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SUMMARY

INTRODUCTION

This document offers a summary of the substantive presentations during an international workshop, Trends in Science and Technology Relevant to the Biological and Toxin Weapons Convention, held 31 October – 3 November, 2010 at the Institute of Biophysics of the Chinese Academy of Sciences. It is meant to provide scientists and other technical experts with factual information about the range and variety of topics discussed at the workshop, which may be of interest to national governments and non-governmental organizations as they begin to prepare for the 7th Review Conference of the Biological and Toxin Weapons Convention (BWC) in 2011. The more extensive final report being prepared by an international committee under the auspices of the National Research Council (NRC) of the U.S. National Academy of Sciences (see below) will be published soon. The final report will incorporate the factual material contained in this summary, include additional detail about the “state of the science” for some of the topics covered by the workshop, discuss the potential implications of scientific advances for both the scope and operations of the BWC, and present the committee’s findings and conclusions.


The Beijing workshop reflected the continuing engagement by national academies, international scientific organizations, and individual scientists and engineers in considering the biosecurity implications of developments in the life sciences and assessing trends in science and technology (S&T) relevant to nonproliferation.1 The workshop was planned by an international committee appointed by the NRC and convened in collaboration with IAP – The Global Network of Science Academies, the International Union of Biochemistry and Molecular Biology (IUBMB), the International Union of Microbiological Societies (IUMS), and the Chinese Academy of Sciences. The statement of task for the project may be found in Box 1; the members of the committee, the workshop agenda, and the participant list are included in the Appendix to this summary.2

1

A discussion of previous engagement by the life sciences community can be found in Chapter 1 of the 2nd International Forum on Biosecurity: Report of an International Meeting, Budapest, Hungary, March 30-April 2, 2008 (NRC, 2009a) and a list of activities undertaken by national science academies and international scientific organizations is also available in Appendix C of Challenges and Opportunities for Education About Dual Use Issues in the Life Sciences (NRC, 2011a).

2

This material, as well as copies of many of the PowerPoint slides used by the speakers, is also available online at http://dels.nas.edu/Past-Events/Trends-Science-Technology-Relevant/DELS-BLS-09-06.



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SUMMARY INTRODUCTION This document offers a summary of the substantive presentations during an international workshop, Trends in Science and Technology Relevant to the Biological and Toxin Weapons Convention, held 31 October – 3 November, 2010 at the Institute of Biophysics of the Chinese Academy of Sciences. It is meant to provide scientists and other technical experts with factual information about the range and variety of topics discussed at the workshop, which may be of interest to national governments and non-governmental organizations as they begin to prepare for the 7th Review Conference of the Biological and Toxin Weapons Convention (BWC) in 2011. The more extensive final report being prepared by an international committee under the auspices of the National Research Council (NRC) of the U.S. National Academy of Sciences (see below) will be published soon. The final report will incorporate the factual material contained in this summary, include additional detail about the “state of the science” for some of the topics covered by the workshop, discuss the potential implications of scientific advances for both the scope and operations of the BWC, and present the committee’s findings and conclusions. The Beijing workshop reflected the continuing engagement by national academies, international scientific organizations, and individual scientists and engineers in considering the biosecurity implications of developments in the life sciences and assessing trends in science and technology (S&T) relevant to nonproliferation.1 The workshop was planned by an international committee appointed by the NRC and convened in collaboration with IAP – The Global Network of Science Academies, the International Union of Biochemistry and Molecular Biology (IUBMB), the International Union of Microbiological Societies (IUMS), and the Chinese Academy of Sciences. The statement of task for the project may be found in Box 1; the members of the committee, the workshop agenda, and the participant list are included in the Appendix to this summary.2 1 A discussion of previous engagement by the life sciences community can be found in Chapter 1 of the 2nd International Forum on Biosecurity: Report of an International Meeting, Budapest, Hungary, March 30- April 2, 2008 (NRC, 2009a) and a list of activities undertaken by national science academies and international scientific organizations is also available in Appendix C of Challenges and Opportunities for Education About Dual Use Issues in the Life Sciences (NRC, 2011a). 2 This material, as well as copies of many of the PowerPoint slides used by the speakers, is also available online at http://dels.nas.edu/Past-Events/Trends-Science-Technology-Relevant/DELS-BLS-09-06. 1

