselves into human chromosomes. HIV, which causes AIDS, is a retrovirus. If smallpox were to be similarly genetically manipulated, our current vaccine may not protect against it. These vectors are not yet very efficient in introducing genes into tissue cells. But if a medical technique is perfected, similar vectors might eventually be used to insert harmful genes into an unsuspecting population.\n
  • The concept of a stealth virus is a cryptic viral infection that covertly enters human cells (genomes) and then remains dormant for an extended time. However, a signal by an external stimulus could later trigger the virus to activate and cause disease. This Next Generation Bioweapons: Genetic Engineering and BW mechanism, in fact, occurs fairly commonly in nature. For example, many humans carry herpes virus which can activate to cause oral or genital lesions\n
  • In nature, animal viruses tend to have narrow, well-defined host ranges. Unlike bacteria, viruses often infect only one or just a few species. When a virus has a primary reservoir in an animal species, but is transmissible to humans, it is called a zoonotic disease. The bat is thought to be the reservoir for Ebola virus, and the chimpanzee is thought to have been the original reservoir for the HIV virus that causes AIDS. When viruses “jump species” they may occasionally cause significant disease. These examples illustrate that manageable infectious agents can be transformed naturally into organisms with markedly increased virulence. \n
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  • 1.Conflicts in Kashmir between Hindu and Islamic factions has lead to increasingly deadly attacks in India.2. US presence in the Arabian Peninsula and the Persian Gulf has lead to more at tacks by Al-Qai’da in the region.3. A suicide attack in Tampa, Florida by an amateur pilot flying a single engine plane into a skyscraper failed to cause mass casualties.4. The current Israeli-Palestinian crisis has shown a propensity to utilize increasingly lethal tactics in their attacks.\n
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  • A process called consolidated bioprocessing attempts to engineer a single organism to encompass all necessary steps in ethanol production from cellulose. This option, if successful, could help create a cost competitive alternative to gasoline. \n
  • This area of synthetic genomics is sometimes called “white biotechnology.” What has traditionally been produced via a petroleum-based matrix, plants and microbes are now being engineered to produce the same products. \n
  • Metagenomics is the study of genetic material recovered directly from environmental samples. Using metagenomic surveys from microorganisms in natural environments, scientists are identifying new genes, some of which can be used to engineer specific pathways into microbes. The importance of this discovery is that synthetic genomics could provide for reconstruction of these genes.\n
  • Genome Design seeks to redesign genomes to make them more efficient at carrying out normal functions or to program them to perform new ones. Researchers at the J. Craig Venter Institute redesigned the bacterium Mycoplasma genitalium to a “bare-bones” structure to be used as a genetic platform to which new genes can be added and create organisms with known characteristics and functionality.\n
  • During the 1980s, Kevin Ulmer of Genex Corporation was inspired by the idea of systematically altering genes that code for certain proteins to achieve desired modifications in protein stability and function. This started a trend that has continued into the present and protein-engineering technology has been applied to develop enzymes that can tolerate high temperatures and acidity levels.\n
  • Also, this rapid method of gene sequencing is proving to be a solid tool in basic evolutionary mechanics understanding at the molecular level. The ability to make subtle modifications to gene sequences will allow for increased efficiency in diagnostic capabilities and vaccines for humans and animals. The most important factor here is the speed with which scientists can construct and mutate gene sequences to allow for broader protections via vaccines. One example is the anti-malarial drug Artemisinin that is naturally produced in the plant Artemesia annua. Due to its complex metabolism, it is not feasible to duplicate this process using conventional methods in a lab. Natural production rates also make it inefficient and prohibitively expensive to produce significant amounts in a timely fashion. So, as a baby-step in the direction of using yeast to produce artemisinin, researchers have implanted a gene for the precursor artemisinic acid into a strain of yeast engineered to produce a high yield of the product.\n
