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Globalization, Biosecurity, and The Future of the Life Sciences 1 Framing the Issue In these early years of the 21st century, scientific discovery and understanding are playing an important and growing role in meeting the challenges—environmental, human health, economic—facing societies everywhere. At the forefront are advances in biology. Indeed, it is reasonable to say we are entering the Age of Biology, paralleling in many ways the Age of Physics in the first half of the 20th century.1 For many thousands of years, humans have been manipulating plant and animal stocks—first by accident and later selectively—to meet changing societal and environmental needs. But the discovery of the structure of DNA in 1953, followed by the invention of DNA recombinant technology two decades later, paved the way for the powerful potential to manipulate genes directly and in such a way that the “nature” of an organism can be altered with precision in a single generation. In 2001, scientists finished the initial draft of the human genome sequence, representing a shift in the way biology is studied and opening a portal to vast post-genomic possibilities—from RNA interference (RNAi) therapeutics to DNA nanotechnology. This rapid pace of technological growth in the life sciences research enterprise reflects a revolutionary change in the way people interact with biological systems and a growing capacity to manipulate such systems. Such advancing technologies offer great promise for improving the quality of human life: promoting health, preventing disease, and ensuring adequate food and even the possibility of new energy sources. However, as with all technological advances, there is a potential dark side, the ability for these technologies to be used, either purposefully or negligently, in ways that cause harm to humans. Devising optimal approaches for preventing this has been the overarching aim of this committee. This chapter provides an overview of recent growth in the life sciences and its associated technologies—with an emphasis on the rapid and shifting nature of this growth. It defines key terms that are used through-
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Globalization, Biosecurity, and The Future of the Life Sciences out this report and explores the broad-based nature of the threat posed by the rapid, unpredictable growth, and widespread dissemination of life sciences knowledge and associated technologies. This overview takes into account contemporary understanding of how naturally emerging pathogens cause disease and recently developed technologies that have opened up novel approaches to engineer potentially more harmful agents from both pathogenic and nonpathogenic microbes or viruses. In reviewing this material, the committee developed a heightened awareness of the tremendous potential of the benefits to be derived from the advancement of knowledge and technological growth in the life sciences. At the same time, committee members came to appreciate the magnitude of what hangs in the balance should society fail to address the potential for these technologies to be exploited to cause harm or, by overreacting and imposing unduly restrictive measures on activities in the life sciences, unwittingly muzzle the ability of the life sciences to contribute to future human good. COMMITTEE CHARGE AND PROCESS As discussed above and in more detail throughout the report, life sciences knowledge, materials, and technologies are advancing with tremendous speed, making it possible to identify and manipulate features of living systems in ways never before possible. On a daily basis and in laboratories around the world, biomedical researchers are using sophisticated technologies to manipulate microorganisms in an effort to understand how microbes cause disease and to develop better preventative and therapeutic measures against infectious disease. Plant biologists are applying similar tools in their studies of crops and other plants in an effort to improve agricultural yield and explore the potential for the use of plants as inexpensive platforms for vaccine, antibody, and other product manufacturing. Similar efforts are underway with animal husbandry. Scientists and engineers in many fields are relying on continuing advances in the life sciences to identify pharmaceuticals for the treatment of cancer and other chronic diseases, develop environmental remediation technologies, improve biodefense capabilities, and create new materials. Moreover, other fields not traditionally viewed as biotechnologies—such as materials science, information technology, and nanotechnology—are converging with biotechnology in unforeseen ways and thereby enabling the development of previously unimaginable technological applications. It is undeniable that this new knowledge and these advancing technologies hold enormous potential to improve public health and agriculture, strengthen national economies, and close the development gap between resource-rich and resource-poor countries. However, as with all scientific revolutions, there is a potential dark side to the advancing
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Globalization, Biosecurity, and The Future of the Life Sciences power and global spread of these and other technologies. Every major new technology has been used for hostile purposes, and many experts believe it is naive to think that the extraordinary growth in the life sciences and its associated technologies might not be similarly exploited for malevolent purposes.2 This is true despite formal prohibitions against the use of biological weapons and even though, since antiquity, humans have reviled the use of disease for hostile purposes. In its most recent unclassified report on the future global landscape, the National Intelligence Council argued that, although most future (i.e., over the course of the next 15 years) terrorist attacks are expected to involve conventional weapons, a bioterrorist attack will likely occur by 2020.3 Official U.S. statements continue to cite around a dozen countries that are believed to have or to be pursuing biological weapons capabilities.4 The threat of bioterrorism, coupled with the global spread of expertise in biotechnology and biological manufacturing processes, raises concerns about how this advancing technological prowess could enable the creation and production of new biological weapons and agents of biological terrorism possessing unique and dangerous but largely unpredictable characteristics. The Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare Threats, an ad hoc committee of the National Research Council and the Institute of Medicine, was constituted to examine current trends and future objectives of research in the life sciences, as well as technologies convergent with the life sciences enterprise from other disciplines, such as materials science and nanotechnology, that may enable the development of a new generation of biological threats over the next five to ten years, with the aim of identifying ways to anticipate, identify, and mitigate these dangers. As part of its study, the committee convened a workshop in September 2004 at the Instituto Nacional de Salud Pública (National Institute of Public Health) in Cuernavaca, Mexico. The purpose of this information gathering workshop was to sample global perspectives on the current advancing technology landscape. Experts from different fields and from around the world presented their diverse outlooks on advancing technologies and forces that drive technological progress; local and regional capacities for life sciences research, development, and application (both beneficial and nefarious); national perceptions and awareness of the risks associated with advancing technologies; and strategic measures that have been taken or could or should be taken to address and manage the potential misapplication of technology(ies) for malevolent purposes. The results of this workshop helped inform the committee as it developed this report.