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2 TRENDS IN SCIENCE AND TECHNOLOGY BOX 1 STATEMENT OF TASK An ad hoc committee with significant international membership will be organized by the NRC to: • Plan an international workshop to survey key trends in areas of science & technology (S&T) that might be potentially relevant to the development of new or more deadly biological weapons and/or to developments in detection, diagnostics, therapeutics, or vaccines that could affect potential prevention and response to biological attacks. The developments in science discussed at the workshop are likely to be in areas such as immunology, neuroscience, synthetic biology, aerosol and other controlled delivery mechanisms, or others; the specific S&T areas and trends to be discussed during the workshop will be selected by the committee. • Prepare a report of the workshop that would provide findings, based on the consensus of the committee, about the state of the science in the topics discussed at the workshop. The report will also explore potential implications for the Biological Weapons Convention as an independent input from the scientific community to the treaty’s 7th review conference in 2011. The report would not make recommendations about actions to address any of the potential implications. • A rapporteur-authored summary of the workshop plenary sessions will also be produced. The workshop provided an opportunity for the scientific community to discuss the implications of recent developments in S&T for multiple aspects of the BWC. For example, a continuing question for the treaty’s review conferences is whether scientific developments yield new or novel types of agents or materials that are not captured by Article I, which defines the scope of the treaty?3 More broadly, however, developments in S&T also affect the other key articles of the convention that provide for the operation of the treaty, such as the adequacy of national implementation of the convention through national policies and regulatory systems, the capabilities to carry out investigations of alleged use of biological weapons, and the design of international cooperation to ensure that all States Parties (i.e., those who have signed and ratified the agreement), have access to the benefits of peaceful applications of biology. 3 Article 1 includes “Microbial or other biological agents, or toxins whatever their origin or method of production, of types and in quantities that have no justification for prophylactic, protective or other peaceful purposes” (http://unhq-appspub-01.un.org/UNODA/TreatyStatus.nsf/ 44e6eeabc9436b78852568770078d9c0/ffa7842e7fd1d0078525688f0070b82d?OpenDocument). An account of decisions taken at various review conferences reaffirming the capacity of Article 1 may be found at http://www.unog.ch/80256EDD006B8954/(httpAssets)/ 699B3CA8C061D490C1257188003B9FEE/$file/BWC-Background_Inf.pdf.

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SUMMARY 3 The summary follows the structure of the plenary sessions at the workshop. It begins with introductory material about the BWC and current examples of the types and modes of science advice available to the BWC and other international nonproliferation and disarmament agreements, in particular the Chemical Weapons Convention (CWC). The S&T material begins with talks on areas having the potential to impact the design, fabrication, and production of biological weapons, continues with a session on dispersal science and delivery technologies, and next moves into scientific developments relevant to detection, identification, and monitoring. Later sections of the workshop focused on medical countermeasures, public health, and agricultural biosecurity, and finally conclude with presentations on ways in which new methods of collaboration are influencing scientific exchange along with a discussion of risk communication. The summary includes only a very brief description of the some of the post-presentation discussions held during the plenary sessions – and does not include an account of the smaller breakout groups – since these were intended to inform the committee’s findings and conclusions and will be reflected in the final report. By necessity, the workshop was able to present only a sampling of current research in relevant areas of science and technology, and was strengthened by being able to draw on the diverse perspectives and active engagement of the participants through both plenary and breakout discussion sessions. Almost 80 scientists and policy makers from 28 countries and several international organizations took part in the workshop, with a mix of scientists and engineers currently engaged in research and technical experts who could help draw out potential implications for the BWC. The speakers for the S&T sessions were asked to focus on the “state of the science” with regard to their topics; in a few cases they also offered additional comments on the implications and applications for the BWC. INTRODUCTION TO THE THEMES, GOALS, AND CONTEXT OF THE WORKSHOP Outline of the Aims and Objectives of the Meeting – Roderick Flower, Queen Mary University of London, UK Dr. Roderick Flower, chair of the Committee on Trends in Science and Technology Relevant to the Biological Weapons Convention: An International Workshop, welcomed participants to the meeting and noted that the review conferences of the Biological and Toxin Weapons Convention have been charged with taking into account new developments in science and technology. Accordingly, Dr. Flower noted that the mission