  • In summer of 2004, the group established a Registry of Standard Biological Parts. The parts in the registry are called “BioBricks”, short pieces of DNA that constitute or encode functional genetic elements. As of April 2006, the BioBricks registry contained 167 basic parts, including sensors, actuators, input and output devices, and regulatory elements. Also included were 421 composite parts, and an additional 50 parts were in the process of being synthesized or assembled. In the spirit of an open-source environment, the registry was placed on a public website (http://parts.mit.edu).\n
  • decoupling, the effort to “separate a complicated problem into simpler problems that can be worked on independently, such that the resulting work can eventually be combined to produce a functioning whole.” Thirdly, abstraction is a method for organizing information describing biological functions into “hierarchies” that operate at different levels of complexity. \n
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  • The GAO also raised concerns that by pushing the limitations of allowable research in regards to the Biological Weapons Convention (BWC), the United States may be subverting its own goals to limit defensive research by other countries. The treaty does allow for work to be done in limited quantities of certain dangerous agents for “prophylactic, protective, or other peaceful purposes.” \n
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  • Synthetic Biology And Emerging Threats

    1. 1. Synthetic Biology andEmerging ThreatsBy Dave Moorer
    2. 2. Six Emerging ThreatsBinary Biological WeaponsDesigner DiseasesDesigner GenesGene Therapy as a WeaponStealth VirusesHost-swapping Diseases
    3. 3. Six Emerging ThreatsBinary Biological WeaponsCombined can create e.coli bacteriaincreased virulence plasmid molecules
    4. 4. Six Emerging ThreatsDesigner diseasesCan turn off the immune systemCould initiate programmedcell death
    5. 5. Six Emerging ThreatsDesigner GenesVirtual Parts list:http://parts.mit.edu red floursecent protein (RFP)“BioBricks” green flourescent protein (GFP)
    6. 6. Six Emerging ThreatsGene therapy as a weaponRetroviruses i.e. HIV/AIDS Cross-section of AIDS virus
    7. 7. Six Emerging ThreatsStealth virusesFairly common in natureCovertly enter human cells andremain dormant Varicella virus: can reactivate to cause oral lesions as herpes zoster
    8. 8. Six Emerging ThreatsHost-swapping diseasesDiseases sometimes “jump species”Ebola & HIV Bat linked to EbolaCan have increased virulence Chimpanzee linked to AIDS
    9. 9. Trends in Terrorism Motivations changing in ways which lead to more indiscriminate and less concern for mass casualties Four basic motivations that are driving terrorist organizations to more destructive attacks:
    10. 10. Trends in TerrorismRadical religious motivation:Local opposition to US hegemonyand military presence in areas withno historical US presence:Amateur terrorists have littleconcern for self-preservation ordetection:Racial and ethnic hatred:
    11. 11. Terrorist OrganizationsInclined to Use Bioterrorism Fundamentalist and religious groups Racist and anti-government groups Millenarian cults (such as Al-Qai’da and Aum Shinrikyo, who believe that a coming historical event will change perceived corrupt and unjust ideologies that will be transformed into a positive future by some apocalyptic event or events). “Amateur” terrorists
    12. 12. Benefits of DNA SynthesisCarbon-neutral energy sourcesConsolidated bioprocessing
    13. 13. Benefits of DNA SynthesisBio-based manufacturing“White Biotechnology”
    14. 14. Benefits of DNA SynthesisEngineering Specific PathwaysMetagenomics
    15. 15. Benefits of DNA SynthesisGenome Design and ConstructionMycoplasma genitaliumfirst genome completedsmallest known bacterial genome(482 protein-coding genes, 43 RNA genes) Map of mycoplasma genitalium
    16. 16. Benefits of DNA SynthesisApplied Protein DesignAllows creation of protein-baseddrugs that can resist rapiddegradation in the body
    17. 17. Benefits of DNA SynthesisNatural Product SynthesisDecreased time to construct andmutate genesPlant: Artemesia annua Artemesia annua (wormwood plant)
    18. 18. Benefits of DNA SynthesisCreation of Standardized Biological Parts and Circuits167 basic parts, including sensors, actuators, inputand output devices, and regulatory elements.421 composite parts, and an additional 50 parts werein the process of being synthesized or assembled