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Globalization, Biosecurity, and The Future of the Life Sciences The committee was charged to: Examine current scientific trends and the likely trajectory of future research activities in public health, life sciences, and biomedical and materials science that contain applications relevant to the development of “next generation” agents of biological origin 5 to 10 years into the future. Evaluate the potential for hostile uses of research advances in genetic engineering and biotechnology that will make biological agents more potent or damaging. Included in this evaluation will be the degree to which the integration of multiple advancing technologies over the next 5 to 10 years could result in a synergistic effect. Identify the current and potential future capabilities that could enable the ability of individuals, organizations, or countries to identify, acquire, master, and independently advance these technologies for both beneficial and hostile purposes. Identify and recommend the knowledge and tools that will be needed by the national security, biomedical science, and public health communities to anticipate, prevent, recognize, mitigate, and respond to the destructive potential associated with advancing technologies. In interpreting its charge the committee sought to examine current trends and future objectives of research in public health and the life and biomedical sciences that contain applications relevant to the development of new types of biological weapons or agents of bioterrorism, with a focus on five to ten years into the future. It is recognized that the global technology landscape is shifting so dramatically and rapidly that any attempt by the committee to devise a formal risk assessment of the future threat horizon exploiting dual-use technologies by state actors, non-state actors, or individuals could be an exercise in futility. Given that within just the past few years the global scientific community has already witnessed the unexpected emergence of some remarkable new technologies, such as RNA interference and nanobiotechnology, biological threats in the next five to ten years could extend well beyond those that can be predicted today. Rather than a formal risk assessment, the committee has proposed a conceptual framework for how to think about the nature of the future threat landscape. Indeed, as the world becomes more competent and sophisticated in the biological sciences, it is vitally important that the national security, public health, and biomedical science communities have the necessary knowledge and tools to address the present and future applications of advances in the life sciences. This report is part of a larger body of work that the National Academies has undertaken in recent years on science and security and the contributions that science and technology could make to countering terror-
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Globalization, Biosecurity, and The Future of the Life Sciences ism, beginning with Scientific Communication and National Security in 1982 and continuing with Chemical and Biological Terrorism: Research and Development to Improve Civilian Medical Responses (1999), Firepower in the Lab: Automation in the Fight Against Infectious Diseases and Bioterrorism (2001), Making the Nation Safer: The Role of Science and Technology in Countering Terrorism (2002), Biological Threats and Terrorism: Assessing the Science and Response Capabilities (2002), and Countering Agricultural Terrorism (2002). Most recently, and of particular relevance to this report, is the National Research Council report Biotechnology Research in an Age of Terrorism (2004). The principal difference between that report and the present report is that the former revolves around issues pertaining to research oversight and the flow of scientific knowledge, with a focus on the United States, whereas this report adopts a more global perspective and broadly considers the use and applications of such knowledge. EMERGING TECHNOLOGIES IN THE LIFE SCIENCES Heralded by Science magazine as the 2002 “Breakthrough of the Year,”5 RNA interference (RNAi) has emerged as a promising therapeutic approach for the treatment of a wide range of diseases, including cancer.6 Yet just a year before it earned its breakthrough title, RNAi was met with doubt and criticism.7 RNAi therapy involves using small interfering RNA molecules (siRNAs) to cleave and destroy sequence-specific RNA and, in so doing, silence endogenous genes that participate in the pathway of human disease. The technology is expected to prove particularly valuable in cases where the targeted RNA encodes genes and protein products with activities that cannot be modulated today by conventional drugs. Several recent experiments indicate that investigators are well on their way to overcoming the clinical challenges of delivering effective RNAi therapy.8 In October 2004, Acuity Pharmaceuticals (Philadelphia, PA) announced that it was beginning a Phase I clinical trial of an investigational drug known as Cand5, making Cand5 the first RNAi therapeutic to enter clinical trial. Cand5 is an siRNA that turns off the expression of proteins contributing to vision loss in patients with age-related macular degeneration. In addition to its therapeutic applications, RNAi has emerged as a key basic research tool for use in functional genomics; by blocking the expression of a particular gene, one can create a phenotype that yields clues about the function of that gene. RNAi technology is forecast to grow at an annual average rate of just over 30 percent between 2003 and 2010.9 Although European and U.S.-based companies currently dominate the market (i.e., there are about 50 U.S. and European companies active in the RNAi market, most of their revenues coming from RNAi reagents and
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Globalization, Biosecurity, and The Future of the Life Sciences research tools),10 this may change over the course of the next several years as Asian companies begin specializing in RNAi applications. Touted alongside RNAi in Massachusetts Institute of Technology’s (MIT) 2004 Technology Review as one of the top 10 emerging technologies that “will change your world,” synthetic biology is the assemblage of gene networks—or circuits (i.e., analogous to silicon circuits)—that can guide the construction of novel, synthetic proteins and direct cells to perform assigned tasks.11 By assembling genes into circuits that direct cells to perform assigned tasks, synthetic biologists have taken genetic engineering to a level so profoundly different from recombinant technology that, in an October 2004 Nature news article, the latter was referred to as “old hat.”12 DNA synthesis applications are now largely limited to places like the MIT’s Independent Activities Period (IAP) course, where students design DNA circuitry, send their designs via the Internet to Blue Heron Biotechnology, Inc. (Bothell, WA), and then introduce the resulting synthetic DNA molecules into E. coli strains.13 Because it is in its early growth phase, the future industrial potential of synthetic biology is unclear.14 Meanwhile, research scientists are using the technology to design unique genomes and test novel hypotheses and models. In just five years, nanotechnology has catapulted from being a specialty of a handful of physicists and chemists to a worldwide scientific and industrial enterprise.15 The U.S. government estimates that the nanotech economy will be worth $1 trillion by 2012, and the White House recently requested $1 billion for fiscal 2006 to develop nanotechnology (up from $442 million in 2001). In April 2005, the National Academies Keck Futures Initiative announced that it had awarded a total of $1 million to 14 interdisciplinary research projects in nanoscience and nanotechnology. The awards, which are considered seed money to allow recipients to develop research approaches and position themselves competitively for other project funding, will be used for a variety of projects ranging from an examination of the interactions of nanoparticles with biosystems to the development of a new approach for capturing solar energy. Nanoparticles are already being used in a variety of commercial products, like sunscreen, paint, inkjet paper, stain-resistant trousers, and highly durable engine parts.16 Some industry analysts predict that by lowering drug toxicity and the cost of treatment (among other benefits), nanotechnology-enabled drug delivery systems will probably be among the first biomedical markets to evolve and to provide significant business revenue opportunities.17 For example, Elan Corporation (Dublin, Ireland) has developed a proprietary technology known as NanoCrystal, which transforms poorly water-soluble drugs into nanometer-sized particles that can be used to create any of a variety of more soluble common dosage forms for both parenteral and oral administration. There are sev-
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Globalization, Biosecurity, and The Future of the Life Sciences eral NanoCrystal-based therapeutics already on the market or in development.18 Nanobiotechnology—also known as DNA nanotechnology—refers to the convergence of nanotechnology with molecular biology.19 In fact, most of the examples in the preceding paragraph fall within its domain. Nanobiotechnology and nanobiotech start-up companies constitute nearly 50 percent of the venture capital invested in nanotechnology.20 Scientists are increasingly reporting discoveries with implications for potential applications of nanobiotechnology. For example, in January 2005, in a paper published in Physical Review Letters, researchers from the University of California, Los Angeles, described a nanoscale mechanism for externally controlling protein function, a technological advance that could ultimately lead to a generation of targeted “smart” drugs that are active only when certain DNA is present or a certain gene is expressed.21 In February 2005, in a paper published in the Proceedings of the National Academy of Sciences, Northwestern University researchers described a nanoparticle-based assay for detecting the onset of Alzheimer’s disease.22 Also in February 2005, an Illinois-based company, Nanosphere, Inc., announced plans to expand and market the application of the same assay to a variety of other diseases, including cancer.23 While new tools, like RNAi therapeutics and nano-based drug delivery are emerging, already proven tools such as the polymerase chain reaction (PCR) and DNA sequencing, are becoming more versatile, more affordable, and faster. For example, real-time, or quantitative PCR (qPCR), which is arguably one of the fastest growing PCR technologies, allows users to quantitatively monitor the amplification process as copies of DNA accumulate (unlike “traditional” PCR, which provides only an end product, a “yes/no” answer, and a qualitative measure of the abundance of the target material).24 In 2004, the least expensive qPCR thermocycler on the market was listed in the mid-$20,000 range. In spring 2005, Bio-Rad Laboratories (Hercules, CA) launched a “personal” qPCR machine that sells for about $16,500 and is one of the smallest machines on the market (i.e., in terms of size and the number of samples it can accommodate). Moreover, it should not be forgotten that PCR itself was not widely anticipated before its arrival on the scene.25 And it is instructive to remember how it developed, first as a relatively straightforward concept in which DNA synthesis was recycled through a series of cyclic thermal manipulations.26 This resulted in a doubling of the product each thermal cycle with an exponential amplification of the product over many thermal cycles of annealing, extension, and denaturation, with the DNA polymerase enzyme being destroyed during the denaturation step. However, it was not until a thermally-resistant DNA polymerase was isolated from nature that the process became widely available and widely utilized.