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4 TRENDS IN SCIENCE AND TECHNOLOGY for the workshop was to review and consider developments in areas of science and technology that might be relevant to the Convention, in order to provide independent input from the scientific community to help inform the 7th Review Conference preparations. Dr. Flower then briefly reviewed the agenda and structure of the meeting. The Biological Weapons Convention: A Brief Overview – Piers Millett, BWC Implementation Support Unit, United Nations Dr. Piers Millet of the BWC Implementation Support Unit opened his remarks by reviewing the basic provisions of the BWC and its modest organizational resources (a staff of three) relative to the other major nonproliferation agreements. He noted that the BWC continues to evolve, becoming more collegial, more informal and more representative in many of its activities, particularly through the development of the intersessional process.4 Dr. Millet emphasized the ways in which the BWC has sought to engage the broader community of stakeholders interested in issues of potential misuse, including scientists and engineers. He commented on the need for the BWC to be better connected to developments in modern life sciences and to be part of a larger context of responsible conduct of science. He noted that the BWC was interested in several potential contributions from S&T developments, both positive and negative: to the risks of new or more deadly weapons; to improved defenses and countermeasures; and to enhanced disease surveillance and response. Dr. Millet pointed to efforts by the international scientific community to contribute to discussions on these issues through forums and workshops, as well as through the participation of scientists as delegates, guests, and representatives of non-governmental organizations at official BWC meetings. He closed by encouraging the community to continue its engagement on topics relevant to the BWC, such as advances in science and technology, particularly in support of evidence-based decision making. Although the formal process of the 7th review conference will be largely state-driven, there will be opportunities for events such as the workshop to make a contribution both to preparations by both national governments and the BWC staff’s own efforts. 4 The Review Conferences of the BWC are held at five year intervals. After the efforts to negotiate a verification protocol collapsed in 2001, the States Parties agreed to a series of annual, intersessional Meetings of Experts and Meetings of States Parties on specific themes. The success of the first series led the 6th Review Conference to agree to a second series from 2007-2010, including national implementation (2007); biosafety and biosecurity measures along with oversight, education, and awareness raising (2008); disease surveillance and containment (2009); and assistance and coordination in cases of alleged use (2010). Further information is available from the United Nations’ Biological Weapons Convention website at http://www.unog.ch/bwc.

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SUMMARY 5 Framework for Evaluating New Science and Technology – Ralf Trapp, CBW Consultant, France Dr. Ralf Trapp continued the theme of the first session by pointing to the importance of non-proliferation treaties regularly considering how advances in science and technology might affect their scope as well as their operations. S&T reviews are undertaken by the States Parties of the different agreements, working through international treaty organisations (if they exist) as well as formal treaty mechanisms such as review conferences. The reviews are supported by input from additional sources such as formal scientific advisory panels, such as the Scientific Advisory Board of the CWC and external actors such as scientific unions and academies, industry associations, and nongovernmental organizations (NGOs). He noted that the 7th Review Conference of the BWC has specifically been charged with considering “new scientific and technological developments relevant to the convention.”5 Dr. Trapp drew comparisons between the BWC and the CWC in how relevant scientific advice has been sought and provided, with a key difference that the CWC has a formal Scientific Advisory Board (SAB) charged to provide advice to the Director General of the Organization for the Prohibition of Chemical Weapons (OPCW). Dr. Trapp provided several examples of independent S&T advice in the context of these two treaties, noting that the OPCW had twice asked the International Union of Pure and Applied Chemistry to carry out workshops on trends in S&T similar to the Beijing workshop because it felt the need for access to a wide array of information from an independent scientific body. He cited a number of reasons for encouraging communication between the BWC States Parties, treaty staff, and the S&T community: The pace and complexity of advances in the life sciences;  The need for connections with cutting-edge science and technology;  The authority and independence of the advice that the S&T community could  provide; The importance of feedback into the scientific community on issues relevant  to the treaty’s operation (e.g., on issues such as awareness raising, adoption of codes of conduct, education); and The importance of engaging the S&T community in the development of  governance measures. 5 The mandate for the 7th Review Conference is available at http://www.unog.ch/80256EE600585943/ (httpPages)/57A642B96534F50CC12577B5004DD75E?OpenDocument.

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6 TRENDS IN SCIENCE AND TECHNOLOGY Perspective from the Chinese Academy of Sciences – Li Huang, Institute of Microbiology, Chinese Academy of Sciences Dr. Li Huang provided a perspective from the Chinese Academy of Sciences (CAS). He noted that China has a long history of S&T developments and provided information on the Chinese Academy of Sciences’ role as a leading life sciences research institution. Dr. Huang pointed to previous engagement by the Academy in discussing ethics and integrity in science and promoting ethical conduct. He highlighted several recent activities including the establishment of a Center for Ethical Studies in Science and Technology (2005), participation in the IAP Biosecurity Working Group, the Declaration of Scientific Ideology (2007), and CAS participation in international workshops and roundtables. Although he noted challenges such as a lack of awareness about the dual-use potential of scientific research among members of the life sciences community, he observed that scientists in China were actively engaged in discussing biosecurity issues and considering what oversight measures might be appropriate to manage potential risks. Discussion The discussion following this session’s presentations touched on ways to make independent input from the scientific community useful to the policy and diplomatic communities of the BWC, as well as ways one might measure the impact of meetings such as the current workshop. For example, some participants noted that producing a relatively brief and accessible summary of the final report would be helpful to convey the key findings and conclusions to the diplomatic and policy communities engaged with the BWC. DEVELOPMENTS IN DESIGN, FABRICATION, AND PRODUCTION Bioinformatics and Computational Tools – Etienne de Villiers, International Livestock Research Institute, Kenya Dr. Etienne de Villiers opened the session with a discussion on the potential of bioinformatics and computational tools. He began by noting that he had never considered the use of his research for offensive weapons development, and rather considered bioinformatics a useful tool for assisting with areas such as vaccine development. Indeed, bioinformatics is useful in enhancing understanding of genome structures and in enabling the identification and manipulation of genes to make clear their functions. To accomplish