    19. 19. Research Obstacles andPotential RisksStandardization: M.I.T. Standard Parts RegistryDecoupling: “separate a complicated problem into simplerproblems that can be worked on independently, such that theresulting work can eventually be combined to produce afunctioning whole.”- Drew EndyAbstraction: organizing information describing biological functionsinto “hierarchies” that operate at different levels of complexity
    20. 20. Research Obstacles andPotential RisksIncrease in BSL-3 and BSL-4 labssince 9/11U.S. Govt. unable to keep up withincreased number of labsBSL-3 & BSL-4 labs only placesdangerous pathogens can beworked on
    21. 21. Research Obstacles andPotential RisksIncidents at different labsTexas A&M lab: Worker exposed to pathogenAtlanta lab: Power outageUK lab: Foot and mouth disease releaseLLNL: Fined $450,000 for two separate shipping errorswith anthrax, one release involving broken vials
    22. 22. Globalization andBiosecurity “Much has been written about the forces of globalization-the relentless expansion of market forces and the constant search for greater economic efficiencies...Many of the things that have left Western societies vulnerable to terrorist attacks are the very efficiencies that have come as a consequence of the relentless search for efficiency and the maximization of productivity, by person, companies, and countries.” - Kurt Campbell
    23. 23. Globalization andBiosecurity The U.S. strategy to reduce biological weapons threat comprises three tactics: Nonproliferation Counterproliferation Consequence Management (Defense)
    24. 24. Globalization andBiosecurity Of the top-six Class A biological threat agents identified by the HHS (anthrax, botulinum toxin, plague, smallpox, tularemia, and viral hemorrhagic fevers such as Ebola), vaccines for all but one (Botulinum toxin) are being developed in cooperation with international biotechnology companies.
    25. 25. Biological and ToxinWeapons ConventionIn 2001, President George W. Bush’s administrationwithdrew support from efforts to strengthen thecornerstone of the U.S. non-proliferation strategy, theBiological and Toxin Weapons Convention (BTWC),arguing that the draft verification protocol put forth atthe Fifth Review Conference would not effectively limitproliferation
    26. 26. Vaccine Development andSupply ProblemsOf the 49 biological threat agents identified, the FederalDrug Administration (FDA) has licensed vaccines toprotect against only four agents on the list (anthrax,cholera, plague, and smallpox).Joint Vaccine Acquisition Program (JVAP) allocated$747 million for developmentLaughed at by the pharmaceutical companies
    27. 27. Vaccine Development andSupply ProblemsProject Bioshield Act of 2004 (Project Bioshield)Allocates 5.6 billion over 10 years for development andpurchase of medical countermeasuresThe “Special Reserve Fund” was provided in theFY2004 Department of Homeland SecurityAppropriations Act.
    28. 28. Policy Goals Enhancing biosecurity Fostering laboratory safety Protecting the environment
    29. 29. Policy Goals:17 options for GovernanceGene foundariesOligo manufacturersDNA synthesizersUsers and organizations
    30. 30. Gene Foundaries &Oligo ManufacturersRequire commercial firms to use approved software for screeningordersPeople who order synthetic DNA from commercial firms must beverified as legitimate users by an Institutional Biosafety Officer orsimilar “responsible official”Commercial firms are required to use approved screening softwareand to ensure that people who place orders are verified aslegitimate users by a Biosafety OfficerRequire commercial firms to store information about customersand their orders
    31. 31. DNA SynthesizersOwners of DNA synthesizers must register theirmachinesOwners of DNA synthesizers must be licensedA license is required to both own DNA synthesizers andto buy reagents and services
    32. 32. Users & OrganizationsIncorporate education about risks and best practices as part ofuniversity curriculaCompile a manual for “biosafety in synthetic biology laboratories”Establish a clearinghouse for best practicesBroaden Instituional Biosafety Committee (IBC) reviewresponsibilities to consider risky experimentsBroaden IBC review responsibilities and add oversight from anational advisory group to evaluate risky experimentsBroaden IBC review responsibilities, plus enhance enforcement ofcompliance with National Institutes of Health biosafety guidelines
    33. 33. ConclusionsWithout a reliable vaccine source, responses tobioterrorism or accidents will result in mass casualtiesPrograms like Project Bioshield need to rapidly develop,license and stockpile current vaccinesPolicymakers need to embrace globalization while writingpragmatic policies that hold users and organizationsaccountable for their actions

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