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Globalization, Biosecurity, and The Future of the Life Sciences Now PCR is as indispensable a “tool” for many 21st-century biologists as a microscope was to a 19th-century microbe hunter. Its impact on accelerating the velocity of life sciences research is readily appreciated by anyone in the field, as most biotechnologists today would have difficulty accomplishing their aims without this technique. Its importance overall to the life sciences is reflected in the relatively unusual actions of the Norwegian Nobel Committee, conferring its award on the inventor of PCR, Kary Mullis, only a few years after the technique was first reported. Parallels to the thinking that went into PCR are seen today in an unrelated field—the investigation of spongiform encephalopathies, like “mad cow disease,” where an analogous cycling technique has been reported recently for in vitro amplification of prions, putative infectious agents that lack genes (i.e., DNA or RNA) and that consist of a protein with “infectious” capacity to initiate misfolding of similar proteins.27 This series of events in the development of PCR recapitulates a theme in the life sciences: the sudden arrival of a new technique, followed by its technological exploitation, further refinement, and subsequent extension to other related fields. Similar scenarios have accompanied the discovery of restriction endonucleases and the development of recombinant DNA, and are unfolding now with RNAi technology or recently described multiplex DNA synthesis capabilities. The speed of DNA sequencing, DNA synthesis, and protein structural analysis—each a different measure of biotechnological power—has increased practically exponentially over the past 15 years.28 Indeed, progress in the life sciences, rather than being “linear,” is often marked by periodic and unpredictable major breakthroughs in our understanding of the living world that consequently radically transforms the growth and development of advances in disparate disciplines.29 At present, the 10 plant and animal genomes and the approximately 100 microbial genomes that are sequenced every year are done so, largely, at a small number of factory-like DNA sequencing centers. It has been estimated that if technological developments continue to improve the efficiency of DNA sequencing as they have up to this point, by 2010 a single lab worker will be able to sequence (or synthesize) about 1010 bases in one day (there are 3 × 109 bases in the human genome).30 The future of DNA synthesis is likely to follow a similarly rapid trajectory, with scientists being able to synthesize complete microbial genomes by 2010 if not sooner.31 In December 2004 Harvard University’s George Church and colleagues published an article in Nature describing a new microchip-based technology for the multiplex synthesis of long oligonucleotides.32 The researchers used the new technology to synthesize all 21 genes that encode proteins of the E. coli 30S ribosomal subunit. This technological advance is coupled with falling prices. In 2000, sequence
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Globalization, Biosecurity, and The Future of the Life Sciences FIGURE 1-1 The plunging cost of DNA sequencing has opened new applications in science and medicine. SOURCE: Reprinted with permission. Service, RF. 2006. Gene sequencing: The race for the $1,000 genome. Science 311(5767):1544-1546. Available online at www.sciencemag.org/cgi/content/full/311/5767/1544. assembly cost about $10 to $12 per base pair. By the beginning of 2005, the cost had dropped to about $2 per base pair (e.g., Blue Heron offers a special price of $1.60 for new customers33), and it is expected to fall to 1 cent per base pair within the next couple of years34 (see Figure 1-1). This has had real and practical consequences. For example, when the first successful autonomously replicating RNA replicons for hepatitis C virus were described by the Bartenschlager laboratory in 1999,35 several other groups immediately synthesized the entire ~7,000 nucleotide-long complementary DNA sequence of this RNA so as to be able to access this technology. De novo chemical synthesis was judged to be a more rapid, or less expensive means to acquire the technology than working through Materials Transfer Agreements, etc., with those who first described the replicons. The DNA synthetic “muscle” for this was readily available on a
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Globalization, Biosecurity, and The Future of the Life Sciences contract basis, even five years ago. Such an exercise would be trivial today, however, given recent advances in DNA synthetic capacities.36 Similar predictions about feasibility, rapidity, and affordability can be made for the structural analysis of proteins and other biologically important molecules. It is not unreasonable to expect that, before long, scientists will develop and have access to computer programs that simulate in detail the molecular processes in cells, so that the interaction of cells with pathogenic microbes and molecules can be fully anticipated and understood. Notable Features of Technological Growth in the Life Sciences Technological growth in the life sciences is characterized by several notable features. These are critically important to recognize if a reasonable estimate is to be made of what is or is not possible in predicting its future. First, as described above, progress in biology has been marked repeatedly by successive serendipitous discoveries and applications that over time have lead to the widespread adoption of new technologies with independent scientific and economic impacts. Indeed, the rapid growth of bio- and other relevant technologies over the past 30 years has been driven by two processes working together: a quantitative increase in performance coupled with a decrease in the cost of existing technologies (such as template independent DNA synthesis) and instruments, as explained in the previous section, and sudden and occasionally dramatic qualitative changes (paradigm shifts) resulting from unanticipated new inventions, unexpected discoveries, and insights, all of which may be significantly enhanced by the occurrence of unforeseen, historically significant events that impact significantly on human society and its everyday concerns. In addition to recombinant DNA technology (which sparked the biotech revolution back in the 1970s), prominent new inventions and discoveries in recent history include PCR (i.e., which originated in the mid-1980s as described above), the transfer of nuclei from cell to cell (i.e., cloning, also known as somatic cell nuclear transfer, or SCNT), the advent of RNAi technology (as described above), and the introduction of new techniques for parallel DNA synthesis capable of greatly accelerating the rate at which genes can be created de novo. New inventions and discoveries like these are a precondition for the rapid growth of technology. They result in the capacity to reduce the development costs associated with new and potentially very useful products, such as the recombinant hepatitis B vaccine, one of the early “fruits” of the recombinant DNA era, or to genetically engineer crops with intrinsic resistance to pests. Equally important, however, are both public and political support for