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SUMMARY 7 this, bioinformaticists use an interdisciplinary approach that combines biology with statistics, mathematics, algorithms, databases and text mining. Dr. de Villiers pointed out that there had been a genomics revolution over the last couple of years resulting in next generation sequencing which exploited the latest technology to achieve millions of sequences an hour. This technology is advancing rapidly—whereas the Human Genome Project cost hundreds of millions of dollars or more and took a great deal of time, it is now possible to sequence a genome in a week for thousands of dollars—resulting in an explosion of genome data.6 By means of examples, he pointed to the international 1000 genomes project, which involves looking at 2500 human genomes for genetic variation, and the 1000 plant and animal genomes reference project conducted by BGI China.7 Dr. de Villiers went on to outline how an explosion in computing power, in combination with lowered costs for computers and greater availability of this technology across the globe, is enhancing bioinformatics. These changes have resulted in the emergence of the concept of cloud computing, whereby individuals can gain legitimate access to high performance computers through the internet to conduct research. Under this model, computational power is a service that can be rented by users to the extent needed to achieve research goals. An alternative approach, termed distributed computing, draws from a network of smaller computers to create a supercomputer-like environment that enables analysis of complex problems. One example is the “Folding@Home” project which has a goal “to understand protein folding, misfolding, and related diseases.”8 Individual participants can donate a portion of their idle computer processing power to the analysis of protein structures. Dr. de Villiers noted that in 2009 40,000 central 6 The Human Genome Project cost several billion dollars (The Human Genome Project Completion: Frequently Asked Questions, available at http://www.genome.gov/11006943), which included more than technology and sequencing expenses. Several companies currently offer human whole genome sequencing services and the prices continue to drop. Illumina, Inc., for example, offers genome sequencing for $19,500 with sequencing in “medically indicated cases” costing $9,500 (www.everygenome.com; accessed 3/14/2011). Similarly, whole genome sequencing by Complete Genomics reportedly costs approximately $10,000 (http://www.completegenomics.com/) and the company has reported its sequencing consumables costs to be approximately $4,400 (Drmanac et al., 2010). Companies continue to pursue advances in technology and to decrease sequencing costs as they race toward a “one thousand dollar genome”, which has been seen as an important milestone below which demand for genome data is expected to explode still further (Wolinsky 2007; Venter 2010). 7 Information about the 1000 Genomes Project may be found at http://www.1000genomes.org and the 1000 Plant and Animal Genomes Reference Project at http://www.ldl.genomics.cn/page/pa-research.jsp. 8 Information on Folding@Home is available at http://folding.stanford.edu/.

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8 TRENDS IN SCIENCE AND TECHNOLOGY processing units (CPUs) supported this project, making it in essence the largest computer in the world.9 Advances in computational power and performance have resulted in ‘metagenomics’, an example of which is the Sargasso Sea community survey (Venter et al., 2004). Dr. de Villiers defined metagenomics as “the sequencing and analysis of DNA of organisms recovered from an environment, without the need for culturing them, using next generation sequencing technologies” and suggested that metagenomics could play an important role in global disease tracking as it enables researchers to identify and track what exists and where pathogen reservoirs are located. Over time this could facilitate the development of diagnostic sequencing capabilities and understanding of disease trends, or even the production of vaccines and drugs. To begin this process Dr. de Villiers and colleagues at the International Livestock Research Institute had begun the process of building a biobank to manage samples, which he suggested could be a unique resource for other researchers to use. Systems Biology – Andrew Pitt, University of Glasgow, UK The second speaker in the session was Dr. Andrew Pitt of the University of Glasgow, who discussed the issue of systems biology. Dr. Pitt began by pointing out that systems biology had become a buzzword for a process of using biological knowledge to produce a mathematical model that describes a system at different levels from the molecular to the ecosystem. Such a model could not only describe the system, but could be used to enable the researcher to make system predictions. In this regard, systems biology lies in the middle ground between informatics and synthetic biology and provides the resources to enable the conversion of biological information into something meaningful from which to generate new systems and biology. Dr. Pitt noted that this is achieved by taking a rational engineering approach which draws from systems engineering and mathematics, along with increasingly diverse approaches to understanding systems including mobile phone networks and traffic management. Using these approaches, researchers have sought to take biological information and convert it into a suitable format from which to build a discrete model that can be described mathematically. Such a model can be used to both describe but also to predict. The latter is particularly important and requires the development of specific models to test predictions, something which becomes more complex as the focus shifts from cells, 9 The central processing units of a computer are involved in carrying out the instructions in a computer program; depending on the nature of the problem to be solved, the number of CPUs may provide an indication of computing power.

