Synthetic Biology And Emerging Threats
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Synthetic Biology And Emerging Threats
- 1. Synthetic Biology and Emerging Threats By Dave Moorer
- 2. Six Emerging Threats Binary Biological Weapons Designer Diseases Designer Genes Gene Therapy as a Weapon Stealth Viruses Host-swapping Diseases
- 3. Six Emerging Threats Binary Biological Weapons Combined can create e.coli bacteria increased virulence plasmid molecules
- 4. Six Emerging Threats Designer diseases Can turn off the immune system Could initiate programmed cell death
- 5. Six Emerging Threats Designer Genes Virtual Parts list: http://parts.mit.edu red floursecent protein (RFP) “BioBricks” green flourescent protein (GFP)
- 6. Six Emerging Threats Gene therapy as a weapon Retroviruses i.e. HIV/AIDS Cross-section of AIDS virus
- 7. Six Emerging Threats Stealth viruses Fairly common in nature Covertly enter human cells and remain dormant Varicella virus: can reactivate to cause oral lesions as herpes zoster
- 8. Six Emerging Threats Host-swapping diseases Diseases sometimes “jump species” Ebola & HIV Bat linked to Ebola Can have increased virulence Chimpanzee linked to AIDS
- 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. Trends in Terrorism Radical religious motivation: Local opposition to US hegemony and military presence in areas with no historical US presence: Amateur terrorists have little concern for self-preservation or detection: Racial and ethnic hatred:
- 11. Terrorist Organizations Inclined 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. Benefits of DNA Synthesis Carbon-neutral energy sources Consolidated bioprocessing
- 13. Benefits of DNA Synthesis Bio-based manufacturing “White Biotechnology”
- 14. Benefits of DNA Synthesis Engineering Specific Pathways Metagenomics
- 15. Benefits of DNA Synthesis Genome Design and Construction Mycoplasma genitalium first genome completed smallest known bacterial genome (482 protein-coding genes, 43 RNA genes) Map of mycoplasma genitalium
- 16. Benefits of DNA Synthesis Applied Protein Design Allows creation of protein-based drugs that can resist rapid degradation in the body
- 17. Benefits of DNA Synthesis Natural Product Synthesis Decreased time to construct and mutate genes Plant: Artemesia annua Artemesia annua (wormwood plant)
- 18. Benefits of DNA Synthesis Creation of Standardized Biological Parts and Circuits 167 basic parts, including sensors, actuators, input and output devices, and regulatory elements. 421 composite parts, and an additional 50 parts were in the process of being synthesized or assembled
- 19. Research Obstacles and Potential Risks Standardization: M.I.T. Standard Parts Registry Decoupling: “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.”- Drew Endy Abstraction: organizing information describing biological functions into “hierarchies” that operate at different levels of complexity
- 20. Research Obstacles and Potential Risks Increase in BSL-3 and BSL-4 labs since 9/11 U.S. Govt. unable to keep up with increased number of labs BSL-3 & BSL-4 labs only places dangerous pathogens can be worked on
- 21. Research Obstacles and Potential Risks Incidents at different labs Texas A&M lab: Worker exposed to pathogen Atlanta lab: Power outage UK lab: Foot and mouth disease release LLNL: Fined $450,000 for two separate shipping errors with anthrax, one release involving broken vials
- 22. Globalization and Biosecurity “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. Globalization and Biosecurity The U.S. strategy to reduce biological weapons threat comprises three tactics: Nonproliferation Counterproliferation Consequence Management (Defense)
- 24. Globalization and Biosecurity 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. Biological and Toxin Weapons Convention In 2001, President George W. Bush’s administration withdrew support from efforts to strengthen the cornerstone of the U.S. non-proliferation strategy, the Biological and Toxin Weapons Convention (BTWC), arguing that the draft verification protocol put forth at the Fifth Review Conference would not effectively limit proliferation
- 26. Vaccine Development and Supply Problems Of the 49 biological threat agents identified, the Federal Drug Administration (FDA) has licensed vaccines to protect against only four agents on the list (anthrax, cholera, plague, and smallpox). Joint Vaccine Acquisition Program (JVAP) allocated $747 million for development Laughed at by the pharmaceutical companies
- 27. Vaccine Development and Supply Problems Project Bioshield Act of 2004 (Project Bioshield) Allocates 5.6 billion over 10 years for development and purchase of medical countermeasures The “Special Reserve Fund” was provided in the FY2004 Department of Homeland Security Appropriations Act.
- 28. Policy Goals Enhancing biosecurity Fostering laboratory safety Protecting the environment
- 29. Policy Goals: 17 options for Governance Gene foundaries Oligo manufacturers DNA synthesizers Users and organizations
- 30. Gene Foundaries & Oligo Manufacturers Require commercial firms to use approved software for screening orders People who order synthetic DNA from commercial firms must be verified as legitimate users by an Institutional Biosafety Officer or similar “responsible official” Commercial firms are required to use approved screening software and to ensure that people who place orders are verified as legitimate users by a Biosafety Officer Require commercial firms to store information about customers and their orders
- 31. DNA Synthesizers Owners of DNA synthesizers must register their machines Owners of DNA synthesizers must be licensed A license is required to both own DNA synthesizers and to buy reagents and services
- 32. Users & Organizations Incorporate education about risks and best practices as part of university curricula Compile a manual for “biosafety in synthetic biology laboratories” Establish a clearinghouse for best practices Broaden Instituional Biosafety Committee (IBC) review responsibilities to consider risky experiments Broaden IBC review responsibilities and add oversight from a national advisory group to evaluate risky experiments Broaden IBC review responsibilities, plus enhance enforcement of compliance with National Institutes of Health biosafety guidelines
- 33. Conclusions Without a reliable vaccine source, responses to bioterrorism or accidents will result in mass casualties Programs like Project Bioshield need to rapidly develop, license and stockpile current vaccines Policymakers need to embrace globalization while writing pragmatic policies that hold users and organizations accountable for their actions
Hinweis der Redaktion
- 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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