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Globalization, Biosecurity, and The Future of the Life Sciences these efforts. Such support can, in turn, drive the availability of government or venture capital funding required to fuel the advancement of research and development activities in the life sciences. Current levels of government support in the life sciences can be attributed in part to unforeseen historical events, such as the political decision to declare a “war on cancer” in the 1970s, the occurrence of the HIV/AIDS pandemic in the 1980s, and the 2001 anthrax mailings, which, in part, contributed to the current “war on terror.” On the other hand, the public perception of risks can readily derail the expansion of this technology, as evidenced by the impact of the “green” movement in Europe on the acceptance of genetically engineered crops by the public. This constantly changing and rapidly growing global technological landscape, marked as it is by the seemingly stochastic arrival of new paradigm-shifting concepts, makes it extremely difficult, if not impossible, to predict specific future trends. Just a year before it earned its “Breakthrough of the Year” title by Science magazine,37 RNAi was met with doubt and criticism. Self-assembling nano-devices, such as the DNAzyme (a device that can bind and cleave RNA molecules one by one) developed in 2004 by Purdue University researcher Chengde Mao, were unimaginable just a couple of years ago.38 About the only thing one can predict is that the life sciences will continue to advance quickly, in a variety of directions, and that new and previously unanticipated paradigm shifts are very likely to occur in the future. Second, as difficult as it is to predict what kind of technological or scientific breakthroughs might occur next, it is practically impossible to know where in the world these breakthroughs might happen. As discussed in greater detail in Chapter 2 of this report and in an earlier workshop summary report from this committee, a number of countries around the world are investing heavily in life sciences technologies.39 Indeed, several countries that are not commonly viewed as being technologically sophisticated, or that have not been considered technologically savvy in the past, are making remarkable progress in biotechnology and are well-positioned to become regional or global leaders in the near future. Importantly, the rapid global dispersion of life sciences materials, knowledge, and technologies is not limited to technologies with proven therapeutic and market value. While India is currently strong in generic and bulk biopharmaceutical manufacturing, several factors, including its growing technological expertise and its 2005 accession to the World Trade Organization, are contributing to its greater capacity for innovation and research and development of novel products. South Korea is rapidly gaining global prominence for its breakthrough contributions to stem cell research, although some of these “breakthroughs” are now in dispute.40 Meanwhile, Singapore has identified biotechnology as a central pillar of its fu-
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Globalization, Biosecurity, and The Future of the Life Sciences 20 Paull, R. et al. 2003. Investing in nanotechnology. Nature Biotechnology 21(10):1144-1147. 21 Choi, B. et al. 2005. Artificial allosteric control of maltose binding protein. Physical Review Letters 94(3):038103. 22 Georganopoulou, D.G. et al. 2005. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proceedings of the National Academy of Sciences 102 (7):2273-2276. 23 www.nanosphere-inc.com/3_media/1_pr/020105.html [accessed February 23, 2005]. 24 First described in the mid-1980s, PCR has become the workhorse of biological laboratories worldwide. Researchers and clinicians use the technology to multiply, or copy, specific regions of genomes for use in various types of downstream analyses (e.g., to detect the presence of a specific DNA sequence). 25 Mullis, K. 1990. The unusual origin of the polymerase chain reaction. Scientific American 262(4):56-61 and 64-65. 26 Saiki R.K., et al. 1985. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230(4732):1350-1354; Saiki R.K., et al. 1986. Analysis of enzymatically amplified beta-globin and HLA-DO alpha DNA with allele-specific oligonucleotide probes. Nature 324(6093):163-166. 27 Castilla, J. et al. 2005. In vitro generation of infectious scrapie prions. Cell 121(2):195-206. 28 Carlson, R. 2003. The pace and proliferation of biological techniques. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 1(3):1-12. 29 Eldredge, N. and S.J. Gould. 1972. Punctuated equilibria: An alternative to phyletic gradualism. Models in Paleobiology. Throughout most of the last century, researchers developing the synthetic theory of evolution primarily focused on microevolution, which is slight genetic change over a few generations in a population. Beginning in the early 1970s, this model was challenged by Stephen J. Gould, Niles Eldredge, and other leading paleontologists. They asserted that there is sufficient fossil evidence to show that some species remained essentially the same for millions of years and then underwent short periods of very rapid, major change. Gould suggested that a more accurate model in such species lines would be punctuated equilibrium. 30 Carlson, R. 2003. The pace and proliferation of biological techniques. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 1(3):1-12. 31 Craig Venter, briefing to the NSABB, Bethesda, MD on July 1, 2005. Reviewer “J” states that “According to John Mulligan, CEO of Blue Heron Biotechnology, his company has already received a proposal to synthesize a complete bacterial genome. This is technologically feasible at Blue Heron today, which means that the year 2010 may be far too conservative.” 32 Tian, J. et al. 2004. Accurate multiplex gene synthesis from programmable DNA microchips. Nature 432(7020):1050-1054. Available online at www.nature.com/nature/journal/v432/n7020/pdf/nature03151.pdf. [accessed January 4, 2006]. 33 www.blueheronbio.com/ [accessed January 14, 2005]. 34 In the next 5 years the net price for long fragments of chemically synthesized DNA seems *very* unlikely to (i.e., will not) drop below $0.10 per base pair. The
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Globalization, Biosecurity, and The Future of the Life Sciences $0.01 per base pair number might become possible for the synthesis process itself, but the synthesis number does not include ancillary costs for essential things like handling of intermediate and final materials, sequence verification, and so on. 35 Lohmann, V. et al. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285(5424):110-113. Available online at www.sciencemag.org/cgi/reprint/285/5424/110.pdf [accessed January 4, 2006]. 36 Tian, J. et al. 2004. Accurate multiplex gene synthesis from programmable DNA microchips. Nature 432(7020):1050-1054. Available online at www.nature.com/nature/journal/v432/n7020/pdf/nature03151.pdf [accessed January 4, 2006]. 37 Couzin, J. 2002. Breakthrough of the year: small RNAs make big splash. Science 298(5602):2296-2297. Available online at http://www.sciencemag.org/cgi/reprint/298/5602/2296.pdf [accessed January 4, 2006]; 10 emerging technologies that will change your world,” Technology Review (February 2004). Available online at www.lib.demokritos.gr/InTheNews/emerging0204.htm [accessed January 4, 2006]. 38 Chen, Y. and C. Mao. 2004. Putting a brake on an autonomous DNA nanomotor. Journal of the American Chemical Society 126:8626-8627; Institute of Medicine/National Research Council. 2005. An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risks. Washington, DC: The National Academies Press: 49-52. 39 Institute of Medicine/National Research Council. 2005. An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risks. Washington, DC: The National Academies Press. 40 Normile, D., G. Vogel, and C. Holden. 2005. Stem cells: Cloning researcher says work is flawed but claims results stand.” Science 310(5756):1886-1887. Available online at www.sciencemag.org/cgi/reprint/310/5756/1886.pdf [accessed January 4, 2006]. 41 Institute of Medicine/National Research Council. 2005. An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risks. Washington, DC: The National Academies Press. 42 Berg, C. et al. 2002. The evolution of biotech. Nature Reviews. Drug Discovery 1(1):845-846. 43 www.bio.org 44 Wheelis, M. 2002. Biotechnology and biochemical weapons. The Nonproliferation Review 9(1):48-53. Available online at cns.miis.edu/pubs/npr/vol09/91/91whee.htm [accessed January 4, 2006]. 45 Of course, there might be an equivalent concern raised by companies holding this information. 46 Carlson, S. 2000. The Amateur Scientist: PCR at Home. Scientific American (July). 47 The definition of a bioweapon, while meant to be inclusive, does not extend to nuclear weapons or devices. 48 It should be noted that in a precedent that is quite informative for attempts described later in the report to introduce codes of ethics and conduct for biological scientists, computer “hacking” is coming to stand for activities that are remotely done to computers and networks without the consent of those who own and oper-