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SUMMARY 9 to tissues, to organisms, and to ecosystems. Indeed, the development of models which account for the relationship between these different levels and scales of complexity is particularly challenging and as a unified science, systems biology has a long way to go. Nonetheless, current research generates the potential to achieve systems medicine in the future and there are a number of enabling technologies, such as genomics and proteomics, which have facilitated progress. Coupled with these developments, advances in mass spectrometry and high throughput screening provide the depth of data required to populate models while the increased understanding of bioinformaticists enables such data to more effectively be captured and converted. Though some of the underlying networks are relatively straightforward and there are key nodes where we can intervene, the complexity of connections nonetheless renders systems biology a challenge, evident in an example from Japan articulating the epidermal growth factor receptor (EGFR) signaling cascade, which illustrates the relationship between proteins and other elements within a systems pathway (Oda et al., 2005). Dr. Pitt went on to elaborate on why a key challenge for systems biology is solving the mathematics, which in the case of the EGFR pathway model requires addressing some 211 reactions in 322 components, forming 7 RNAs based on 202 proteins, and the calculations here only cover a small portion of the mapping process. To understand how the complete system works, a massive number of interactions must be examined: at the genetic level it is likely to require some 4,000 calculations with a further 5,000 calculations at RNA level and 50,000 interactions in one mathematical equation at the level of proteins. In this regard, Dr. Pitt suggested that the number of numerical parameters is one of the main limits to advances in systems biology, particularly given that biological data reduction is slow and expensive and computational power is limited because of scale. A further challenge identified by Dr. Pitt was the difficulty in overcoming the stochastic nature of some of the interactions, which is difficult to model using mathematics. He then elaborated on the potential for an approach which focused on building platforms to generate data more quickly. He noted, however, that even this approach still requires advances in computational power, and that while this is improving, there is still some way to go to achieve the improvements required to build substantial models and intervene at the cellular level.

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10 TRENDS IN SCIENCE AND TECHNOLOGY Emerging Trends in Synthetic Biology – Pawan K. Dhar, University of Kerala, India Dr. Pawan Dhar of the University of Kerala discussed emerging trends in synthetic biology in the third presentation of the session. Dr. Dhar began by pointing out that there was enormous possibility of creating useful applications using a rational design approach in biology. Accordingly, he suggested there was a need for building standards and rules of composition to engineer novel biological applications. Dr. Dhar said that in contrast to the top down traditional approach, the engineering “bit by bit” strategy focused on the composite sections of the system to create useful devices and networks. He observed that scientists learnt biology by making ‘junk’ (mutations, knockdowns) and ‘garbage’ (knockouts) out of genes. He asked if one could do the opposite, i.e., make genes out of ‘junk’ DNA. His work has led to the effective conversion of “junk sequences into genes”, with the ‘junk’ being non-protein-coding genes within a genome. Dr. Dhar presented an example of E. coli research to illustrate this approach, where six intergenic sequences with no history of transcription were artificially activated to code for proteins (Dhar et al., 2009). His research indicated that although most of the gene activations had little or no effect on cell growth, activating one of the intergenic sequences resulted in cell death. Subsequent deactivation of this gene restored cells to normal growth, although why this happened was unclear at the molecular level. Further, given that a DNA sequence could now be artificially expressed in several frames, he proposed the emergence of combinatorial genomics as a new way of doing biology. Dr. Dhar then described some of the outreach work being conducted at the Centre for Systems and Synthetic Biology, in India. The Centre recently organized Biodesign India, the first synthetic biology event in the country. The aim was to try and understand what bio-design related activities were underway in India and address a degree of sensitivity to the surrounding ethical questions of this type of research. To provide an open access platform for synthetic biology research in India, the Centre has set up a synthetic biology wiki (a webpage that enables users to create and edit content) for information sharing among labs. On the global stage, Dr. Dhar suggested that in the future we were going to see arrival of faster and cheaper DNA synthesis technologies and cited the work of Robert Carlson, who recently predicted rapid fall in the cost of long DNA synthesis (Carlson, 2009) and Craig Venter, whose group experimentally developed a “synthetic” microbial cell

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SUMMARY 11 (Gibson et al., 2010).10 He pointed out that Dr. Venter’s approach was prohibitively expensive and time consuming, and thus not likely “scalable” in the present form. However, Dr. Dhar predicted that rapid and cheaper organism construction strategies, whole genome cloning, synthetic chromosomes, and application-oriented minimal synthetic cells would emerge in future. Dr. Dhar suggested that ideas like non-natural genetic codes, RNA structural engineering, and computer aided design of pathways may be more accessible and he envisions the emergence of several major non-biobrick initiatives in the near future.11 He also predicted a trend toward a greater number of graduate programs (Masters and Ph.D.) in synthetic biology worldwide. He observed that due to lack of experience in constructing organisms it was difficult to accurately predict the potential adverse effect of this approach, and noted that it makes him nervous to visualize the scenario of someone firing microbes as bullets, given the fact that such bullets think. As a result, he concluded by noting that it is not possible to maintain absolute control over developments in the biological sciences such as synthetic biology, but that “big challenges, [an] unclear roadmap, [and a] fear of the unknown” remain. Discussion The session moved to an open discussion during which a number of key themes emerged. Many participants noted that our knowledge and understanding still remains limited in terms of an ability to predict the outcomes and functions of biology resulting from genetic modification or modulation. Accordingly, the challenge of developing appropriate risk assessment strategies to accommodate unpredictable systems is difficult. Equally, participants suggested that it would be difficult to regulate the things “we don’t know that we don’t know”, although participants pointed to the value of bringing together the science and policy communities to discuss these issues. Finally, participants noted the continuing worldwide expansion of biological sciences research capacity, such as the active synthetic biology community in India and the ability of research institutes in Kenya to draw on advanced computational resources. 10 As described in the cited article, Dr. Venter’s group chemically synthesized the genome of the bacterium Mycoplasma mycoides based on the genetic sequence of the naturally occurring organism with the addition of certain distinguishing chemical “watermarks” and inserted this synthesized genome into a recipient cell of the related bacterium Mycoplasma capricolum, from which the natural genetic material had been removed. The synthesized M. mycoides genetic material was successfully able to instruct the resulting cell to grow and self replicate (Gibson et al., 2010). 11 The bio-brick model seeks to create standardized DNA “parts” with defined functions for combination into new systems. More information is available through the BioBrick Foundation at http://openwetware.org/wiki/The_BioBricks_Foundation and the Registry of Standardized Biological Parts, available at http://partsregistry.org/wiki/index.php/Main_Page.

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28 TRENDS IN SCIENCE AND TECHNOLOGY methods, resulting in 5 percent community infection by clinical surveillance, 13 percent by seroconversion data, and 13 percent by predictive modeling. Dr. Lin observed that clinical surveillance with laboratory confirmation can provide relatively real-time information but requires a high volume of testing to achieve accurate statistics. Seroepidemiology is accurate for retrospective infections and can be used to analyze particular subgroups, but can be difficult to organize. Modeling is predictive and easy to organize, but disagreement remains about how useful modeling approaches are to predicting disease and such models need to be verified by other surveillance methods. Countries are also exploring the use of Google search data or social media such as twitter as alternate disease monitoring strategies. So far, however, there is limited data on whether such methods are useful and results may be affected by news-driven peaks (Cook et al., 2010). Dr. Lin next noted that the 2009 H1N1 outbreak was unprecedented for the speed with which the genomes from viral isolates were sequenced in many countries. He described several ways in which observed or constructed mutations in H1N1 isolates were studied for potential effects on virulence, including D222G in the receptor-binding region and E627K in polymerase basic protein 2, a mutation which had been observed in previous pandemic influenza strains (Maurer-Stroh et al., 2010). However, Dr. Lin noted that study results varied with regard to the effects of these mutations, revealing the limits of our knowledge of the flu. In epidemiology, effective tools for accessing and mining massive amounts of digitized data are needed to draw out significant clusters and alerts. Dr. Lin briefly discussed one such framework, the Care Quest Infection Surveillance and Management (CQ/ISaM) for multi-drug resistant staphylococcus aureus (MRSA), in which clinical data streams are compiled in a central point and can be queried using natural language to generate real-time charts. However, Dr. Lin concluded by emphasizing the important role for front-line physicians to identify outbreaks at the local scale while they remain below the threshold observable through national surveillance systems. Agricultural Biosecurity: Threats to Crop Production – Michael Jeger, Imperial College London, UK Dr. Michael Jeger spoke to the workshop about crop security issues. He began by drawing comparisons between traditional and modern methods of crop production, noting that traditional methods often feature small, irregular fields with mixed crops and low use of inorganic fertilizers, herbicides and pesticides, while modern methods feature large, single-crop fields with specially bred cultivars and routine use of chemical products. Dr.