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Globalization, Biosecurity, and The Future of the Life Sciences ate those machines and networks, regardless of motivation. The Information Technology community is working to develop an ethic that this is not acceptable, even if there is no malice involved. Some such activity may be playful, or pranks, or done without malice; other hacking causes massive damage without any real intent to do so, and still other such activity is intended to, and succeeds at, causing real damage. But all are illegitimate. 49 “Human security” means to protect the vital core of all human lives in ways that enhance human freedoms and human fulfillment … [by] creating political, social, environmental, economic, military and cultural systems that together give people the building blocks of survival, livelihood and dignity. From United Nations Commission on Human Security. 2003. Human Security—Now. Available at www.humansecurity-chs.org/finalreport/English/FinalReport.pdf [accessed February 27, 2006]. 50 One of the earliest recorded instances of biological warfare occurred in 600 BC, when the Athenian leader Solon used the noxious roots of the Helleborus plant to poison the water supply in the city of Kirrha. Later, the Greeks and Romans may have used human and animal corpses to poison drinking water wells. And Alexander the Great is thought to have catapulted dead bodies over the walls of besieged cities, possibly as a means of spreading disease and inciting terror among the urban inhabitants. A related technique, used in the Middle Ages, was to deliberately leave dead human or animal corpses behind, in areas that would be occupied shortly by invading troops; catapults were used as well. For further details about these and other later examples of germ-based warfare, including allegations that U.S. government agents deliberately infected the Plains Indians in the 1800s by trading with the Indians smallpox-laden blankets, see National Research Council. 2004. Biotechnology Research in an Age of Terrorism. Washington, DC: The National Academies Press: 34-35. 51 Stockholm International Peace Research Institute (SIPRI). 1971. The Rise of CB Weapons. Vol 1. In: The Problem of Chemical and Biological Warfare. New York: Humanities Press. 52 Wheelis, M. 1999. Biological sabotage in World War I. in Geissler E. and J.E. Van Courtland Moon, eds. 1999. Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945. SIPRI Chemical and Biological Warfare Studies 18 London: Oxford University Press; 52. 53 Redmond, C. et al. 1998. Deadly relic of the great war. Nature 393(6687):747-748. 54 Geissler, E., and J.E. Van Courtland Moon, eds. 1999. Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945. SIPRI Chemical and Biological Warfare Studies 18 London: Oxford University Press. 55 Bernstein, B. 1988. America’s biological warfare program in the Second World War. Journal of Strategic Studies 11(September): 292-317, especially 304 and 308-310. In addition to Bacillus anthracis and Clostridium botulinum, pathogens studied at Camp Detrick included the causative agents of: glanders; brucellosis; tularemia; melioidosis; plague; smallpox; psittacosis; coccidiomycosis; a variety of plant pathogens including the causative agents for rice blast; rice brown spot disease; late blight of potato; and cereal stem rust. Animal and avian pathogens studied included rinderpest virus, Newcastle disease virus, and fowl plague virus. The
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Globalization, Biosecurity, and The Future of the Life Sciences Problem of Chemical and Biological Warfare, SIPRI I, London: Oxford University Press, 1971:122. See also Cochrane, R.C. 1947. Biological Warfare Research in the United States. In History of the Chemical Warfare Service in World War II (1 July 1940-15 August 1945), Vol. II (declassified). Historical Section, Office of Chief, Chemical Corps. 56 U.S. Department of the Army. 1977. U.S. Army Activity in the U.S. Biological Warfare Programs I. (unclassified) February 23:1-3. 57 See Williams, P. and D. Wallace. 1989. Unit 731: The Japanese Army’s Secret of Secrets. London: Hodder and Stoughton: 280-281; and Harris, S.H. 1994. Factories of Death: Japanese Biological Warfare, 1932-45, and the American Cover-Up. London: Routledge. 58 Ibid. 59 At least 3,000 people, including Chinese civilians, Russians, Mongolians and Koreans, died in the experiments between 1939 and 1945, Chinese state media have said. Outside the site, more than 200,000 Chinese were killed by biological weapons produced by Unit 731, they said. (Reuters, July 18, 2005) 60 Guilleman, J. 2001. Anthrax: The Investigation of a Deadly Outbreak. Berkeley and Los Angeles, CA: University of California Press. 61 Meselson, M. et al. 1994. The Sverdlovsk anthrax outbreak of 1979. Science 266(5188):1202-1208; Meselson, M. 2001. Note regarding source strength. The ASA Newsletter 87:1, 10-12. 62 Dimitri Vladimir Pasechnik was a Soviet microbiologist whose defection to Britain in 1989 disclosed the fact that Moscow’s germ warfare programme was 10 times greater than previously feared in the West. See portal.telegraph.co.uk/news/main.jhtml?view=DETAILS&grid=&targetRule=5&xml=/news/2001/11/29/db2903.xml. 63 Kelly, D.C. The trilateral agreement: Lessons for biological weapons verification. In Finlay, T., and O. Meier, eds. 2002. Verification Yearbook 2002. London: VERTIC: 93-109; Domaradskij, I.V. and W. Orent. 2003. Biowarrior: Inside the Soviet/Russian Biological War Machine. Amherst, NY: Prometheus Books. 64 Alibek, K. and S. Handelman. 1999. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from the Inside by the Man Who Ran It. New York: Random House. 65 For personnel numbers, see Leitenberg, M. 1993. The Conversion of Biological Warfare research and Development Facilities to Peaceful Uses. in Control of Dual-Use Threat Agents: The Vaccines for Peace Programme, SIPRI Chemical and Biological Warfare Series, 15 London, Oxford University Press. For the environmental impacts associated with biological weapons field testing, see Choffnes, E. 2001. Germs on the Loose. The Bulletin of the Atomic Scientists 57(March/April):57-61; Alibek, K. and S. Handelsman. 1999. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from the Inside by the Man Who Ran It. New York: Random House. The Soviet military had tested smallpox. Although Moscow has denied that it ever conducted open-air testing of smallpox, a detailed report prepared by the Monterey Institute of International Studies Center for Nonproliferation Studies asserts that the former Soviet Union did conduct such tests on Vozrozhdeniye Island. For more on this program, see Bozheyeva, G., Y. Kunakbayev, and D.