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SUMMARY 29 Jeger also noted the extensive biodiversity of plant pathogens, which include viruses, bacteria, fungi, and nematodes. Dr. Jeger commented that there are several epidemiological scales of disease spread – field level affecting farmers, nationally and regionally affecting national economies, and globally due to both natural and anthropogenic influences. He pointed to the increasing scale of international trade and the potential movement of pathogens through shipping and questioned whether national agricultural health systems are fully prepared to respond to potential outbreaks. He also presented several examples of significant agricultural diseases including the regional and global spread of wheat yellow rust (Brown and Hovmøller, 2002), and noted that devastating banana disease has spread to all of the major growing regions in the world. Dr. Jeger presented data documenting a four-fold increase in identified geminiviruses from 1991-2005 (Rodoni, 2009), and noted that this increase does not appear to be an artifact of increases in sequencing. He highlighted the potentially large economic costs from crop disease outbreaks, suggesting that these diseases may have a major impact whether from accidental or deliberate disease spread. Dr. Jeger also raised several questions to consider with regard to invasive plant diseases and biosecurity, including the nature of the threat, whether pathogen eradication is feasible, what safeguards should be built into national plant health systems, whether there will be impacts from global trade or climate changes, whether it is possible to predict upcoming concerns, and whether the pathogen that first arrives in a new region or the one that follows is likely to be the most serious problem. With regard to this last point, Dr. Jeger presented a model for how new pathogen strains evolve when introduced into a reservoir (adapted from Antia et al., 2003). He noted that there will be frequent failures of the pathogen to cross over into a new crop species; however a strain will eventually evolve with properties that enable it to emerge as a new pathogen. He also noted that formal plant health regulations may take months or years to be developed, which may not be adequate to respond to accidental or deliberate plant disease outbreaks. Dr. Jeger concluded that improved biosurveillance is needed, along with properly validated methods for collecting and analyzing the information. Discussion The discussion following the presentations touched on surveillance systems and ways for the public and agricultural health communities to achieve increased lead time in recognizing emerging disease outbreaks. Among the points noted during the discussion was that current surveillance systems largely rely on passive surveillance, rather than on

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30 TRENDS IN SCIENCE AND TECHNOLOGY the use of active surveillance of sentinel groups. It was also suggested that advances in biotechnology can contribute to the generation of new, pathogen-resistant plant varieties. COMMUNICATION How the Internet has Changed Scientific Interchanges – James Meadway, The Royal Society, UK James Meadway opened the last session with a discussion of the impact of the internet on scientific interchange, pointing out that there has been a significant increase in the amount of information transferred over the internet. To illustrate this point he highlighted how one site, YouTube, now consumes the same bandwidth as the entire internet in 2000. In parallel, there has been a growth in internet access, which although not ubiquitous is becoming increasingly available. Although only a small percentage of the developing world is on the internet, expansion in access in these areas is especially rapid. Advances in physical infrastructure and wireless technology have been complemented by changes in the social infrastructure, and indeed it was suggested that the former enables the latter. While the old World Wide Web “1.0” system was used largely for the replication of mass media technology which was passively consumed, the internet today has become much more interactive and has resulted in the emergence of more user-generated content, much greater depth and complexity of interaction and significant changes in the way people communicate. This is particularly important for science given that the production of scientific knowledge is fundamentally a social process involving information sharing, collaboration and the mobilization of outputs. The old hierarchy based largely on email enabled instant collaboration and group creation, thus removing some of the barriers to cooperation that previously existed, but also presented limitations for science. New hierarchies like cloud computing have the potential to change the system of collaboration further by making the process of sharing and multi-authoring documents much easier and by placing ideas within a “social” context to allow even more people to contribute. Dr. Meadway suggested that the development and now potential transformation of the internet may have significant consequences for scientific discovery, including the emergence of new means of conducting research using web 2.0 software, resulting in what some have termed “Science 2.0” (Shneiderman, 2008). The emergence of Science 2.0 through the collaboration and mass dispersal of information eliciting the ‘wisdom of crowds’ can enable a large number of people to examine the same problem. This process

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SUMMARY 31 has the potential to diminish the distinction between formal and informal processes of knowledge creation. The so-called Climate-gate affair illustrates how the release of emails broke down the formal process of knowledge production and allowed the public to enter into the debate. Dr. Meadway stated that patterns of use differ across disciplines and that we are not quite to Science 2.0 yet. Current developments are largely an extension of existing practices, rather than genuinely new features. Nonetheless, he concluded that it is likely that web 2.0 tools will become more prevalent and there is great potential for a more prevalent science 2.0 approach in the future. Influence of Technology on Scientific Collaboration – Herawati Sudoyo, Eijkman Institute for Molecular Biology, Indonesia The second presentation, by Dr. Herawati Sudoyo, addressed the influence of technology on scientific collaboration using the example of disease management in the context of Indonesia. The Indonesian archipelago is the fourth most populous country and experiences serious problems with endemic diseases as well as periodic epidemics, including new emerging diseases. This burden is added to by environmental, ecological and demographic factors spread by travel and trade. As a geographically unique country with a diverse population, Indonesia faces a challenge in managing public health problems, reducing biological risks and promoting capacity building. Due to this diversity, Dr. Sudoyo noted that management of disease is complex and she presented a number of examples of disease challenges including: 15 million cases and 42,000 deaths from malaria in 2005; 529,000 tuberculosis cases in 2007; and 123,174 cases and 1,251 deaths caused by dengue fever in 2007. She noted that hepatitis is particularly problematic, with five sub-genotypes of the virus prevalent in Indonesia as a result of different virus migrations from neighboring countries and regions. As a result, extensive disease surveillance is necessary and has to be supported by the capacity to respond to new emerging infectious diseases. Dr. Sudoyo detailed how a collaborative partnership of hospitals and research institutions such as the South East Asian Infectious Disease Clinical Research Network (SEAICRN) (Wertheim et al., 2010), had been established and enabled participants in Thailand, Vietnam, and Indonesia to build a multilateral network based on shared principles of respect, sharing and commitment to improve patient management through quality clinical research. The network was intended to build collaboration, cooperation and capacity to tackle disease outbreaks and enabled Indonesia access to state of the art technology and technical training from University of Oxford and its partners. A massive effort to catalog

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32 TRENDS IN SCIENCE AND TECHNOLOGY genetic variation among Asians has also been established with the availability of new technology in the region. She noted that this Pan-Asian SNP Initiative was uniquely conceived by Asians in Asia and executed, funded and completed by an Asian Consortium (The HUGO Pan-Asian NSP Consortium et al., 2009). Japan, Singapore, China and Korea provide technical and scientific training for scientists in less developed countries. In these contexts, internet communication has been particularly useful in sustaining the collaborative process and drawing together 93 researchers from 40 institutions in 11 Asian countries at minimum cost. In the future, a project is planned for the mapping of genetic markers to develop medical countermeasures building on existing Asia-Asia collaboration. Conveying the Concept of Risk – Terence Taylor, International Council for the Life Sciences The final speaker in the session, Dr. Terence Taylor, posited that advances in science and technology are the best defense and accordingly noted the need to be cautious when assessing the risks of science to security in order to avoid the demonization of science or the impression that science is dangerous. However, he also emphasized that advances in science raise a number of issues to be considered, including ethics and safety. On this basis, it was suggested that science and technology should be understood along a spectrum of risks with natural risks at one end of the spectrum and deliberate misuse at the other. Moreover, these problems are not limited to any specific country or region, but rather are emerging across the world and pose risks which transcend traditional state boundaries. Dr. Taylor referred to the work of Robert Carlson on the doubling and proliferation of computational power (Carlson, 2003; Carlson, 2008), and noted that while in 2002 it took 2 years to synthesize polio (Cello et al., 2002), more recently viruses of comparable complexity had been synthesized in only two weeks. The cost of synthesis was also declining at a similar rate. He suggested that it is useful to think about the drivers of S&T, including the information technology (IT) revolution and the diffusion and domestication of IT which propel developments forward, although predicting the future remains extremely difficult. He proceeded to underline the importance of not viewing the biosecurity implications of advances in science as a developed versus developing country issue, and emphasized the importance of implementing a range of actions for dealing with the full spectrum of potential risks. Such actions can include ethics codes and awareness- raising in the life science community, personnel screening, lab security, and building of resilience into systems.

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SUMMARY 33 Discussion The discussion from the last session raised the issue of tacit knowledge and the impact of the internet, with several participants suggesting that the internet allows knowledge to be acquired in a way that would not be possible under other circumstances. There was also further discussion on models and examples of international cooperation. Participants noted the challenges in conducting risk assessments of scientific and technical advances, and the need to both determine the real risks and benefits and to put these into context. WORKSHOP DISCUSSION SESSIONS AND FINAL REMARKS In addition to the plenary presentations, the workshop featured two small-group breakout sessions and a final plenary discussion session in which participants were provided with questions that encouraged them to consider the most significant recent and predicted future developments in the areas discussed at the workshop, whether they thought these developments might affect concepts, materials, or delivery mechanisms related to biological weapons, and what technical hurdles could be overcome before there would be cause for concern. Participants were also asked to consider how developments in science and technology could affect biodefense, countermeasures, and mitigation capabilities to address emerging concerns, as well as how future S&T developments might continue to be effectively evaluated in the context of the BWC. The input provided by workshop participants during these sessions informed the discussions of the National Research Council’s Committee on Trends in Science and Technology Relevant to the Biological Weapons Convention, and will be incorporated more fully in its forthcoming report.

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