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Globalization, Biosecurity, and The Future of the Life Sciences Yeleukenov. 1999. Former Soviet Biological Facilities in Kazakhstan: Past, Present and Future. Center for Nonproliferation Studies, Monterey Institute of International Studies: 6. 66 Alibek, K. and S. Handelsman. 1999. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from the Inside by the Man Who Ran It. New York: Random House. 67 Gould, D. and P. Folb. 2002. Project Coast: Apartheid’s Chemical and Biological Warfare Programme. Geneva: UNIDR. See also Burgess S. and H. Purkitt. 2001. The Rollback of South Africa’s Chemical and Biological Warfare Program. USAF Counter Proliferation Center. Maxwell Air Force Base, AL: Air War College. 68 Institute of Medicine/National Research Council. 2005. An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risks. Washington, DC: The National Academies Press: 42-43. 69 Ibid. 70 Institute of Medicine. 2003. Microbial Threats to Health: Emergence, Detection, and Response. Washington, DC: The National Academies Press. 71 Institute of Medicine. 2003. Microbial Threats to Health: Emergence, Detection, and Response. Washington, DC: The National Academies Press. 72 Specter, M. 2005. Nature’s bioterrorist. The New Yorker (February 28):50-61. 73 For detailed discussions of antigenic drift and shift in influenza A virus, see Krug, R.M. 2003. The potential use of influenza virus as an agent for bioterrorism. Antiviral Research 57(1-2):147-150; and Wright, P.F. and R.G. Webster. 2001. Orthomyxoviruses. In: D.M. Knipe and P.M. Holwey eds, Field’s Virology 4th Ed. Philadelphia: Lippincott Williams & Wilkins: 1533-1579. 74 Influenza viruses are defined by two protein components on the virus surface: haemagglutinin (H) and neuraminidase (N). 75 Institute of Medicine. 2005. The Threat of Pandemic Influenza: Are We Ready? Washington, DC: The National Academies Press. 76 Ibid. 77 See www.who.int/csr/disease/avian_influenza/country/cases_table_2006_04_21/en/index.html, [accessed April 25, 2006]. 78 Chen, H. et al. 2004. The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences 101(28):10452-10457; Institute of Medicine. 2005. The Threat of Pandemic Influenza: Are We Ready? Washington, DC: The National Academies Press; Keawcharoen, J. et al. 2004. Avian influenza H5N1 in tigers and leopards. Emerging Infectious Diseases 10(12):2189-2191. Available online at www.cdc.gov/ncidod/EID/vol10no12/04-0759.htm [accessed March 17, 2005]. 79 Finlay, B.B. and S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiology and Molecular Biology Reviews 61(2):136–169. 80 Casadevall, A. and L-A. Pirofski. 1999. Host-pathogen interactions: redefining the basic concepts virulence and pathogenicity. Infection and Immunity 67(8):3703-3713. 81 Casadevall, A. and L-A. Pirofski. 1999. Host-pathogen interactions: redefining the basic concepts virulence and pathogenicity. Infection and Immunity. 67(8): 3703-3713; Falkow, S. 1997. What is a pathogen? ASM News 63:359–365; Finlay,
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Globalization, Biosecurity, and The Future of the Life Sciences B.B. and S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiology and Molecular Biology Reviews 61(2):136–169. 82 Savage, D.C. 1977. Microbial ecology of the gastrointestinal tract. Annual Reviews of Microbiology 31:107-133, as cited in Hooper, L.V. et al. 1998. Host-microbial symbiosis in the mammalian intestine: exploring an internal ecosystem. BioEssays 20(4):336-343; Bäckhed, F. et al. 2005. Host-bacterial mutualism in the human intestine. Science 307(5717):1915-1920; Buchanan, M. 2004. A billion bacteria brains are better than one. New Scientist (2474):34. 83 Bäckhed, F. et al. 2005. Host-bacterial mutualism in the human intestine. Science 307(5717):1915-1920. Also, Rakoff-Nahoum, S. et al. 2004. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118(2):229-241. The protective advantage of Lactobacillus spp. is being exploited in probiotic therapy—the administration of live, benign microbes, including genetically-engineered bacteria, that benefit the host and aid in the treatment of disease. Institute of Medicine. 2003. Microbial Threats to Health: Emergence, Detection and Response. Washington, DC: The National Academies Press; Hooper, L.V. and J.I. Gordon. 2001. Commensal host-bacterial relationships in the gut. Science 292(5519):115-1118; Gionchetti, P. et al. 2000. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119(2): 305-309; Cunningham-Rundles, S. and M. Nesin. 2000. Bacterial infections in the immunocompromised host. In Nataro, J., Blaser, M., Cunningham-Rundles, S., eds. Persistent Bacterial Infections. Washington, DC: ASM Press: 145-163. See also, Rao et al. 2005. Toward a live microbial microbicide for HIV: Commensal bacteria secreting an HIV fusion inhibitor peptide. Proceedings of the National Academy of Sciences 102(34):11993-11998. 84 Blaser, M. 1997. Ecology of Helicobacter pylori in the human stomach.” Journal of Clinical Investigation 100(4):759–762; Merrell, D.S. and S. Falkow. 2004. Frontal and stealth attack strategies in microbial pathogenesis. Nature 430(6996):250-256. 85 Casadevall, A. and Pirofski, L-A. 2000. Host-pathogen interactions: Basic concepts of microbial commensalism, colonization, infection, and disease. Infection and Immunity 68(12):6511–6518; Pirofski, L-A. and Casadevall, A. 2002. The meaning of microbial exposure, infection, colonisation, and disease in clinical practice. Lancet Infectious Diseases 2(10):628–35; Casadevall, A. and Pirofski, L-A. 2003. The damage-response framework of microbial pathogenesis. Nature Reviews Microbiology 1(1):17-24. 86 Blaser, M. 1997. Ecology of Helicobacter pylori in the human stomach. Journal of Clinical Investigation 100(4):759–762. It may also be possible to produce more dangerous pathogens by intentionally or inadvertently disrupting this dynamic equilibrium. 87 Merrell, D.S. and S. Falkow. 2004. Frontal and stealth attack strategies in microbial pathogenesis. Nature 430(6996):250-256. 88 It should, however, be noted that severe disease or mortality enhances the transmissibility of some pathogens—eg., intestinal pathogens (Vibrio cholera, Bacillus anthracis) and host mortality may provide food for others. 89 Merrell, D.S. and S. Falkow. 2004. Frontal and stealth attack strategies in microbial pathogenesis. Nature 430(6996):250-256; Mascie-Taylor, C.G. and E. Karim. 2003. The burden of chronic disease. Science 302(5652):1921-1922.
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Globalization, Biosecurity, and The Future of the Life Sciences 90 Blaser, M. 1997. Ecology of Helicobacter pylori in the human stomach. Journal of Clinical Investigation 100(4):759–762. 91 Staskawicz, B. et al. 2001. Common and contrasting themes of plant and animal diseases. Science 292(22):2285-2289. 92 Plotnikova, J.M. et al. 2000. Pathogenesis of the human opportunistic pathogen Pseudomonas aeruginosa PA14 in arabidopsis. Plant Physiology 124(4):1776-1774; Woolhouse, M.E. et al. 2001. Population biology of multihost pathogens. Science 292(5519):1109-1112. 93 Reeve, J.N. 1999. Archaebacteria then…Archaes now (are there really no archaeal pathogens?). Journal of Bacteriology 181(12):3613-3617; Eckburg, P.B. et al. 2003. Archaea and their potential role in human disease. Infection and Immunity 71(2):591–596. 94 Lepp, P.W. et al. 2004. Methanogenic Archaea and human periodontal disease. Proceedings of the National Academy of Sciences 101(16):6176-6181. 95 Worobey, M. 2000. Extensive homologous recombination among widely divergent TT viruses. Journal of Virology 74(16):7666-7670. Available online at www.cdc.gov/ncidod/EID/vol10no12/04-0759.htm [accessed January 4, 2006]. 96 Shimono, N. et al. 2003. Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon. Proceedings of the National Academy of Sciences 100(26):15918; Foreman-Wykert, A. and Miller, J.F. 2003. Hypervirulence and pathogen fitness. Trends in Microbiology 11(3):105-108. 97 Mouslim, C. et al. 2002. Conflicting needs for a Salmonella hypervirulence gene in host and non-host environments. Molecular Microbiology 45(4):1019-1027. 98 Lorange, E.A., et al. 2005. Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis. Journal of Infectious Diseases 191(11):1907-1912. 99 The Committee recognizes that virulence can evolve to increase or decrease in a pathogen, in response to specific circumstances, such as how the pathogen is transmitted from person to person. 100 Kagan, E. 2001. Bioregulators as instruments of terror. Clinics in Laboratory Medicine 21(3):607-618. See also, Wheelis, M. 2004. Will the new biology lead to new weapons? Arms Control Today 34(6):6-13. 101 Casadevall, A. and L-A. Pirofski, 1999. Host-pathogen interactions: redefining the basic concepts of virulence and pathogenicity. Infection and Immunity 67(8): 3703-3713; Ingham, H.R. and P.R. Sisson. 1984. Pathogenic synergism. Microbiol. Sci. 1(8):206-208; Janeway, C.A., C.C. Goodnow and R. Medzhitov. 1996. Immunological tolerance: danger—pathogen on the premises! Current Biology 6:519-522. For an easy to read guide on Polly Matzinger’s work on molecular “danger signals” see en.wikipedia.org/wiki/Polly_Matzinger. 102 Kagnoff, M.F. and Eckmann L. 1997. Epithelial cells as sensors for microbial infection. Journal of Clinical Investigation 100(1):6-10. 103 Bäckhed, F. et al 2005. Host-bacterial mutualism in the human intestine. Science 307(5717):1915-1920; Rakoff-Nahoum, S. et al. 2004. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118(2):229-241. 104 Kobayashi, K.S. et al. 2005. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 301(5710):731-734; Maeda, S., et al. 2005. Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-
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Globalization, Biosecurity, and The Future of the Life Sciences 1beta processing. Science 307(5710):734-738; Girardin, S.E. et al. 2003. Lessons from Nod2 studies: towards a link between Crohn’s disease and bacterial sensing. Trends in Immunology 24(12):652-658; Girardin, S.E. et al. 2003. Nod1 detects a unique muroopeptide from gram-negative bacterial peptidoglycan. Science 300(5625):1584-1587; Girardin, S.E. et al. 2003. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. Journal of Biological Chemistry 278(11): 8869-8872; Fiocchi, C. 1998. Inflammatory Bowel Disease: Etiology and Pathogenesis. Gastroenterology 115(1):182-205. 105 Nixdorff, K. and W. Bender. 2002. Ethics of university research, biotechnology and potential military spin-off. Minerva 40(1):15-35. 106 Proliferation: Threat and Response. Available online at www.defenselink.mil/pubs/prolif97/annex.html#technical [accessed February 24, 2005]. 107 Block, S. 1999. Living nightmares: Biological threats enabled by molecular biology. In Drell, S.D., A.D. Sofaer, and G.D. Wilson. 1999. The New Terror: Facing the Threat of Biological and Chemical Weapons. Stanford, CA: Hoover Institution Press: 39-75. 108 Krug, R.M. 2003. The potential use of influenza virus as an agent for bioterrorism. Antiviral Research 57(1-2):147-150. 109 Kobasa, D. et al. 2004. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 431:703-707. 110 Tumpey, T.M. et al. 2005. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310(5745):77-80; Taubenberger, J.K. et al. 2005. Characterization of the 1918 influenza virus polymerase genes. Nature 437(7060):889-893. Available online at www.nature.com/nature/journal/v437/n7060/full/nature04230.html [accessed January 4, 2006]. 111 Ibid. 112 Institute of Medicine/National Research Council. 2005. An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risks. Washington, DC: The National Academies Press; also Bokan, S. et al. 2002. An evaluation of bioregulators as terrorism and warfare agents. ASA Newsletter 02-3(90):1. Available online at www.asanltr.com/newsletter/02-3/articles/023c.htm [accessed January 4, 2006]; Kagan, E. 2001. Bioregulators as instruments of terror. Clinics in Laboratory Medicine 21(3):607-618. 113 In determining whether to list a biological agent, the Secretary of HHS, in consultation with scientific experts representing appropriate professional groups, is required to consider the agent’s effect on human health, its degree of contagiousness and methods by which the agent is transferred to humans, and the availability of immunizations and treatments for illnesses that may result from infection by the agent. The list was initiated in 1997, when the Antiterrorism and Effective Death Penalty Act of 1996 required the Secretary of HHS to establish and enforce safety procedures for the transfer of listed biological agents (select agents), including measures to ensure proper training and appropriate skills to handle such agents, and proper laboratory facilities to contain and dispose of such agents. An expanded list of pathogens and toxins went into effect on February 11, 2003. Agricultural plant and animal pathogens are now also included; other changes reflect taxonomic changes and a few reassessments of what constitutes the most dangerous biothreat agents.
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Globalization, Biosecurity, and The Future of the Life Sciences 114 See Table 2-2 in National Research Council. 2004. Biotechnology Research in an Age of Terrorism. Washington, DC: The National Academies Press; 54-57. 115 Our current biosafety system and select agents lists are mostly concerned with full systems or whole organisms. But as we start to construct new things via the combination of many functions in novel ways, the current scheme will not scale. Although beyond the scope of this study, governments and regulatory bodies may need to consider whether or not a biosafety system that is based at the “parts” level might be more useful. 116 Meselson, M. 2000. Averting the hostile exploitation of biotechnology. The CBW Conventions Bulletin.48(June): 16-19. 117 Information about current biological weapons capabilities summarized in Squassoni, S. 2004. Nuclear, biological, and chemical weapons and missiles: Status and trends. CRS Report for Congress, July 2 (RL30699); National Research Council. 2004. Biotechnology Research in an Age of Terrorism. Washington, DC: The National Academies Press. 118 See www.opbw.org/ [accessed October 28, 2004]. 119 Theodore Kaczynski, the Unabomber, was charged in 1998 with making and delivering four bombs that killed two men and maimed two scientists. In all, Mr. Kaczynski was alleged to have killed three people and injured 29, in 16 attacks between 1978 and 1995. See www.cnn.com/US/9805/04/kaczynski.sentencing/index.html [accessed January 4, 2006]. 120 Hacking the genome. 2003/2004; 2600 The Hacker Quarterly 20(4), Winter 2003/2004. 121 “National security experts and even … biologists themselves are concerned that rogue scientists could create new biological weapons—like deadly viruses that lack natural foes. They also worry about innocent mistakes: organisms that could potentially create havoc if allowed to reproduce outside the lab.”… [W]e live in an age that many tools and technologies can be turned into weaponry,” said Laurie Zoloth, a bioethicist at Northwestern University. “You always have the problem of dual use in every new technology.” See Elias, P. 2005. Light-sensitive bacteria used to create pictures:UCSF Scientists Make Living Film. Associated Press, November 24. Available online at www.montereyherald.com/mld/montereyherald/business/technology/13251114.htm?template=contentModules/printstory.jsp, [accessed January 4, 2006]. 122 Much of this discussion draws from Chyba, C.F. 2002. Toward biological security. Foreign Affairs 81(3):122-136; and Chyba, C.F. and A.L. Greninger. 2004. Biotechnology and bioterrorism: An unprecedented world. Survival 46(2):143-162. 123 Weapons of Mass Effect (i.e., truck bombs or hijacked airliners) are used, as Time magazine says, “to cause great loss of life and spread chaos and despair” among the populace. See www.worldnetdaily.com/news/article.asp?ARTICLE_ID=24804 [accessed June 14, 2005]. 124 Weiss, L. 2003. Atoms for peace. Bulletin of the Atomic Scientists November/December:34-44. 125 And because these nuclear materials advertise their presence by emitting various distinctive signatures as radioactive emissions from the source. 126 Many states attached reservations to their instruments of ratification that
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Globalization, Biosecurity, and The Future of the Life Sciences had the effect of making this protocol an agreement to only ban first use, not retaliation. 127 Chyba, C.F. and A.L. Greninger. 2004. Biotechnology and bioterrorism: An unprecedented world. Survival 46(2):143-162. For a more in-depth discussion of this point see, National Research Council. 2004. Biotechnology Research in an Age of Terrorism. Washington, DC: The National Academies Press. 128 Meselson proposal to make use of biological weapon a crime against humanity; A Draft Convention to Prohibit Biological and Chemical Weapons Under International Criminal Law. The Draft Convention and a discussion about the need for such a convention may be found at www.sussex.ac.uk/Units/spru/hsp/CRIMpreambleFeb04.htm [accessed January 4, 2006]. 129 It should be noted that a biological “arms race” is between protective measures and malevolent applications of potentially benevolent technologies, rather than between protective measures and offensive weapons programs. The protective technologies that are developed in such a competition are very unlikely to be classified (for all the reasons described) and hence may enable malicious applications of that same technology. This means that it is difficult for defensive applications to win, and bears on the question (which should be discussed to a greater extent) of whether defense can win an offense-defense competition. For a discussion of “can defenses run faster than offenses,” see the section with that name, 17-19 of Epstein, G.L. 2005. Global Evolution of Dual-Use Biotechnology: A Report of the Project on Technology Futures and Global Power, Wealth, and Conflict. Center for Strategic and International Studies. 130 Some of the implications of creating a regime of “sensitive” information are discussed in Epstein, G.L. 2001. Controlling biological warfare threats: Resolving potential tensions among the research community, industry, and the national security community. Critical Reviews in Microbiology, 27(4):321-354, especially pp. 347-348. This analysis was extended in a presentation given to the Committee on June 23, 2004 titled “Sensitive Information in the Life Sciences.” A presentation very similar to that one, and available online, was delivered at the International Forum on Biosecurity in Lake Como on March 21, 2005 and can be found online at www7.nationalacademies.org/biso/Biosecurity_Epstein_2.0.ppt [accessed January 4, 2006]. 131 Institute of Medicine/National Research Council. 2005. An International Perspective on Advancing Technologies and Strategies for Managing Dual-Use Risk. Washington, DC: The National Academies Press. 132 Daar, A.S. et al. 2002. Top 10 biotechnologies for improving health in developing countries. Nature Genetics 32:229-232. 133 We are mindful, however, that crops are indeed monocultures and thus exquisitely sensitive to epidemics of the next “new” fungus or virus; they usually require a lot of water (increasingly scarce in our world) and fertilizer (increasingly expensive and polluting); they are often disruptive of local social structures. As an exercise in practical GM crops, consider the lessons of Lansing, J. S. 1991. Priests and Programmers: Technologies of Power in the Engineered Landscape of Bali. Princeton, NJ: Princeton Univ Press. 134 Hoyt, K. and S.G. Brooks. 2003/2004. A double-edged sword. International Security 28(Winter):123-148.
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Representative terms from entire chapter: