Preventing a Biochemical Arms Race 9780804786157

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PREVENTING A BIOCHEMIC AL ARMS R ACE

PREVENTING A BIOCHEMIC AL ARMS R ACE

Alexander Kelle, Kathryn Nixdorff, and Malcolm Dando

Stanford Security Studies An Imprint of Stanford University Press Stanford, California

Stanford University Press Stanford, California © 2012 by the Board of Trustees of the Leland Stanford Junior University. All rights reserved. The authors gratefully acknowledge the support of this work by the German Foundation for Peace Research (Deutsche Stiftung Friedensforschung, DSF). No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying and recording, or in any information storage or retrieval system without the prior written permission of Stanford University Press. Special discounts for bulk quantities of Stanford Security Series are available to corporations, professional associations, and other organizations. For details and discount information, contact the special sales department of Stanford University Press. Tel: (650) 736–1782, Fax: (650) 736–1784 Printed in the United States of America on acid-free, archival-quality paper. Library of Congress Cataloging-in-Publication Data Kelle, Alexander, author.   Preventing a biochemical arms race / Alexander Kelle, Kathryn Nixdorff, and Malcolm Dando. pages cm   Includes bibliographical references and index.  ISBN 978-0-8047-8275-3 (cloth : alk. paper)   1. Chemical arms control. 2. Biological arms control. I. Nixdorff, Kathryn, author. II. Dando, Malcolm, author. III. Title. JZ5830.K46  2012 327.1'745—dc23 2012005965

Contents



List of Tables and Figures

1

Arms Dynamics, the Changing Threat Environment, and the Chemical and Biological Weapons Prohibition Regimes

1

Threats to the CBW Prohibition Regimes: The Changing Nature of Warfare

11

Threats to the CBW Prohibition Regimes: The Revolution in the Life Sciences

34

Threats to the CBW Prohibition Regimes: Advances in Neuroscience

61

Threats to the CBW Prohibition Regimes: Biodefense Pushed Too Far

88

Embedding the CBW Prohibition Regimes in the Web of Responses

110

2 3 4 5 6

7 Evolution of the BW Prohibition Regime: Assessing Achievements and Weaknesses 8

Evolution of the CW Prohibition Regime: Assessing Achievements and Weaknesses

vii

137

157

vi

Contents

9

Conclusion

180

Works Cited

199

Index

229



Tables and Figures

Tables 2.1

The evolution of old wars

16

2.2 Commercial applications of chemical weapons precursors

32

3.1 Examples of mid-spectrum agents

57

4.1 Progress in understanding mental illness

62

4 .2 Nobel Prizes in Physiology or Medicine

65

4.3 Some principles of neuropsychiatry

73

6.1 Laboratory biosafety: Agents are assigned to risk groups

118

8.1 CWC universality and increase in membership 2003–2011

169

8.2 Implementation of CWC Article VII

172

vii

viii

Tables and Figures

Figures 1.1 Biological agent evolution in relation to threat

6

4.1 Oxytocin effects in the trust game

81

7.1 Layers of undertakings under the Biological Weapons Convention

141

1

Arms Dynamics, the Changing Threat Environment, and the Chemical and Biological Weapons Prohibition Regimes

Introduction The development and application of military technology over time has taken many different forms. In the area of chemical and biological weapons (CBW), this has manifested itself in the deliberate spread of disease in premodern siege warfare (Wheelis 1999a, 10–16) and the large-scale deployment of chemical warfare agents during World War I enabled partially by the industrial revolution (Robinson 1998; SIPRI 1971a; Martinetz 1995). With the advent of the information age and the dawning of the “biotech century,” questions about the relationship between military or dual-use technologies, and the political motives of state and substate actors, arise anew. These questions are especially pertinent because of wider changes in the nature of warfare (discussed in chapter 2 below), the ongoing revolution in the life sciences that opens up to malign interference regulatory systems—such as the nervous and immune systems—in the human body (see Kelle, Nixdorff, and Dando 2006 and chapters 3 and 4 below), and the renewed emphasis on biodefense activities in response to the perceived rise in the threat emanating from potential bioterrorist attacks (see chapter 5 below). However, these risks are in principle dealt with by the prohibition regimes that were set up in the late 1960s/early 1970s (for biological weapons [BW]) and late 1980s/early 1990s (for chemical weapons [CW]) in order to address the threat stemming from these weapons. The multilateral regimes thus created and revolving around the 1972 Biological and Toxin Weapons Convention

1

2

Chemical and Biological Weapons Prohibition Regimes

(BWC) and the 1993 Chemical Weapons Convention (CWC),1 respectively, were unambiguously products of their time. Both Conventions reflected (1) an international consensus on the prohibition of, inter alia, the development, production, and use of CBW; (2) the depth of the provisions contained in the two legal instruments—quite shallow in case of the BWC and considerably more intrusive in the CWC; and (3) the requirements for an international organization to oversee implementation of the treaty provisions by states’ parties—none in the BWC and a 500-staff strong Organisation for the Prohibition of Chemical Weapons (OPCW) for the CWC. The underlying consensus on these issues was in turn informed by the state of the art in military technologies, the historical experience of state programs, and the use of CBW over the course of the twentieth century and resultant assessment of the usefulness of continuing to pursue or prohibit biological and chemical weapons, respectively. It is thus useful to reconsider the reasoning on arms dynamics and arms control approaches prevalent at the time as well as their application to CBW. Following Buzan and Herring (1998) we reject a simple dichotomy of arms racing and non-arms racing and instead apply their concept of a continuum of an arms dynamic (ibid., 79). They use the latter term “to refer to the entire set of pressures that make actors (usually states) both acquire armed forces and change the quantity and quality of the armed forces they already possess” (ibid.). Buzan and Herring continue to explain that “arms racing is reserved for the most extreme manifestations of the arms dynamic, when actors are going flat out or almost flat out in major competitive investments in military capability” (ibid., 80). “Maintenance” of the military status quo in this logic is located at the other end of the spectrum of the arms dynamic. In between the two, the concept of an “arms competition” is located. None of these are immutable states of affairs. Rather, individual policies and relationships between actors can move across this spectrum through arms build-ups or arms build-downs. Applied to the CBW issue area during the first half of the Cold War for BW and practically all of the Cold War’s duration for CW, the numerous BW and CW state-level programs attest to the presence of an arms competition between East and West in this area too. In the biological field, such programs 1.  The text of the BWC is available at http://www.opbw.org/convention/documents/btwctext. pdf (accessed 9 October 2011); and the text of the CWC is at http://www.opbw.org/int_inst/ sec_docs/CWC-TEXT.pdf (accessed 9 October 2011).



Chemical and Biological Weapons Prohibition Regimes

3

in the United States, the United Kingdom, and other countries up until the late 1960s (van Courtland Moon 2006; Balmer 2006; Lepick 2006; Hart 2006; Pearson 2006) were terminated when under U.S. and Soviet leadership the BWC was negotiated. This multilaterally agreed-upon arms build-down became possible due to several factors: the advent of the nuclear age with a concomitant interest and partial successes in (nuclear) arms control during the 1960s, the Soviet Union’s willingness to separate BW and CW negotiations, the limited tactical utility of BW from the perspective of the Nixon administration in the United States, the emergence of a nongovernmental champion of discussions on the prohibition of CBW (in the form of the Pugwash movement), and difficulties in implementing those provisions of the Brussels Treaty of 1954 that prohibited Germany from acquiring inter alia BW (Tucker 2002; Guillemin 2005; Chevrier 2006). Success in negotiations on BW came at the expense of putting a builddown in the CW area on the back burner. Completion of negotiations for the CWC took another two decades until this treaty was opened for signature in January 1993. This does not come as a complete surprise given the degree to which already in the latter stages of World War I CW “were being integrated into the prevailing doctrine, organisation and day-to-day routines of armed forces. They were now . . . caught up in that process of ‘assimilation’ which is discernible in the history of most technologies, civil as well as military” (Robinson 1989, 112). Robinson points out that despite the nonuse of CW during World War II, three major technological changes— the discovery of nerve gases, the advent of aerobiology, and the discovery of antiplant CW agents—resulted in significant institutional consequences insofar as they led to the survival of “chemical warfare bureaux . . . within military bureaucracies” (ibid., 116). These, in turn, “have shaped the situation of chemical warfare in the 1980s” (ibid.). This situation was characterized by a renewed interest in CW as a deterrent of offensive CW use by the Soviet Union and its allies. In the context of the general arms build-up under the Reagan administration in the first half of the 1980s, plans to develop and produce binary chemical weapons were revived in the United States (Adams 1990, 152ff.). In addition to the binary CW program, in 1986 “the Pentagon requested a further $12 million to begin research on ‘novel lethal and incapacitating compounds,’ and was reported to be developing ‘a master plan for future development of retaliatory systems’ to incorporate greater range, accuracy and stand-off capabilities” (ibid., 165).

4

Chemical and Biological Weapons Prohibition Regimes

This not only provides another illustration of the assimilated character of CW in United States (and other) military doctrines but also puts a finger on the issue of research for defensive purposes. Considering the BWC, Adams rightly points out that this treaty does not prohibit research into biological warfare agents (ibid.) and that, according to the U.S. defense establishment, testing of BW agents “must involve not only agents known to exist in the current Soviet stockpile, but also those which might be produced in the future” (ibid. 1990, 165). Moving on to more recent debates, it appears that the logic of the argument put forward by proponents of a strong biodefense effort has not changed much—apart from the shift in the nature of the opponent and the much greater urgency with which biodefense and biopreparedness policies are being pursued in the United States and elsewhere. Evolution of the Threat Spectrum Along this line of reasoning, recent warnings have made it clear that we could well face an increasing range of different biological agents being used for hostile terrorist and warfare purposes in the coming decades. George Poste (2000), for example, has emphasized the need to think “beyond bugs.” More generally, Mathew Meselson has argued convincingly that as the century progresses, more and more of life’s fundamental processes will become open to both benign and malign manipulation: During the century ahead, as our ability to modify fundamental life processes continues its rapid advance, we will be able not only to devise additional ways to destroy life but will also become able to manipulate it—including the processes of cognition, development, reproduction, and inheritance. . . . Therein could lie unprecedented opportunities for violence, coercion, repression, or subjugation. . . . We appear to be approaching a crossroads—a time that will test whether biotechnology, like all major predecessor technologies, will come to be intensively exploited for hostile purposes or whether instead our species will find the collective wisdom to take a different course. (Meselson 2000, 16)

A report provided by three U.S. defense analysts (Petro, Plasse, and McNulty 2003) sets a framework for thinking about future trends in this context. These authors consider the evolution of biological warfare agents in three phases (see fig. 1.1). The first phase includes what is referred to as “traditional



Chemical and Biological Weapons Prohibition Regimes

5

biological weapons agents.” They are the naturally occurring organisms or their toxic products, which have intrinsic properties that determine their suitability for biological warfare, such as infectivity, lethality, time to effect, and environmental stability. Petro and coauthors contend that although the threat posed by traditional agents has been increasing since the early twentieth century, it will eventually level off because of (1) the development of medical countermeasures such as antibiotics, antiviral drugs, antitoxins, and vaccines; and (2) the fact that there is only a limited number of these agents that meet the requirements to be suitable for biological warfare. The second phase in the evolution of biological agents encompasses genetically modified traditional agents. The first successful genetic engineering experiment, in which plasmid genes from one bacterium (Staphylococcus aureus) were transferred to and expressed in another unrelated bacterium (Escherichia coli), was carried out shortly after the conclusion of the BWC in 1972 (Chang and Cohen 1974). It was quite apparent a few years later that this new development was perceived as a potential threat to biological weapons control (Wade 1980; Budianski 1982). Petro and coauthors argue that, like traditional agents, the threat posed by genetically modified traditional agents will also eventually plateau because “only a finite number of properties and genetic modifications can be used to enhance a traditional agent without altering it beyond recognition” (Petro, Plasse, and McNulty 2003, 162). The third phase involves what has been called “advanced biological warfare (ABW) agents” by these authors. The hallmark of the developments in science and technology over the past three decades is the explosive nature of the accumulation of knowledge concerning molecular mechanisms and functions of biological systems. While this knowledge is essential for countering disease more effectively and promoting public health security in general, it can at the same time be malignly misused for waging biological warfare. Indeed, as the process described by Meselson continues through the century, an ever-increasing number of targets will become available for which specific ABW agents may be designed in a systems approach to creating novel biochemical weapons that would be able to attack vitally important bodily functions such as respiration, blood pressure, heart rate, body temperature, mood, and consciousness as well as innate and adaptive immune responses. Petro, Plasse, and McNulty have noted that this “capability-based threat posed by ABW agents will continue to expand indefinitely in parallel with advances in biotechnology” (Petro, Plasse, and McNulty 2003, 162). This is

Chemical and Biological Weapons Prohibition Regimes

Threat

6

Advanced Biological Agents Genetically Modified Traditional Agents/ Biochemical Agents Traditional Agents Pre-Genomic Era 1940s

Genomic Era (Age of Biotechnology) 1999 2003 Human Genome Sequenced

2020

F I G U R E 1 .1 . Timeline describing the three phases of the evolution of potential

biological warfare agents and their impact on the biological weapons threat level. source: Petro, Plasse, and McNulty 2003, modified.

compounded by rapid advances in vector and aerosol technologies designed to deliver an ABW agent to specific targets in a way that will be effective (see chapter 3). Thus, defense will be confronted with the problem of a diffuse and fundamentally unknowable range of agents with the potential of targeting individuals in ways not normally associated with traditional biological weapons. It is important to realize that such ABW agents that can manipulate life processes have the properties of both biological and chemical substances (bioactive chemicals), and they are thus relevant for both chemical and biological weapons control. To meet the challenge posed by the third stage of development of such agents, Petro, Plasse, and McNulty argue that there is a need for “next generation” approaches to biodefense. In effect, their solution is to increase allocation of biodefense resources that would: (1) permit the evaluation of emerging biotechnologies that might foster ABW agent development, (2) provide for the establishment of a federally funded facility to consolidate and conduct research into biotechnology threat assessments, and (3) promote research into the development of next-generation systems for



Chemical and Biological Weapons Prohibition Regimes

7

environmental detection of agents, medical diagnostics, therapeutics, and prophylactics. These are of course legitimate activities that could contribute to countering present and future threats from biological weapons agents, but is this approach sound enough to really do the job? We do not believe so, for several reasons. In the first place, the solution is too narrow in scope, focusing entirely on biodefense to counter offensive BW programs and not taking into account the need for developing both CW and BW prohibition regimes further to meet these new challenges. These treaties represent the cornerstones of the prohibitions against CBW use. The measure of the effectiveness of an arms control regime to meet immediate and future challenges is embodied in a number of features such as the availability of verification measures and the adaptability of the regime structure to changing circumstances, such as the regime’s capacity to adapt to science and technology change (Kelle, Nixdorff, and Dando 2006; Kelle, Nixdorff, and Dando 2008). The slow evolution of the CBW regimes in these respects, which we have outlined elsewhere (see also chapters 7 and 8 below), matched against the explosive developments in science and technology that are relevant for both regimes, underscores the need for further development of these regimes in order to prevent erosion of the norms against CBW. Secondly, reliance on the development of effective defensive countermeasures is too much of a long-term approach to be useful for immediate and near-future needs. While the development of next-generation countermeasures, such as systems for environmental detection of agents, medical diagnostics, therapeutics, and prophylactics, is surely desirable, the timeline needed to achieve these goals, if they can be achieved at all, is simply too long for immediate or near-future use. This is made especially apparent by reviewing the status of where we are today with regard to the development of such countermeasures directed against traditional agents that belong to just the very first phase of biological agent evolution. In this regard, a recent assessment (Matheny, Mair, and Smith 2008) of U.S. biodefense countermeasures development concerning these agents is particularly revealing. In that report, the authors present a cost/success analysis for development of medical countermeasures that would satisfy the U.S. Department of Health and Human Services (HHS) requirements to protect citizens against biological weapons and bioterrorism, in particular the funds needed for the Biomedical Advanced Research and Development

8

Chemical and Biological Weapons Prohibition Regimes

Authority (BARDA) to see developments through the costly clinical trial process. The analysis involved eight classes of existing countermeasures candidates, including 12 small-molecule drugs, 15 vaccines, and 5 biological therapeutics. Twenty-one of these are in preclinical development, 10 are in phase I clinical trials, and one is in phase II trials. The authors estimated that a huge increase in funds—from the $723 million requested in FY 2009 (for 2009–2015) by President Barack Obama to $14 billion—would be necessary in order for HHS to respond to all of the traditional biological agents designated as material threats. This, however, would by no means guarantee successful production of the required countermeasures, given the high failure rate of biopharmaceutical development. Although others (Klotz and Pearson 2009) have estimated these costs to be somewhat less ($6.3 to $11.6 billion), the fact remains that “drug and vaccine development is a long, high-risk and expensive endeavour” (Matheny, Mair, and Smith 2009), and some voices have questioned whether the threat is great enough to pour these huge sums into the uncertain development of countermeasures directed against these agents (Leitenberg 2005; Enserink and Kaiser 2005; Kahn 2007). Given that the production of vaccines and therapeutics needed to protect against all traditional agents is so uncertain, it is illusory to believe that protective countermeasures of this sort could ever be achieved for the endless array of potential agents that will result from continuing advances in the life sciences. Finally, the increased biodefense-related activities called for by Petro, Plasse, and McNulty (2003) may actually be viewed as part of the biological weapons proliferation problem itself. For example, the enormous increase in funding for biodefense in the United States after 9/11 and the anthrax attacks that followed (Pearson 2008; Franco and Kirk Sell 2011) has been cause for serious concern among prominent arms control analysts, the greatest concern being that the call for a decided increase in biodefense work with dangerous pathogens would greatly increase the risk of accidents or malign misuse (Ebright 2002; Kahn 2007). Indeed, this approach has been termed “highly problematic . . . because it could undermine the ban on offensive development enshrined in the Biological and Toxin Weapons Convention (BWC) and end up worsening the very dangers that the U.S. government seeks to reduce” (Tucker 2004).



Chemical and Biological Weapons Prohibition Regimes

9

Structure and Content of the Book We share the concern that the markedly increased biodefense activities, particularly those of the United States, combined with wider changes in the life sciences and the nature of warfare could very well lead to a resurgent interest in chemical and biological weapons capabilities. This could lead to a destabilizing biochemical arms race among major powers and “rogue states” or—much further in the future—substate actors, such as terrorist groups, which will in all likelihood result in offense dominance for most of the twenty-first century. Framed in this way, our approach clearly departs from the currently dominating orthodoxy that puts the threat of bioterrorism at center stage. We reject this as misguided and not borne out by historical evidence of successful bioterrorist attacks. In addition, as demonstrated in subsequent chapters, the nature of the revolution in the life sciences is favoring early adoption of advanced biological warfare agents—to use the term coined by Petro, Plasse, and McNulty (2003)—by states and not by substate actors. The following four chapters will be devoted to an analysis of the changing nature of warfare, the changing nature of the life sciences, and current largescale biodefense programs, all with a view to their implications for new utilities of CBW. In doing so, our approach ties in with different bodies of academic and policy-oriented research on both the changes in the life sciences, with implications for the biothreat spectrum, and the changing nature of warfare. With respect to the former, the U.S. National Research Council has conducted two major studies on Biotechnology Research in an Age of Terrorism (the so-called Fink Committee Report, National Research Council 2004a) and Globalization, Biosecurity, and the Future of the Life Sciences (the so-called Lemon-Relman Committee Report; National Research Council 2006). In regard to the latter body of scholarship, our approach ties in with an emerging consensus about the changing nature of warfare. Münkler (2005) and Kaldor (2007), for example, have convincingly made this argument. General Rupert Smith (2008) has since substantiated these points with his concept of “wars amongst the peoples,” derived from decades of involvement in military planning. Informed by this debate, Robinson (2008a) has highlighted the issue of new utilities for chemical weapons and identified the above-mentioned “wider changes in the nature of warfare” as one of the underlying reasons for possible resurgence in the interest of chemical weapons. Although our analysis of the evolving threat scenario coincides with the one put forward by the above quoted three U.S. defense analysts (Petro,

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Chemical and Biological Weapons Prohibition Regimes

Plasse, and McNulty 2003), the measures we propose to prevent a biochemical arms race, or to contain its negative consequences should one occur, could not be more different. In contrast to their prescriptions for action, we regard the existing international regime structures revolving around the BWC and CWC as in principle capable of reform and strengthening. Hence, after having analyzed the changing biothreat spectrum and its underlying causes, in chapters 6 to 8 we will analyze these international regimes, their achievements and shortcomings, and the wider web of responses they are part of. The concluding chapter of the book will return to the course of events suggested by Petro, Plasse, and McNulty (2003) concerning the offensedefense arms race in the biological arena, as this proves useful in focusing attention on those policy options that need to be conceptualized and should be implemented with a view to the 2011 BWC and 2013 CWC Review Conferences. On this basis, we will develop policy proposals that will (1) deal with both the CW and BW prohibition regimes individually and (2) address the perceived political-psychological gap between them. The chapter—and book—will conclude with a consideration of additional measures to strengthen the wider web of responses.

2

Threats to the CBW Prohibition Regimes The Changing Nature of Warfare

Introduction The nature of warfare, or armed conflict more broadly, is one of the three factors determining the perceived utility of CBW. From such a purely utilitarian or functional perspective the prohibition of CBW flows from the decreasing value of these weapons as instruments of warfare. And indeed part of the military history of the Cold War years seems to bear out such a utilitarian approach: when nuclear weapons became available as the ultimate deterrent during the early stages of the bipolar confrontation, some states— such as France and the United Kingdom—concluded that they no longer needed to rely on their BW arsenals for a capacity to retaliate in kind (Lepick 2006; Balmer 2006). However, several states held on considerably longer to their chemical weapons arsenals, as, in contrast to BW, their utility as a weapon of war had been demonstrated during World War I (see below). This utilitarian logic was supplemented by the strong normative aversion to using toxic chemicals and disease-causing agents as means of warfare. Such normative considerations had been finding their way into the rules of warfare since the late nineteenth century. The Hague Conference of 1899, for example, sought to ban chemical warfare agents by issuing a declaration in which signatories “agree[d] to abstain from the use of projectiles the object of which is the diffusion of asphyxiating or deleterious gases” (SIPRI 1973, 152). However, neither this declaration nor the efforts of the subsequent Second Hague Conference in 1907 could prevent the widespread use of CW during

11

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Threats to the CBW Prohibition Regimes

World War I (SIPRI 1971a, chap. 2; Martinetz 1995). Following the horrific effects of using chemical weapons during World War I, renewed efforts to prevent their future employment in war resulted in the 1925 Geneva “Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous, or Other Gases, and of Bacteriological Methods of Warfare” (SIPRI 1971b, chap. 2). However, given the large number of unilateral reservations attached to the ratification of or accession to the 1925 Geneva Protocol, it has until recently been mostly regarded as a no-first-use agreement among States Parties to the agreement. Together these utilitarian and normative considerations underpinned the creation of the biological and chemical weapons prohibition regimes, which revolve around the 1972 BWC and the 1993 CWC, respectively. However, a recent study has raised the issue of new utilities for chemical weapons and identified three sources of a possible resurgence in the interest of (bio) chemical weapons (Robinson 2008a). These are, firstly, “wider changes in the nature of warfare” (ibid., 226); and secondly, the propensity of knowledge gained in the life sciences to suggest novel modes of attack that could be the basis for militarily or politically attractive new forms of [chemical and biological] weapons. (Ibid., 227)

Lastly Robinson identified potential utilities of CBW in counterterrorist operations as one of the underlying reasons in increased interest. While the second of these motivational factors will be dealt with in subsequent chapters, this one will address the first and last in Robinson’s troika. A more detailed assessment of his proposition is clearly warranted as such a reassessment of the utility of chemical and biological weapons could easily undermine the regimes that have partially been built on the erstwhile conclusion that CBW did not possess sufficient military utility to outweigh the taboo that use of such weapons carries with it (Price 1997). The chapter will, therefore, in a first step discuss the traditional form of industrial interstate warfare as it had developed during the nineteenth and twentieth centuries. This will be followed by an analysis of the evolution of the usages that were anticipated primarily for chemical weapons from their widespread use during World War I to the close of the Cold War, the latter of which was closely followed by the conclusion of the Chemical Weapons Convention. The following section will then discuss the changing nature of warfare as analyzed by scholars (Kaldor 2007; Münkler 2005) and military



Threats to the CBW Prohibition Regimes

13

practitioners (Lind et al. 1989; Smith 2008) as well as the implications this has for the potential utility of chemical and biological weapons for state and nonstate actors.

Old Wars and Their Implications for the Prohibition of CBW The Notion of Old Wars There clearly is not one type of “old” warfare, as any history of the evolution of warfare through the centuries will quickly reveal. In addition, and not surprisingly, there is not just one attempt to categorize different manifestations of war through the centuries. Boot’s seminal work (2006) on the changing nature of warfare since 1500, for example, discusses four military revolutions that have substantially changed the face of war: the gunpowder revolution, the first industrial revolution, the second industrial revolution, and the information revolution. Acknowledging the resulting different manifestations of old wars, the term is used here—as by those mostly associated with introducing the term in the academic discourse (e.g., Kaldor 2007, chap. 2)—as a shorthand to signify the paradigmatic change that the nature of warfare has undergone in recent decades. With a view to the topic of the following section, that is, the relationship between the nature of old wars and CBW development and usage, another early attempt at characterizing the contours of the paradigmatic shift in the nature of warfare was formulated already by 1989 in Lind et al. They addressed the likelihood of a fourth generation of warfare emerging, which they argued was clearly distinguishable from the preceding three generations of mass warfare, industrial warfare, and Blitzkrieg. As Robb summarizes: The first two generations were about scale and firepower. Military forces grew in size through greater mobilization of the state’s citizens, who were motivated by nationalism. . . . In World War II, the conflict between states then turned to technology of maneuver to negate the effectiveness of firepower and mass. (2007, 23)

Implicit in the above quote is the linkage between modern warfare and the emergence of the modern nation-state. Beginning in the nineteenth century wars clearly were fought between territorially defined nation-states, who,

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Threats to the CBW Prohibition Regimes

in order to remain competitive on the international stage, had to establish standing armed forces and saw themselves confronted with “an increasing need for ‘rational’ organization and ‘scientific’ doctrine to manage these large conglomerations of force” (Kaldor 2007, 26). As Münkler has elaborated, the “statization of war” occurred and manifested itself within the context of “six distinctions and demarcations that the state performs and guarantees” (2005, 38ff.). First, the state defines through its recognized territorial boundaries the “inside,” over which it exerts the politically and legally binding allocation of values, and the “outside” where these state powers do not exist. Second, through the control of its borders, a state acquires the power to define border crossings as a violation of its sovereignty and thus an act violating the peace that may result in a transition to war. From this power over territorial borders flows thirdly the “state’s exclusive claim to define who, in a political sense, is to count as a friend and who as an enemy” (Münkler 2005, 39, emphasis in original). These three primary demarcations that distinguish the modern territorial state and provide the basis for it to wage war against its peers are supplemented by another three demarcations that have developed during the area of the old wars. The first of these was based on the growing importance of the battle in warfare—in contrast to the level of economic damage inflicted during the wars of the Middle Ages—and is related to the distinction between combatants and noncombatants in warfare. The symbolism of combatants wearing uniforms and also the more generic symbolism of waging war on the battlefield allowed for the identification of those involved in warfighting and also those winning and losing the war as the result of a decisive battle. This latter point has been of particular relevance for a return to peaceful relations of the actors involved in a war after the conclusion of hostilities. In addition, states have been generally able to distinguish between “the permissible violence of acts of war and criminal violence” (Münkler 2005, 40). In the international sphere this allowed the development of a body of international law from the middle of the nineteenth century onward that aimed at regulating the lawful conduct of war. Beginning with the 1856 Declaration of Paris and through the St. Petersburg Declaration of 1868, this led to the above-mentioned Hague conferences in 1899 and 1907 and the 1925 Geneva Convention with its protocols. Lastly, the “statization” of war—through the establishment of a taxation-based system to fund interstate warfare—allowed a better



Threats to the CBW Prohibition Regimes

15

distinction between war and commercial activities. In the words of Münkler: “What the literature often terms the militarization of politics initially led to a civilizing of society, since it largely prohibited the use of violence as a means of appropriating goods and services” (2005, 41). The evolution of old wars has been shown by Kaldor to have moved through several phases . . . from the relatively limited wars of the seventeenth and eighteenth centuries associated with the growing power of the absolutist state, to the more revolutionary wars of the nineteenth century such as the Napoleonic Wars or the American Civil War, both of which were linked to the establishment of nation states, to the total wars of the early twentieth century, and the imagined Cold War of the late twentieth century, which were wars of alliances and, later, blocs. (2007, 15)

However, the evolution of old wars was even more complex and, in addition to the type of polity waging war, according to Kaldor, occurred along four additional key dimensions: goals of war, type of army, military technique, and war economy. While the goals of war shifted from the consolidation of borders to national and ideological conflicts, the type of army involved in the warfighting evolved from mercenary, to conscription, to mass and professional armies, the latter of which have been backed up by a scientificmilitary elite during the second half of the twentieth century. In a similar fashion military tools and techniques saw a dramatic evolution: from the use of simple firearms in the seventeenth century through the development of massive firepower, which led to the threat and use of nuclear weapons. Last but not least, the underlying economic parameters of old wars have changed substantially over time, ranging from the “regularization of taxation and borrowing” of the absolutist state to the emergence of a military-industrial complex in the late twentieth century. Table 2.1 below provides an overview of these different developments. Yet, while the goals of wars have evolved over time and as a function of the types of polities predominantly engaged in warfare, as Smith (2008) points out, the central objective of all old wars was to decide a political outcome, usually in a clearly marked period of time and on the battlefield. All these parameters have changed with the advent of what he calls the “war amongst the people.” In addition, Kaldor’s summary of developments is somewhat misleading as far as the emergence of this second, competing type of war during the second half of the twentieth century is concerned. While she is

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Threats to the CBW Prohibition Regimes

TABLE 2.1. The evolution of old wars 17th and 18th centuries

19th century

Early 20th century

Late 20th century

Type of polity

absolutist state

nation-state

coalition of states; multinational states; empires

blocs

Goals of war

reasons of state; dynastic conflict; consolidation of borders

national conflict

national and ideological conflict

ideological conflict

Type of army

mercenary/ professional

professional/ conscription

mass armies

scientific-military elite/professional armies

railways and telegraph, rapid mobilization

massive firepower; tanks and aircraft

nuclear weapons

expansion of administration and bureaucracy

mobilization economy

military-industrial complex

use of firearms, deMilitary technique fensive maneuvers, sieges War economy

regularization of taxation and borrowing

Matrix shows evolution of old wars over time in relation to five different criteria. source: Kaldor 2007, 16.

right that the advent of the nuclear age overshadowed conventional warfare, and in a way can be said to have helped reduce the likelihood of conventional war breaking out—at least among major powers and in Europe at the dividing line of the East-West conflict—her depiction of old wars somewhat camouflages the emergence of the new war phenomenon during the same period of time. However, before discussing this new form of warfare, it is necessary to relate the development and use of CBW to the old wars as they evolved over time. Chemical and Biological Weapons Development and Use in the Era of Old Wars One of the striking features of a review of the scholarly literature on the evolution of warfare (van Crefeld 1991; Boot 2006; Münkler 2005; Kaldor 2007; Smith 2008; Shaw 2005) is the practically complete absence of any analysis of the development and use of chemical and biological weapons. One conclusion that can be drawn from this lack of discussion is that these types of weapons did not have a major impact on the evolution of war as such, but rather fitted in with the general trends of the evolving old wars. However, these types of weapons have been developed and—in the case of CW—used on a large scale.



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Chemical Weapons Toxic chemicals that have been developed, produced, and used as CW agents are usually subdivided into four categories: pulmonary toxicants, blood agents, vesicants, and nerve agents. The first three of these types of CW agents were developed and used on a large scale as chemical weapons during World War I. Pulmonary toxicants, sometimes referred to as lung irritants or choking gases, such as chlorine or phosgene, were the most widely used CW agents during World War I (Martinetz 1995). According to some estimates they account for more than 80 percent of the fatalities attributable to chemical warfare on the battlefields of World War I (WHO 1970, 27). During World War II they were stored in the CW arsenals of many belligerent states, without being used, however. Up until today, chlorine and phosgene are used on a large scale as industrial chemicals in a variety of applications. The second category of warfare agents, so-called blood agents like hydrogen cyanide (HCN) or cyanogen chloride (ClCN), were first developed for chemical warfare purposes early in World War I. However, because of their physical properties they were used for only a short period of time. The high volatility of the cyanides made it impossible to produce them in high enough concentrations on the open battlefield. Current industrial operations of cyanide-based compounds are widespread and thus also demonstrate the dual-use character of many traditional CW agents. The third category of CW agents, vesicants or blistering agents, fall into two subgroups: one includes the mustard agents, and the other is a group of arsenic compounds. They are much more persistent in the environment than the weapons in the previous two categories. These weapons were extensively used during World War I, stockpiled on a large scale during World War II, and in the case of mustard agents are still considered major CW agents, which were also used by the Iraqi regime under Saddam Hussein during the 1980s against many Kurdish villages in northern Iraq, including the town of Halabja. Lastly, nerve agents like Tabun, Soman, and Sarin were first developed by German chemists in the 1930s and subsequently weaponized by Nazi Germany. However, as in the case of the other types of CW, they were not used during World War II. As one study into the history of chemical warfare has shown, Adolf Hitler did not authorize CW use due to the uncertain military utility and unknown retaliatory capabilities of the Allied forces. By early 1945, the “military situation had grown so desperate that the Nazi leadership was more preoccupied with safeguarding its arsenal of nerve agent weapons than with

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planning for their use” (Tucker 2007a, 73). Similarly, the “strong antipathy of [U.S.] President Roosevelt and many of his top generals toward chemical weapons had limited their integration into U.S. force structure and military doctrine” (ibid., 102). However, this changed after World War II when both the United States and the then Soviet Union tried to exploit the German advances in the field of nerve agents to their own advantage in the unfolding Cold War (ibid., 121).Thus, the superpower competition during the Cold War was not confined to conventional and nuclear weapons, but extended also to CW. After having exploited and developed further German first-generation nerve agents, this phase involved mainly the development and deployment of a second generation of nerve agents during the 1950s, including VX on the part of the United States and its allies (Smart 1997), and a series of even more toxic organophosphorous compounds, including the so-called A-230 and A-232, in the early 1970s by the then Soviet Union. These were part of a program called “Foliant,” which sought to “acquire a new class of nerve agents with greater toxicity, stability, persistence, ease of production, and other militarily relevant properties” (Tucker 2007a, 231). Another trend in CW development during the Cold War period sought to address logistical and safety issues in dealing with, and especially storing, chemical warfare agents in weapon systems over long periods of time. As one semiofficial U.S. history summarized: Back in the 1950s, the army had begun looking at binary weapons. Until that time, chemical weapons were unitary chemical munitions, meaning that the agent was produced at a plant, filled into the munitions, and then stored ready to be used. Since most agent was extremely corrosive, unitary munitions were logistical nightmares for long-term storage. The binary concept was to mix two less-toxic materials and thereby create the nerve agent within the weapon after it was fired or dropped. Because the two precursors could be stored separately, the problems of long-term storage and safe handling of chemical weapons were therefore solved. (Smart 1997, 65)

However, it took several decades, numerous studies, and heated political debates until the U.S. government in the mid-1980s could authorize the replacement of tens of thousands of unitary chemical weapons with more modern binary ones. Given the continued criticism within the United States of this replacement, the Reagan administration was at one point presenting this armament decision as part of a “double track” strategy along the lines



Threats to the CBW Prohibition Regimes

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of NATO’s nuclear rearmament decision a few years before, arguing that without a credible U.S. CW deterrent the Soviet Union and its allies could not be expected to seriously engage in CW arms control negotiations (Tucker 2007a, 260). Not surprisingly then, the U.S. Congress authorized the binary CW program under the condition that the Reagan administration had to seek consent from its NATO allies for the stationing of the new weapons on European soil. In addition to the United States pursuing a binary CW program, several other states were considering these new types of CW, including the United Kingdom, France, and the Soviet Union, the latter in the context of the above-mentioned secret “Foliant” CW program. According to one insider account, the above-mentioned nerve agents A-230 and A-232— together with the Soviet VX equivalent, called “substance 33”—formed the basis of the Soviet binary CW efforts. Two of the resulting Novichok agents were after extensive tests in the late 1980s adopted as chemical weapons by the Soviet army (Mirzayanov 1995, 24f.). It has to be noted, though, that CW development and—more importantly—use were not confined to the two superpowers and their military allies. Rather, these types of unconventional weapons were also used in conflicts in the developing world. Two examples, the Egyptian CW use in the war against Yemen and, even more so, the Iraqi CW use against Iran and against its own Kurdish population, stand out not only in terms of the devastating effects on their victims but also with a view to the silence with which the international community treated these violations of the 1925 Geneva Protocol. According to one account of the repeated Egyptian CW use during the civil war in Yemen, [f]or five years (1963–67), the Egyptian Air Force employed CW in Yemen, delivering them mainly with Soviet made Ilyushin-28 aircraft. The chemical attacks were targeted primarily at royalists who had found shelter in the caves of Yemen’s mountains, where conventional warfare was ineffective. (Shoham 1998, 48)

However, other assessments raise doubts concerning the credibility of at least some of the reported instances of CW use by Egyptian forces. Especially the earlier incidents of reported Egyptian CW use in the early to mid-1960s are based on weak documentary evidence, whereas the reported CW use in 1967 that was investigated by the International Committee of the Red Cross (ICRC) enjoys a higher credibility according to such a more cautious assessment (SIPRI 1971c, 225–238).

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In contrast, the veracity of reports about Iraqi CW use during its 1980s war with Iran and against its own Kurdish population is uncontested. Beginning in the summer of 1982 Iraqi forces began to use tear gas against Iranian troops in a battle near the town of Basra. Due to the tactical success of its employment and the lack of an international condemnation soon afterward, the Iraqi leader began to authorize the escalation to the use of mustard agents on the battlefield (Tucker 2007a, 250). Despite confirmation of Iraqi nerve agent use by an international team of experts who had been dispatched by the UN Secretary General to investigate the Iranian government’s accusations, the international response to Iraqi atrocities remained largely muted. Having learned that violations of the 1925 Geneva Protocol do not carry any substantial penalties inflicted by the international community, in 1988 the Iraqi leadership began to use CW also against its indigenous Kurdish population. The most widely known incident of CW usage as part of the so-called Anfal campaign occurred in March of that year in the Kurdish town of Halabja (Human Rights Watch 1993). Biological Weapons In contrast to CW, biological weapons have never been used in traditional interstate warfare. As we have argued elsewhere, BW are often subdivided into four categories: bacteria, viruses, rickettsiae and fungi (Kelle, Nixdorff, and Dando 2006, 36f.) Another categorization that also indicates areas of overlap between BW and CW breaks biological warfare agents down into disease-causing microorganisms, toxins produced by living organisms and bioregulators (Koblentz 2009, 9f.). While the first two categories have been the object of BW concerns for a long time, bioregulators, that is, biochemical substances produced by the human body in tiny amounts for the regulation of physiological functions, have only recently become an issue of concern (Dando 2001; Dando and Furmanski 2006). Early attempts at BW use can be traced back to siege warfare in the Middle Ages and the “gifting” of pox-infested blankets by British troops to Native American tribes (Wheelis 1999a). Yet, it was only after the mechanisms of infectious disease began to be understood in the late nineteenth and early twentieth centuries that systematic efforts to utilize disease as a weapon of war were undertaken, first in World War I with BW sabotage campaigns by both sides (Wheelis 1999b) and subsequently during the interwar years. Beginning in the 1920s biological weapons research and production activities were undertaken in a number of countries including Germany, France, the



Threats to the CBW Prohibition Regimes

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United Kingdom, Canada, the United States, and the Soviet Union (Geissler and van Cortland Moon 1999). The one BW program that undoubtedly had the biggest impact on subsequent developments was the one undertaken by imperial Japan (Harris 1999). As part of this program, Japanese scientists and military personnel experimented on human subjects with different agents, conducted open-field experiments, and tried to develop usable weapons to disseminate BW. Despite all the efforts put into the program over more than a decade, it did not result in a usable biological weapon for the large-scale dispersal of biological agents—instead the Japanese army had to rely on sabotage techniques (Guillemin 2005, 84f.). As a result, the most interesting data to be derived from the Japanese program from a U.S. point of view were documents of medical experiments on humans (including some eight thousand microscopic slides and detailed autopsy data). The autopsies included those of victims of inhalational anthrax, of special interest to the Americans. (ibid., 79)

In the judgment of a U.S. BW expert in 1947, the United States was “well ahead of the Japanese in production on a large scale, in meteorological research, and in practical munitions. . . . However, data on human experiments, when we have correlated it with data we and our Allies have on animals, may prove invaluable” (quoted in Guillemin 2005, 85). It was on the basis of the assumed value of this kind of information, along with the beginning of the Cold War with its concomitant superpower competition, that leading Japanese BW scientists were granted immunity from prosecution for war crimes (Guillemin 2008). In other words: a race for enemy CBW knowledge and expertise similar to the one for German CW plans was taking place with respect to Japanese BW program data. As Dando et al. have summarized, during the early Cold War period some states continued or restarted their pre–World War II BW programs—Canada, the United Kingdom, the United States, and the Soviet Union were in the former category, France in the latter (Dando et al. 2006). Others, most notably Iraq and South Africa, only started their programs in the 1970s and 80s, respectively. While most programs were aiming at producing weapon systems with effects as devastating as nuclear weapons (Guillemin 2005, chap. 5), others like the South African one were more geared toward sabotage and assassination strategies. The first category of BW programs clearly has to be seen in the context of the bipolar confrontational Cold War logic of at least

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initially emphasizing an ability to retaliate in kind to a large-scale BW attack. As these perceptions changed and states like the United Kingdom and France acquired their own nuclear deterrent, their offensive BW programs began to be phased out in the 1950s and 60s, respectively. In the late 1960s the U.S. government under President Richard Nixon reinforced this trend and abandoned its offensive BW program (Tucker 2002; Guillemin 2005, chap. 6). As Dando et al. have pointed out, this represents a shift in the perceived utility of BW and signifies a somewhat contradictory policy given successful large-scale openair tests of BW during the mid- to late 1960s: Increasing reliance on nuclear deterrence was thus removing the major incentive for states to acquire BW as an element in ensuring their national security at just the time that their potential utility for attacking large targets was becoming apparent. (2006, 357)

In contrast to the large majority of BWC States Parties, who have lived up to their treaty obligation to not develop, produce, stockpile, or use biological weapons, the then Soviet Union intensified its efforts and expanded its offensive BW program into the largest one ever having been undertaken on the state level (Rimmington 2003; Hart 2006). At its height, the program’s research, development, and production activities involved a workforce of several tens of thousands employees and a huge infrastructure, and it reportedly was utilizing the latest developments in the life sciences to create genetically modified pathogens (Alibek 1999). The program’s existence was officially acknowledged only in 1992 by Russian President Boris Jelzin. Despite a series of trilateral inspections jointly conducted by U.S., U.K., and Russian BW experts, there remains some residual uncertainty as to the character of Russian BW activities since then (Kelly 2002; Knoph and Westerdahl 2006). Like the offensive Soviet BW program, the one pursued by Iraq from the early to mid-1980s onward clearly violated the international legal norms against BW, as embodied in the 1925 Geneva Protocol and the 1972 BWC. During the few years of its existence it included research into and weaponization of predominantly three biological agents: Clostridium botulinum toxin, Bacilus anthracis spores, and, somewhat unusually, an Aflatoxin. The last of these is not a commonly known warfare agent, but it is known to have “toxic, immunesuppressive, mutagenic, and carcinogenic” effects (Madsen 2005, 277). According to Iraqi accounts, several thousand liters of the first two of these agents were filled into munitions. Although much shorter in duration and



Threats to the CBW Prohibition Regimes

23

smaller in scope than the Soviet BW program, details of the Iraqi program have been equally difficult to ascertain—despite the very intrusive access regulations contained in the 1991 UN Security Council Cease-Fire Resolution, which required Iraq to open all its former BW facilities to the inspection regime that was initially implemented by UNSCOM (United Nations Special Commission), subsequently continued by UNMOVIC (United Nations Monitoring, Verification, and Inspection Commission), and intensified after the second Gulf War by the ISG (Iraq Survey Group) (Pearson 2006). The offensive South African BW program is instructive in that it departs from the otherwise emerging pattern of weaponization of biological warfare agents by states in order to inflict casualties on a massive scale and thus move within the realm of the classical industrial, interstate warfare paradigm. As mentioned above, the South African program, in contrast, was more focused on sabotage and assassination, thereby giving an indication that BW might be perceived as useful by states in a strategic setting that is not dominated by old-war thinking. Situated halfway along the spectrum between classical CW and BW agents are so-called bioregulators—such as neurotransmitters—or mid-spectrum agents. Bioregulators are chemicals normally produced in the human body that control communication between cells and that play a crucial role in governing the nervous, endocrine and immune systems. (Koblentz 2009, 10)

During the Cold War a number of states supplemented their offensive CW and BW programs with research, development, and production of this category of agents. As Dando and Furmanski have shown, the British search for such a mid-spectrum incapacitant and the U.S. program to weaponize 3-quinuclidinyl benzilate (BZ) are telling examples of states’ procurement efforts in this area (Dando and Furmanski 2006). They conclude that the “effort to find a non-lethal chemical incapacitant during the Cold War was a distinct failure” (ibid., 250). Similarly, the fentanyl-derivative use by Russian special forces to end the October 2002 Moscow theater hostage crisis demonstrates that Russian authorities had a clear interest in developing and employing such mid-spectrum agents but were not able to control all its effects. Yet, as another review of the scientific literature shows, there is increasing concern that bioregulators will emerge as “a new class of weapons that can damage the nervous system, alter mood, trigger psychological changes and

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Threats to the CBW Prohibition Regimes

kill” (Bokan 2005, 205). This is due to the fact that “over the last twenty years, neuroscience has produced an explosion of knowledge about receptor systems in nerve cells that are of critical importance in receiving chemical transmitter substances released by other nerve cells” (ibid.)—a trend we shall return to in the chapter on scientific and technological developments below. In summary, during the era of old wars chemical and biological weapons have been developed not only by major states but also by (aspiring) regional powers like Egypt, Iraq, or South Africa for a range of different uses. The use of CW during World War I was clearly driven by attempts to break the stalemate of trench warfare. As far as the subsequent planning for CW use both in the interwar period and during the Cold War was concerned, major powers seem to have largely followed the logic of deterrence and retaliation in kind. More advanced research and development efforts were—in the case of the binary CW programs—aiming at increasing both the shelf life of the agents and the safety margins for troops handling chemical weapons. In contrast, CW development and usage by developing states has been characterized by attempts to either use chemical warfare agents as force multipliers against unprotected enemy troops, insurgents, and civilian populations, or to develop them for sabotage and assassination contingencies. It has to be noted, however, that with the exception of Iraqi CW use against Iranian troops, none of these uses actually occurred in conflicts that conform to the patterns of old, interstate wars. Similarly, BW have not been used in old war settings. At the same time, the character of the offensive BW programs of major powers both during the interwar period and the Cold War was a function of the larger prevailing strategic trends of the time. The early Cold War offensive programs of both the United Kingdom and France of initially pursuing and later abandoning BW acquisition are a case in point, as both courses of action were largely a function of these countries’ development of nuclear weapons. In addition, all major offensive BW programs, for as long as they lasted, sought to employ the latest scientific and technological developments (Dando 1999). Again, the above-mentioned utilization of genetic engineering techniques in the Soviet BW program serves to illustrate the point. However, as with the CW programs discussed previously, there are also examples in which states sought to employ BW outside the old war context for assassination and sabotage purposes.



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New Wars and Potential New Utilities of Chemical and Biological Weapons The “New Wars” Concept As much as the old wars were not a monolithic concept that resulted in a singular manifestation, the notion of “new wars” is not to suggest that they either have emerged overnight or do not carry with them some of the characteristics of old wars. Kaldor (2007, 3), for example, acknowledges that the new war concept overlaps with certain characteristics of earlier wars for which the labels of “small wars” and “low-intensity conflicts” had been introduced. Notwithstanding these overlaps, she argues that “new wars” are sufficiently different from the old ones in three dimensions, so as to justify the use of a new term. These three dimensions are the goals of the new wars, the means with which they are fought, and the way they are financed. According to Kaldor, the goals are now related to an updated version of identity politics which is pitting “cosmopolitanism, based on inclusive, universalist, multicultural values” against the “politics of particularist identities” (2007, 7). Related to the changed goals are “[t]he strategies of the new warfare [which] draw on the experience of both guerrilla warfare and counter-insurgency” (ibid., 8). They seek to avoid battles in the classical military sense and can either attempt to “win the hearts and minds” of populations or to destabilize whole areas by spreading “fear and hatred.” New wars are usually fueled by what Kaldor calls a “globalized war economy,” built on decentralized war economies in which “the fighting units finance themselves through plunder, hostage-taking and the black market or through external assistance” (ibid., 10). It is this latter characteristic of the new wars that has led Münkler (2005, chap. 2) to identify similarities between the new wars and the wars of the Middle Ages, before the statization of war took care of its financing through a taxation-based system. While Kaldor’s characterization of new wars is mostly based on a detailed case study of the war in Bosnia-Herzegovina from 1992 to 1995, her findings clearly have a wider applicability. Expanding on Kaldor’s argument, General Rupert Smith traces the emergence of the new wars, which he has labeled “wars amongst the people,” back to the days of revolutionary and guerrilla warfare developed in the nineteenth and twentieth centuries. After reviewing in detail both the evolution of industrial interstate war and its “antithesis” of revolutionary and guerrilla warfare, he summarizes that

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[b]y 1946 there were clearly two models of war: the paradigm of interstate industrial war, a trial of strength to force the opponent to our will, and its antithesis of revolutionary and guerrilla warfare, a clash of wills between the militarily weak and the strong, in which the weak engaging only in tactical acts of its choosing attempts to turn the power of the state against itself— aiming to win the clash of wills rather than the trial of strength. . . . The two would jostle along for over forty years, obscuring the new paradigm that evolved in the wake of the Second World War: war amongst the people. (Smith 2008, 182)

Camouflaged was the evolution of the new paradigm of war amongst the people by the nuclear weapons–fueled standoff between the United States and its superpower rival, the Soviet Union. As Smith convincingly argues, early signs of wars among the people could be observed as early as the 1950s in Indochina. However, given the dominance of the nuclear logic, military planning, even after the end of the Cold War, continued to be guided by the paradigm of interstate warfare, resulting in a situation where even today the dominant conceptualizations of war and the formulation of new security strategies, as well as force planning and procurement decisions, are not matched to the new-war-amongst-the-people paradigm. According to Smith, the new paradigm is characterized by “six basic trends” (2008, 271): · The ends for which we are fighting are changing from the hard objectives that decide a political outcome to those of establishing conditions in which the outcome may be decided · We fight amongst the people, not on the battlefield · Our conflicts tend to be timeless, even unending · We fight so as to preserve the force rather than risking all to gain the objective · On each occasion new uses are found for old weapons and organisations which are the products of industrial war · The sides are mostly non-state, comprising some form of multi-national grouping against some non-state party or parties. (Ibid.)

These characteristics of war amongst the people will first be briefly discussed and subsequently related to potential new utilities of CBW.



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Changing Ends Whereas in old wars clear-cut strategic goals were informing the conduct of war, this has given way in the new wars to attempts to “create a conceptual space for diplomacy, economic incentives, political pressures and other measures to create a desired political outcome of stability, and if possible democracy” (Smith 2008, 272). Such changing ends inevitably require a change in approach, whose crucial feature, according to Smith, is the need to “capture the will” of the people. Although in his mind a “clear and basic concept” and “whilst for many years the military has understood the need to win the ‘hearts and minds’ of the local population, this is still seen as a supporting activity to the defeat of the insurgents rather than the overall objective” (ibid., 279f.). In a nutshell, many politicians are seeking to employ military force following the logic of classical interstate warfare and not the logic of the new wars in which the “clash of wills” has replaced a military “trial of strength.” Fighting among the People The second trend relates to the increasing porousness and eventual dissolution of the borders of traditional military battlefields. While the origins of this trend could be observed as early as the Vietnam War when the “battlefield” was extending to large stretches of the country, and distinguishing between enemy combatants and the civilian population was oftentimes difficult to accomplish, this has become one of the defining features of the new wars. As Smith notes, the people are involved in this new form of warfare in a number of ways: Military engagements can take place against formed and recognizable groups of enemies moving amongst civilians, against enemies disguised as civilians, and unintentionally and intentionally against civilians. (Smith 2008, 280)

As the first two of three scenarios indicate, the enemy insurgents, guerrillas, or terrorists can use the population in a given territory for different purposes to further their own ends: they can use the people to disappear among them in between operations, thereby providing them with a “sanctuary area.” Alternatively, they can use the people as a “preparation area” for their next attack against an intervention force. Lastly, the people are at risk of being in the “operational area” when an attack occurs. There are many examples in which civilian casualties in the new wars exceed military ones due to insurgents setting off improvised explosive devices or similar attacks.

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What this clearly points to is the fact that once an intervention force has occupied a territory, the initiative largely moves to the insurgents opposing the intervention. Developments in Iraq since major combat operations were declared over in 2003 have clearly borne out this assessment. Hence, Smith concludes, “We do not intervene in order to take or hold territory; in fact; once an intervention has occurred a main preoccupation is how to leave the territory rather than keep it” (2007, 272). Timeless Conflicts Yet despite the intentions to withdraw forces as quickly as possible without jeopardizing the overall goals pursued by a military intervention, the changing ends of the new wars, the disappearance of the battlefield in the traditional sense, and the concomitant changes in the modus operandi of the enemy all tend to draw out military conflicts. As Smith summarizes: [T]he trend of our recent military operations is that the more the operation is intended to win the will of the people, the more the opponent adopts the method of the guerrilla and the more complex the circumstances, the longer it will take to reach the condition in which a strategic decision can be made and a solution found. (2007, 293f.)

Primacy of Force Preservation A further characteristic of the new wars, which is often adding to the already discussed factors in prolonging military conflicts, is the need to preserve the Western military forces intervening in conflicts. Although this can be partly attributed to attempts to minimize the “body-bag” effect of killed troops being repatriated to their home countries, Smith argues that the underlying rationale is more complex. Mostly, not trying to preserve men and material is “bad economics” at a time when practically all Western armed forces have been reduced in size and resources and, as a result, many of these forces are overcommitted (2007, 295). The notion of force preservation ties in with the concept of “risk-transfer war” that has been developed by Martin Shaw. One of his fifteen rules for such wars stipulates that “wars must, above all, minimize casualties to Western troops” (2005, 79). However, as Smith points out, the same logic applies to enemy insurgents or guerrillas as well, except for cases where their operations demand and can draw upon a sufficiently large supply of candidates for suicide missions.



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New Uses for Old Tools Suicide bombings, AK-47s, and, most of all, machetes have been the most effective weapons in military conflicts since the end of the Cold War. In contrast to these dramatic changes on the side of enemies encountered by Western forces, those forces are still mostly organized to succeed in the interstate industrial war paradigm fighting the Warsaw Pact threat. As Smith rightly points out, “the enemies we face today are of a completely different nature, mostly armed with much lighter weapons” (2007, 299). And although there are of course developments taking place in military technology, “[o]perational concepts and organizations tend to be adjusted to take advantage of the technology rather than to fight in a different way” (ibid., 300). In addition, the enemy has adapted in operational terms so as “to drop below the threshold of the utility of our weapon systems. They have learned not to present a target that favours the weapons we possess and the way we use them” (ibid., 301). Emergence of Nonstate Actors What has become clear from discussing the first five trends of the waramongst-the-people paradigm is that state-to-state confrontations have given way to (usually) multinational intervention forces being opposed by substate entities in the form of insurgents, guerrillas, or terrorist networks. Concerning the emergence of multinational intervention forces, Smith succinctly summarizes the reasons for their emergence as the predominant actor on one side of the new wars: [W]e need more forces, or more space; we want the legitimacy of numbers; we want to spread the risk—of failure, to our forces and resources, of responsibility; and we all want a seat at the table. (2007, 303)

In only a few instances have such multinational coalitions in recent years been confronted by nation-states, and in these instances the states—think Afghanistan or Iraq—were disposed of rather quickly and unceremoniously. It is after the quickly achieved military “victory” in the classical sense that substate actors that are taking part in an insurgency are coming to the fore. As already alluded to in relation to the other five trends of the new wars among the people, these insurgents or guerrillas engage with the enemy, at a time and in a modus operandi of their choosing, in a way that will increase their chances of winning the will of the people. Smith summarizes the fundamental

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differences of the multinational coalitions and their enemy substate groups as follows: In contrast to the formality of the multinational organization, and its dependence on the formulas and procedures that states impose so as to manage their affairs at the least risk to themselves, the non-state actors appear formless. (2007, 305)

The following section will draw together the trends and patterns identified in the discussion of the traditional uses of CBW during the era of old wars with the main characteristics of new wars thus identified. Potential New Utilities of CBW For this purpose two of the three types of new utility for (bio)chemical weapons that Robinson (2008a) has identified are worth recalling. These are “wider changes in the nature of warfare” (ibid., 226) and the potential use of CBW as a tool in counterterrorist or counterinsurgency operations. Utilizing both Kaldor’s characterization of new wars and Smith’s six basic trends of his concept of war amongst the people, it is now possible to unpack Robinson’s concern over new utilities for CBW and identify some of the areas in which characteristics of the new wars might impinge on both states’ and substate actors’ interest in these kinds of weapons. Both Kaldor and Smith note the different goals that are driving new wars. While Kaldor emphasizes the clash between cosmopolitanism and particularist identities, Smith is more value-neutral and sees the changing ends simply in establishing a condition under which means other than the military can then be employed to solve the underlying political conflict. Both agree that it is essential in the new war context to capture the “hearts and minds” or the “will” of the people. Kaldor’s notion of spreading “fear and hatred” is more closely associated with the pursuit of particularist identities, and thus such groups might be more readily assumed to be interested in using CBW among unprotected enemy military personnel or civilian populations. To the extent that these particularist identities are being pursued by substate groups, one is led into the debates about terrorist use of CBW. However, based on the historical record and the knowledge, materials, and equipment required for sufficiently large attacks to have a militarily significant effect, we maintain that the more likely perpetrator interested in using CBW is a state actor with such a particularist identity and corresponding goals. Reviewing the historical record of CW use, it would seem



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that both Egypt’s involvement in the Yemeni war and Iraq’s use of CW in its war with Iran fall in this category. It is also easy to see how at the other end of a spectrum of potential CBWuse scenarios the argument could be made that it is more “humane” and in line with universalistic values to biochemically incapacitate, rather than to shoot, suspected guerrillas or enemy insurgents. Proponents of so-called nonlethal CW in the United States and elsewhere have long attempted to cast their efforts in such a positive light. Unfortunately, the pitfalls in such an approach were all too clearly demonstrated during the Moscow theater hostage-taking in October 2002. The hostage situation lasted for three days during which two of the hostages were killed. When the Russian security forces stormed the building to free the hostages, they did so only after large quantities of a “gas” had been dispersed in the theater. The chemical agent, whose identity initially remained undisclosed by Russian authorities, put to sleep practically everybody within the theater. Unfortunately, its impact did not stop there: the chemical used, which later was revealed to be a fentanyl derivative, killed more than 130 of the approximately 830 hostages. In addition, all the Chechen insurgents who had taken the hostages were executed by security forces while knocked-out by the chemical incapacitant. Thus, in this instance, as in the previous cases of the Egyptian CW use in Yemen and U.S. use of chemical irritants and incapacitants during the Vietnam War, the chemical agent had actually been used in conjunction with the application of lethal force and had thus acted as a force multiplier, not a more humane form of warfare (Editorial 2003). Nonetheless, such a supposedly value-based argument might find additional support from more operational considerations, such as the very fact that the fighting takes place among the people who might be used as a shield by the enemy. Again, to be able to incapacitate larger groups of people might reduce the likelihood of civilian casualties. Furthermore, as proponents of the risk-transfer war approach would most likely point out, use of CBW could be used to support the goals of force preservation and of ending an otherwise potentially timeless conflict, identified by Smith (2008) as two of the characteristics of wars amongst the people. A different scenario that leads us back to the issue of the dual-use nature of many chemical compounds involves the use of either toxic industrial chemicals or the acquisition and use of nontoxic dual-use precursors of known chemical warfare agents by insurgents. Table 2.2 gives an overview of the widespread civilian applications in which dual-use precursors are utilized.

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TABLE 2.2. Commercial applications of chemical weapons precursors. Type of chemical agents

Commercial uses of chemical ingredients

Mustard agents

Lubricant additives; ballpoint pen ink; manufacture of plastics, paper, and rubber; . . . textile dyes, pesticides.

Tabun

Petrol additives, hydraulic fluids, insecticides, flame retardants, pharmaceuticals, detergents, pesticides.

Sarin

Flame retardants, petrol additives, paint solvents, ceramics, antiseptics.

Soman

Lubricants, cleaning, and disinfectants for brewery, dairy, and other food-processing equipment.

VX

Organic synthesis, insecticides, lubricant oil, pyrotechnics.

source: Coleman 2005, 144, adapted from CIA 1996, The Chemical and Biological Weapons Threat, Washington, D.C., 9–16.

What this points to is the increased dangers of CBW usage—either in the “traditional” sense or in more uncommon scenarios such as the spread of toxic industrial chemicals—in areas in which, on the one hand, chemical industry is present and, on the other, state authority is not. In other words, an increased danger exists where the statization of the war economy has been reversed and the pursuit of the new wars has reverted back to plunder and other unlawful “means of appropriating goods and services” (Münkler 2005, 41). Summary and Conclusions This chapter has set out to discuss the threats emanating from the changing nature of warfare for the chemical and biological weapons prohibition regimes. This concern was at least partly triggered by Robinson’s (2008a) observation that there might be three new utilities for (bio)chemical weapons, two of which can be clearly related to new wars and the characteristics that distinguish them from traditional interstate warfare. The third of these new utilities is linked to the revolution in the life sciences and will be discussed in subsequent chapters. As this brief review of the academic literature on the new wars has shown, these differ in several respects from classical industrial interstate wars. Some of these features of new wars lend themselves to create new opportunities and/ or pressures for the use of chemical and biological warfare agents. On the part of Western governments involved in the new wars as part of an intervention



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force, these features are linked to issues such as protection of their own forces and equipment, attempts to extract insurgents from a population in which they are hiding or from locations that are not amenable to the use of conventional forces, and a desire to shorten the duration of seemingly endless conflicts. To some extent similar motivations could be observed in the past in the case of Egyptian CW use in Yemen, U.S. use of chemical irritants and incapacitants in Vietnam, and Russian use of a calmative in the freeing of the Moscow theater hostages. There is thus precedent of giving in to the abovementioned pressures to use CBW in counterinsurgency operations that could now and in future be reinforced by perceptions of greater usability due to increased scientific and technological understanding. While threats to the CBW prohibition regimes from such use would emanate from the deliberate development and use of CBW by state actors, a less severe set of scenarios, in terms of their implications for regime robustness, are located at the opposite end of the spectrum of technological innovation. These scenarios are related to the availability—in the overall context of strongly reduced or absent state authority in a new war context—of toxic industrial chemicals or (toxic) precursors of known chemical warfare agents. The 2007 attacks in Iraq involving chlorine are a case in point (Weitz, Al-Marashi, and Hilal 2007). However, it is to the revolution in the life sciences and its implications for the viability of the CBW prohibition regimes that we will now turn our attention.

3

Threats to the CBW Prohibition Regimes The Revolution in the Life Sciences

Introduction After having discussed the impact of the changing nature of warfare on the perceived utility of CBW and a potential resurgence in the interest of states in such weapons in a new war context, we will now turn to the revolution in the life sciences as a factor potentially undermining the CBW prohibition regimes. In this context it is important to note that scientific understanding of the nature of infectious diseases dates only from the latter part of the nineteenth century, and during the twentieth century a series of offensive biological weapons programs by major states demonstrated quite clearly that it was possible to use biological and toxin weapons effectively against humans, animals, and plants on a variety of different scales. Anti-agriculture and some forms of antipersonnel attacks—for example, the contamination of food—could clearly be possible for terrorists with low levels of technical sophistication. But large-scale attacks against people, despite having been shown to be possible in several state offensive programs in the last century, are almost certainly still beyond the capability of terrorist groups today. Using biological and toxin weapons would, in some ways, be easier for a terrorist group than for the military forces of a state. The need for effective storage, transport, multiple weapon systems, doctrine, and training would be far less onerous. However, in order to carry out a large-scale attack against people, the biological or toxin weapon would have to be prepared— weaponized—so that it would reach numerous victims. A crucial question, 34



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therefore, is whether ongoing advances in science and technology could bring such capabilities into the hands of terrorists. Characteristic of the developments in science and technology over the past three decades is the enormous accumulation of knowledge concerning the molecular mechanisms and functions of biological systems. While this knowledge is essential for countering disease and promoting public-health security in general, it can at the same time be malignly misused for waging biological warfare. These developments are occurring in an “environment in which globalization is impelling diffusion of industrial and other technologies around the world at what seems to be an accelerating rate” (Robinson 2008a, 231). Two reports of the U.S. National Academies have dealt in particular with the dual-use dilemma regarding advances in science and technology in a biosecurity context. The work of the Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology was chaired by Gerald R. Fink and hence called the “Fink Committee Report” (National Research Council 2004a). It made several recommendations, but most important for this discussion the committee identified seven classes of “experiments of concern” that should “require review by an Institutional Biosafety Committee.” These experiments of concern include those that: 1. Would demonstrate how to render a vaccine ineffective. 2. Would confer resistance to therapeutically useful antibiotics or antiviral agents. 3. Would enhance the virulence of a pathogen or render a nonpathogen virulent. 4. Would increase transmissibility of a pathogen. 5. Would alter the host range of a pathogen. 6. Would enable the evasion of diagnostic/detection modalities. 7. Would enable the weaponization of a biological agent or toxin.

This report has served to shape some of the approaches of the United States to biosecurity. The work of the Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare Threats followed directly behind the Fink Committee and was cochaired by Stanley M. Lemon and David A. Relman, hence called the “Lemon-Relman Report” (National Research Council 2006). Most notably, the report of a workshop (Institute

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of Medicine/National Research Council 2005) conducted early on by this committee dealt with the very newest of advancing technologies within the framework of managing dual-use risks. In an article (Choffnes, Lemon, and Relman 2006) summarizing the findings of the Lemon-Relman committee work, titled “A Brave New World in the Life Sciences,” the authors made the very clear point that using science for biological warfare or bioterrorism takes on an added dimension with respect to the synergy effect that emerging and enabling technologies can have on the misuse potential. They go on to predict that “previously unanticipated paradigm shifts are likely to occur in the future” (Choffnes, Lemon, and Relman 2006, 28) because new technologies can be combined in unexpected ways, creating applications far different from those originally intended. One present-day paradigm shift that has been taking on more and more relevance has emerged in the relatively nascent field of systems biology, which tries to understand the function of interacting biological systems as a whole. Vital physiological systems such as the immune, nervous, and endocrine systems do not operate alone but are intricately connected through regulatory mechanisms directed by biochemical substances such as cytokines, neurotransmitters, and peptide hormones (biochemical regulators) acting within this vast and very complex network. In this context, the focus is shifted away from the possibility of using microorganisms malevolently to the possibility of using biochemicals as weapons to disrupt the operation of interacting physiological systems (Kelle, Nixdorff, and Dando 2006; Kelle, Nixdorff, and Dando 2008). Although there is clear indication of the rising threat from these agents, the full misuse potential of biochemicals in manipulating interacting physiological systems, and the corresponding need for strengthened control against their potential misuse, has not yet been realized. A major theme of the Lemon-Relman Report (National Research Council 2006) was that bioregulators may pose a more serious threat than has been previously appreciated. These substances have not been generally viewed as potential threats in the past, mainly because of the lack of effective delivery technology. However, the report suggests that this picture is changing rapidly, because new technological developments have made dissemination of these substances much more feasible. This chapter presents an update on advances in science and technology that have particular implications for biosecurity. It focuses on the areas of functional genomics, synthetic biology, systems biology, nanotechnology, and targeted



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delivery systems that have advanced most significantly and appear to be most relevant. In addition, it will revisit the issue of mid-spectrum agents as related to advances in these areas. Although the misuse potential surrounding these agents has been known for some time (Dando 2001; Dando and Furmanski 2006), they are often overlooked, and BW control or prevention efforts are nowhere near addressing their dual-use potential in a satisfactory manner. Functional Genomics Genome analyses are concerned with the determination of the nucleotide base sequence of the entire hereditary information of an organism encoded in deoxyribonucleic acid (DNA) or, in some types of viruses, in ribonucleic acid (RNA). Nucleotides make up the structural units of nucleic acids (RNA and DNA) and contain a sugar, a phosphate molecule, and a base. The sequence of the bases of the nucleotides defines the specific structure of a nucleic acid molecule. Simply expressed, genes are regions of the nucleic acid molecule that encode a functional protein. Functional genomics includes efforts to determine the functions of the genes that can be identified through base sequence analyses. It is hoped that targets for the development of diagnostic and chemotherapeutic reagents as well as vaccines can be defined in the course of these investigations. Advances in sequencing methods over the past three years have reduced sequencing costs by over two orders of magnitude, and next-generation sequencing technologies are rapidly evolving (Shendure and Ji 2008). There are still many challenges facing next-generation methods. Nevertheless, the goal of reducing sequencing costs to $50,000 per human genome has in effect been reached, and some companies claim to be able to accomplish this feat for just $5,000 or less (Podolak 2009). The thirdgeneration sequencing race to produce a human genome sequence for just $1,000 is on and running. “Once the $1000 goal is reached, developers are likely to set their sights on the $100 genome, and, perhaps, someday on the $1 genome” (Podolak 2010, 111). Next-generation technologies will further allow the sequencing of metagenomes (genomes of microorganisms from microbiological communities) without requiring their prior cultivation (Lederman 2009a). This method is still in its infancy, but it could be of particular relevance for the identification of certain microorganisms in an environmental sample, as well as determining what these microorganisms are doing, by identifying the presence of various functional genes.

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Sequencing the entire genome of a microorganism is becoming easier, quicker, and more routine for the identification of fine genetic variations in different strains of the same microorganism, which can help determine the source of the agent as well as provide insight into the pathogenic mechanisms of highly virulent strains (Rasko et al. 2011; Grauer 2011) and thus contribute to the prevention of or response to biological attacks in a positive way. The further development of microbial forensics in accuracy and consistency could contribute greatly toward helping to monitor compliance with the BWC in the future (Tucker and Koblenz 2009; Koblenz and Tucker 2010; National Research Council 2010). Of particular concern is the use of modern methods of genomics, molecular biology, and information technology to create microorganisms. This has been accomplished, for example, with the poliovirus (Cello, Paul, and Wimmer 2002) and a bacterial virus (Smith et al. 2003). Many experts are quick to point out that the poliovirus and the bacterial virus have fairly simple compositions, so that this feat could not be readily repeated at least at the present time in the case of more complex viruses, such as poxviruses. Be that as it may, there have been notable improvements in the ability to manipulate viruses that could lead to the creation of dangerous pathogens from less virulent strains. The genome of poxviruses consists of a linear, double-stranded DNA molecule of 130,000–350,000 nucleotide base pairs, whereas the poliovirus genome is a single-stranded RNA molecule consisting of only about 7,500 nucleotides. The replication (reproduction) of poxviruses is also very complex. Even if the large smallpox genome could be synthesized, this DNA would not be infectious. To be infectious, the DNA requires the activities of protein enzymes packaged into and delivered by the virus upon infection of a host cell. Indeed, poxviruses have been shown to contain more than a hundred different proteins. However, several reports in the literature point to ways of getting around these restrictions. For example, work by Yao and Evans (2003) has shown that this barrier can be overcome by transfecting DNA from a poxvirus into cells already infected with another poxvirus. (Transfection is the process of using a virus as vector to deliver foreign nucleic acids to host cells.) This resident poxvirus will then provide the viral components needed to reactivate the transfected DNA into an infective virus particle. The most prominent example of viral manipulation that has caused considerable concern of late is the resurrection of the extinct 1918 Spanish



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influenza virus. The feat was accomplished by outfitting a relatively avirulent (nonpathogenic) influenza virus with all eight viral gene segments of the 1918 strain, which, as a result, conferred the unique high-virulence characteristics of the 1918 strain on this (formerly avirulent) engineered virus (Tumpey et al. 2005). With each new advancement in methodology, the manipulation of complex viruses to meet designer specifications is becoming easier, and this is more of a reality and has just as wide implications as creating organisms from scratch.

Synthetic Biology A technology that is “on the threshold of synthesizing new life forms” (Ball 2004) is that of synthetic biology. This technology requires collaboration in different disciplines such as engineering, computer science, and biology. Synthetic biology has been defined as an attempt to “engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications” (Andrianantoandro et al. 2006, 1). The Subfields of Synthetic Biology Four different subfields of synthetic biology have developed since the early years of the twenty-first century: (1) engineering DNA-based biological circuits by using standardized biological parts, (2) identifying the smallest possible (minimal) genome that can “run” a cell, (3) constructing protocells, and (4) creating atypical biological systems through chemical processes (Schmidt 2009). A top-down approach to synthetic biology has been to start with a living system and reengineer it to perform a task that it normally does not. The design and assemblage of interacting genes into circuits with the aim of directing cells to perform new tasks was first accomplished when the bacterium Escherichia coli was refitted with gene circuitry that enabled it to synthesize a precursor to the antimalarial drug artemisinin (Martin et al. 2003). This technology requires collaboration in different disciplines such as engineering, computer science, and biology. There is, however, a concerted effort to make biological engineering simple, primarily through standardization, decoupling, and abstraction (Endy 2005). Standardization envisions devising and promulgating a set of “standard, interchangeable biological parts,” a catalogue of “BioBricks” that can be built together and

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placed into living cells, where they can impart new functions to those cells (Registry of Standard Biological Parts 2009). Decoupling of design and fabrication is seen as a further step toward simplification. Abstraction would allow individuals to work at one level of complexity without having to know any details of the work going on at another level. These principles have been tested in the International Genetically Engineered Machine (iGEM) competitions at the Massachusetts Institute of Technology (MIT) in which students, some with little background in biology, design and build new genetic circuits that can function in living cells (MIT 2009). The construction of artificial living systems is “something that grasps the imagination of researchers since it directly relates to crucial questions regarding the definition and the origin of life” (Roodbeen and van Hest 2009, 1). This notion has inspired the search for a minimal functioning genome. One approach has been to transplant a synthetic genome into a living host cell and let the biosynthetic machinery of that cell drive the genome to function. In this vein, researchers have synthesized a 582,970-base pair genome of the bacterium Mycoplasma genitalium, which is known to have the smallest genome of any independently replicating organism (Gibson et al. 2008). Although this synthetic genome could not reproduce itself on its own, it was cloned into a yeast cell and could be isolated and identified from this clone. However, the researchers did not show that the synthesized genome could encode a bacterium. The recent announcement that researchers from the J. Craig Venter Institute have created the first self-replicating bacterial cell comprised exclusively of synthetic DNA (Gibson et al. 2010) shows that this work has taken a giant step forward. What the researchers actually did was to synthesize and assemble a modified version of an intact bacterial genome of one species (Mycoplasma mycoides) and transfer this to a living bacterium of a different species (Mycoplasma capricolum). Of particular significance was that this synthetic genome was able to direct the bacterium to produce cells of the transferred genomic species (M. mycoides). While this accomplishment represents essentially a “resynthesis of a naturally occurring genome” and thus falls short of actually creating synthetic “life,” it is nonetheless a milestone in the ability to genetically modify organisms on a scale never previously achieved, and “the subject is rife with potentially misleading terms and ethically charged concepts” requiring careful communication of risks and benefits (Cho and Relman 2010).



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In any case, the methods described will no doubt be useful for future work involving the construction of large DNA molecules from chemically synthesized pieces in search of a minimal genome. Further steps would be to reduce such a bacterial genome down to minimal size by deleting “unnecessary” DNA material and demonstrating that this minimal genome can still function in a living cell. A different “bottom-up” approach to creating novel organisms by synthetic biology would be to assemble nonliving components into “protocells” or artificial cells. This type of synthetic cell research, which embraces the concept of minimal chemical cellular life, involves enclosing genetic material and complex metabolic or biosynthetic cascade-reaction components into vesicles or micells, usually composed of water-in-oil-emulsion-forming substances (Bedau et al. 2009). The vision is to create artificial but viable cells having specified capabilities, such as the synthesis of RNA, DNA, or proteins and self-replication of the vesicle. The complexity of such a minimal cell would then be gradually increased when a better understanding of the biosynthetic systems driving the cell is gained (Roodbeen and van Hest 2009). Protocell research is conducted with the aim of being able to better understand life, but it is also of enormous commercial interest, for example, in creating simple but efficient bioreactors. Although some low-level synthetic activity has been achieved in artificial cells, the systems that have been assembled to date are still far removed from an autonomous living cell. Nevertheless, many experts believe that the first autonomously replicating protocells could be produced in the laboratory within the next five to ten years, and that they would be able to survive in the natural environment within the next ten to twenty years (Bedau et al. 2009). The fourth subfield of synthetic biology is concerned with creating biological systems with unnatural biochemical structures (Schmidt 2009). This is the most far-fetched of the subfields, which might involve, for example, changing structurally conservative informational molecules such as DNA to contain bases or sugars that would be different from those found in the natural biological molecule. Of course the functionality of the molecule would have to be assessed. Biosecurity Implications Synthetic biology has “opened up extraordinary possibilities for biomedical discovery and environmental engineering,” but at the same time the “scope

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for abuse or inadvertent disaster could be huge” (Ball 2004). The potential risks of synthetic biology have been discussed among stakeholders, and various proposals to minimize these risks have been offered. One of the earliest proposals was made by George Church at Harvard University (Church 2004). The package included licensing of instruments and reagents used to produce synthetic oligonucleotides, screening synthetic oligonucleotides for similarities with select agents, and finally testing the screening system frequently to counteract failure. Church also suggested setting up a clearinghouse with oversight assigned to one or more U.S. government agencies. On the other hand, a proposal from a group at the University of California at Berkeley favors more community-based self-governance options (Maurer, Lucas, and Terrell 2006). Options for governance of synthetic genomics have been proposed by a group of collaborators from the Center for Strategic and International Studies, MIT, and the J. Craig Ventor Institute (CSIS-MIT-Venter group; Garfinkel et al. 2007), which include policies for gene- and genome-synthesis firms, policies for oligonucleotide synthesis firms, licensing of equipment and reagents, and policies for users in the conduct of synthetic biology research. The policies outlined in this last category, which are directed at users instead of suppliers, primarily address ways of ensuring biosafety (safety of laboratory workers and the surrounding community as well as protection of the environment). The few governance options outlined that addressed biosecurity concerns, such as education about risks and best practices, broadening institutional biosafety committee (IBC) review to consider risky experiments, and oversight by a National Advisory Group, were scored by the authors as being only minimally to moderately effective. According to one analysis of the CSIS-MIT-Venter report, “the most effective intervention point for preventing the misuse of synthetic genomics identified by the authors is at the level of DNA synthesis itself, that is, gene-synthesis firms, oligonucleotide manufacturers and DNA synthesizers” (Kelle 2009a, S26). These suppliers of the building blocks for synthetic biology have in turn been active themselves in formulating governance options for the industry. The International Consortium for Polynucleotide Synthesis (ICPS) has submitted a tiered DNA-synthesis order-screening process (Bügl et al. 2007) that would rely on agreed-upon guidelines. Individuals placing the orders would supply identifying and biosafety information, orders would be screened for select agents or sequences, and the companies would work together



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through the ICPS and interface with appropriate government agencies (worldwide) to improve technologies and identify potentially dangerous sequences. It would thus provide “an international platform for industrygovernment interactions needed to work through remaining issues in an open and cooperative fashion” (Bügl et al. 2007, 629). In like form, the European industry consortium International Association of Synthetic Biology (IASB) has been very active in the past few years in the area of synthetic biology self-regulation. At a workshop in Munich in 2008 (IASB 2008), a set of work packages was agreed on, including (1) harmonization of screening strategies through shared information, (2) setting up a virulence factor information repository (VIREP), (3) writing a publication on the status quo of synthetic biology, (4) establishing a technical biosecurity group in cooperation with ICPS to discuss improvements and next steps for biosecurity measures, and (5) demonstration of a commitment to biosecurity screening in which all IASB members will describe and advertise their screening efforts. The IASB has now drawn up a code of conduct for providers of synthetic biology products and services that include gene screening standards. This code was presented at the Meeting of States Parties to the Biological Weapons Convention (BWC) in Geneva 2008 (United Nations 2008a). While it may be expected that a code of conduct will include a certain amount of education and awareness-raising about risks, “no systematic efforts are underway to raise biosecurity awareness among synthetic biologists” (Kelle 2009b, 116), which has been determined to be low in the first place (Kelle 2009a). In recognition of IASB efforts, an editorial in the scientific journal Nature stated that “the IASB has taken laudable first steps in providing government regulators with guidelines they can build from. Now, the regulators need to act” (Nature editorial 2008). Thus, while self-regulation is considered a good initial step, a need for independent oversight is recognized. A relatively new coalition of synthetic biology companies called the International Gene Synthesis Consortium (IGSC), which they claim represents 80 percent of the gene synthesis industry, has created guidelines similar to those of the IASB (Check Hayden 2009). Also, the U.S. Department of Health and Human Services has in turn drafted guidelines (US DHHS 2009) that ask companies to screen for DNA sequences that are unique to the U.S. select agents and toxins registry. If a “hit” occurs, the company would initiate follow-up screening to try to determine the end use of the order and

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whether that customer is scientifically legitimate. If that does not resolve concerns, the providers are asked to contact designated U.S. government entities for further guidance. Unlike the IASB and IGSC standards, the U.S. government regulations do not require human experts to examine all matches (Fischer and Maurer 2010). While these guidelines are voluntary, “many specific recommendations serve to remind providers of their obligations under existing regulations” (US DHHS 2009). In analysis of current efforts to address biosecurity risks in synthetic biology, the need to broaden these efforts to include the different subfields of research in this area (Schmidt 2009; outlined above) has been called for (Kelle 2009a; Bedau et al. 2009). Most efforts up to now have concentrated on self-governance at the level of DNA synthesis, focusing primarily on the U.S. government’s list of select agents and toxins. Within this approach, the misuse potential of biological agents other than select agents and toxins, such as peptide and protein bioregulators of physiological systems, has not been considered. What is required is a mixture of top-down approaches (laws and regulations) and bottom-up approaches involving individual scientists, industry, and professional societies. In this context, Alexander Kelle has proposed a 5P-strategy “that would not only focus on the provider and purchaser of synthesised DNA, but also the principal investigator, the project, and the premises at which research is being conducted would be integrated into a comprehensive biosecurity governance system. Once the ideal policy intervention points and the measures with which to address them are determined, a discussion involving the relevant stakeholders about the content of the measures to be adopted can commence” (Kelle 2009b, 117; emphasis added). Potential biosecurity measures touching on these intervention points would be awareness-raising, education/training guidelines, codes of conduct, regulation, national laws, and international treaties/agreements. Systems Biology: From Genes to Complex Networks The relative new area of systems biology looks at interacting physiological systems and seeks to understand how all the parts of the body operate as a whole, by integrating all levels of functional information into a cohesive model (Thiel 2006). It is “an emerging field that is characterised by the application of quantitative theoretical methods and the tendency to take a global view



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of problems in biology” (Goldbeter 2004, R601) to aid, for example, in the elucidation of the complexity, structure, and function of some physiological networks in different organisms. In this context, systems biology has been applied in attempts to address the enormous complexity of innate immunity, which represents the all-important first line of defense against pathogens. Ways of controlling inflammation through intervention in the production of inflammatory cytokines by administration of agonists (substances that induce a cellular response) and antagonists (substances that inhibit a cellular response) have been the subject of many experimental and several clinical studies over the past few years. Innate immune responses are absolutely essential for keeping an infection in check before adaptive immunity can be induced. The subversion of innate immunity would be a particularly effective attack, as it would undermine defenses at the very base of the immune reaction chain. Macrophages and dendritic cells are members of the essential cellular component of innate immunity, and their activation is dependent upon Toll-like receptor (TLR) functions. Recent studies have taken crucial steps in the global network analysis of TLR regulatory pathways in macrophages (Litvak et al. 2009) and dendritic cells (Amit et al. 2009) using systems biology approaches of integrating transcription-factor (protein elements directing the expression of genes into messenger RNA molecules for initiating protein synthesis) binding-site analysis and dynamic computational modeling to construct regulatory networks. Of particular interest is the fact that an international collaboration consortium called “FANTOM” (Functional Annotation of the Mammalian Genome) involving more than a hundred labs is looking into regulatory networks of transcription factors, which is called “transcriptome profiling” (Ledford 2009). It is safe to follow that this work could open up new ways to manipulate gene expression, such as by facilitating gene-silencing techniques using RNA interference (RNAi) molecules (Lederman 2009b) to block transcription. Within the field of proteomics, systems biology is being used to aid in the analysis of complex protein interactions in cells (Shimizu and Toh 2009). In this case there is a shift from focusing on single proteins and receptors to viewing the entire set of signal chains in an organism as the target. The target is defined by the net effect on an entire physiological system or even several interacting systems rather than by any separate target-receptor interaction. This type of proteome profiling has been actively applied in the search for new

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molecular targets for drugs (Rix and Superti-Furga 2009), an activity that has particular biosecurity relevance. Although the field of computational systems biology has been in existence for some time, the convergence of high-throughput methodology for biological data-gathering, next-generation sequencing, and computational processing power has led to a redefinition and expansion of the field (McDermott et al. 2009), which underscores the synergy effect that several emerging technologies can have for a specific application (Choffnes et al. 2006). With systems biology the reality of just how complex the situation can be in trying to deal with the dual-use dilemma becomes more visible. Physiological systems do not work alone, rather they interact intricately and interdependently with one another. An example of how systems biology relates to the dual-use problem can be seen in the interaction of physiological systems in the human body. The nervous, the endocrine, and the immune systems are three vital physiological systems that interact intricately and interdependently with one another, and the proper functioning of these systems is regulated to a great extent by biochemical substances produced by the body itself, including cytokines, such as the proinflammatory agents interleukin (IL) 1 beta (IL-1b), IL-6 and tumor necrosis factor alpha (TNFa), or cytokines regulating immune responses (IL-2, IL-4, IL-12, IL-10); hormones (e.g., catecholamines, insulin); neurotransmitters and neuropeptides; eicosanoids (e.g., prostaglandins, leukotrienes); and nucleic acids, such as DNA and RNA (Institute of Medicine/National Research Council 2005). These substances play key roles in many vitally important bodily functions such as respiration, blood pressure, heart rate, body temperature, mood, and consciousness, as well as innate and adaptive immune responses. The normal functions of interacting physiological systems are extremely vulnerable to modulation or manipulation with these biochemicals, if the body encounters them in greater or lesser than normal concentrations. The perturbation of one system with a biochemical regulator will also have profound effects on the others (Kelle, Nixdorff, and Dando 2006). Here then is an ideal target for those with malign intent. Clearly, if the complex balancing-feedback system that regulates these systems together could be disrupted by the use of a biochemical regulator, an ideal method of incapacitation would be available to the attacker. From the point of view of potential malign manipulation, it follows that there is necessarily a new level of complexity. If malign



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manipulation of one system can affect two or three systems, the defender’s problem of diagnosis and treatment increases out of all proportion to the attacker’s effort (Kelle, Nixdorff, and Dando 2006). Nanotechnology Nanotechnology encompasses a very diverse range of technological approaches, from extensions of conventional device physics to those based upon molecular self-assembly involving the development of new materials on the nanoscale. “Nano” describes a dimension dealing with a billionth of some unit of measurement. Nanoparticles usually range in size between 1 nanometer (a billionth of a meter, or around 10 times the size of an atom) and 100 nanometers (the size of large molecules) (for a review see Walker and Mouton 2006). Because of their small size, nanoparticles have the potential to penetrate into tissues more easily than larger particles, especially when they have been designed with particular physicochemical properties to enhance their uptake over the nasal and respiratory routes or across the blood-brain barrier (Suri, Fenniri, and Singh 2007). This application of nanotechnology has particular relevance for delivery of biological agents in connection with drug therapy (see next section), where chemical composition, shape, size, and surface charge all play a role in how rapidly nanoparticles will be translocated from the lung airspaces to the bloodstream and organs (Choi et al. 2010). Another area of nanotechnology that is of relevance for the BWC is the production of nonbiological nanostructures that bind to specific targets (aptamers) and exert effects on biological systems. An example is the synthesis of nonbiological nanoparticles made from acrylic chemicals that nevertheless have antibody-like affinity and selectivity and have thus been called “plastic antibodies,” which have been shown to function as such in the bloodstream of living animals (Hoshino et al. 2010). While some might argue that the prohibitions of Article I with its General Purpose Criterion still cover such developments, others might claim that these aptamers have no biological origin since they were synthesized from acrylic chemicals. In any case, this recent development conjures up possible controversy over the issue, and closer scrutiny and assessment of such developments by the States Parties to the BWC clearly would be beneficial.

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Advances in Targeted Delivery Technology At the bottom line, the possibilities of either use or misuse of biological agents depend in great part on the ability to deliver the payload to the target in a way that it will be effective.1 Targeted delivery systems are comprised of components that allow an activity to be directed to a particular site in the body where that activity is desired. There are several potential means of achieving this, but two areas that have progressed most significantly and appear to be most relevant are advances in aerosol delivery technology and viral-vector delivery technology. Some of the recent advances in these two areas designed to fight serious diseases in biomedical-research and clinicalapplication contexts will be described. By examining these developments, an assessment of the feasibility of using them malignly for the dissemination of biological agents can be made. Aerosol Delivery Aerosols are particles in the form of a liquid or a powder that are suspended in air and can be inhaled. Many infectious microorganisms can enter the body over the mucous membranes lining the nasal and respiratory as well as the intestinal tracts. The size of the droplets determines to a great extent where they will be deposited in the airway after inhalation. Particles up to 5 micrometers in diameter can reach deep lung areas (alveoli or air sacs); larger particles will be deposited in more anterior parts of the respiratory tract (Scheuch et al. 2006). Aerosol Delivery of Traditional Biological Agents For the delivery of traditional biological agents such as those infectious microorganisms found in nature, the aerosol route has long been considered to be the superior means of disseminating these agents as biological weapons over large areas. This was a conclusion drawn mainly from the results of extensive tests that were carried out over land and sea with microbial agents or simulants prior to the ban on biological weapons (van Courtland Moon 2006). An interesting study (Levin and Valadares de Amorim 2003) on the potential for aerosol dissemination of biological agents involved the use of the bacterium Bacillus thuringiensis (which produces an insect toxin) to 1.  This section is an expanded version of K. Nixdorff, “Advances in Targeted Delivery and the Future of Bioweapons,” Bulletin of the Atomic Scientists 66 (2010):24–33.



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control insurgent populations of the European gypsy moth, which was posing a threat to the lumber industry in and around the Victoria region of British Columbia. The report describes the results of aircraft spray application of the biological insecticide Foray 48B (a solution of B. thuringiensis endospores) over approximately 30,000 acres including residential and rural areas in the Victoria, British Columbia, region. The undertaking resulted in greater than 99 percent mortality of the gypsy moth population in that area. A surprising finding was that enough small (2 to 7 micrometers) droplets were formed that could penetrate houses and contaminate the nasal passages of residents inside their homes, even though the equipment used was designed to generate droplets of 110 to 130 micrometers in diameter. While exposure to B. thuringiensis should have no detrimental effects on humans, this tells us something about the effectiveness of dissemination of microorganisms over a large area without using sophisticated technology. Aerosol Vaccine Administration Vaccination with whole microorganisms via the aerosol route is known to be effective, which is generally more successful than using components or parts of microorganisms. For example, field trials in Mexico established the effectiveness of mass immunization of children with the measles vaccine virus via the aerosol route (Cutts, Clements, and Bennett 1997). The children were exposed to the aerosol output of a classic jet nebulizer driven by an air compressor for a 30-second period via a paper conical mask held over the mouth and nose. Subsequent tests showed that this type of vaccination compared favorably with that of conventional methods of administration and used a third of the dose normally required. In the former Soviet Union, thousands of people were successfully vaccinated with aerosols of live, attenuated strains of anthrax, plague, tularemia, and smallpox agents using tent-exposure systems (Laube 2005; Roth, Chapnik, and Cole 2003). Although the aerosols were produced in an enclosed environment (a tent), these practical experiments demonstrated that vaccination against a wide array of biological weapons–relevant microorganisms could be achieved by inhaling aerosol clouds containing the agents. Thus, the microorganisms were successfully delivered to and taken up from the respiratory tract. Considering some recent advances that have been made in vaccine delivery technology via the aerosol route, the focus has now shifted away from vaccination with whole microorganisms to improving delivery and uptake of antigens, the components of microorganisms that can elicit protective

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immune responses. In addition, aerosol delivery of genetic- or DNA-based vaccines, which contain genes that direct protein antigen synthesis after uptake, is being intensively investigated. Among the various mucosal sites, nasal delivery is especially attractive because this is a site of relatively high permeability, low activity of destructive enzymes, and the presence of a considerable number of immune response cells (Csaba, Garcia-Fuentes, and Alonso 2009). While lipophilic (having an affinity for fat) substances are readily absorbable over the nasal mucosa, more polar (hydrophilic, having an affinity for water) compounds such as peptide and protein antigens or DNA vaccines are taken up relatively poorly, so that methods aimed at improving their permeability properties have been developed (Lai, Wang, and Hanes 2009). In this context, the design of nanoparticles with specific properties is of particular interest. Nanoparticles are taken up by cells more efficiently than larger particles (Suri, Fenniri, and Singh 2007). In addition to particle size, the physico-chemical properties of the nanoparticles are important for uptake. Accordingly, several strategies to enhance their affinity for mucosal surfaces have been explored (Csaba, Garcia-Fuentes, and Alonso 2009). Among these, coating the particles with cationic (positively charged) substances such as chitosan (a polysaccharide derived from shellfish chitin), polymeric nanocarriers such as poly (lactic acid) or poly (lactic-co-glycolic acid), or a combination of these substances, has been shown to improve uptake. In addition, the stability of the particles could be increased by incorporating poly (ethylene glycol) or polyoxyethelene derivatives into the nanocarrier as a method of encapsulation. Further improvements have been achieved by crosslinking chitosan with tripolyphosphate in order to increase the release time of encapsulated peptides and proteins or to enhance gene expression of DNAbased vaccines. Aerosol Delivery of Biochemical Therapeutics The potential of aerosols for delivery of drugs is a current area of particular interest. “A major challenge [in drug delivery] is to engineer nanostructures that can efficiently encapsulate drugs at high concentration, cross the cell membrane, and controllably release the cargo at the target site over a prescribed period of time” (Liu et al. 2009). Delivery of therapeutics via the aerosol route is attractive for a number of reasons. The surface area of the lung is between 80 and 140 square meters. Also, the alveolar (air sac) epithelium



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in most pulmonary regions is only about 0.1–0.2 micrometers thick, and the distance between epithelial surface and the blood is much less than it is in the bronchial system, which should facilitate drug uptake (Scheuch et al. 2006). There are, however, a number of absorption barriers in the human lung including the mucus layer, alveolar lining fluid layer, and competing uptake pathways such as particle engulfment by macrophages. The absorption of drugs over the mucosal surface can be increased by the strategies that were outlined above for aerosol vaccine administration (such as packaging the bioactive agent into nanoparticles coated with cationic substances), and phagocytosis can be reduced by packaging substances into porous particles (Scheuch et al. 2006). Shoyele and Slowey (2006) have offered a list of some fifteen proteins/peptides that could feasibly be delivered via the lungs in order to treat various illnesses. These include the interferons, several interleukins, erythropoietin, calcitonin, insulin, amylin, and growth hormone. As in vaccine administration (see above), the nasal route has emerged as being particularly advantageous for the delivery of drugs. This route also has the added potential of providing direct access of drugs to the brain by entry into the olfactory bulb (Graff and Pollack 2005). For a more detailed description of the mechanisms involved in this route to the brain, see chapter 4 of this book. With the use of substances to enhance absorption, biological agents transported in the blood can enter the brain by breaking through the bloodbrain barrier. Normally, the brain is protected from the potentially harmful effects of biologically active substances or cells in the circulation by the bloodbrain barrier, which is manifested by the extremely tight junctions between the endothelial cells lining blood capillaries (Petty and Lo 2002), which prevent circulating substances of a particular size and chemical property (as well as cells) from entering the brain. The mechanism of absorption enhancement by chitosan and other polycation substances appears to be a combination of bioadhesion and a transient opening of the tight junctions in epithelial cell layers lining the mucosal surface (Ranaldi et al. 2002). This is also relevant for delivery of drugs across the blood-brain barrier, as the cancer drug doxorubicin was able to cross the intact blood-brain barrier when attached to nanoparticles coated with polysorbate, another absorption enhancer (reviewed in Suri, Fenniri, and Singh 2007). Several examples of clinical applications and other studies have shown that aerosol delivery of bioactive biochemicals is feasible not only in principle but also in effect. Inhaled insulin delivery has been explored for over a

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decade, and one formulation called “Exubera” has been administered by a special inhaler in the form of a spray-dried powder of a particle size optimal for alveolar deposition (Guntur and Dhand 2007). Despite the success in treatment of diabetes, this product has been withdrawn from the market, partly due to disappointing sales but also because of trial results showing an increase in lung cancer in patients receiving the drug. Other companies are continuing development of inhaled insulin, one reporting that their studies in mice and rats have shown no indications of carcinogenicity (Kling 2008). Another example of successful aerosol delivery of a drug concerns the neuropeptide oxytocin, which was reported to increase trusting behavior in humans given a single dose by nasal spray (Kosfeld et al. 2005). It is significant to note that oxytocin has been marketed in nasal spray form by Vero Labs under the name Liquid Trust: “Liquid Trust is the world’s first Oxytocin product, specially formulated to create a trusting atmosphere!” (Vero Labs). For a more detailed description of oxytocin and its effects see chapter 4. The most prominent example of the feasibility of the aerosol delivery of drugs is the incident in which Russian military special forces tried to rescue hostages held at the Moscow Dubrovka Theatre Center by introducing an unidentified “gas” (supposed to have incapacitating effects) into the theater ventilation system. Of the 800 hostages held in the theater, 127 died and more than 650 of the survivors required hospitalization (Wax, Becker, and Curry 2003). Many of the patients had classic signs of opioid (narcotic) intoxication, and the Russian health minister announced several days later that a derivative of the opioid fentanyl had been used. The precise derivative and its dosage were, however, never revealed. Viral Vector Technology Advances in molecular biology, immunology, and tumor genetics have led to the design of novel viral vectors for the very legitimate use in vaccine therapy, cancer therapy, drug treatment, and immunotherapy (Gilbert and McFadden 2006). In general, these viruses act as ferries or vehicles that carry and deliver foreign genes to the body. The strategy is that infection with the virus would lead to expression of the foreign gene in the cells of affected tissues and subsequent synthesis of the active substance (the gene product), which would then exert its effect. The use of viral vectors is the subject of intense research and development. Clinical trials with humans have shown that several of the vectors already developed and armed to deliver specific payloads in cancer



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and gene therapy have proven to be successful in principle and in some cases in effect. In the biomedical and clinical application context these are perfectly legitimate undertakings that can counter disease and promote health, but the dual-use implication here is that these same technologies could be used to arm viruses with a destructive or even deadly payload. Vaccinia virus is showing some promise as an oncolytic (tumor-celldestructive) agent for treatment of cancers that are resistant to established methods of therapy. For such studies the virus has been engineered to acquire tumor specificity (Yang et al. 2007; Hung et al. 2007) and to deliver substances that can boost antitumor immune responses. In clinical trials with metastatic melanoma patients, an engineered vaccinia virus armed to deliver an immunostimulatory substance to boost antitumor responses showed that the virus could in effect successfully deliver its package to selected tissues (Liu, Galanis, and Kirn 2007). Vaccinia virus enhanced for tumor selectivity has also been armed with a prodrug activation system which has been termed “suicide gene therapy” (Chalikonda et al. 2008; Erbs et al. 2008). In this case the virus delivers a gene encoding a nontoxic yeast enzyme that is converted to its highly toxic form when the gene is expressed in tumor cells. This recombinant virus has shown promise in investigations of human and murine ovarian tumor models (Hung et al. 2007; Chalikonda et al. 2008). Adenoviruses and adeno-associated viruses have also been developed for therapy purposes, but the clinical benefits have been only modest (Griesenbach and Alton 2009). Besides showing generally poor gene transfer and expression, these two vectors induce potent immune responses that compromise their efficacy. To solve this problem, new immune evasion strategies for the virus, including the generation of “immuno-stealth” proteins (invisible to the immune system) to coat the viruses (Zaldumbide and Hoeben 2008), are actively being researched. Much work has been invested in the development of lentivirus (the subfamily of retroviruses to which the AIDS virus belongs) delivery systems, as these viruses are very efficient in infecting even nondividing cells and achieving stable expression of the transferred genes in those cells, and they are only weakly immunogenic (Schambach and Baum 2008). Although lentiviruses have a very narrow host range, this can be broadened or altered by pseudotyping, which involves exchanging the surface proteins of particular strains of viruses during packaging of the virus. Other innovative approaches

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include (1) outfitting the virus with targeting ligands fused to envelope proteins to infect specific cells; and (2) using tissue-specific gene-regulating promoters to restrict gene expression to certain target cells and reduce the risk of gene-induced immune responses to new proteins expressed on the surface of targeted cells (Frecha et al. 2008). The great promise of lentiviral vector development for clinical use is dampened by the fact that lentiviruses are retroviruses that integrate randomly into the genome of the host. This could lead to adverse mutational events such as that which occurred when two children developed leukemia as a result of treatment of their bone marrow cells with a retroviral vector in gene therapy for severe combined immunodeficiency (Check 2002). Nevertheless, the efficacy of the retroviral system to correct the genetic defect has been confirmed, as seventeen of eighteen patients treated in London and Milan thus far have gained a functionally reconstituted immune system (Nature Methods Editorial 2006). On the other hand, the property of retroviruses to integrate into the host genome has the advantage of potentially long-lived expression of the delivered gene due to its stable insertion, and lentivirus vectors have been designed for improved safety (Frecha et al. 2008). There is much interest in developing lentiviruses as vectors in combination with RNA interference (RNAi), which is emerging as one of the most potent, effective, and practical methods of interfering with or silencing the expression of a specific target gene (Lederman 2009b). Although the use of the RNAi system to target genes in vivo for research and therapeutic purposes has not yet been fully developed, there has been a transition of lentiviral vectors to human clinical trials for therapy of infectious and genetic diseases (Schambach and Baum 2008) and improvements are inevitable. Artificial Viruses as Vectors Another area of advancement that is rapidly growing and needs to be closely monitored is the creation of so-called artificial viruses for gene and cancer therapy. These are polymer-based complexes of nanoparticle size containing DNA, and they are being developed in an attempt to overcome the negative aspects of using viruses to deliver genes, such as safety and manufacturing problems, immunogenicity, limited targeting ability, and limited transport capacity. Artificial viruses usually consist of DNA compacted into particles with polycationic substances such as polyethylenimine, oligoethylenimine coupled with short diacrylate linkages, polyaspartylhydrazide, and chitosan (Douglas 2008; Russ et al. 2008; Ogris et al. 2007). Shielding molecules such as



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polyethylenegylcol to protect the DNA cargo and surface structures to target the vectors to specific tissues can be added to these basic particles. However, the main problem with nonviral vectors is that they have not yet consistently demonstrated gene transfer efficiency comparable to that of viruses, which limits their practical use (Douglas 2008). Nevertheless, a significant degree of effectiveness in gene delivery to airway cells in mice using a cationic nonviral vector administered through the nasal route has been demonstrated (Kim et al. 2005). There is great interest in developing these vectors further so that rapid advancement in this area can be expected, which could pose a huge potential for misuse in the near future. Feasibility of Aerosol Delivery of Viral Vectors In most research and clinical studies viral vectors are administered by injection, in some cases using repeated application, which would not be practical for delivery of weapons. However, some studies have indicated that administration over natural routes such as inhalation is feasible. For example, treatment of cystic fibrosis patients by inhalation of an adeno-associated virus vector engineered with a gene to deliver the transmembrane conductance regulator, which is defective in cystic fibrosis, resulted in “encouraging trends in improvement in pulmonary function” (Moss et al. 2004). In some twenty clinical trials that have been carried out, use of gene-transfer agents including adenovirus and adeno-associated virus has demonstrated “proof of principle for gene transfer to the airway,” but efficiency is still low (Laube 2005). It was further shown that lentiviral vectors pseudotyped with the glycoprotein from the Ebola Zaire EboZ filovirus envelope for specific airwaycell targeting could achieve gene transfer in the lungs of mice (Medina et al. 2003). Although the mice were infected by direct instillation of a single dose of the vector, the potential for infection by inhalation was at least given by the investigation. This can be seen in another study with mice using a lentivirus vector carrying a foreign gene, which was administered to the mice by inhalation in a nose-only exposure chamber (Hwang et al. 2007). The results showed that lentivirus-mediated delivery of the foreign gene via aerosol was effective to a significant degree. Many viruses (such as lentiviruses) are quite sensitive to environmental stress, which would reduce the feasibility of their dissemination via aerosols in the atmosphere. However, the development of methods for encapsulating or packaging sensitive substances for controlled drug delivery over the nasal and respiratory routes is an area of intense investigation, which could yield

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benefits for increasing the stability of viruses and as well as nonviral agents to environmental stress (Mahajan and Gattani 2009; van der Walle, Sharma, and Ravi Kumar 2009; Nayak et al. 2009). Mid-Spectrum Agents: Bioregulators and Toxins A number of major studies, such as the well-known Lemon-Relman Report of the United States National Academies (National Research Council 2006), have warned that the threat of misuse of the modern life sciences ranges far beyond traditional microbial agents. The seriousness of the problem caused by this conception of a wider range of agents can be gathered from a paper—produced in a “Terrorism Special Report” in the journal Prehospital and Disaster Medicine—by Professor Pal Aas (Aas 2003) of the Norwegian Defence Research Establishment. Aas’s paper was titled “The Threat of MidSpectrum Chemical Warfare Agents” and began by presenting a wider view of the chemical and biological weapons threat. He argued that this should be seen as a spectrum, which ranges from classical chemical warfare agents such as nerve agents, mustard gas and cyanide through toxic industrial chemicals (pharmaceuticals and pesticides) to human neuro-hormones (such as bioregulators) and plant, animal, bacterial, and fungal toxins as well as to traditional biological warfare agents such as anthrax and plague. (Aas 2003, 306)

This view should come as no great surprise because we know that some toxins, such as botulinum toxin, were weaponized in previous offensive biological weapons programs by a number of major states. What may be a surprise, however, is Aas’s further explanation that the term “mid-spectrum agents” is used to describe the part of the spectrum covering toxins and bioregulators and that examples of such agents are the neurotransmitters substance P and neurokinin A, the biotoxins saxitoxin, ricin and botulinum, and many other agents. . . . The primary target of these substances is the nervous system and many have a very high neurotoxicity [emphasis added]. (Aas 2003, 307)

Some of the many examples of mid-spectrum agents that Aas lists (in his Table 2) are shown here in Table 3.1. He suggests, also, that there are many reasons why an attacker might turn to the use of these agents as weapons:



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TABLE 3.1. Examples of mid-spectrum agents Bioregulators · Substance P · Neurokinin A · Opioids (endorphins and enkephalins) · Neuropeptide Y · Vasopressin · Cholecystokinin · Somatostatin · Neurotensin · Bombesin Biotoxins · Botulinum toxin · Tetanus toxin · Saxitoxin · Diphtheria toxin source: Aas 2003.

First, chemical and toxin weapons are cost-effective, particularly when utilized against concentrated forces or populations. Second, they may be used at lower levels of concentration to hamper military forces using protective equipment, or with the aim to cause panic and disorder among civilians. (Aas 2003, 307)

In short, mid-spectrum agents represent a serious threat. Moreover, as our knowledge of these substances and of how they act on the nervous system increases, that threat is unlikely to decrease. Toxins are a diverse set, being either proteins (long, folded chains of amino acids) or nonproteins (small, complex molecules produced by many animals, plants, fungi, and bacteria). Aas suggests that exposure to such agents could come about as a result of contamination of food or water supplies or by inhalation. Bioregulators are far less well known. They are either proteins or peptides (smaller chains of amino acids). They are naturally occurring regulatory compounds active at very low concentrations in the body. Aas noted the very wide range of their normal control functions as in “systems controlling emotions, blood pressure, temperature control, fear, mood, sleep, consciousness” and so on. He stressed that: The result of exposure to such agents orally or by means of inhalation could have serious consequences including fatigue, fear, physical and mental incapacitation, and ultimately death. (Aas 2003, 308)

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Thus these agents could be used lethally or as so-called nonlethal incapacitants. The natural opioids (endorphins and enkephalins) are involved in the control of pain, blood pressure, and respiratory depression. Substance P is known as a neurotransmitter in pain sensory neurons, but it can also cause skin irritation. Neuropeptide Y is involved in feeding and drinking behavior but also in the control of blood pressure and body temperature. So just from these few examples it can be easily seen that an attack using such substances could have very complex effects and, Aas points out, given their high levels of activity at low concentrations, they could be extremely difficult to detect. It should also be realized that it has become clear that direct delivery of these substances to the brain is possible. As long ago as 2002 researchers aiming to deliver therapeutic drugs to the brain reported: We administered three peptides, melanocortin . . . vasopressin and insulin, intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream. (Born et al. 2002, 514)

So the blood-brain barrier would not protect the brain from an inhalation route of attack. As the researchers commented: Our data validate in humans the idea that intranasal administration allows peptides to penetrate the CSF. These data corroborate previous human studies in which recordings of evoked brain potentials provided functional evidence for a facilitated access of neuropeptides to the brain after nasal delivery. (Born et al. 2002, 515)

They also noted that animal studies had shown that not only peptides but also some larger molecules could accumulate in the brain after intranasal administration. Conclusions Advances in science and technology over the past few years have initiated new and improved approaches to countering disease and promoting health in general that are a boon to society. At the same time, the rapidity with which the advances occur and the possibilities for misuse that they reveal give us a clear indication that we have reached a critical point in being able to deal with the biosecurity implications of these developments (Kelle 2005a).



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Progress in genomics is enabling the very rapid and cost-effective analysis of gene functions as well as facilitating the manipulation of even very complex microorganisms to meet designer specifications. Synthetic biology is advancing beyond sophisticated engineering of microorganisms to perform new tasks by outfitting them with DNA-based biological circuits built from standardized biological parts. Subfields of synthetic biology are now reaching into the realm of creating artificial life from chemical components. Although there has been a substantial amount of thought put into minimizing the risks involved in synthetic biology, the governance proposals made to date are not in any way keeping pace with the developments. Advances in systems biology represent perhaps one of the largest scopes for abuse. This is a field of biology that seeks to understand the working of complex physiological systems within and between cells. An enormous amount of knowledge is accumulating through this work that pinpoints vital cellular targets and ways of manipulating them. Although there is clear indication of the increasing risks that such work creates, the full misuse potential and the corresponding need to control abuse of the knowledge gained has not been realized. Concerns about advances in science and technology leading to the creation of novel biological warfare agents are compounded by the recognition that new and improved ways of delivering them are already at hand and will be developed further at a rapid pace (Nixdorff 2010). Significantly, great strides are being made in biological agent delivery techniques, particularly in connection with interests in drug development and delivery. The production of defined nanoparticles, combined with new methods for making substances absorbable through the nasal and respiratory tracts and across the blood-brain barrier, creates a potential for greatly improved aerosol delivery of bioactive compounds. Furthermore, when advances in aerosol delivery technology are combined with improvements in targeting and gene-transfer efficacy of viral vectors, the potential synergy effects raise the dual-use risk aspect to a whole new dimension. It must also be stressed that the goals of using armed viruses for gene and cancer therapy are quite different from those of using armed viruses as weapons. For example, the stringent efficacy demands of therapeutic use might not be so crucial in the case of weapons delivery, and the concerns about the safety of highly efficient retroviral vectors or so-called nonlethal agents would presumably be of little concern for a determined aggressor bent on delivering a biological weapons agent to a chosen target. All of these advances have a potential for increasing to an even greater extent the steadily building

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interest in the use of mid-spectrum agents in warfare. This is a serious situation particularly in light of the convergence of chemistry and biology and the gap this creates between the CWC and the BWC (Robinson 2008b). It is not only the rapidity with which these advances are occurring that is of particular concern, it is also the immensity and complexity of the knowledge that is accumulating from such studies that complicate efforts to deal with the potential risks. The most sophisticated of these advances in science and technology are certainly not easy to put into practice, but they require extensive expertise, well-equipped laboratories, and substantial funds. Thus, state-supported actors are more likely than terrorists to have such means, and this places a particular burden on the States Parties to the BWC to ensure that illicit biological warfare programs using these technologies are not being developed. Some suggestions about how this might be more effectively dealt with than it has been in the past are discussed in the concluding chapter 9 of this volume.

4

Threats to the CBW Prohibition Regimes Advances in Neuroscience

Introduction The overview of key developments in the life sciences provided in the previous chapter has clearly demonstrated that the main danger that arises from such advances in regard to future biological weapons is the increased possibility of specific attacks on biochemical and physiological systems of living organisms. Nowhere is this more obvious than in the advances in our mechanistic understanding of the brain. Hence, we will turn our attention now to this particular subfield of the life sciences. Nancy Andreasen (1984), editor in chief of the prestigious American Journal of Psychiatry, wrote a key book in the early 1980s titled The Broken Brain: The Biological Revolution in Psychiatry. This book described the shift in American psychiatry from reliance on a psychodynamic model of human behavior to an increasing reliance on biomedical and neurobiological thinking. By the turn of the millennium so much new knowledge had been accumulated, particularly through efforts in the 1990s—which had been designated the “Decade of the Brain” in the United States—that she decided a fresh book bringing that new information together was required. The new book, Brave New Brain: Conquering Mental Illness in the Era of the Genome (Andreasen 2001), was published in 2001. It did not minimize the remaining challenges for those hoping to assist people suffering from mental illnesses. As can be seen from Andreasen’s “Report Card” on progress in understanding mental illnesses, part of which is reproduced in Table

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TABLE 4.1. Progress in understanding mental illness

Syndromal definitions

Pathophysiology

Treatment

Dementias

A-

B+

D+

Schizophrenia

B+

B-

C+

Mood disorders

B+

C

A

Anxiety disorders

B+

C

B+

Disease

source: Basec on Andreasen 2001.

4.1, we have a long way to go before we have the means to deal effectively with even the major mental illnesses. Only in regard to mood disorders is treatment awarded an “A,” and even in that case it is not based on a thorough understanding of what goes wrong to create the disorder in the first place or how and why the treatment is effective. Yet Andreasen is very upbeat about the possibility for rapid progress because she believes that we are living in the golden age of neuroscience. This she sees as the result of both progress in understanding the brain and the advances being made in our understanding of the genes of living organisms. In her view, the research at these two very different levels of analysis will come together in the next decade or two and will produce enormous benefits. As she notes: We will understand how the cells in our brains go bad when their molecules go bad, and we will understand how this is expressed at the level of systems such as attention and memory so that human beings develop diseases such as schizophrenia and depression. (Andreasen 2001, 7)

She continues by saying that “[o]nce mind and molecule meet, prevention is possible. Improvements in treatment are certain” (ibid., 7). Such progress must surely be welcomed because, as Andreasen’s case studies make clear, mental illnesses cause terrible distress to sufferers and to their family and friends. They are also enormously costly for the health systems of societies and countries as a whole.



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Setting Priorities for Research The United States National Institute for Mental Health (NIMH) is one of the world’s major research and funding organizations devoted to the task of reducing the burden of mental illness. In late 2003 it established a highlevel working group to review its basic research funding. In 2004 the group produced its report (NIMH 2004), Setting Priorities for Basic Brain and Behavioral Science Research at NIMH, and it is possible to use this report to gain an initial appreciation of what are presently considered important research areas by neuroscientists. The working group considered three fundamental issues in making their judgments: 1 Which areas of research are poised to begin integrating findings across levels of analysis from the molecular to the behavioral . . . ? 2 Which areas of basic research are most readily translatable into clinical science . . . ? 3 Which research approaches are most likely to advance our knowledge? (NIMH 2004, 3)

The working group suggested three sets of priorities: areas for increased emphasis; new and improved research tools; and areas of current research ready for refocus In regard to the first priority set, the NIMH working group noted six areas of basic research that they thought should be given greater emphasis. Among these were emotion, social interactions, and neural circuits. According to the group’s report, disruption of emotional regulatory processes is a key feature of many mental illnesses. They suggested that particular attention should be given to investigations of the neurobiology of emotion, mood, and motivation and to the interaction of emotion and cognition. These suggestions were made by a group interested, as noted above, in research that would integrate studies across different levels from molecular to behavioral, that would translate into clinical science, and that would best advance knowledge. Clearly, then, the study of emotion was thought likely to rapidly produce usable knowledge with practical applications. Similarly, social interactions that were aberrant were seen by the group to be characteristic of psychopathologies. They suggested investment in research that looked at social processes and behaviors alongside brain functioning,

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giving as an example study of the brain circuits involved in social attachment. In regard to neural circuits more generally, the working group’s report stated: The advent of new tools and technologies provides a special opportunity to advance understanding of the structure and functioning of brain circuits underlying healthy and abnormal behaviour. (NIMH 2004, 6)

Among the topics that the group listed for more work were the circuits involved in psychotropic drug action. Not surprisingly, granted that interest in brain circuits, one of the research tools considered worthy of further investment, in the second set of priorities, was neuroimaging. Despite recent advances in such technology, the working group argued that there was a need to determine more precisely what was being measured by the new neuroimaging techniques and how this related to other measurements, such as traditional electrophysiological recordings from neurons in the brain. In the third set of priorities there were six areas of ongoing NIMH research that the working group thought required a refocus. These included sleep research, circadian biology, and stress. In all of these it is possible to see a desire to move toward a mechanistic understanding of complex behaviors. For example, in regard to sleep research, the report stated: Further investigations could include understanding the molecular neurobiology and neural circuitry of sleep, arousal, and attentional states as well as studies of sleep’s influence on cognition, memory, affect, and other cognitive and emotional functions in the waking state. (NIMH 2004, 10)

For circadian biology, the group suggested “studies of the molecular and neural systems basis of circadian phenomena that relate to aspects of higher brain function” (ibid., 10). Stress was seen as very relevant to mental illness and “ripe for neurobiological focus” (ibid.). The picture that surely emerges from a reading of this document—and many similar documents from other sources could equally well have been used—is of an area of science very likely to produce significant results in the near future. Furthermore, the kinds of topics suggested are obviously often in areas where greater understanding might result in misuse or misapplication. However, given Andreasen’s summary, shown in part in Table 4.1, it might reasonably be asked whether significant results will actually be forthcoming. One way to test whether that is likely, perhaps, is to ask if neuroscientists



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TABLE 4.2. Nobel Prizes in Physiology or Medicine Year

Prizewinners

Subject

1991

E. Neher and B. Sakmann

Function of single ion channels in cells

1994

G. A. Gilman M. Rodbell

Discovery of G-protein coupled receptors and their role in signal transduction

1997

S. B. Prusiner

Discovery of prions; a new biological principle of infection

2000

A. Carlsson

Signal transduction in the nervous system/dopamine

P. Greengard

Signal transduction in the nervous system

E. R. Kandel

Signal transduction in the nervous system/learning

2003

P. C. Lauterbur Sir P. Mansfield

Discoveries concerning magnetic resonance imaging

2004

L. B. Buck R. Axel

Discovery of odorant receptors and the organization of the olfactory system

source: Nobel Prize - Neuroscience. Available at http://faculty. washington.edu/chudler/nobel.html, accessed 9 October 2011.

received any of the Nobel Prizes for Medicine in the 1990s or since the start of the new century. A large number of such prizes would argue for the worldwide physiology and medicine community assessing that discoveries of real significance were being made in neuroscience.

Neuroscience Nobel Prizes Nobel Prizes for Physiology or Medicine are awarded once each year and, as can be easily seen from Table 4.2, neuroscientists have been very well represented since 1990 (Nobel Prize–Neuroscience). Details of what these prizes were awarded for may be found on the website of the Nobel organization in the Presentation Speeches and Nobel Lectures given by the prizewinners (http://nobelprize.org/nobel_prizes/medicine/laureates/). The connection between advances in our understanding of genomics and of neuroscience that was stressed by Andreasen in her book Brave New Brain

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is clearly evident in the work that won Linda Buck and Richard Axel the 2004 prize. It had long been known that our sense of smell was based on olfactory receptor cells located in the nose and that these cells sent information straight to a part of the brain known as the olfactory bulb. However, the basic mechanism by which this system operated was not known. It was found that in the mouse no fewer than 3 percent of all its genes are coded for olfactory receptors. These receptors are the large molecules located on the surface of the olfactory receptor cells in the nose that react to different odors and cause the cells to send information to the brain. The large number of genes allows about a thousand different types of receptors to be produced by the mouse, and each of these different receptor types responds to a few odors only. Each olfactory receptor cell only expresses one type of receptor on its surface, but there are many copies of each cell type (and thus receptor type) spread across the lining of the nose. In humans there are perhaps only 350 different receptor types, so our olfactory world is much poorer than that of the mouse! Each receptor cell type, although spread across the nasal mucosa, was found to send its information to a specific part of the olfactory bulb of the brain in what is termed a “labeled line.” Thus the higher parts of the brain are continuously informed about the extent of activation of the different receptors. Each characteristic scent or smell will be made up of a mixture of different chemical molecules that will trigger activity in a particular combination of different olfactory cells by each different chemical molecule “docking” onto the receptors of its particular type of cell. Thus the specific combination code of activation that reaches the cortex of the brain from the olfactory bulb allows a mouse or a human to perceive a particular scent or smell. The remarkable ability of mammals to discern so many different types of odor has thus been thoroughly elucidated. The link between genomics and neuroscience in this work is even stronger than might at first appear because the receptor molecules on the surface of the olfactory receptor cells are, in fact, of the G-protein coupled type for which Rodbell and Gilman received the 1994 Nobel Prize. Rodbell and his colleagues were interested in how a chemical signaling molecule—such as a neurotransmitter or hormone—could bring about changes in the cell that it affected. They discovered that the transduction of the signal across the cell membrane was a three-step process. The cell must first recognize the molecule via a “discriminator” on its surface—step one. Finally there has to



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be an “amplifier,” which ensures that the signal is strong enough to alter the cell’s activity—step three. Rodbell discovered that there was a switch, which he called a “transducer,” between these two processes that could be turned on by a high-energy molecule called “guanosine triphosphate” (the “G” stands for this molecule in the term “G-protein coupled”)—hence step two. The Nobel Prize Presentation Speech in 1994 on Gilman and his colleagues’ contribution stated: Using a combination of genetic and biochemical techniques they managed, after a heroic effort, to isolate the G protein from all other parts of the cell membrane.

This then allowed them to study the functions of the G protein in detail and helped to open up the search for the many different types of G protein that have proved so important to our understanding of the nervous system since then. The point about the ubiquity of G-protein coupled receptors was made in an amusing way at the end of the 1994 Nobel Prize Presentation Speech. The presenter pointed out that: When our eyes perceive the procession of “Parfait glace Nobel” at the Nobel Banquet, various G proteins in the retina cooperate to transmit sensations of colour, or of light and shadow. The aroma of the food activates other G proteins in our nostrils. When we taste the parfait, yet other G proteins on the tongue come into play. When, finally, all these sensory impressions are analysed and interpreted in the brain, many different G proteins play vital roles.

It is clear, then, that there are many G-protein coupled receptors operating in signal transduction in the nervous system. In his 2004 Nobel Prize Lecture, for example, Richard Axel described how he and his colleagues approached the problem of odor reception by searching for likely G-protein coupled receptor genes in the olfactory mucosa. This was made possible because of the polymerase chain reaction (PCR) that could be used to amplify any genes of this kind that were expressed in olfactory sensory neurons. In the polymerase chain reaction a small piece of DNA with a structure having a particular characteristic (say of a certain G-protein coupled receptor gene) can be added to material from a particular tissue. If there are genes with a similar structure naturally present, the chain reaction allows the initial small piece of DNA to bond to the similar DNA from the tissue and then, by

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manipulation of the conditions for binding and unbinding of the two strands of DNA combined with replication steps, the scientist can produce many copies of the natural DNA from the tissue in amounts suitable for biochemical experiments. This technique, what might be called a “fishing expedition,” has been very important because it has allowed the discovery—particularly in the 1990s—of many new types of G-protein coupled receptors and, subsequently, the many new types of neurotransmitter that affect these newly discovered receptor types. The winners of the 2000 Nobel Prize in Physiology or Medicine, Arvid Carlsson, Paul Greengard, and Eric Kandel, received their prize for work on the transduction of signals in the nervous system. Arvid Carlsson demonstrated that the chemical dopamine is a neurotransmitter in the brain. He was able to use another chemical called reserpine, which eliminated dopamine from the nerves of experimental animals, and to show that the treated animals then lost the ability to move, in a way reminiscent of people suffering from Parkinson’s disease. Carlsson went on to demonstrate that in animals depleted of dopamine it was possible to use a precursor called L-DOPA to restore the dopamine levels—and the animals’ ability to move. This led to the use of L-DOPA to help people suffering from Parkinson’s disease, where dopamine in a crucial set of neurons is indeed depleted, and there have been enormous worldwide health benefits as a result. Paul Greengard was awarded his share of the 2000 prize for his investigation of what happens when a neurotransmitter like dopamine interacts with a nerve cell. It has been found that there are two classes of interaction between neurotransmitters and receptors. In one the response is very fast, the action of the neurotransmitter causing the receptor to rapidly allow ions to move across the cell membrane through a so-called ion channel. The result is the generation of an electrical event. In the other class of interaction there is a slower response. Studies of ion channels had previously brought Neher and Sakmann their Nobel Prize in 1991. G-protein coupled receptors, such as those involving dopamine, are of the second, slower-responding type. Here Greengard was able to show that receptor activation by the neurotransmitter is only the first link in a chain of physiological responses in the cell. These can eventually lead not only to the opening of channels for ions to pass through the cell membrane, and an electrical event, but also to other complex changes in the cell’s metabolism. Eric Kandel received his share of the 2000 prize for demonstrating how such complex changes are involved in the formation of memory. Kandel,



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who trained originally in psychiatry, used a simple invertebrate animal, the marine sea slug Aplysia, a mollusc, for his famous studies of this complex phenomenon. Aplysia has far fewer neurons in its body than the human brain and many of these cells are large and relatively easy to identify and study. The sea slug has a withdrawal reflex to protect its external gills from harm. If the slug is touched softly a number of times, however, the withdrawal response diminishes—just as our response to an unexpected touch would diminish if the touch were repeated. Kandel showed that these responses are caused by changes at the synapse between particular neurons. In the diminishing response to repeated soft touches (called “habituation”), less and less neurotransmitter is released and thus the response diminishes. A forceful touch repeated a small number of times, on the other hand, causes the withdrawal to be amplified rather than diminished. In both of these cases we can say that the slug exhibits a short-term memory as the enhanced or diminished response only lasts a few minutes. A completely different reaction occurs if a longer repeated series of forceful stimuli causes the sea slug to form a long-term memory. Here the kind of chain reaction in the cell described by Greengard (see above) leads eventually to the activation of genes in the cell nucleus and the production of new proteins. This in turn leads to a profound change in the form and function of the synapse in question. In his Banquet Speech on behalf of the three prizewinners, Kandel left no doubt about what he thought of the significance of their work. He stated: The key principle that guides our work is that the mind is a set of operations carried out by the brain.

He went on: We three have taken the first steps in linking mind to molecules by determining how the biochemistry of signaling within and between nerve cells is related to mental processes and to mental disorders.

We shall reconsider Kandel’s thinking later in the chapter because, as senior editor of the classic volume Principles of Neural Science, his views are of importance. What should be noted here is how the clear view that the biomedical and neurobiological approach to the brain and behavior, which we saw in Andreasen’s thinking at the start of this chapter, will allow an understanding of the most complex operations of our minds including

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memory. Indeed, in his speech Kandel stated that he and his colleagues had “attempted to translate abstract philosophical questions about mind into the empirical language of biology.” Perhaps the most striking and widely known example of our developing capabilities to understand the workings of the brain is in the area of neuroimaging. This set of techniques has recently allowed investigators to “see” with ever more precision what is happening in the brain when people carry out certain behaviors. It was for their contributions to magnetic resonance imaging (MRI) that Paul Lauterbur and Peter Mansfield shared the Nobel Prize in Physiology or Medicine in 2003. In the 1970s Paul Lauterbur discovered that it was possible to produce a two-dimensional image from emitted radiowaves and to determine where they originated. Peter Mansfield showed how these signals could be analyzed mathematically and thus made it possible to develop a useful imaging technique. Of course, magnetic resonance imaging has medical applications much wider than just in neuroscience but it has been very significant in that field. Magnetic resonance imaging is one of a series of developments in neuroimaging techniques. In the 1960s and 1970s computerized tomography (CT) scans allowed an image of brain structures to be produced because X-rays are absorbed to different extents by different brain tissues. Positron emission tomography (PET) scans, however, allow brain activity rather than brain structure to be detected. Because more oxygen is consumed by active cells, more blood will flow to active regions of the brain. If, therefore, radioactively labeled water or glucose is injected into the blood this will accumulate preferentially in active regions of the brain. As the radioactive material decays it gives off positrons, which collide with electrons to create gamma rays that can be detected by the scanner and converted into an image of the active regions. Magnetic resonance imaging also produces an image of the structure of the brain, but by a different method that gives better results. The MRI technique is based on the detection of hydrogen nuclei (protons). The scanner has a powerful magnet that orientates the protons, and then radiowaves are passed through the brain to induce resonance in the protons. The scanner picks up energy signals as the protons return to their resting state. In the 1990s this technique was also developed to allow detection of brain activity. Functional magnetic resonance imaging (fMRI) detects the magnetic properties of blood haemoglobin that change in relation to oxygen concentration in the blood,



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which again provides an indication of brain activity in different regions. The advantage of fMRI, of course, is that it does not involve radioactive materials being introduced into the brain. On this evidence it is surely reasonable to conclude that neuroscience is making major progress, an advancement that is widely acknowledged in the medical and life sciences community. But what do neuroscientists themselves think has been achieved and where do they think the important issues lie now? A New Science of Mind In mid-2006 Eric Kandel contributed an essay, “The New Science of Mind,” to the popular science journal Scientific American Mind. He began with these words: “Understanding the human mind in biological terms has emerged as the central challenge for science in the 21st century” (Kandel 2006, 62). He argued that we need to understand perception, learning, memory, thought, consciousness, and free will in biological terms. The meaning of the ongoing scientific revolution for many neuroscientists could not have been made any clearer. In Kandel’s view, the discovery of the structure of DNA by James Watson and Francis Crick in the early 1950s provided the necessary intellectual framework for understanding how genes control cellular function and thus put biology alongside chemistry and physics in the constellation of sciences. Our understanding of genes was thus seen as equivalent to our understanding of the periodic table in chemistry and the laws of physics. According to Kandel, over the following decades the accumulation of new knowledge and increasing confidence allowed biologists to turn their attention to understanding the human mind. The result, he believes, is that there is now a new science of the mind based on the powerful science of molecular biology. In his essay Kandel argues that this new science is based on five key principles, the first being that “mind and brain are inseparable” (ibid., 64). By this neuroscientists mean that the mind is, in fact, the operations carried out by the brain. The second principle is that “each mental function in the brain . . . is carried out by specialized neural circuits in different regions of the brain” (ibid., 65). So on this basis, a simple reflex is understood to be carried out by one specialized circuit in the central nervous system, but so is something as complex as the use of language or the creation of music or art. Thirdly, of

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course, neuroscientists believe that “all of these circuits are made up of the same elementary signalling units, the nerve cells” (ibid.). Fourthly, “the neural circuits use specific molecules to generate signals within and between nerve cells” (ibid.). Fifthly, and finally: “[T]hese specific signalling molecules have been conserved—retained . . . through millions of years of evolution” (ibid.). The final principle means that it is possible to gain insights into the operations of the human brain from the study of simpler organisms, because the same kinds of molecular mechanisms are involved, as Kandel’s own Nobel Prize work demonstrates. However, in this essay, he points out that the new science of the mind also provides us with a new perspective on our evolutionary past. It is very important for those who are not members of the life sciences community to grasp how widespread, even mainstream, this kind of mechanistic thinking is among neuroscientists. As another example, we can look at the chapter on “Principles of Neuropsychiatry” by Jeffrey Cummings and Michael Mega, which appears in the 2003 text Neuropsychiatry and Behavioral Neuroscience, published by Oxford University Press (Cummings and Mega 2003). Cummings had published an earlier successful text in 1985, Clinical Neuropsychiatry, but the preface to the 2003 book noted that there had been a tremendous explosion of information since the publication of the original book. Its successor was an attempt to put this new information into a single book with an identical framework and integrate findings that ranged from behavioral neurology to psychiatry. This second example is part of another important text and, it has to be emphasized, illustrates again the mainstream thinking of neuroscientists. Cummings and Mega’s chapter on principles lists thirty regularities that they feel can be distilled from studies of brain-behavior relationships across individuals and across different disorders. These regularities or principles thus relate more to clinical issues than the five more biological points made by Kandel. It is not necessary to review all thirty here, but Table 4.3 shows a selection that demonstrates how the same scientific viewpoint as Kandel’s underlies these principles. The first principle in Table 4.3 is, if anything, even clearer than Kandel’s bold first statement! The second principle follows on from the first: If all mental processes derive from brain processes then neuropsychiatric symptoms are caused by dysfunctions of the brain (these dysfunctions themselves, of course, can have many causes, from genetic to environmental). As in Kandel’s thinking, principle 7 of Cummings and Mega’s list focuses on the circuits in the brain. Thus they argue that most



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TABLE 4.3. Some principles of neuropsychiatry 1.

All mental processes derive from brain processes.

2.

Neuropsychiatric symptoms are manifestations of brain dysfunction.

7.

Neuropsychiatric disorders typically reflect disruption of a system or circuit.

11.

The occurrence and type of neuropsychiatric disorders are contingent on which brain regions are affected.

24.

Disturbances in transmitters or transmitter systems have specific associated neuropsychiatric symptoms.

source: Cummings and Mega 2003.

neuropsychiatric disorders reflect abnormalities in the limbic system or frontal-subcortical circuits. Obviously, principle 11 is implied by principle 7, as the circuits that can be affected in mental disorders are located in particular brain regions. This principle 11 is illustrated in the text by a table that shows how numerous characteristic symptoms arise from dysfunctions in particular brain regions. A famous example dates from an accident in the middle years of the nineteenth century when Phineas Gage, a railway foreman, had an iron bar blasted through his skull. Remarkably, he survived and lived for an additional eleven years. However, he was not the same person, turning from an efficient and capable man to someone who was rude, was disrespectful to his fellows, paid little attention to any advice, and was unable to hold down a job. It seems likely that he had extensive damage to his orbital frontal cortex—damage now known to be associated with the disinhibition of behavior. Principle 24 focuses on neurotransmitters and their malfunctions. We have already discussed an example in this chapter relating to Arvid Carlsson’s pioneering studies on dopamine, studies that enable doctors nowadays to use L-DOPA to help people suffering from Parkinson’s disease. When we think of transmitter systems, however, we have to consider not just the transmitter chemical itself but the specific receptor it affects and how the transmitter’s function is brought to an end. Malfunctions at this and other points cause natural illnesses and, in regard to lethal nerve gases and the incapacitant BZ, malfunctions can also be induced by hostile activities. In his essay, Kandel, having set out his five principles, basically announces that “so far, so good,” but in his view not good enough. Looking at his own

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work, for example, he says that much has been learnt about the cellular and molecular mechanisms of memory storage but now it is time to move on from that level and study more about how the systems work in the brain. He asks, for example, which neural circuits are critical for which kinds of memory? How does the brain encode internal representations of a face, scene, melody or experience? (Kandel 2006, 65)

He suggests that neuroscientists will have to make major new conceptual shifts in how they think about the brain to get from where they are now to where they want to be in the future. The Future of Neuroscience In his Nobel Prize Lecture Kandel (2003) explained that his original interest was in the mammalian hippocampus—a part of the brain known to be involved in learning. However, he came to the view that the mammalian system had too many neurons and too many complex connections to make much headway at that time, in the late 1950s. He therefore decided to take a reductionist approach, seeking a system simple enough to allow understanding of the principles of neuronal organization. Kandel carried out an extensive search and eventually decided to study learning in the marine sea slug Aplysia. This animal only has about 20,000 neurons divided into about ten or so groups (ganglia) of some 2,000 neurons each. Each ganglion deals with a variety of behaviors, so some simple behaviors may only involve about 100 cells. More than that, the ganglion neurons are very large—visible to the naked eye—and often characteristically pigmented, so that it is possible to recognize the same cell in different animals! The strategy that Kandel and his associates adopted was in four stages. First they wanted to define a simple behavior that can be modified by learning and that gives rise to memory storage. (Kandel 2003, 396)

Secondly, they wished to identify the cells that make up the neural circuit of that behaviour. (Ibid.)

Having thus isolated the system that was operational in the learning and memory storage, they wanted to



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locate the critical neurons and interconnections that had been modified by learning and that store memory. (Ibid.)

Finally, they wanted to be able to analyse the changes that occur at those sites in response to learning and memory storage, first on the cellular level and then on the molecular level. (Ibid.)

The lecture dealt in sequence with the four stages by which the strategy was carried out. Eventually, Kandel and his associates were able to study what happened during transmission between a single sensory cell and a single motor neuron in a culture dish. However, they were well aware that in the intact animal the circuit they were studying had twenty-four mechanoreceptor sensory neurons, which synapsed onto the six gill motor cells, and that these sensory neurons also made indirect connections with the motor cells through small groups of both excitatory and inhibitory interneurons. In his recent essay for Scientific American Mind, Kandel (2006) appears to be saying that neuroscientists have now to move on to study how such whole systems of neurons operate. He had made the same point in his Nobel Lecture, showing first how he had been able to move back to the study of memory in the much more complex mammalian system. This work was done on the mouse but, as he pointed out, though it has a much simpler brain than humans, the mouse has a system involving the hippocampus for storing memories of places and objects, much as we do. With regard to the storage of long-term memory, Kandel’s work with the mouse system showed where it differed from, but also where it resembled, the system he had found in Aplysia. In an overall conclusion, he differentiated between this increasingly well understood memory storage problem and what he called the “systems problem of memory.” He suggested that there were many important questions about how different regions of the brain interact in memory storage, and he argued that answers to these questions will require not just the reductionist molecular biology approach but also the top-down approach of psychology, neurology, and psychiatry. The Nobel Lecture ended on a nice note, with Kandel envisaging a whole series of new neuroscience laureates coming to Stockholm to receive their Nobel Prizes, as the biology of the mind captures the imagination of the scientific community in a way reminiscent of how the biology of the gene captured its imagination in the last century.

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We cannot know what subjects the future Nobel Prize winners will be rewarded for, but Kandel in his essay in Scientific American Mind (Kandel 2006) gives some insights into the kind of work he would begin to undertake if he were starting afresh now. His criteria for choice were that the work would occupy him for a long time and that the problem would be at the intersection of two or more disciplines. What then does Kandel select now as potential targets for future neuroscience research, and what might that tell us about the future trajectory of neuroscience? Not too surprisingly, his first choice follows on directly from his previous research. He would try to find out how the brain processes sensory information consciously and then how that conscious attention stabilizes memory. His choice would focus on the “place” cells in the hippocampus, which are known to allow an animal to determine its location in space, and on how these place cells enable an animal to create a long-term spatial map when it focuses its attention on its surroundings. Crucial questions are clearly: what actually is this spotlight of attention and how does it trigger the encoding of spatial memory in the neural circuit? Kandel’s second choice of research question seems a much more ambitious step. He asks, “How do unconscious and conscious mental processes relate to one another in people?” (Kandel 2006, 66). From a neuroscientist’s perspective, he argues, most of our mental life is unconscious and only becomes accessible through our use of words and images. So he suggests that it should be possible, at least in principle, to use brain-imaging techniques to make connections between brain structure and functioning and psychoanalytic disease processes that were previously only studied from the outside of the person. If such a connection became possible, Kandel suggests that we might then learn how disease states change normal unconscious processes and how psychotherapy might reconfigure these processes. His third suggestion for future work is probably the most surprising to those outside the life sciences community. He suggests the question: How can we link molecular biology of mind to sociology and thus develop a realistic molecular sociobiology? (Kandel 2006, 66)

The idea of a molecular sociobiology (Frith and Frith 2010) is surely quite farfetched to most of us, but Kandel is of the view that several areas of research are showing that this is possible. As he says, several researchers “have made a fine start towards this goal.” What then is this research? The first example



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involves the nematode worm Caenorhabditis elegans. Sydney Brenner, John Sulston, and Robert Horvitz shared the 2002 Nobel Prize in Physiology or Medicine for their work on this animal (Nobel Website). Brenner was looking for a simple system in which cell differentiation and organ development could be effectively studied. This small worm has only 959 cells and is transparent, so that every cell division and differentiation could be seen under the microscope. The animal’s genetics were also amenable to research, and Brenner showed that mutations in many genes resulted in distinct developmental changes, thereby creating a very important research tool. Sulston worked in Brenner’s laboratory and demonstrated the great precision of cell division, with identical cell lineages in each individual worm. He showed that certain cells in the line always die at the same point in the animal’s development and identified the first gene important in the process of programmed cell death. Horvitz worked with Brenner and Sulston and carried out a systematic study of genes controlling programmed cell death. He also showed that there were many human genes homologous to the genes in the worm and that these had corresponding functions. The net result of all this and associated work was that the genetics of Caenorhabditis became very well known. Like many animals, nematodes may collect together both in the wild and in laboratory cultures. Isolates of natural (wild) Caenorhabditis feed either in groups or alone. It has been found that a single change in the amino-acid sequence in a single G-protein coupled neuropeptide receptor is associated with this major difference in behavior. Animals with one type of the receptor are strongly social in their feeding; those with the other type are solitary (de Bono and Borgmann 1998). So in contrast to commonly accepted ideas, this behavioral change does not result from the action of many different genes but from a single change in a single gene! Similar examples of the effects of a single change in a gene have also now been found in humans. These examples link molecular biology and social behavior. Kandel’s second example of “molecular socio-biology” concerns the fruit fly Drosophila melanogaster. The genetics of this animal, as every biology student knows, have been the subject of intensive research over very many years. The following example of behavioral change is even more spectacular than that described for the nematode worm. A particular gene called fruitless has been found to be expressed differently in male and female flies (the gene produces a male-specific protein in males but not in females). It has

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been found that if female flies are genetically engineered to express the male protein, this causes the anatomical female to direct male courtship behavior toward normal female flies (Denier and Dickson 2005). The scientists who made this discovery were well aware of the general problem they were researching. They pointed out that animals have a characteristic body plan and morphology and that it has been found that their body parts are frequently specified by “switch” genes which are necessary and sufficient to trigger the development of a complete anatomical structure. The work of ethologists like Lorenz and Tinbergen showed long ago that animals have sets of instinctive behaviors (instincts) that are seen as stereotyped responses to environmental stimuli, but it is not clear whether these are the results of complex gene interactions or, as the researchers ask: Are there behavioral switch genes that create the potential for a complex innate behaviour? (Denier and Dickson 2005, 785)

They argue that since males and females generally have very distinct and innate sexual behaviors this may be a good place to look for such switch genes. Ongoing work on the fruitless gene has shown that in the male it is active in various sets of neurons in different parts of the nervous system relevant to sexual behavior. It thus appears that there is genetic specification of the neural mechanisms for this complex behavior. Kandel’s third example involves the quite remarkable “mirror” neurons recently discovered by Giacomo Rizzolatti and his colleagues in Italy (Dobbs 2006). Giacomo and Rizzolatti were recording electrical activity in single neurons of a monkey’s brain as the monkey reached for different objects. To their surprise they found that the cells active when the monkey reached for something were also active when the monkey watched someone else reaching for the object. They named these cells “mirror” neurons to signify that they had this fascinating function. The finding that in a monkey mirror neurons are active when it cannot actually see the action, but has sufficient clues to have a mental picture of what the experimenter is doing, strongly supports the idea that these neurons are involved in understanding actions. Since they were discovered some ten years ago, mirror neurons have been found in many other parts of the monkey brain and subsequently, through neuroimaging studies, in humans. The thrust of the findings in humans suggests that mirror neurons may be very important in helping us to understand other people’s actions, to learn through imitation and perhaps in



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language. Such findings support the argument that a molecular sociobiology could be developed. What needs to be appreciated is that biology has changed from a diffuse, small-scale scientific endeavor to a large-scale multinational enterprise with large amounts of money being directed to the achievement of specific goals. This was clearly demonstrated in the success of the Human Genome Project, but similar large co-operative enterprises are also involved in achieving the objectives of neuroscience. Brain research is, for example, one of the key priorities in health research in the European Union’s Seventh Framework Programme 2007–2013 (Olesen and Freund 2006). The combination of many potentially successful lines of mechanistic research, large-scale funding, and international co-operative research enterprises should alert everyone to the dangers and to the urgent need to consider how to safeguard the results of brain research from misuse. Malign Manipulation There are many examples of current research that could be used to illustrate the point that the increase in our mechanistic understanding of the brain could allow much more specific malign manipulation. One example is particularly pertinent as it involves the direct use of a bioregulator to alter behavior. In June 2005 the major scientific journal Nature published a paper about trust in humans, but the paper (Kosfeld et al. 2005), titled “Oxytocin Increases Trust in Humans,” reported findings that most of us would find extremely surprising. The authors reported work on a game with two players, one called “the investor” and the other “the trustee.” At first the investor has the option of donating money to the trustee. If the investor does transfer money both players in the game can gain but, initially, the trustee alone receives the reward. The trustee is then informed of the investor’s donation and can share the rewards with the investor. If the investor donates money and the trustee shares the reward both end up with higher payoffs, but the trustee can also just keep all the money. This violation of the investor’s trust does not harm the trustee as the game is only played once between the two players. The investor, therefore, clearly faces a dilemma. If he has faith in the trustee, and the trustee is worthy of his trust, the investor increases his own payoff. But there is a real risk that the trustee will not share the reward and

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the investor will be worse off than if he had not donated money in the first place to the trustee—and in this event, of course, the trustee will be even better off. There are good reasons to believe that most of us, if asked to play the role of the investor, would be rather averse to taking the risk of placing too much trust in the trustee! In the game described in the publication the investor and the trustee each received 12 monetary units. The value of these units in real money was known in advance by both players. The investor could then choose to donate 0, 4, 8, or 12 monetary units to the trustee. The experimenters then tripled what was donated. So if 12 monetary units were donated the trustee received 12 times 3, or 36, monetary units to add to his original 12 and therefore had 48 monetary units for himself. After being informed of the investor’s donation, the trustee could choose to transfer back any amount, but this amount was not increased by the experimenters (see fig. 4.1). The investors played the game under two conditions. Twenty-nine investors played normally (the placebo group) and another twenty-nine investors played after receiving an intranasal dose of oxytocin. Oxytocin is a neuropeptide which is known to pass through the blood-brain barrier after such administration. The experimenters found a marked effect produced by the oxytocin: Out of the 29 subjects, 13 (45%) in the oxytocin group showed the maximal trust level, whereas only 6 of the 29 subjects (21%) in the placebo group showed maximal trust. (Kosfeld et al. 2005, 674)

and: In contrast, only 21% of the subjects in the oxytocin group had a trust level below 8 monetary units [transferred to the trustee], but 45% of the subjects in the control [placebo] group showed such low levels of trust. (Ibid.)

The experimenters eliminated the possibility that it was aversion to risk as such rather than the risk in the social interaction that was affected by the oxytocin. They did so in a second experiment in which the investors again played the game, but with the actions of the trustee replaced by a random mechanism. So the risk structure of the problem facing the investor was the same, but no other person was involved. In this situation the administration of the oxytocin did not affect the investors’ behavior. Indeed, the behavior of the placebo group of players in the social interaction form of the game was



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Investor and Trustee each receive 12 monetary units from the experimenter

Investor decides to give trustee 0, 4, 8, or 12 monetary units

Experimenter multiplies donation by 3 times so the trustee gets 0, 12, 24, or 36 monetary units to add to his original 12 monetary units

Trustee decides what to give back to the investor from his original 12 monetary units and what had been donated by the investor

Oxytocin increased the amount of trust (levels of donation) shown by investors

FIGURE 4.1. Oxytocin effects in the trust game. Boxes in figure show different

steps in trust game. source: Based on Kosfeld et al. 2005.

quite similar to both the placebo group and the oxytocin group in this riskonly experiment. The authors of the paper naturally stressed the beneficial utility of their findings, but they were certainly not unaware of potential misuse, stating, “[O]f course, this finding could be misused to induce trusting behaviours that selfish actors subsequently exploit” (ibid., 675). What is of interest here is to know exactly what is going on. How does the administration of a relatively simple chemical through the nose into the brain change a person’s trusting behavior?

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A number of alternative answers are examined in the paper, for example, that oxytocin might make the investors more optimistic about the chance of the trustee sharing or that it helps the investors overcome their natural aversion to being betrayed in the social interaction. However, the authors’ view is that the oxytocin’s action is best understood on the basis of what is known from animal studies. They indicate that in addition to its well-known hormonal functions during labor, oxytocin receptors are found in the brain regions associated with behaviors such as maternal care and the ability to make social attachments. Thus they state that “there is substantial evidence that oxytocin promotes prosocial approach behaviour by inhibiting defensive behaviours” (ibid.) and conclude that the oxytocin facilitates the investors making the first step in the social interaction. What then do we know about the role of oxytocin and oxytocin receptors? Oxytocin was the first peptide hormone to have its structure determined and the first to be chemically synthesized in an active form. The structure of the oxytocin (OT) gene was worked out as long ago as 1984, and the sequence of the OT receptor was determined in 1992. The functions of oxytocin that were known early on were the stimulation of uterine smooth-muscle contraction during labor and milk ejection in lactation, but its functions in relation to reproduction are much wider. As one review noted recently: The actions of OT [oxytocin] range from the modulation of neuroendocrine reflexes to the establishment of complex social bonding behaviours related to the reproduction and care of the offspring. (Gimpl and Fahrenholz 2001, 629)

In short: Overall, the cyclic nonopeptide OT and its structurally related peptides facilitate the reproduction in all vertebrates at several levels. (Ibid.)

With that profile of activity, it is not too surprising that the oxytocin system has been the subject of a great deal of research, and not just directly in relation to reproduction. For example, human autism appears to involve a disruption of normal social interaction skills, and animals in which the oxytocin system is disrupted could therefore provide important insights into what goes wrong and what might be done to correct autism (Lim, Bielsky, and Young 2005). A press release from the NIMH suggested how oxytocin worked in building trust in the trust game (NIMH Press Release 2005). The press release



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noted that pioneering work on animals by Dr. Thomas Insel (then NIMH director) had shown the key role oxytocin played in complex emotional and social behaviors and described a novel study that had been inspired by Nature’s publication on oxytocin in the trust game. The new study involved fifteen healthy men who were asked either to sniff oxytocin or a placebo prior to having their brain functions examined in a functional magneticresonance-imaging scan. Crucially, the volunteers were asked to match angry or fearful faces and threatening scenes while undergoing their scans. As expected from previous work (to be discussed later in the chapter), the threatening pictures produced strong activation of the amygdala. This response, however, was “markedly” reduced following the oxytocin inhalation. The differences between normal and oxytocin-affected responses being particularly marked in regard to threatening faces suggested a role for oxytocin in regulating social fear. These findings in humans were in line with an earlier study of the mechanism by which oxytocin and the related peptide vasopressin affect the amygdala in rat brains. The authors of the rat brain study began their report by noting the important role the amygdala is known to play in anxiety and fear. They then set out the sequence by which this happens: Fear learning involves its [the amygdala’s] lateral and basolateral parts, where the association between incoming fearful and neutral stimuli leads to potentiation of synaptic transmission. (Huber, Veinante, and Stoop 2005, 245)

They continued: These parts project to the central amygdala (CeA), whose afferents to the hypothalamus and brainstem trigger the autonomic expression of fear. (Ibid.)

So if means could be found to interrupt this flow of information, the fear response (e.g., in anxiety states) might be moderated in a beneficial way. The central part of the amygdala expresses numerous neuropeptides and receptors for such neuropeptides. Included among the receptors expressed are those for vasopressin and oxytocin—and they are present at high levels. Previous studies had shown that activation of these receptors produced different outcomes: Vasopressin enhances aggressiveness, anxiety and stress levels and consolidation of fear memory. (Ibid., 246)

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whereas: Oxytocin decreases anxiety and stress and facilitates social encounters, maternal care and the extinction of conditioned avoidance behaviour. (Ibid.)

Curiously, however, both vasopressin and oxytocin have been found to have excitatory effects on neurons in the central region of the amygdala. This raises the question of how the two neuropeptides exert their contrary effects. The answer, these investigators discovered, was that there were two different groups of neurons in the central region. Oxytocin receptors were found on neurons in the lateral and capsular regions of the structure whereas those with vasopressin receptors were found in the medial part. Furthermore, the two different groups did not overlap in their distribution. While it was found that the neurons with oxytocin receptors were excited by the application of oxytocin, such excitation of the oxytocin neurons also led to an inhibition of the vasopressin neurons through projections from the oxytocin neurons having gamma-amino butyric acid as an inhibitory transmitter (Huber, Veinante, and Stoop 2005). Thus different inputs to the amygdala can be integrated into a common output to the autonomic nervous system. The important role of the amygdala was also demonstrated in a study of mice in which the gene for oxytocin had been “knocked out” by genetic manipulation (Winslow and Insel 2002). Different species have different distributions of neurons with oxytocin receptors in their brains to match their species-particular behaviors. So these mice did not show all of the social deficits that would have been expected from studies of rats but, remarkably, these oxytocin knockout mice failed to recognize other mice even after repeated social encounters. They therefore lacked a crucial social skill that ordinary mice need. The deficit was shown not to result from an abnormality in the mice’s sensory capabilities (recognition is predominantly by smell) or in a generalized impairment of learning and memory. Instead, injections of low doses of oxytocin into the amygdala restored the capability for social recognition! So the problem was in the central processing of information in the amygdala. The authors of the trust game with which we began this account are working in the new field of neuroeconomics. One of them recently coauthored a more detailed account of further work using the game. The authors of this new paper explained that in standard economic theory it is predicted that



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rational self-interested individuals should never trust another person in a one-shot interaction, and if someone does trust you, you should not be trustworthy. (Zak, Kurzban, and Matzner 2005, 523)

This follows from the assumption that the trustee prefers more money to less so he or she should not send money back to the investor, and that the investor, knowing that, should not send money to the trustee in the first place. Yet it has been found in many different studies that investors usually send substantial amounts to the trustees and that the trustees nearly always send something back—although there are great individual variations in the amount returned. What the experimenters here wanted to discover was not the effect of giving the investors intranasal oxytocin but the levels of natural oxytocin found in different players of both roles. There were thirty-eight participants in the game reported. Half were investors and half were trustees. Nineteen games were therefore played, and they were played under two conditions. The first was where the intent was clear. The players received $10 each and the investors were asked via a computer to choose how much to send to the trustees. The amount was tripled by the experimenters and the trustees then made their decision via the computer interface. In the second condition the investor had to publicly draw a ball from an urn, and this indicated the amount that had to be sent to the trustee. So in this second random draw condition, there was no intention attached to the investor’s decision. Immediately after the players had made their decisions under both conditions blood samples were taken from the players and used to test for levels of oxytocin in the blood. The experimenters had predicted in advance that when trustees received a monetary transfer as a result of voluntary and intentional transfer— indicating trust—there would be a higher level of oxytocin than when they received money as a result of a random draw. This indeed turned out to be the case. The mean level of trustees’ oxytocin was found to be 41 percent higher on average in the intentional condition over what was found in the random draw condition. The experimenters were very careful in the inferences they drew from the work that they reported. For example, they cautioned against the interpretation that because the peripheral blood oxytocin levels were higher the same levels of oxytocin would necessarily be found in the brain. Although such a relationship has been shown in animal studies, they noted that it had not been shown in humans. On the other hand, they suspected that

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their use of the computer interface minimized the social cues available to the trustees. As they noted: Our findings suggest that social interactions outside the laboratory involving intentions of trust might also produce OT [oxytocin] responses because of two features that bias the results against finding a physiologic reaction. (Zak, Kurzban, and Matzner 2005, 526)

These features were the lack of face-to-face communication and the anonymity of the players. They argued, reasonably, that in real social interactions there would be additional information that could well augment the oxytocin response that they found in the experimental situation. So if the first set of experiments we described with the trust game showed that intranasal oxytocin administration increased trusting behavior in the investor, the second set just described showed that the recipients of such trusting behavior responded with an increasing output of oxytocin. Clearly we do not act as the indifferent rational actors of economic theory! In fact, we are creatures produced by a process of evolution, and we have emotions that give significance to the information we receive from the external world and that drive our behavior. These powerful forces are obviously of importance to those seeking to help sufferers from mental illness, as is well demonstrated by a 2007 study (Hollander et al. 2007) of the effects of oxytocin on autism. The authors of this autism study began by noting a number of previous studies that linked oxytocin with autism. One such study had found much lower levels of this neuropeptide in the blood of children diagnosed with autism as compared with that of normal children. Another had taken off from the findings of animal studies—on the influence of vasopressin and oxytocin on excessive grooming and repetitive behavior in animals—and found that oxytocin infusion produced a significant reduction in repetitive behaviors characteristic of people with autism and Asperger’s syndrome. The authors of the study therefore attempted to discover if oxytocin would help with another feature of autism—dysfunctional social cognition. They found that infusion of oxytocin did indeed help with some aspects of assignment of emotional significance to sentences read aloud. In particular, they found that “subjects who received oxytocin first showed increased retention of effective speech comprehension after a delay” (Hollander et al. 2007, 500). Yet, as the authors of the trust game (Kosfeld et al. 2005) recognized, an improved understanding of such powerful forces as emotions might be misused by those



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with malign rather than benign intent. This point was clearly demonstrated by the appearance of advertisements for oxytocin on the Internet in 2007. These advertisements suggested that salespeople, for example, could be more successful if their clients were covertly given oxytocin! Given the enormous efforts made by major states in the last century to develop lethal nerve agents and various chemical incapacitants that disrupt the operations of the nervous system, it hardly needs adding that such precise new knowledge of the circuits and transmitter systems of the brain could be subject to much more serious hostile abuse unless sustained efforts are continued to prevent such malign misuse. Thus far we have analyzed the impact of both the changing nature of warfare and the revolution in the life sciences on the perceived utility of CBW and—closely related to this—on the future of the CBW prohibition regimes. Both of these factors can be expected to have a major impact, and given the limitations of the two regimes, it might appear as a legitimate question whether states would not be better off supplementing measures to strengthen the regimes with determined defensive efforts along the lines suggested by Petro, Plasse, and McNulty (2003) (see chapter 1 above). While in principle permitted under the BWC and CWC, defensive measures going beyond a certain point can start adding to the problems by inducing an arms competition instead of preventing it. These issues will be discussed in the following chapter.

5

Threats to the CBW Prohibition Regimes Biodefense Pushed Too Far

Introduction In the introductory chapter we have briefly reviewed the arguments put forward by Petro, Plasse, and McNulty (2003). While we do not share their emphasis on biodefense at the expense of other policy tools, one clearly needs to recognize the important and legitimate contribution that biodefense efforts can make in responding to the threat emanating from CBW. In a similar assessment in 1993, following the first Gulf War, Graham Pearson, then director general and chief executive of the United Kingdom’s Chemical and Biological Defence Establishment at Porton Down, put forward the idea of a “web of deterrence” to prevent anyone thinking they might benefit from the development or use of chemical or biological weapons (Pearson 1993). This web consisted of an integrated set of policies covering intelligence, export controls, international arms control agreements, biodefense, and coordinated responses to deviations from the norm that such weapons are unacceptable. As we will discuss in more detail in chapter 6, subsequently, both conceptually and in terms of practical policies, elements of the web have been considerably developed. One thing that has not changed, however, is the view that there is a key place for sensible biodefense within the web (Kelle, Nixdorff, and Dando 2006). This view is supported by the texts and implementation of both the CWC and the BWC. So, the issue we are concerned about is not biodefense as such.

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However, if biodefense is pushed too far, the question naturally arises whether this can cause problems that threaten the regimes or undermine other elements of the wider web of responses (see chapter 6) and lead to an arms dynamic that might deteriorate into a biochemical arms race. Since the events of 2001, biodefense has been expanded in many countries, but the expansion has taken place to the most extreme extent in the United States. So it is to the debates provoked by the expansion of U.S. biodefense that we should look in order to most easily follow the possible threats to the regimes from this source. Criticisms of the Entire U.S. Biodefense Buildup The Executive Summary of World at Risk, the report of the Commission on the Prevention of WMD Proliferation prepared in late 2008 for the incoming new U.S. administration, opened with two unequivocal statements: The Commission believes that unless the world community acts decisively and with great urgency, it is more likely than not that a weapon of mass destruction will be used in a terrorist attack somewhere in the world by the end of 2013. (Graham et al. 2008, xv)

and: The Commission further believes that terrorists are more likely to be able to obtain and use a biological weapon than a nuclear weapon. The Commission believes that the U.S. government needs to move more aggressively to limit the proliferation of biological weapons and reduce the prospect of a bioterror attack. (Ibid.)

There is surely cause to be somewhat skeptical about the possibility of terrorists being easily able to launch a WMD biological weapons attack in that time frame, but there is no doubt that the United States has expended vast mounts of money on its whole biodefense program since 2001. As the Center for Arms Control and Non-Proliferation noted in April 2008: Since the 2001 terrorist attacks on the United States, the U.S. government has spent or allocated nearly $50 billion among 11 federal departments and agencies to address the threat of biological weapons. (Center for Arms Control 2008, 1)

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The center’s assessment of this expenditure suggests that the Department of Defense (DoD) has received over $12 billion since 2001 and that “[o]ver 90% of all bioweapons-related funding goes to the three lead departments: Health and Human Services, Defense, and Homeland Security (through which Project Bioshield is funded)” (Center for Arms Control 2008, 1). This expenditure has continued at such levels (Franco and Sell 2010) and been subject to significant criticism from within the United States. The main lines of criticism of the whole effort are briefly reviewed in this section of the chapter in order to inform the subsequent analysis of the Department of Defense’s part of the expenditure. Such criticisms cannot be taken lightly, for as Senator Tom Daschle stated, in a report to the United Kingdom’s Institute for Public Policy Research (IPPR) Commission on National Security for the 21st Century: The threats of bioterrorism and naturally occurring epidemics are already upon us, yet we remain under-resourced and fundamentally unprepared for this new challenge . In the United States, the Bush Administration failed to release a comprehensive plan outlining the goals of a national biodefense strategy for six years after the anthrax attack on my office [emphasis added]. (Daschle and O’Toole 2008, 1)

This report, by an experienced senator, with a quite personal interest in the issue, goes on to suggest that the response in both the United States and the United Kingdom has been “through some traditional but unfortunately not very effective techniques” such as announcing the importance of the problem, carrying out reorganizations, and throwing money at the problem with the end result that progress is modest and uneven, and as with relabelling and reorganisation, money without a meaningful strategy simple leads to constituencies capturing funds to increase what they were previously doing or to do largely irrelevant things without beneficial progress. (Ibid., 2)

So what specific criticisms have been made by other U.S. observers? Reasonable Scale and Distribution of Funds? Daschle and his coauthor, Tara O’Toole, are of the opinion that the scale of funding is quite inadequate as a response to the threat. They argue that the Bush administration tried to convey a sense that something new was



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happening by grouping ongoing measures together under new labels, but they suggest: Those US biodefense initiatives that are novel—such as the Bioshield programme . . . have been underfunded, understaffed and have received little attention from policymakers. (Ibid., 2)

A contrary view was put forward by the historian Susan Wright, who clearly thought that far too much was being spent when she wrote: As the news of the first casualty from pulmonary anthrax broke on October 4, 2001, the Bush Administration launched a dramatic expansion of counterbioterrorism programs, requesting emergency funding of $1.5 billion. A frightened Congress increased the amount to $2.5 billion. Funding for counter-bioterrorism began to soar and has been soaring ever since. (Wright 2004, 61)

A perhaps more interesting argument was put forward by the Center for Arms Control and Non-Proliferation when it pointed to the very low levels of funding for prevention: “[C]umulative funding for efforts to prevent the development, acquisition, and use of biological weapons is expected to reach approximately $1.13 billion in FY2009. . . . This is less than 5% of the total funding for biodefense RDT&E” (Center for Arms Control 2008, 3). In short, the funding is, on this view, far too much orientated to response rather than prevention. Risk/Threat Assessment? In 2007 the Congressional Research Service produced a report on the Department of Homeland Security’s (DHS’s) risk assessment methodology, describing how it had evolved and setting out various options for Congress to consider for its further development (Congressional Research Service 2007). The DHS’s first Bioterrorism Risk Assessment (BTRA) appeared in 2006 and, at the department’s request, the National Research Council established a special committee to provide a scientific peer review of the assessment. This peer review does not make easy reading for those basing their work on the risk assessment. It stated: The Committee found a number of shortcomings in the BTRA, including a failure to consider terrorists as intelligent adversaries in their models, unnecessary complexity in threat and consequence modeling and simulations, and a lack of focus on risk management. (Parnell et al. 2008, 353)

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If that were not bad enough, Parnell and his colleagues, who were all members of the committee, went on to report that although changes had been made in the 2008 assessment, these would not “alter the Committee’s assessment of the BTRA methodology or render the Committee’s findings irrelevant” (ibid., 354). Effectiveness? If the major tasks of U.S. biodefense are seen to be effective biosurveillance, medical countermeasures, and meaningful mass casualty response, then it is clear that, although current methods of surveillance take too long and an effective replacement system is some years away, and the mass casualty response is still not organized at a national level (Kahn 2008), the major difficulties and criticisms appear to concern the development of medical countermeasures. Shortly after the Biomedical Advanced Research and Development Authority (BARDA) was created in 2006 to galvanize the development of new products, Nature Biotechnology carried a detailed review of the availability of vaccines and therapeutics for the treatment of the Centers for Disease Control and Prevention’s Category A and B agents and a further four Category C agents. The review concluded: Despite many products currently in development, the outlook for biodefense vaccines and therapeutics is a bleak one, with few products on the market to counter most bioterrorism agents and only a few in late stages of development. (Trull et al. 2007, 184)

A more recent review in September 2008 by a group from the Center for Biosecurity at the University of Pittsburgh Medical Center adds to this analysis by attempting to estimate how much it would cost to meet the U.S. objectives in this area. In a letter to the editor of Nature Biotechnology this group set out their aims as follows: We performed a survey of candidate biodefense countermeasures in development and estimated their future clinical development costs, based on historical drug and vaccine development data. (Matheny et al. 2008, 981)

The analysis was concerned only with the eight Department of Health and Human Services (HHS) Biodefense Medical Countermeasures defined as essential to protect civilians. The authors came to three very clear conclusions. First:



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The cost of supporting existing candidates is estimated to be $4.1 billion over the next seven years, with costs of $817 million in fiscal year 2009, alone. (Ibid.)

Then: Given the high failure rate of biopharmaceutical development, the probability of developing approved products from the existing pipeline is between 12% and 85% per HHS requirement. (Ibid.)

Finally: To increase the probability to 90%, two to nine additional candidates will be needed per requirement, at a total seven-year clinical development cost of $14.0 billion. (Ibid.)

As they add, “[t]o date, the primary government program tasked with supporting clinical development of medical countermeasures has received only $201 million” (ibid.), on this analysis there is a massive problem at the heart of the U.S. biodefense enterprise. Dangerous? One criticism of the focus of research funding on biological weapons threat agents has been that it has drained money away from more important medical issues such as finding cures for, or protection against, much more prevalent and important diseases (MacKenzie 2005). That view was contested but others have argued that the buildup of researchers and institutions specializing in work on biological threat agents is likely to distort the trajectory of life science research in the United States in the future as these people and institutions compete for further funding (Reppy 2008). It has also been suggested that more sensible funding decisions might come about if assessments of the threat were made by taking into account potential bioweapons attacks, potential influenza epidemics, and endemic diseases at the same time. This combined risk assessment, it is suggested, would lead to a more rational distribution of funds, with work on biological weapons threat agents having a lower priority (Klotz 2007). Another criticism of the biodefense buildup has been that, by increasing the number of people working on dangerous pathogens and increasing the number of BSL-3 and BSL-4 laboratories doing such work, there is an inevitable increase in the probability of accidents and releases of disease

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agents that could threaten the general population. These are far from idle concerns, with one recent study pointing to major weaknesses in federal oversight and regulation, official disregard for siting criteria, inadequate self-regulation and management of lab safety practices, breakdowns in reporting systems, and obstacles to organizational learning and emergency response created by secrecy and security policies. (Baram 2009, 890)

Not surprisingly, in such circumstances, there has been local opposition to the siting of facilities. Counterproductive? One argument against the increase in biodefense funding, of course, is that it produces precisely the kinds of materials and knowledge that can be misused for bioterrorism. As the Bulletin of the Atomic Scientists (Editorial 2008) noted: One potential threat is that posed by scientists working in sophisticated state biodefense programs. In the light of recent FBI findings that Bruce Ivins, a scientist working within the U.S. biodefense complex, was the sole perpetrator of the anthrax attacks in the fall of 2001, the issue . . . takes on greater meaning. (Ibid., 6)

The editorial went on to argue that insufficient accounting has been given of all the work being done in the U.S. biodefense program and that this “has raised suspicions among friends and foes about the program’s goals” (ibid.). This line of criticism is essentially suggesting that it would be very counterproductive if the program were misperceived as actually being offensive rather than defensive. Inappropriate Post–President Bush? In a presentation on the Department of Defense Chemical and Biological Defense Program, Jean Reed, special assistant for Chemical and Biological Defense and Chemical Demilitarization Programs, listed eight mission areas for combating weapons of mass destruction: interdiction; threat reduction cooperation; security cooperation and partnership activities; active defense; elimination; passive defense; offensive operations; and WMD consequence management (Reed 2009). Clearly, these missions can be grouped uncontroversially into prevention, defense, and consequence management.



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An interesting question is whether the balance among these three groups of activities is likely to change under the Obama administration. One indicator is what influential commentators suggested. In general terms, one group of well-known commentators has argued: In recent years, the U.S. government has strengthened its national preparedness and response capabilities for catastrophic disease events, including bioterrorism. But it has paid inadequate attention to prevention and response measures internationally, thereby increasing our vulnerability to a significant biological event and heightening the skepticism of other countries about our commitment to either improving global public health or reducing deliberate and accidental biological risks to global security. (Ratta et al. 2009, 1–2)

They then listed a series of policy proposals for the Obama administration designed to correct this lack of attention to prevention and internationalism. One of their suggestions, not surprisingly, is for further development of international mechanisms of threat reduction programs. The same point was made by Kenneth Luongo, president of the Partnership for Global Security. In his view: [T]he new administration needs to act quickly to adapt its . . . biological proliferation prevention strategies and threat reduction programs. . . . This effort will require significantly increasing programmatic budgets, creating a robust globalized agenda. . . . The Obama administration needs to create a next-generation Global Proliferation Prevention Initiative. (Luongo 2009, 1)

In contrast, he pointed out that in recent years the threat reduction budget has remained essentially static. More recently, however, Senator Lugar has begun such a reorientation of the Nunn-Lugar Cooperative Threat Reduction Program (Dando 2010). Another suggestion from Ratta et al. was that the United States should now [p]ursue stronger confidence-building and other transparency measures designed to provide mutual reassurance that national biodefense and other dual-use activities comply with the BWC [Biological Weapons Convention]. (Ratta et al. 2009, 2)

A very similar view was taken by Gigi Kwik Gronvall in a collection of articles that made proposals for the new administration. In her view:

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The U.S. should strongly support the Biological Weapons Convention and other international treaties. (Gronvall 2009, 31)

This is an issue that will be taken up later in this chapter. DoD-Funded Biodefense As the Department of Defense–funded part of U.S. biodefense activities is not distinct from the rest of the program, it has to share responsibilities if the criticisms just reviewed have some validity. However, the DoD-funded part of the program is also distinct in that it has special specific responsibilities. The Chemical Biological Program Strategic Plan makes this quite clear in stating: The threat associated with WMD attack has evolved over recent decades. The WMD programs undertaken by nation states remain the primary focus of DoD’s CBRN defense programs. The potential that our opponents in overseas operations might use CBRN weapons continues to drive development, acquisition, and integration of a modernized generation of CBRN defense capabilities [emphasis added]. (DoD 2008, 6)

This does not mean, of course, that U.S. forces can ignore use of chemical and biological weapons by terrorists in the wars we shall face—see, for example, reports of the use of chemicals to prevent girls in Afghanistan going to school and the associated call for U.S. forces to protect the rights of women against the Taliban fundamentalists (Starkey 2009; Sengupta 2009). What it does mean, surely, is that the military has to take a very serious look at the idea that terrorists have the capability to easily attack the United States itself with biological weapons of mass destruction. If the case for such a presumption is weak, as we believe it is, then focusing on the military’s problem of dealing with the use of chemical and biological weapons in warfare is reinforced as the primary issue for the Department of Defense (Mauroni 2008). The problem here, as Secretary Robert M. Gates noted , is that adequately addressing this new form of warfare will require a cultural change. Recalling studies of the Vietnam War, he reviewed tendencies such as “the reluctance to change preferred ways of functioning, and when faced with the lack of results, to do more of the same” (Gates 2009, 7) that prevent large organizations from changing. He also pointed out that



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apart from the Special Forces community and some dissident colonels, for decades there has been no strong, deeply rooted constituency inside the Pentagon or elsewhere for institutionalizing our capabilities to wage asymmetric or irregular conflict—and to quickly meet the ever-changing needs of our armed forces engaged in such conflicts. (Gates 2009, 6)

On those grounds it is hardly likely that the Department of Defense part of the biodefense program will not have to undergo considerable change to meet future needs. An obvious example of the present failure to come to grips with the problem is clear in the section of the Annual Report to Congress on the Chemical and Biological Defense Program (DoD 2009b) concerned with “Doctrine, Training, Education and Exercises.” Here, in a report for Congress eight years on from 9/11, it is stated that in a gap analysis on NBC defense joint training, the following primary gaps were identified: Policy disconnects; Lengthy processes that delay doctrine updates; Doctrine and requirements inconsistencies; Need for advanced military education and training; Low priority in the Military Services for NBC defense training; Lack of realism in NBC education and training at the individual, unit and higher command levels. (DoD 2009b, 55)

Yet, as the Annual Report rightly states, “[t]roops should never encounter a real world threat or situation that they have not already experienced in exercises or other training activities” (ibid., 53). It remains to be seen how the “Doctrine, Training, Leadership, and Education Strategic Plan” (DoD 2009a) turns into implementation, but one might suspect that it will not be easy to gather the necessary commitment and funding. That theme, about the difficulty of achieving cultural change, runs through the rest of this section. Reasonable Scale and Distribution of Funds? In his article on the U.S. national defense strategy Secretary Gates stressed the need for a balanced use of resources, stating, for example, the need to balance doing everything we can to prevail in the conflicts we are in, and being prepared for other contingencies that might arise elsewhere, or in the future. (Gates 2009, 2)

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This search for an appropriate balance, in present circumstances, is very likely to be set against overall cuts in expenditure by the U.S. government. As Gordon Adams noted (Adams 2009), the Defense Department put forward a request for an expansion of its budget by 14 percent, but this was rejected and a much smaller increase was suggested by the new White House. Secretary Gates did not contest the rejection. In Adams’s view, “[w]hile some in Congress argued that Defense could have been constrained even further, this was a clear signal to the armed services that a new sheriff was in town” (Adams 2009, 2). Earlier in the year, in one of the proposals for the new administration published in Biosecurity and Bioterrorism (Franco 2009), it was argued that one necessary reform was to make the biodefense budget more transparent so that it was possible to track what was being achieved by the complex expenditures under different headings and different institutions. However, it was also pointed out that: The Obama Administration regards biodefense and biosecurity as a national priority, but there is little evidence that the agencies responsible for biodefense programs regard biosecurity as a core mission, insofar as agency priorities are reflected in budgets or the time cabinet heads spend on issues. (Franco 2009, 30)

In such circumstances, of cuts and lack of priority as a core mission, one wonders whether, for example, the National Academies recommendations in its 2007 report on The Biological Threat Reduction Program of the Department of Defense—that “[t]he U.S. government should provide strong and sustained support for BTRP and related programs” (National Research Council 2007)— will be acted upon in coming years. The idea that biodefense is not a core mission of the DoD is supported by specific criticisms that have been made of its spending in this area. According to a leaked report of the Defense Inspector General, spending is so split up and uncoordinated that it is impossible for officials to be sure what they are achieving with the funds expended (Davison 2008). In regard to balance, one is at a loss to understand why the United States has not trained its troops properly for the wars we are in today while, for example, it has allowed a situation to develop in which “the battle fleet of the Navy, by one estimate, is larger than the next 13 navies combined—and 11 of these 13 navies are allies or partners” (Gates 2009, 4).



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Risk/Threat Assessment? Before discussing the problem of threat assessment, we should again make it clear that we think it is very sensible—indeed necessary—to develop means of sensing, protecting, and treating chemical and biological agent attacks that military forces are likely to encounter. However, we go along with the arguments put forward by Mauroni (2008) when he describes what he calls “[f]ourth generation warfare (1995 to the present).” In his view: Future terrorist CBR incidents will be single attacks with limited casualties, intended to disrupt specific government or commercial activities and create wide-scale panic and economic chaos. Future state use of CB weapons will be focused on the disruption of fixed sites and critical infrastructure. (Mauroni 2009, 25)

Thus what will be encountered for some time to come is much more likely to be easily obtainable toxic industrial chemicals or crude biological weapons rather than high-technology genetically modified or synthetic organisms. The recent rise of “science-based threat assessment” in the United States, involving as it does the laboratory study of offensive biological weapons agents so that countermeasures can be developed, has been widely criticized. Jonathan Tucker (2004) summarized as follows: first, that there is a risk that the novel agents or knowledge would leak out to other states or terrorists; and second, that it risks “undermining the norms in the BWC and provoking a biological arms race at the state level, even if the countries involved merely seek to anticipate and cover offensive developments by potential adversaries” (Tucker 2004, 1). In short, there is a real concern among knowledgeable analysts that such science-based threat assessment could take us down the road that will lead to state-level offensive programs that would produce technologically advanced biological agents of the kind described by Petro, Plasse, and McNulty (2003). In particular, the recent development of the National Biodefense Analysis and Countermeasures Center (Shea 2007) has been of much concern on account of its possible activities (Leitenberg, Leonard, and Spertzel 2003). Effectiveness? In their interesting account, Bioterrorism and Threat Assessment, for the Weapons of Mass Destruction Commission, Ackerman and Moran (2004) attempted to provide a holistic framework for thinking about the issue. To begin with, they noted that “[t]he basic argument presented in this paper

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is that inadequate threat assessment leads to sub-optimal policy decisions” (Ackerman and Moran 2004, 4). This is true, but even optimal policy decisions can go wildly astray. A case in point is the efforts of the Department of Defense to provide vaccines against probable biowarfare agents for its forces. The National Academies report Giving Full Measure to Countermeasures noted: The military has considered vaccination to be the primary medical strategy for battlefield protection of a defined and relatively small population. Mass vaccination of the civilian population against a range of potential biological threats is less appropriate and much less feasible. (National Research Council 2004b, 3)

However, the report began with the following startling statement: At the time of the Gulf War, only one medical countermeasure approved by the Food and Drug Administration (FDA)—the vaccine against anthrax— was available. . . . In 2003, despite congressional attention and good faith efforts on the part of DoD scientists, no new vaccines against biowarfare agents are available to service members. (National Research Council 2004b, ix)

So the Department of Defense had fallen down on a primary responsibility, according to this report. The report was not isolated in this view. Writing in 2007 on Biodefense Research Supporting the DoD: A New Strategic Vision, Colonel Coleen K. Martinez, U.S. Army, noted: It is puzzling that despite the repeated emergence of common themes in the study outcomes such as recognition of “disjointed and ineffective management” and an organizational structure that is unnecessarily complex and counterproductive and quite explicit recommendations with regard to the same, the DoD has not improved the research and development program substantially in accordance with any of these recommendations. (Martinez 2007, 6)

In considering this amazing situation, she concludes that: the only explanation is that the recommended solutions are “too hard to do.” The DoD is like the giant sloth, too large, heavy, and slow to be able to transform its structures and processes. (Ibid., 6)



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Or, as a sociologist might suggest, cultures are very difficult to change. Martinez points out, for example, that “[o]ne significant obstacle is that many key DoD leadership positions lack individuals knowledgeable in, and appreciative of, the complexities of medical product development” (Martinez 2007, 6–7). The pharmaceutical industry has learned from experience that the complex process of vaccine development demands a streamlined management system, yet a repeated criticism of the DoD biodefense program is its fragmented organizational structure. In contrast to the streamlined industry model . . . the DoD’s research and development structure is complex and diffuse, with many stakeholders . (Martinez 2007, 7)

No wonder, then, that there is little evidence of successful product development and much evidence of waste and delay. Some of this evidence is difficult to credit—vaccine candidates being studied for eighteen years with no end product, or another vaccine candidate having been moved forward very successfully within four years and then being “effectively terminated, based on unknown criteria of which scientific review of the product does not appear to have been a part” (Martinez 2007, 21). After 9/11 the decision to channel funding for work on protection against biological threats through the National Institutes of Health may have caused “shockwaves” to echo around the biodefense community in the Department of Defense, but it is hardly surprising given the record of failure. It would appear that the Transformational Medical Technologies Initiative has been constructed to overcome some of these problems by using a system much closer to pharmaceutical industry practice. The initiative aims to develop broad-spectrum medical countermeasures against advanced bioterror threats, including genetically engineered, intracellular bacterial pathogens and hemorrhagic fevers. (DoD 2007, 3)

And it aims to take a new approach so as to develop countermeasures that are truly “broad-spectrum” and effective against a range of pathogens. Some of these countermeasures will be developed by targeting pathogen pathways or mechanisms of action, while others will enhance the host innate immune response. (Ibid., 3)

The initiative has run into funding problems in the past, but perhaps faces a much bigger problem in the future.

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In 2008 the Research Advisory Committee on Gulf War Veterans’ Illness produced its report, Gulf War Illness and the Health of Gulf War Veterans: Scientific Findings and Recommendations. This at last had a very clear set of conclusions, firstly that: Gulf War illness is a serious condition that affects at least one-fourth of the 697,000 U.S. veterans who served in the 1990–1991 Gulf War. . . . No effective treatments have been identified for Gulf War illness and studies indicate that few veterans have recovered over time. (Research Advisory Committee on Gulf War Veterans’ Illnesses 2008, 1)

Some 175,000 veterans are suffering from this illness and, if this report is correct, we now know why: Evidence strongly and consistently indicates that two Gulf War neurotoxic exposures are causally associated with Gulf War illness: 1) use of pyridostigmine bromide (PB) pills, given to protect troops from effects of nerve agents, and 2) pesticides used during deployment. (Ibid., 1)

So these former servicemen are ill because of the “protection” they were given during the conflict. The impact of these countermeasures is predominantly on the brain and nervous system, but because the nervous system interacts with the immune and endocrine systems (see Kelle, Nixdorff, and Dando 2006, chap. 6) these are also affected. The report further concludes that, historically, federal Gulf War research has not been effective in addressing the health of these veterans and that [r]ecent Congressional actions have brought about promising new program developments at the Departments of Defense and Veterans Affairs, but overall federal funding for Gulf War research has declined dramatically since 2001. (Research Advisory Committee on Gulf War Veterans’ Illnesses 2008, 2)

A major priority, surely, has to be adequate funding to improve the health of these veterans not only because this is the proper thing to do but also to promote confidence in newly developed medical countermeasures. Dangerous? Given the determination by the FBI that Bruce Ivins was the perpetrator of the 2001 anthrax letter attacks on his own country, little more needs to be added on this point. Although a recent review by the U.S. National Academies of



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the scientific evidence assembled in the FBI case against Ivins was overstated, nothing in its report contradicts the FBI finding (National Research Council 2011; BBC 2011). Counterproductive? To its allies, the U.S. rejection in 2001 of the chairman’s proposed text for a verification protocol to the Biological Weapons Convention was a grave mistake that suggested that the United States did not support the Convention as the primary restraint against the growth of state-level offensive biological warfare programs (Dando 2002). Compounding this rejection of a decadelong international effort was the discovery that the United States had been involved in a series of research projects that, at the very least, were questionably defensive. Project Jefferson and Project Bacchus were bad enough, but Project Clear Vision was of particular concern since this effort “to reconstruct and test a Soviet-designed biological bomblet so as to assess its dissemination” appeared to clearly violate Article I.2 of the Convention (Tucker 2004, 3). Article I.2 states that each party to the Convention undertakes never in any circumstances to develop, produce, stockpile, or otherwise acquire or retain [w]eapons, equipment or means of delivery designed to use such [biological] agents or toxins for hostile purposes or in armed conflict. (United Nations 1972)

Some suggested that the project was legal, for example, because the intent was defensive, but as one State Department official was quoted as saying “[a] bomb is a bomb is a bomb” (Miller, Engelberg, and Broad 2001a). Little wonder then that some queried whether the Convention could survive. As it is, the Convention has been on “life support” for the last decade discussing lesser issues, but the question remains as to whether it can survive in coming decades without an effective system of assuring States Parties’ biodefense activities are in line with their treaty obligations in a period of rapid scientific and technological change. Inappropriate Post–President Bush? So far in this section of the chapter, criticisms of the DoD-funded part of the whole U.S. biodefense program have been organized under the same headings as in the previous section that dealt with the entire program.

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However, as noted at the beginning of the section, the DoD has a special responsibility in regard to the activities of other states. Therefore a large section of the 2009 Annual Report to Congress of the Chemical and Biological Defense Program deals with work in support of the Chemical Weapons Convention. Yet the report has nothing to say about so-called nonlethal chemical weapons (Dando 1996), the pursuit of which, by major states, is a likely way in which the prohibition of chemical and biological weapons could be eroded. As Julian Perry Robinson asked in his consideration of the future of the Chemical Weapons Convention: What happens when an influential state party seems not to care very much about the treaty, as when its representatives are inadequately informed about details or about what the treaty is meant to be doing? For example, was President Bush in sufficient possession of the facts when, at a press conference on 18 November 2002, he publicly praised President Putin for having authorized the use of an opiate to end the Moscow theatre siege during the previous month. (Robinson 2008a, 234)

What seems clear from the material already in the public domain is that the drift toward the development and use of such new weaponry will not be stopped unless major states take a very careful and coordinated look at the implications and agree on some well-constructed bans or limitations. Of course, the issue that most obviously is lacking in the annual report is activities in support of the Biological Weapons Convention! What might such activities involve? One possibility is raised by an Associated Press report of May 2009. The report began surprisingly as follows: A single word from Barack Obama has put new life into the stale old disarmament talks in Geneva, where diplomats are hailing a “remarkable shift” by the Americans in favor of a treaty clamping down on the production of the stuff of nuclear bombs. (Hanley 2009, 1)

The report then continued: The U.S. president’s word—verifiable —has set the Conference on Disarmament on a possible course towards negotiating a treaty after years of deadlock, most recently because the Bush administration argued that a pact couldn’t be verifiable by inspections and monitoring [emphasis added]. (Ibid., 1)



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We know from officials who took part that the United States administration was split on whether to follow its European and other allies and agree on a verification system for the Biological Weapons Convention based on declarations, visits, and inspections (Ward 2004). At the time much blame was placed on the U.S. pharmaceutical industry for opposing the agreement because it was suggested that any system intrusive enough to be of value in checking declarations and suspicions would put commercial confidential information at risk. However, a recent thorough study of the activities of the industry at that time concluded, on the contrary, that it would seem a mistake to lay the blame for this rejection at the industry’s doorstep, when the U.S. government was ultimately responsible for the decision—both in terms of having its own reasons to regard the protocol unfavorably, and for ultimately being accountable for all national security decisions regardless of industry’s opinion of them. (Winzoski 2007, 494)

It has certainly been argued that the industry was put up as a front while the real reason for the rejection by the United States was to keep its secret biodefense activities from scrutiny. What was evident at the time of the negotiations was that the United Kingdom and a number of other countries carried out practical trials to see if visits and inspections could be applied to facilities without endangering important information. These efforts were reported to the negotiations in Geneva in official papers and made available to the public. They demonstrated that successful visits could be carried out and information guarded by managed access techniques. The United States, however, if it did carry out such trials (as it certainly did during the earlier negotiations of the Chemical Weapons Convention), did not report them in official papers for the negotiations that were available to the public. This seemed to damage the United States’ argument and contributed to the poor perception of its activities. Maybe it is time for the DoD to look again at its position—as the industry has already done. In the view of one such industry report: In sum, the industry experts appreciate that a BWC trial inspection would be a burden, but it would not be an intolerable beast. Rather, they believe that the need to stem the proliferation of biological weapons makes it incumbent on the U.S. pharmaceutical and biotechnology industry, the U.S. government,

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and the international community as a whole to begin to resuscitate the BWC. (Center for Strategic and International Studies 2004, ix)

Thus, the report continues: Should the proposed trials be conducted and demonstrate that inspectors can differentiate between legitimate commercial facilities and those masquerading as such, international negotiations should be swiftly restarted. (Ibid., ix)

The Seventh Review Conference of the BWC took place in late 2011 and although there were expectations of major improvements, for example, in developing better mechanisms of transparency, the eventual outcome was modest and leaves a lot more work to be done. Official and nongovernmental thinking and publications are beginning to look at what could best be done to strengthen the Convention then, and it seems that just continuing the present intersessional process alone is unlikely to be acceptable to many as a means to make sure that biodefense activities stay within the limits of what is permissible under the BWC. Conclusions The most dangerous and costly scenario that can be imagined is the largescale application of the life sciences for hostile purposes by states and thereafter substate groups. Given the history of major technologies, this is perceived as a serious risk in the future. However, in the near term it seems most unlikely that U.S. forces are going to face the use of sophisticated chemical and biological weapons. Moreover, without leaks from its own biodefense program, it is not conceivable that the U.S. civilian population is going to face such sophisticated attacks either. So in general terms, the whole U.S. biodefense program has been far too much structured around the idea that sophisticated biological attacks are going to happen and that the key to dealing with this is to vastly improve national response capabilities. That considered, it seems more likely that we have some time before we face such dreadful possibilities and can therefore work more on an integrated set of policies—a web of responses—which, while including sensible response capabilities for likely threats, also promotes and facilitates cooperative international policies designed to prevent the large-scale application of the modern life sciences for hostile purposes in the future.



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If this analysis is correct, then it suggests that there should be a major restructuring of the total U.S. biodefense program. However, unless there is a demand for huge cuts in the funding of the program caused, for example, by a continuing deep recession, such a major overhaul is an unrealistic expectation. Our suggestions are therefore conditioned by that constraint and attempt to suggest ways in which modifications might be made to better meet the current and near-term challenges of possible chemical and biological agent use and to contribute to the goal of the United States taking a leading role in preventing the worst-envisaged scenario coming about in the future. In regard to the non-DoD part of the biodefense program it is alarming, but not entirely unexpected, that the response to the use of a biological agent in the United States would probably be inefficient because of lack of the necessary coordination across different states (Kahn 2008). Remedies for such practical deficiencies should be given considerable priority in our opinion (DHHS 2010). We also believe that much of the criticism of the program could be blunted by a widely publicized policy of being as open as possible and attempting to share the benefits of the work internationally, particularly with the developing world (Singer and Daar 2009). In regard to the DoD part of the overall program, however, our main proposal relates to the work done over the last several years with practicing life scientists in many different countries. It is very clear that most life scientists have little or no knowledge of the dual-use aspects of their work or of their responsibilities to help prevent the hostile misuse of the knowledge, materials, and technologies they produce. As agreed on at the meeting of States Parties to the Biological Weapons Convention in December 2008, there would be great value in improving the education of all life scientists about these matters, but this will require concerted and costly efforts by States Parties (Dando 2009). The U.S. National Science Advisory Board for Biosecurity (2008) published a Strategic Plan for Outreach and Education on Dual Use Research Issues, which recommended in part: All federal agencies involved in the conduct and support of life science research, e.g., the U.S. Departments of Agriculture, Commerce, Defence and Energy, Health and Human Services, should require that their employees, contractors, and institutional grantees train all research staff in the identification and management of dual use research of concern. (NSABB 2008, 10)

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If this program were fully funded and reported out to the other States Parties to the Biological Weapons Convention as a model of what can best be done in other countries, it would be a major contribution to preventing the hostile application of the life sciences in the future—and it is doubtful that any other country is going to take the lead in this endeavor. It is a long-held view that the United States spends far too much on defense and that this has been part of its living beyond its means (Dando 2006). So the current economic crisis can be seen as a correction of an unsustainable situation, and it can be expected that some cuts in the defense budget will be made as part of the necessary correction. Whether the inbuilt influence of groups who are still in the thrall of previous types of warfare can be quickly overcome seems doubtful, but it is not unreasonable to suggest that some of the DoD’s money released from planning for force-on-force warfare needs to be reallocated to chemical and biological defense, because fighting among the people is likely to involve dealing with chemical and biological attacks— albeit relatively unsophisticated attacks for the present. Four areas of current funding, on this analysis, should receive priority in such a redistribution. First, for the reasons already given, the obligations to veterans suffering Gulf War illness should be met. As the Research Committee on Gulf War Veterans’ Illnesses recommends, there should be expanded federal support to identify effective treatments for these people. Secondly, it seems that very much improved safe medical countermeasures for agents that are most likely to be met should be sought with urgency. Therefore, the Transformational Medical Technologies Initiative should be fully supported. Thirdly, it is surely necessary to ensure that troops that may encounter the use of chemical and biological weapons when they are deployed have been given the proper education and training and have taken part in realistic exercises. So there should be a great expansion of such activities, and we accept that to do the job properly would be costly in terms of people, time, and money. Finally, as a preventive measure, the cooperative Biological Threat Reduction Program, particularly in an expanded version (Ostfield 2009), seems to be a venture that should be supported as much as is possible. In regard to what should be added and what might be cut, the guiding principle should be to give as strong an impression as possible that the United States is in favor of building an effective comprehensive web of responses along with its international partners. Therefore, we would argue for the DoD



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to take a comprehensive look again at how confidence in compliance with the Biological and Chemical Weapons Conventions can be best improved. Most of all, we would like the United States to take vigorous action to lead the international efforts with the aim of making real progress in strengthening the prohibition against chemical and biological warfare and terrorism. This would require efforts on all fronts to strengthen the web of responses as we will discuss in the next chapter.

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Embedding the CBW Prohibition Regimes in the Web of Responses

Introduction The previous four chapters have analyzed the different issues that present the greatest threats to the CBW prohibition regimes—the changing nature of warfare, the revolution in the life sciences, and the resurgence of biodefense— which, in combination, threaten to result in a negative biochemical arms dynamic or even an outright CBW arms race. As outlined above, the existing treaty-based CBW prohibition regimes are the cornerstones of any attempt to prevent such a development. However, the disarmament- and nonproliferation-orientated CWC and BWC do not exist in isolation. Rather, they are embedded in a complex web of responses to the threat of the misuse of chemistry and biology for malevolent purposes. The idea of such a web was first propagated by Graham Pearson (initially) in 1993 when he proposed a “web of deterrence” to address the CBW threat spectrum (Pearson 1995). In addition to “comprehensive, verifiable and global CB arms control” (ibid., 293), he argued for the inclusion of · broad CB export monitoring and controls to make it difficult and expensive for a proliferator to obtain necessary materials; · effective CB defensive and protective measures to reduce the military utility of CB weapons; and · a range of determined and effective national and international responses to CB acquisition and/or use. (Ibid., 293) 110



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As Pearson’s policy recommendations make clear, his focus was on state acquisition and/or use of CBW. The web of deterrence is to influence state calculations in a way that the CBW option will be judged as not worth pursuing. About a decade later the International Committee of the Red Cross (ICRC) took up the notion of a web of interrelated measures when it proposed a “web of prevention” to address the potential misuse of the revolution in the life sciences. Again, chemical and biological arms control was one of the key elements of the web (ICRC 2003). In addition, the ICRC advocated that biosafety measures, disease surveillance mechanisms, and counterbioterrorism tools be integrated in their proposed web of responses. This reflects not only the institutional mandate of the ICRC, but also shifts the focus of attention away from state-level CBW programs to substate actors with respect to both the perpetrators and the victims of an attack. Again, a few years later the U.S. National Research Council (2006) published a report on Globalization, Biosecurity and the Future of the Life Sciences—the so-called Lemon-Relman Report, named after the two chairs of the committee producing the report—in which the idea of a “web of protection” was suggested. The committee “envision[ed] a broadbased, intertwined network of steps—a web of protection—for reducing the likelihood that the technologies discussed in this report will be used successfully for malevolent purposes” (National Research Council 2006, 5). The Committee recommended: 1. to maintain to the greatest extent possible an open exchange of information in the life sciences; 2. to broaden the threat spectrum beyond the “select agents” currently dominating U.S. policies ; 3. to enhance the S&T expertise within the security communities; 4. to promote a common culture of awareness of the dual-use problem among life scientists; and 5. to strengthen public health infrastructures so as to better cope with both natural and man-made disease. (Ibid., 6–7)

Acknowledging that there is no silver bullet available to tackle the misuse of chemistry and biology for malevolent purposes, the Committee still maintained that

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implementation of these recommendations in aggregate will likely decrease the risk of inappropriate application or unintended misuse of increasingly widely available knowledge and technologies, favor the early detection of malevolent applications, and mitigate the loss of life or other damage sustained by society in both the short and the long term, should the worstcase scenario occur. (Ibid., 218)

These different approaches to the context in which CBW arms control is situated reflect both an evolving problem definition and—corresponding to this—a variation in terms of the elements included in the web of responses. In the following sections we will focus on elements from each of these three conceptualizations of the web and will discuss the following measures both individually and in relation to the CBW prohibition regimes, whose strengths and weaknesses will then be detailed in the subsequent two chapters. CBW Export Controls Export controls on biological and chemical materials, technology, and knowhow that could be used for hostile purposes is not a recent addition to the international web of responses to prohibit chemical and biological warfare. Already during the negotiations for the 1925 Geneva Protocol, a proposal was made that foresaw such controls, but at the time it was rejected as being impractical. During the Cold War, more generic export controls were employed in the East-West confrontation in an attempt by the United States and its allies to prevent the transfer of weapons-usable materials and technology to the then Soviet bloc. More relevant to the CBW web of responses was the inclusion of transfer provisions in both the BWC and CWC, the harmonization of national controls through the Australia Group (AG), and the passing of UN Security Council Resolution 1540 in 2004. The following three subsections will provide an overview of each of these three areas. Transfer Provisions in the BWC and CWC Both the BWC and CWC contain transfer provisions in relation to the issue areas they cover. Article III in the BWC obliges States Parties not to transfer to any recipient whatsoever, directly or indirectly, and not in any way to assist, encourage, or induce any State, group of States or international organizations to manufacture or otherwise acquire any of the



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agents, toxins, weapons, equipment or means of delivery specified in article I of this Convention.

Given the practical absence of transparency or verification mechanisms attached to the BWC, adherence to the nontransfer requirement by States Parties is not subject to regular international assessment by the community of BWC States Parties. Instead, such assessments are left to the national devices of individual BWC member states. The situation looks somewhat more promising in the context of the CWC, which contains a similar transfer provision in its Articles I and VI. The CW prohibition regime goes beyond the BWC’s very generic prohibition insofar as Parts VI, VII, and VIII of the CWC’s Verification Annex provide different sets of rules for chemicals that are listed on Schedules 1 to 3, respectively. Simply put, Schedule 1 chemicals cannot be transferred to non-CWC States Parties. Schedule 2 chemicals could under certain conditions be transferred to nonparties for a transition period of three years after the CWC’s entry-into-force, but not afterward. According to Part VIII of the Verification Annex, when transferring Schedule 3 chemicals to nonstate parties, “each State Party shall adopt the necessary measures to ensure that the transferred chemicals shall only be used for purposes not prohibited under this Convention” and at a minimum request an end-user certificate of the receiving state. It is worth noting that implementation of any of the above transfer provisions is not verified by the Organisation for the Prohibition of Chemical Weapons (OPCW). Given the generally mixed picture of national implementation of CWC treaty provisions (see chapter 8 below), one has to assume that a significant part of CWC States Parties have not established the necessary national organizational structures and procedures to fully implement the CWC transfer provisions. In addition to adopting the necessary measures to comply with their treaty commitments, CWC member states are also under the obligation to report to the Technical Secretariat (TS) of the OPCW on an annual basis imports and exports of chemicals on any of the three schedules. This shows a further limitation of the CWC-based transfer guidelines, as information about transfers of scheduled dual-use chemicals is becoming available only after the transfers have already taken place, and not before such transfers are made. In other words, the CWC transfer guidelines are conceptually distinct from export control systems that aim at providing decision-making guidance for potentially problematic export requests. In light of this conceptual distinction it is not surprising that members of the Australia Group (AG) are continuing to adhere

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to and develop further the lists and guidelines for export controls that have been evolving since the mid-1980s (Kelle, Nixdorff, and Dando 2006, 47–48). Work of the Australia Group According to their own representation, states participating in the AG “aim to ensure that exports from their countries do not contribute to the development of chemical or biological weapons. They do this by licensing the export of certain chemicals, biological agents, and dual-use chemical and biological manufacturing equipment which can be used in chemical or biological weapons programs” (Australia Group 2007, 2). As such the AG regards its activities as being fully in compliance with BWC and CWC provisions. Yet, its activities are controversial for at least two reasons. First, in the final phase of CWC negotiations, AG members presented this forum as an interim measure until the CWC has been fully implemented. Since then, the AG has taken on a much more permanent character in the web of responses to CBW, which in turn has led some members of the Non-Aligned Movement (NAM) to repeatedly voice their criticisms of what they see as the discriminatory behavior of AG participants. As a matter of fact, there is a lack of discrimination at the heart of this dispute, which is the second underlying reason for the contestation of AG export control measures. While some NAM states are expecting preferential treatment for CWC States Parties when it comes to the transfer of dual-use chemicals and equipment, the AG does not make such a distinction along the lines of CWC membership. The unwillingness on the part of AG participants to exempt CWC States Parties from their export control measures is closely related to a further key function of the group: the sharing of sensitive information concerning transfer requests that group members have received (Roberts 1998). As one more recent assessment of the AG’s performance has pointed out: There has been some criticism of the AG’s practice of conducting meetings in confidence. Critical to the deliberative process leading to the formulation of the export control list is the exchange of information relating to national intelligence, past and pending sensitive enforcement issues, proprietary industrial practices, as well as the export patterns of individual nations. (Seevaratnam 2006, 409)

Thus, even if the obstacles of integrating the export control harmonization function into the operation of the CWC’s transfer controls could be



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overcome, it is doubtful that AG participants in the foreseeable future would be willing to share the kind of sensitive information mentioned by Seevaratnam in the wider group of CWC States Parties. Continuation of the AG’s activities is even more likely in the area of BW export controls where neither the CWC’s more detailed rules and procedures nor the OPCW’s infrastructure is available to control the spread of pathogens and dual-use material and equipment. UNSC Resolution 1540 While the establishment of the AG in the mid-1980s had its origins in the revelations about the Iraqi CW program and related procurement activities targeted at several Western countries, the passing of United Nations Security Council (UNSC) resolution 1540 and creation of a committee to oversee its implementation (henceforth the “1540 Committee”) in April 2004 was motivated by the increased risk perception of nuclear, biological, and chemical weapons and related material falling into the hands of terrorist groups. As the existing multilateral NBC nonproliferation regimes were deemed inadequate to address this threat, and an urgent need was perceived to fill the identified gap, the UNSC—under Chapter VII of the UN Charter—adopted a farreaching resolution aimed at combating NBC terrorism. This Resolution 1540 obliges all UN member states to undertake a variety of measures to prevent the proliferation and transfer to terrorist and other nonstate actors of biological, chemical, and nuclear weapons, their delivery systems, and related materials (UN Security Council 2004). In a nutshell, UNSC Resolution 1540 was designed to complement the existing international NBC treaties that focus on state and not substate activities (Parker and Pate 2005). In some detail and after lengthy negotiations, the UN Security Council in Resolution 1540: 1. Decides that all States shall refrain from providing any form of support non-State actors that attempt to develop, acquire, manufacture, possess, transport, transfer or use nuclear, chemical or biological weapons and their means of delivery; 2. Decides also that all States, in accordance with their national procedures, adopt and enforce appropriate effective laws which prohibit any non-State actor to manufacture, acquire, possess, develop, transport, transfer or use nuclear, chemical or biological weapons and their means of delivery, in particular for terrorist purposes, as well as attempts to engage in any of

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the foregoing activities, participate in them as an accomplice, assist or finance them; 3. Decides also that all States shall take and enforce effective measures to establish domestic controls to prevent the proliferation of nuclear, chemical, or biological weapons and their means of delivery, including by establishing appropriate controls over related materials and to this end shall: . . . (d) Establish, develop, review and maintain appropriate effective national export and trans-shipment controls over such items, including appropriate laws and regulations to control export, transit, trans-shipment and re-export and controls on providing funds and services related to such export and trans-shipment such as financing, and transporting that would contribute to proliferation, as well as establishing end-user controls; and establishing and enforcing appropriate criminal or civil penalties for violations of such export control laws and regulations. (UN Security Council 2004)

Early implementation efforts of UN member states and the 1540 Committee had shown that a longer-term effort would be required to increase levels of compliance with the obligations contained in Resolution 1540. As one early, but detailed, analysis has shown for 84 key states, not a single one of them had fulfilled all 1540 obligations related to border and export controls. Countries reaching the highest scores were the United States (81.4%), Malta (56.9%), Romania (56.7%), Germany (54.5%), and France (50.0%) (Crail 2006, 372f.). Thus, in April 2006 the Security Council extended the mandate of the 1540 Committee for a further two years with the adoption of Resolution 1673 (UN Security Council 2006), which was again extended in April 2008, when the Security Council adopted Resolution 1810 (UN Security Council 2008), which prolonged the mandate of the 1540 Committee for another three years, until April 25, 2011. Acknowledging the long-term nature of the work of the 1540 Committee, Security Council Resolution 1977 (UN Security Council 2011) extended the Committee’s mandate for another 10 years until 2021 (UN Security Council 2011). As part of the extended mandate contained in Resolution 1810, the 1540 Committee was tasked to conduct a Comprehensive Review of Resolution 1540. This took place in September–October 2009 and revealed that up to this point 160 UN member states (out of 192) had submitted the required report



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relating to their compliance with the provisions of the resolution. Based on an assessment of the reports received it had become evident that owing to a wide range of obligations derived from resolution 1540 (2004), some States still have some lacunae in addressing all of them in their legislation, including the adoption of penalties and preventive enforcement measures. (UN Security Council 2010)

Given these continued gaps in implementation of Resolution 1540, outreach efforts of the 1540 Committee have shifted progressively from fact finding to capacity building, either in a regional, subregional, or national context. The continued importance of the UN Security Council Resolution derives partly from its legally binding character—as it had been adopted under Chapter VII of the UN Charter—and partly from subjecting all UN member states, not just States Parties to the CWC or BWC, to its provisions. However, as in the context of the two treaty-based regimes, where, for example, efforts to achieve universal membership in the treaties has been pursued through cooperation with regional organizations, the persistent implementation gaps in relation to Resolution 1540 show the limits in achieving full compliance with even legally binding obligations. Biosafety and Biosecurity The anthrax letter assaults that were launched in 2001 in the United States heightened the feeling of insecurity and vulnerability that the terrorist attacks of 9/11 initially induced. This feeling of insecurity was perhaps all the more exaggerated because of the psychological state of fear induced by the specter of a weapon that is largely invisible and whose effects can be particularly heinous. Following those incidents, the United States took the lead in enhancing the country’s protection against a possible bioterrorist attack by imposing stricter regulations on the handling of dangerous biological materials, but soon thereafter other countries started to review their biosecurity status as well (Koblenz 2009). Indeed, after the collapse of the Ad Hoc Group’s negotiations over a legally binding Protocol to the BWC, which were aimed at strengthening the Convention’s weaknesses in the area of compliance assurance, biosafety and biosecurity were prominent topics for discussion and action during both intersessional processes in the years between the Fifth, Sixth, and Seventh BWC Review Conferences (see chapter

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TABLE 6.1 Laboratory biosafety: Agents are assigned to risk groups Risk Group 1 (no or low individual and community risk) · unlikely to cause human or animal disease Risk Group 2 (moderate individual risk, low community risk) · laboratory exposure may cause infection, but effective treatment and preventive measures are available Risk Group 3 (high individual risk, low community risk) · usually causes serious disease, but does not normally spread · effective treatment and preventive measures are available Risk Group 4 (high individual and community risk) · usually causes serious disease, is readily transmitted · effective treatment and preventive measures are not usually available source: Laboratory Biosafety Manual, 3rd ed., Table 1, 1. Obtained from http://www. who.int/csr/resources/publications/biosafety/Biosafety7.pdf, accessed 13 April 2012.

7). This section will outline some of the main biosecurity developments that occurred during these periods. Biosafety versus Biosecurity When the States Parties to the BWC gathered to discuss the topic of “national mechanisms to establish and maintain the security and oversight of pathogenic microorganisms and toxins” at the first intersessional meeting in 2003, it was soon realized that there was some uncertainty about just what the terms “biosafety” and “biosecurity” meant to different States Parties. For example, some languages do not have separate words for these terms. In this regard, biologische Sicherheit in German generally translates to “biosafety”; there is no separate word for “biosecurity.” There have been involved discussions about the meaning of the two terms, but there is now general agreement on the definitions. Biosafety generally applies to principles and practices to prevent unintentional exposure to or accidental release of pathogens and toxins (WHO 2004a). These are measures to protect laboratory workers and the community from potentially harmful biological materials. Biological agents are assigned to risks groups 1–4, which are categorized according to the individual and community risks these agents pose. For working with these agents, appropriate measures to regulate laboratory and equipment specifications as well as laboratory personnel



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qualifications and training have been formulated (WHO 2004a; USDHHS/ CDC/NIH 2007). Some factors that could pose certain safety problems receive particular attention in formulating the specific regulations. These include the use of genetic manipulation procedures, the formation of aerosols during work with agents, work with large volumes and high concentrations of agents, overcrowding and too much equipment, and unauthorized entrance to the laboratories (WHO 2004a). Possible weak areas of biosafety regulation include the incomplete or total lack of implementation of the guidelines into enforceable regulations in some countries, different regional perceptions of risk, proper oversight of biosafety regulations, and proper training programs and training evaluation. Laboratory biosecurity, on the other hand, “describes the protection, control and accountability for valuable biological materials . . . within laboratories, in order to prevent their unauthorized access, loss, theft, misuse, diversion or intentional release” (WHO 2006, iv). These are measures preventing potentially harmful biological materials from being misused, for example, for nonpeaceful purposes. However, whether or not there are two separate words to describe the meaning of the terms, in the end it is important to understand both aspects when formulating the regulating legislation. Although the German language does not have a separate word for “biosecurity,” German biologische Sicherheit laws and regulations govern both aspects (Germany 2003). Of course, effective biosafety practices are the very foundation of laboratory biosecurity. Nevertheless, biological arms control is traditionally most concerned with wider biosecurity aspects as defined above in the web of preventive policies, so that the following subsections will deal primarily with these broader issues. National Legislation and Regulations concerning Biosecurity The U.S. government responded to the anthrax letter assaults with a whole array of new legislation. In October 2001 President Bush signed the Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act, known as the USA PATRIOT Act (USA 2001). Acting in the atmosphere of fear that gripped the nation, the U.S. Congress included a provision in the USA Patriot Act limiting who could possess select agents. Aliens from countries designated as supporting terrorism and those

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persons who could not purchase handguns were restricted from possessing select agents within the United States. No provision was made for exemptions to these restrictions under any circumstances. (Atlas and Reppy 2005, 54)

Furthermore, it is now a criminal offense in the United States for a person to possess any biological agent if it is not reasonably justified for prophylactic or other peaceful purposes, including research (Atlas and Reppy 2005). In addition, the Public Health Security and Bioterrorism Response Act of 2002 added further requirements for the possession of select agents in the United States, and U.S. military laboratories have instituted particularly stringent biosecurity measures (ibid.). Even before 9/11 and the anthrax attacks the American Type Culture Collection, a private nonprofit undertaking that supplies microorganisms and cell cultures to the community worldwide, tightened its shipment and supply policies in 1995 after it was made public that a member of the radical group the Aryan Nations obtained the causative agent of plague from this supplier (Stern 2000). The U.S. Congress passed the Antiterrorism and Effective Death Penalty Act of 1996, which provided for further regulations governing the transfer of biological agents that pose a threat to public health and safety. Beginning in 1997 the Centers for Disease Control and Prevention (CDC) instituted the Laboratory Registration/Select Agent Transfer of Regulations (see DHHS 2005 and CDC 2006 for the select agent lists), which restricted transfer of pathogens and toxins posing the greatest risk to registered laboratories. Other nations have adopted similar measures, but the select agent lists are not uniform. The United Kingdom in 2001 placed restrictions on who may possess selected agents and has given extended powers to their law enforcement agencies to control access to dangerous pathogens (United Kingdom 2001). In a comparison of the biosecurity policies to prevent bioterrorism in the United States and in Germany, Jonathan Tucker reported that Germany has responded in a way different from that of the United States, possibly due to the fact that Germany has never experienced a bioterrorist attack: Whereas the United States framed bioterrorism prevention as a security problem and responded by tightening controls on a targeted list of select agents and toxins that could be used as weapons, German officials viewed the risk of bioterrorism mainly in public health terms, as a subset of the broader challenge of infectious disease. Accordingly, whereas the US Select



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Agent Rule focuses narrowly on pathogens considered suitable for bioterrorist use, Germany relies on an extensive framework of “biosafety” laws and regulations, which are designed to ensure the safe handling of dangerous pathogens by legitimate researchers and to minimize the risks to public health and the environment from research conducted for peaceful purposes. (Tucker 2007b)

While such national legislative measures can potentially contribute to biosecurity and thus have relevance for managing the risks involved with dual-use aspects of research, it has been suggested that some particularly stringent measures could have a negative impact on the development of science and technology in general. In an investigation of the effects of the USA PATRIOT Act and the 2002 Bioterrorism Preparedness Act on select agent research, Dias et al. (2010) reported that research involving viable virulent B. anthracis and Ebola virus did not appear to have been directly inhibited by the biosecurity laws, but that research became more tedious and less efficient as seen in the decline in the number of publications per annum. Furthermore, the regulations have increased the cost of dangerous-pathogen research. Of even greater significance, it has been argued that focusing primarily on countering bioterrorism at the national level through legislative measures to safeguard dangerous biological agents and screening personnel working with such agents is “highly problematic . . . because it could undermine the ban on offensive development enshrined in the Biological Weapons Convention (BWC) and end up worsening the very dangers that the U.S. government seeks to reduce” (Tucker 2004). Promotion of Research into Development of Countermeasures As highlighted in the previous chapter, the anthrax letter incidents also prompted a huge increase in biodefense spending in the United States (Pearson 2008; Matheny, Mair, and Smith 2008) to promote the development of therapeutic and prophylactic countermeasures such as antibiotics, antiviral drugs, and vaccines to combat biological threat agents. Although the development of countermeasures against disease-causing agents would generally be of benefit to all, this substantial increase in biodefense funds for this purpose has been subject to very legitimate criticism. For one thing, some voices have questioned whether the threat is great enough to pour these huge sums into combatting bioterrorist agents, given that there is a much greater infectious disease threat coming from non-bioweapons agents (Leitenberg

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2005; Pearson 2008). It has also been argued that an increase in work on dangerous pathogens will make biosecurity even harder to manage (Ebright 2002; Kahn 2007). The development of drugs and vaccines has been of unparalleled value in combating infectious disease over the years, and these are certainly undertakings that should receive continued support. However, the direction/ object of research and development and the amount of resources invested in such work should be based on a proper agent threat assessment. As the futility of trying to develop countermeasures to an ever-increasing, unknown array of novel biological weapons agents is obvious, the prevention of the use of such agents for malign purposes becomes all the more urgent. Research Oversight The U.S. National Academies Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology (known as the Fink Committee) identified seven categories of “experiments of concern” that should be added to the National Institutes of Health Guidelines for Research Involving Recombinant DNA (NIH Guidelines). The committee rejected prohibition of research as a biosecurity measure because “even experiments that have the greatest potential for diversion to offensive applications or terrorist purposes may also have potentially beneficial uses for public health promotion and defense” (National Research Council 2004a, 108), but it also recommended that a national board be set up to oversee and develop a voluntary scheme of research oversight. In answer to this challenge the U.S. government founded a National Science Advisory Board on Biosecurity (NSABB), which held its inaugural public meeting in Washington, D.C., in mid-2005. The Fink Committee proposed a tiered review system in which experiments in the designated classes would be subject to local review by an Institutional Biosafety Committee and then, if there were difficulties at that level, the national system would become involved. The NSABB has now developed a set of recommendations for oversight of research of concern that are not intended as guidelines but rather as a “framework for the oversight of dual use research that includes a criterion and guidance for the evaluation of the dual use potential of research” (NSABB 2008, 1). The key features of the proposed oversight system include the development and application of federal guidelines of oversight based primarily on the NIH Guidelines; establishment of an enhanced culture of awareness of dual-use research concerns, issues,



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and policies; institution of ongoing, mandatory education about dual-use research issues and policies; institution of local evaluation and review of research having dual-use potential; institution of risk assessment and risk management mechanisms to assess the degree of oversight to be applied; periodic evaluation of the oversight system; and establishment of mechanisms for ensuring compliance. A group of researchers at the Center for International Security Studies at Maryland (CISSM) has drafted an alternative research oversight program as part of their Project on Controlling Dangerous Pathogens. For the latest version of this proposal see Steinbruner et al. (2007). The protective oversight system is known as the Biological Research Security System and contains two key elements. One of these is the national licensing of relevant personnel and research facilities; the second element is an independent peer review of relevant research projects (Harris 2007). The Maryland group sees three main areas in which the NSABB program falls short: it is limited to the United States, it is not legally binding, and it does not apply to research at those private labs that do not receive U.S. government funding. In contrast, the Maryland review process would be a mandatory, tiered procedure (at the local, national, or international level according to the potential danger) and would apply comprehensively to all institutions (government, private sector, or academic) conducting relevant research. The peer review process includes a risk assessment mechanism for determining the degree of danger and thus the review response procedure. Furthermore, this type of oversight would not be prohibitory to any research under review, but rather it would allow the scientist to reflect and direct the research in a responsible manner. The topics of biosafety and biosecurity were discussed extensively during both BWC intersessional processes, but the focus was mainly on national measures. During these discussions it became clear that, while many States Parties employ some of the elements of a biosecurity system, the measures are heterogeneous. Biosecurity, however, is a global issue that can only be dealt with effectively on a multilateral basis. An important step forward would be the international harmonization of basic biosecurity and oversight regulations.

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Disease Surveillance/Public Health Security The incidence of many infectious diseases has dropped dramatically over the past hundred years, largely because of improvements in living conditions, but also through the rigorous application of public health measures such as epidemiological surveillance, detection, diagnosis, and treatment of infectious diseases (Madigan, Martinko and Parker 2000, 908). Although developed countries have benefited most from these measures, infectious diseases are recognized as global health problems, given the increased international travel and commerce as well as the human population shifts encountered today. Indeed, basic health problems in the developing world will affect us all directly (Dando 1998), and there is general recognition of the fact that in the case of epidemiological surveillance, all countries benefit in some way from knowledge of the outbreaks of infectious diseases (Zacher 1999). The establishment of an international epidemiological surveillance network is crucial to providing early warning in order to respond effectively to natural or deliberately caused outbreaks. Mark Wheelis (1992) was one of the first to address the need for and outline a global early warning system of disease outbreaks. At the sixth session of the Ad Hoc Group negotiations on the Protocol to strengthen the BWC, France proposed the establishment of an international epidemiological monitoring network (United Nations 1997). During a NATO Advanced Research Workshop in Bucharest in June 1999, representatives of the three international organizations dealing with human (WHO), animal (Office Internationale des Epizooties, OIE), and plant health (Plant Protection Service of the Food and Agriculture Organization, FAO) met with experts involved in the Ad Hoc Group negotiations and others for interactive technical discussions (Pearson 1999). These talks provided insight into what epidemiological reporting was taking place globally and stressed the importance of reporting disease outbreaks by States to human, animal, and plant health organizations nationally, regionally, and internationally. When the negotiations on the Protocol to the BWC broke down, this topic was picked up for discussion during the first intersessional process in 2004 under the heading of “strengthening and broadening national and international institutional efforts and existing mechanisms for the surveillance, detection, diagnosis and combating of infectious diseases affecting humans, animals and plants” (United Nations 2004, 1). A similar topic was considered during the second intersessional process in 2009 (United Nations 2006a, 21).



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A survey of online reporting of infectious disease outbreaks emphasized that swift, timely reporting of outbreaks is a critical element of biosecurity, and argued that effective surveillance can never be achieved by nations acting alone but only if global resources are pooled (Woodall and Aldis 2003). This report also identified large gaps with regard to surveillance at several national and regional levels. In past years, health issues were not considered to be in the context of security policy, but for two main reasons the strict separation of health and security has become increasingly blurred (Kelle 2007a). The first of these is related to the emergence of a perceived bioterrorism threat in the mid- to late 1990s, which was heightened dramatically by the anthrax letter assaults in 2001. The second is coupled with a reduced reliance on arms control to address the “spectre of biological warfare” (Kelle 2006a). This is most evident in the failure of the Ad Hoc Group Protocol negotiations and the subsequent reluctance of States Parties to deal with strengthening the BWC in its weak areas except within the arena of informal talks during the intersessional processes, where mostly national implementation issues are discussed and no formal adoption of any proposals is the iron rule. Instead, biodefense measures, with the concomitant securitization of public health, have taken centerstage in the effort to counter the newly identified existential threat of bioterrorism (Kelle 2007a). Given this situation, some States Parties, with the United States at the forefront, have started looking more and more to public health measures as a possible means of countering biowarfare attacks. In the absence of an international organization responsible for preparedness against the deliberate use of biological agents, the international community turned to the WHO for assistance and advice concerning human infectious diseases. From the start of its conception in 1948, the WHO has proceeded to implement its mandate through a disease-oriented policy, which found its expression in the adoption of the International Sanitary Regulations in 1951, whose name was changed in 1969 to International Health Regulations (IHR). As Fidler has summarized, the “IHR failed massively to achieve their objective” (Fidler 2004, 35). This can firstly be attributed to the widespread noncompliance of member states with the reporting requirements under the IHR. In addition, the large number of newly emerging or reemerging infectious diseases, particularly of HIV/AIDS, demonstrated the growing irrelevance of the reduced list of diseases that WHO member states were obliged to report. The World Health Assembly

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(WHA), the WHO’s highest governing body, acknowledged this failure in 1995 and tasked the WHO with revising the IHR (Tucker 2005). In 2001 an intergovernmental working group was set up to revise the IHR (WHO 2004c), and the new regulations were adopted by the WHA in May 2005 (WHO 2005). Major changes introduced into the new IHR include a new, expanded basis for states’ reporting as well as a wider range of sources that can be considered by the WHO secretariat. With respect to the former, WHO States Parties were now under the obligation to “notify all events potentially constituting a public health emergency of international concern”; set up a national IHR focal point; and implement “the minimum core surveillance and response capacities required at the national level in order to successfully implement the global health security, epidemic alert and response strategy” (Kelle 2006a). However, negotiations on the refocusing of the IHR were not uncontested. According to one account: [T]he debate over whether or not the revised regulations should make explicit reference to accidental or deliberate releases of toxic or infectious agents turned into a struggle between two groups of countries; those that sought to use health as a means of strengthening international security and expanding WHO’s role in responding to unconventional terrorism, and those that viewed health solely as an arena for peaceful international cooperation. (Tucker 2005, 342)

The compromise that was eventually arrived at in the revised IHR made no direct reference to deliberate releases of pathogens or toxins. But it implied at several points that other than natural disease outbreaks might occur that would trigger the reporting mechanism under the new IHR, so that the public health consequences of such acts could be addressed. Thus, the wording allowed both the proponents of the securitization (Waever 1995) of international public health as well as its opponents to claim success in the negotiations. From the WHO’s perspective, this is an important outcome, as it does not undermine its wide acceptance as an authority in preserving public health. As such the WHO can certainly achieve much in the way of strengthening public health preparedness and response capacities, for example, through its program of Preparedness for Deliberate Epidemics (WHO 2004b). This program includes work in the areas of international coordination and collaboration, national capacity strengthening on preparedness for and response to biological (and chemical) agents, and public health preparedness



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for diseases associated with the deliberate use of biological agents. A biological weapons incident could cause a serious public health crisis, and as the major parts of the public health response to infectious diseases are the same whether the incidents are of natural, accidental, or intentional origin (Hansen 2009), strengthening national, regional, and international capacity for preparedness and response would of course be beneficial. However, both the IHR negotiations as well as national public health policies demonstrate that there are very divergent views among countries with respect to the securitization of public health systems (Kelle 2005b, 2006a, 2007a; Tucker 2005). Although infectious disease is being described ever more frequently in terms of security, and the WHO is increasingly being drawn into this arena (Isla 2009), it has to be recognized that the WHO focuses exclusively on the public health aspects of preparedness and response and that regulatory aspects of disarmament and nonproliferation of the BWC clearly lie outside of its mandate. This position has been pursued by the WHO secretariat throughout the IHR negotiations and is clearly expressed in the regulations themselves: The purpose and scope of the IHR (2005) are “to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks.” (WHO 2005, 1)

The neutrality of the WHO in this respect is absolutely essential so as to encourage and not to inhibit countries in reporting infectious disease outbreaks. Thus, while the WHO can play a major role in strengthening national, regional, and international capacity for preparedness and response to outbreaks of infectious diseases, and is generally recognized as being the leading global actor in disease surveillance (Australia 2004), there are good reasons why it cannot become entangled in the process of verification of alleged or suspected use of biological weapons, and indeed the WHO has no intention of getting involved in the process (WHO 2004b). In describing its concept of public health protection, the WHO frequently uses the word “security.” However, in doing so it is not so much referring to the protection against biological weapons but rather to the broader concept of human security, which includes the right of access by individuals to human rights, health, and education (Kelle 2007a; Isla 2009). As the previous discussion has shown, the securitization of public health as a result of changed threat perceptions based on a newly emerging bioterrorist

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threat is by no means fully endorsed by all countries. John-Erik Stig Hansen points out the importance of the preventive factor in dealing with arms control and has argued that “it is very dangerous to neglect the specific nature of each type of hazard, as prevention of intentional bioattacks requires an entirely different strategy than prevention of natural outbreaks of infectious disease” (Hansen 2009). He goes on to say that it is furthermore essential to have “realistic assessments of the actual threats” (ibid.). Given these arguments, plus the reluctance of the WHO to be drawn into the verification of noncompliance with the BWC, there seems to be little chance that those advocating the securitization of international public health will succeed in their endeavors. For all contingencies in which an international institutional response to the security aspects of disease outbreaks is required, this can only be provided within the BWC prohibition regime or by the United Nations Security Council. Awareness Raising among Life Scientists Article IV of the BWC is often understood only to require national legislations as discussed above. However, the article actually states that Parties are required to take “any necessary measures to prohibit and prevent” what is banned in Article I. So in addition to legislation States Parties have to give consideration to a much wider array of preventative measures covering the scope of Article I. For this reason codes of conduct and oversight systems for dual-use work by scientists have been investigated as means of prevention, but such systems are unlikely to succeed if scientists are not even aware of the need for them. Recognition of the importance of such awareness can be traced back to the Second Review Conference of the BWC, which already in its Final Declaration in 1986 noted the importance of inclusion in text books and in medical, scientific and military educational programmes of information dealing with the prohibition of microbial or other biological agents or toxins and the provisions of the Geneva Protocol. (United Nations 1986a)

Similar statements were agreed on by the States Parties at subsequent Review Conferences. However, during the first Intersessional Process, Australia reported at the Meeting of Experts in 2005 that: 1. Amongst the Australian scientific community, there is a low level of awareness of the risk of the misuse of the biological sciences to assist in the



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development of biological or chemical weapons. Many scientists working in “dual-use” areas simply do not consider the possibility that their work could inadvertently assist in a biological or chemical weapons programme. (Australia 2005, 1)

At the same meeting in 2005 work was reported by Bradford University and Exeter University in the United Kingdom on interactive seminars designed to determine what the views were among those engaged in carrying out practical work in the life sciences regarding the “dual-use” potential of their work. In total, twenty-five seminars (twenty-four in the United Kingdom and one in Germany) were held and an analysis of these seminars led the authors to conclude that: There is little evidence from our seminars that participants: a. regarded bioterrorism or bioweapons as a substantial threat; b. considered that developments in life sciences research contributed to bio-threats; c. were aware of the current debates and concerns about dual-use research; or d. were familiar with the BTWC. (Dando and Rappert 2005, 25)

In the next year, 2006, a second report by the same authors was made to the Sixth Review Conference on further seminars. It was found that despite the international attention given to the problem of the potential misuse of the life sciences, the initial findings reported at the Meeting of Experts in 2005 were essentially replicated in later seminars in the United Kingdom as well as the other countries visited (Finland, Germany, Netherlands, South Africa, and the United States). From this the authors concluded that “in-depth implementation of the BTWC within States Parties requires a significant effort on education and outreach for such implementation to be effective. To achieve this, a simple declaration as at previous Review Conferences about the importance of education will be insufficient and States Parties will need to take concerted action to ensure increased educational provision and outreach” (Rappert, Chevrier, and Dando 2006, 34). Subsequent experience of carrying out seminars also in ten different countries (Argentina, Australia, India, Israel, Japan, Kenya, Sweden, Switzerland, Uganda, Ukraine) with, in total, three thousand life scientists in over ninety different departments, confirmed and consolidated these findings (Rappert

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and Gould 2009; Mancini and Revill 2008). It is thus evident that awareness raising and education have a key role in achieving the effective implementation of the Convention. The Education Gap These findings showing the lack of biosecurity awareness of those engaged in the life sciences require explanation. Physicists have long been aware of the dangers of the misuse of their science and have played important roles, for example, in the Pugwash Conferences on Science and World Affairs. which have since 1957 brought together influential policy officials, scientists, and public figures to seek ways of eliminating nuclear weapons and reducing the threat of war. Chemists were also influential in helping to bring the negotiations in the 1980s of the Chemical Weapons Convention (CWC) to a successful conclusion, and the International Union of Pure and Applied Chemistry (IUPAC) has contributed major reviews of relevant science and technology to the first two Review Conferences of the CWC. However, although the situation has not been investigated in detail, anecdotal evidence strongly suggests that most practicing chemists have little awareness of the CWC and that it is only at the level of national academies and experts that such awareness exists. It is consequently not unreasonable to ask why practicing life scientists are so unaware of the BWC and the problem of dual-use despite the increasing attention being given to these issues, for example, by the U.S. National Academies. A number of related reasons probably account for this lack of understanding. For example, to advance a career it is necessary to be at the cutting edge of research and this leaves little time for other activities; but another possible major part of the explanation is that life scientists are unaware of biosecurity issues because the subject does not feature in their university education. In order to investigate this possibility a study was carried out through an Internet survey on the extent of biosecurity education in life science degree courses in Europe (Mancini and Revill 2008). Using a sample of 142 courses from 57 universities in 29 countries speaking 25 different languages, the authors looked for evidence of modules on biosecurity, bioethics, and biosafety as well as for references to biosecurity, the BWC, biological weapons and/or arms control, dual-use, and codes of conduct. The results were quite startling, as it was found that:



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This research suggested that only 3 out of 57 Universities identified in the survey currently offered some form of specific biosecurity module and in all cases this was optional for students. (Ibid., 5)

On the other hand the study revealed that: There is evidence of a considerable number of bioethics modules and nearly half of the degree programmes surveyed evidenced some form of bioethical focussed module. In terms of biosafety modules . . . roughly one-fifth of life science degrees in the sample contained a specific dedicated biosafety module although several of these specific modules were optional. (Ibid.)

So it was found that there were a reasonable number of biosafety modules; a large and, it was suspected, an increasing number of bioethics modules; and virtually no biosecurity modules. An attempt was then made to investigate in more detail by looking for any kind of reference to biosecurity issues in the course material. Again the picture was bleak: Exactly what constitutes a reference varies; however, based on the quantitative data from the investigation, we found a total of 37 life science degree courses out of our sample of 142 where there was clear evidence of a reference to biosecurity. Only a minority of the degree courses in the study—a total of 22 out of 142— made a reference to the BTWC, BW and/ or arms control and a similar number, 29 degree courses, exhibited some reference to the dual-use issue. (Ibid.)

When a similar survey was carried out in Japan, of 197 life science degree courses in 62 universities, the authors found a similar picture with only 3 specific biosecurity modules (Minehata and Shinomiya 2009). In Japan the investigation was taken a stage further by sending out a questionnaire to lecturers asking why biosecurity and dual-use were not being taught. Clearly some lecturers did not see these subjects as relevant to their courses, but others certainly did. Where people thought the topics relevant but they were not taught, the reasons cited were a lack of expertise and access to necessary resources and a lack of space on a very crowded timetable in the modern life sciences. Similar results were found in surveys in Israel in a comprehensive survey of 35 courses in 6 research universities (Minehata and Friedman 2010) and also in studies in the Asia-Pacific Region (Australia, China, India, Indonesia, Malaysia, New Zealand, Philippines, South Korea, Singapore, Thailand, and Taiwan) (Minehata 2010).

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Correcting the Deficiency Certainly a range of measures will be required to expand life scientists’ view of the scope of their responsibilities to include dual-use and biosecurity in all their complexity. Yet it will be a massive task even to correct this deficiency in the education and awareness levels of life scientists. This is one requiring urgent action by State Parties. In the meantime there is a potential role for civil society in providing models of what might be done to close the gap in the most effective way in a short time frame. The University of Bradford has over the past few years been developing a Dual-Use Biosecurity Educational Module resource (BEM). A report by the U.S. National Science Advisory Board for Biosecurity (NSABB) on a Strategic Plan for Outreach and Education on Dual Use Research Issues considered what needs to be done in some detail. In their view, developing such a strategic plan requires: First and foremost, the target audience must be identified and assessed as to their level of understanding of the issues since this will guide educational strategies. . . . Messages should be tailored to specific target audiences. Key points must be identified and specifically crafted to effectively convey the nature and importance of the information while simultaneously addressing the unique concerns of different stakeholder groups. (NSABB 2008, 3)

And because there are so many different possible methods of communication, the report pointed out that “it is important to select those methods that will most effectively reach the intended audiences” (ibid., 3). When the Bradford group applied this method of analysis to its work, it was evident that the intended target audience—university-level lecturers and students—did not have a high level of awareness of biosecurity and dual-use issues. Furthermore, given the prevalence of the use of the Internet in universities, it was clear providing information on the web was by far the most efficient and effective way forward. However, given the different pressures on the timetable in different universities, it was decided not to design a one-sizefits-all module and instead to design a BEM resource that could be used by individual lecturers around the world to draw upon so as to fit relevant parts into their own courses. The design of the module was also much influenced by the consensus about education of life scientists that developed at the 2008 Meeting of the States Parties that considered oversight, education, and awareness-raising. The report stated:



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States Parties noted that formal requirements for seminars, modules or courses, including possible mandatory components, in relevant scientific and engineering training programmes and continuing professional education could assist in raising awareness and in implementing the Convention. (United Nations 2008b, 7)

The core idea for the BEM was to address as many of the concrete ideas contained in this report as possible based on the concept of having a web of integrated prevention policies that together would deter anyone from breaking the BWC prohibition and that at the same time would provide f lexible teaching material that could be readily understood by life scientists. The BEM consists of 21 lectures, each consisting of 20 Powerpoint slides and notes for the lecturer, and with direct Internet links to the references used. Each lecture also includes some suggested essay questions. The BEM has an introduction to all the material for lecturers, and a small number of briefing papers cover material that would be less familiar to life scientists. Biosecurity Education Module Thus the Bradford BEM resource has been designed in five parts with the specific aim of producing an easily accessible source of wide-ranging information. Part A gives a brief overview of the whole of the module resource in order to orientate the user. Part B then sets out the misuse of modern biology after the discovery of the causes of infectious diseases in the late nineteenth century by scientists such as Pasteur and Koch. This history is largely unknown among life scientists and forms a basis for the consideration of the possible misuse of future advances. This part ends by briefly reviewing how the international community has dealt with the threat of the proliferation of biological weapons through the 1925 Geneva Protocol, the 1972 BWC, and the 1993 Chemical Weapons Convention, given that there is an overlap between the BWC and CWC in the area of midspectrum agents such as toxins and bioregulators. This part also contains modern accounts of the traditional agents such as anthrax, smallpox, and botulinum toxin in order to better engage scientists’ interest in the issue of biosecurity. Lectures 2–10 in Part B begin with a consideration of the different stages in the history of biological warfare, discuss the assimilation of BW in statelevel programs, introduce international legal agreements, analyze efforts since

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1980 to strengthen the BWC, and end with the BWC recent annual meetings in which scientists have become increasingly involved—at least at the level of national academics and industrial leaders. This then sets the scene for Part C in which lectures start from the recognition that it is through bioethics courses that life scientists are becoming familiar with the ethical problems that new research brings up and that the teaching of bioethics is growing in universities. Thus it is probable that biosecurity and dual-use issues are best presented to life scientists in this context of the moral and ethical implications of research—a point that was made in the above-mentioned report of the 2008 Meeting of States Parties. Consequently, Part C of the module starts with a review of standard bioethical analyses that students are likely to have encountered before introducing the growing literature on dual-use bioethics. The section then leads on to a consideration of the key U.S. National Academy Fink Report and the subsequent Lemon-Relman Report, which began the closer examination of the dual-use problem from within the scientific community. Lecture 15 examines classic dual-use experiments such as the mousepox experiment, and Lecture 17 examines concerns over the misuse of advances in neuroscience so as to illustrate the contention by Lemon-Relman that the dual-use problem is far wider than just microbiology. Lecture 18 concludes Part C by reviewing the various papers that have recently discussed the regulation of the security implications of the life sciences. Parts D and E of the module continue this theme on national and international regulation, concluding with a lecture on the “Web of Prevention.” The BEM was launched at the 2009 Meeting of States Parties (Ayub and Whitby 2010). The module is currently available in English, Japanese, French, and Russian (courtesy of the Government of Canada, which facilitated its translation), and Romanian, Spanish, and Urdu versions are currently in preparation. It is important to stress that the BEM is available “open source” on the Internet for anyone to use and that tests have shown that it is not difficult for lecturers to integrate different parts of the module into their courses. However, clearly much more needs to be done to bring this awareness and education of life scientists up to an acceptable standard as part of the overall web of prevention and thus lay a firm basis for other measures of prevention within the in-depth national implementation of the Convention. It is almost certainly true also that similar measures will be required to develop the education and level of awareness of practicing chemists particularly as chemistry



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and biology effectively merge and require a coming together of the CWC and BWC. Conclusions The three different versions initially presented, portraying a wider web of measures to address the risks stemming from chemical and biological weapons proliferation and use, provide different conceptual lenses that prioritize different aspects of such responses—whether focusing on deterrence, prevention, or protection. As our discussion has demonstrated, such a web of responses has to operate on and integrate a number of different levels, from the global to the individual. On the global level the intergovernmental, treaty-based regimes revolving around the CWC and BWC have been supported since 2004 by the continuous attention and sustained action on the part of the UN Security Council and its 1540 Committee. While discussed here mainly under the heading of its contribution to the strengthening of export control, its mandate is clearly broader and its activities have progressively moved from fact finding to capacity building. Discussions about the interrelation of preventing biological warfare and securing public health have been carried out at a global level as well. As the analysis of this sometimes tense relationship has revealed, understandings among WHO member states about the appropriate role of this organization in the fight against BW have sometimes differed. In other words, attempts by some BW regime members to externalize functions of this regime, and seek their realization in the WHO context, threatened to create a conflict in the international public health regime. Important from our perspective has been the ability of the WHO to withstand attempts to securitize its mandate and scope of activities. In the longer term, the thus preserved political neutrality of the WHO may be one of the organization’s biggest assets should it have to investigate a disease outbreak that turns out to be deliberately caused. Equally global in its implications are the activities of the group of likeminded states coming together in the Australia Group to harmonize its export control policies. From the perspective of both the BW and the CW prohibition regimes, the Australia Group represents a subset of member states that collaborate in this forum in order to give meaning to and operationalize their understanding of the nontransfer norm contained in the two regimes. As this interpretation has been contested by other regime members, it has led

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to the introduction of a conflict into the core institutional framework of the regimes from the wider web of responses. It cannot be ignored, however, that at the heart of both these global and multilateral efforts are national capabilities and actions to either comply with or exceed the requirements of the regimes. Especially with a view to the latter, national policies need to make sure that, for example, in the biosecurity area—due to the somewhat different focus of activities—the standards established are compatible with the two regimes and do not undermine the very goals they seek to strengthen. For this, as for the oversight of life science research or awareness raising among life scientists, increased levels of international cooperation are required to create a level playing field for researchers and the biotech industry alike. What this also points toward is the relative increase over the past decade in the importance of substate actors in the realization of the goals of the CW and BW prohibition regimes. It is against this background that the calls for awareness raising and education and the activities of learned societies and national academies acquire their importance for the strengthening of both the wider web of responses and the two regimes in a narrower sense. It is to these two regimes, their achievements, and their weaknesses that we now turn our attention.

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Evolution of the BW Prohibition Regime Assessing Achievements and Weaknesses

Introduction As we have highlighted in the introductory chapter, both the CW and the BW prohibition regimes have their origins in the strong moral or normative conviction that the use of such weapons would be abhorrent and—in the words of the preamble of the BWC—“would be repugnant to the conscience of mankind and that no effort should be spared to minimize this risk” (United Nations 1972). It is from such a moral perspective that Joshua Lederberg, the pioneer of modern micro/molecular biology, characterized biological warfare as “the absolute perversion of medical science” (Lederberg 1999, 5). He went on to conclude that what distinguishes biological warfare “is the understanding that its habitual practice would be ruinous to personal security and civil order, perhaps more grievously than any other weapon likely to get into the hands of disgruntled individuals or rogue states” (ibid.). The BWC, which was agreed on in 1972 (United Nations 1972) and brought into force in 1975, was touted as “the first international agreement since World War II to provide for the actual elimination of an entire class of weapons from the arsenals of nations” (USA 1972, 553–554). Yet, at the 1996 Fourth Review Conference of the BWC, the director of the United States Arms Control and Disarmament Agency noted that “twice as many countries now have or are actively pursuing offensive biological weapons programs as when the Convention went into force” in 1975 (Holum 1996, 2). The proliferators included the startling example of the Soviet Union, which carried out a

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massive offensive program despite being one of the three Depositary States for the Convention. The question of how the BWC is to be strengthened in order to further restrict such proliferation is of crucial concern. It is clear from the historical record that since the causes of infectious diseases began to be elucidated in the last decades of the nineteenth century, the knowledge gained has also been applied in a series of offensive biological weapons programs. These were undertaken by major states such as Germany, France, Japan (which also carried out large-scale, antipersonnel use of biological agents in China), the United Kingdom, the United States, the former Soviet Union, Iraq, and South Africa (Geissler and van Courtland Moon 1999; Wheelis, Rozsa, and Dando 2006). Efforts to prevent the use of biological weapons did not, of course, begin with the 1972 BWC. In discussions about international controls toward the end of the nineteenth century, biological weapons were considered together with chemical weapons. Following the large-scale use of chemical weapons in World War I, the use of both types was banned by the 1925 Geneva Protocol. This has now become accepted as customary international law, binding on all states. Following World War II, biological weapons were classified along with chemical and nuclear weapons in a special category of “weapons of mass destruction,” but little was done to tighten international control until the negotiation of the BWC. For quite some time following the Geneva Protocol it was extremely difficult to strengthen controls by moving toward a ban not only on use but also on production and possession of chemical and biological weapons. After World War II, negotiations that considered both chemical and biological weapons together were contentious and reached an impasse. There was an indication that the United States was concerned that CBW disarmament might set a precedent for nuclear weapons (Chevrier 2006). It was subsequently reasoned that it might be easier to agree to a treaty on biological weapons if it were handled separately. This was no doubt due to the reluctance of some states to give up completely an established and proven chemical weapons capability, which could be used for deterrence or retaliation. Biological weapons on the other hand were not as extensively developed and regarded by many to be of uncertain utility. In the end, a British proposal to handle biological weapons separately was followed (Chevrier 2006). Negotiations over a Biological Weapons Convention



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received a decided boost when Richard Nixon announced on 25 February, 1969 that the United States was unilaterally renouncing its offensive BW program and would from that time on engage solely in defensive BW research. Several explanations for this startling announcement have been offered (Tucker 2002). One reason was that extensive U.S. analysis of BW capabilities concluded that these weapons had limited tactical utility and were not a reliable strategic deterrent. The military nevertheless preferred to retain an offensive capability because of the realization that biological weapons could have equivalent lethality to nuclear weapons, but they yielded to the argument that it was important to discourage other countries from acquiring them. Indeed, it has been suggested that the United States had actually become convinced about how devastating the use of biological weapons could be (Dando 2002, 3–4). Thus, labeling these weapons as unreliable and achieving an international ban on their development would be a better option than continuing with a massive offensive program that others would surely copy. At the same time, Nixon could deflect criticism of the United States over the war in Vietnam, in which it had used chemical riot-control agents and herbicides. During the negotiations over the BWC, one very contentious issue from the start was that over the verification of compliance. The U.S. view was that a verification regime would have to be totally intrusive if it were going to be effective, and it demanded tough verification measures accordingly. The Soviet Union on the other hand was stubbornly unwilling to accept on-site inspections. The reasons why the Soviet Union did not want an effective verification system became clear in later years, when it became known in 1992 that it had engaged in a massive offensive BW program all along, even after signing the Convention (Dahlberg 1992). Although the United States insisted throughout negotiations upon tough verification measures, it actually held the view that the types of measures it was calling for still could not guarantee a foolproof system of verification. Possibly for this reason, the United States finally gave up its insistence upon a tough verification regime (Tucker 2002; Chevrier 2006), and the BWC was finally agreed on in 1972. The Convention is a remarkably slim document of some four to five pages and contains fifteen Articles. Notably, the system of five-yearly Review Conferences (to date held in 1980, 1986, 1991, 1996, 2001–2002, and 2006) has allowed States Parties to consider how elements of the regime have operated and how they might be improved. The evolution of the review process has taken place at different levels of undertakings (see fig. 7.1):

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The BWC itself contains a number of legally binding obligations. Legally binding obligations can be considered the things that States Parties MUST do. The review conferences reached additional agreements as to how to implement the obligations of the BWC. They represent active agreement by States Parties to do certain things. As they have not been endorsed by a specific act of parliament or Presidential Decree, they are considered to be politically (as opposed to legally) binding. Politically binding obligations are the things States Parties SHOULD do. Finally, the intersessional processes have led to the development of common understandings on elements that might be useful when a States Party addresses its politically or legally binding commitments. These are shared national positions on mechanisms that might strengthen the implementation of the BWC—or the things States Parties COULD do. (Millett 2009, 30–31)

Strengths and Weaknesses of the BWC Although negotiations for the BWC were difficult and contentious, an agreement was finally reached that was based on the extremely effective device of a General Purpose Criterion. This General Purpose Criterion is embodied in the scope of the Convention set out in Article I, which states, in part: Each State Party to this Convention undertakes never in any circumstances to develop, produce, stockpile or otherwise acquire or retain: 1. 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 [emphasis added]. (United Nations 1972)

Clearly, the General Purpose Criterion (italicized above) allows peaceful activities with biological agents but prohibits any activity that is not for peaceful purposes. The Convention is thus not locked into the technology of the 1970s but applies to all current or future developments. This allencompassing prohibition is one of the great strengths of the Convention. The problem with the BWC does not lie, therefore, in its intended scope but in its ineffective implementation. Despite suggestions to the contrary in the literature, there was, in fact, a vigorous debate over the inadequacy of the BWC’s verification provisions at the time of its negotiation. Major states such as Sweden and France were



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Text of the Convention (Legally binding obligations) Final Documents of Review Conferences (Politically binding obligations)

Reports of Meetings of States Parties (Shared national positions)

FI GU R E 7.1. Layers of undertakings under the Biological Weapons Convention.

Figure depicts different levels of legal and political obligation under the BWC. source: Millett 2009.

particularly critical, and a number of other states made suggestions as to how verification might be improved. However, it is clear that the two superpowers of the day did not then wish to strengthen this aspect of the Convention. As the former Soviet Union vastly expanded its offensive program at the very same time as it negotiated the BWC, the reasons for its objection to proper verification are clear. The reasons why the United States opposed stronger measures of verification appear to be connected with its long-held view that verification information sufficient to produce an unequivocal verdict of guilty on a proliferator would not be obtainable. More sophisticated views of the function of verification put forward by other states at the time—related to transparency, reassurance of other parties, and dissuasion through the possibility of discovery—were not accepted, and as a result, the treaty was agreed on in 1972 with only the rudimentary provision for verification in Articles V and VI (United Nations 1972). Article V of the BWC calls upon States Parties to “undertake to consult one another and to cooperate in solving any problems which may arise in relation to the objective of, or in the application of the provisions of, the Convention.” It does not, however, specify how these consultations are to proceed. It merely states an obligation to consult in a cooperative manner when there is a question of noncompliance and that these consultations can take place either

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on a bilateral or multilateral basis, in response to a reasonable request. This mechanism has been invoked in two instances, but the results in both cases were inconclusive. One of these attempts employed a bilateral procedure under Article V. The United States tried on three separate occasions to obtain an official clarification from the Soviet Ministry of Foreign Affairs about the outbreak of human anthrax in the Soviet city of Sverdlovsk in April 1979. Each time, Moscow denied any wrongdoing and claimed the outbreak was of a natural origin, occurring from the ingestion of infected meat. However, many questions remained unanswered, so the question of compliance remained unresolved (Sims 1988). Years later, a forensic investigation of the Sverdlovsk incident reached the conclusion that the outbreak was the result of accidental release of anthrax spores from a military facility (Meselson et al. 1994). Article V also provides for multilateral consultations. This mechanism was invoked for the first time in answer to an allegation by Cuba that the U.S. government had deliberately released a crop-destroying insect pest over the island from an aircraft in order to disrupt its agricultural system (Zilinskas 1999). Again, the issue could not be resolved bilaterally, so Cuba turned to the Russian Federation (which was one of the BWC depositary states to be approached in the event of a request for a multilateral consultation procedure) in 1997 and requested a meeting of the States Parties to consider the issue. The consultations were subsequently held in Geneva on 25–27 August that year. The evidence was reviewed and thirteen States Parties submitted their written comments on the case. Most of these said they were not convinced of a causal link between the flight of the U.S. aircraft over the island and the infestation, and three states argued that the lack of detailed information and the technical complexity of the issue made it impossible to reach a clear verdict. As a result, it was concluded that it “has not proved possible to reach a definitive conclusion with regard to the concerns raised by the Government of Cuba” (BWPP 2004, 38).1 In both cases outlined above, the United States and Cuba chose not to invoke the mechanisms available in Article VI. This Article provides that any party “which finds that any other State Party is acting in breach of obligations deriving from the provisions of the Convention may lodge a complaint with the Security 1.  From a letter addressed to all States Parties from Ambassador S. I. Soutar, UK, chairman of the multilateral meeting. See BioWeapons Report 2004, 38. Available at www.bwpp.org (accessed 9 October 2011).



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Council of the United Nations. Such a complaint should include all possible evidence confirming its validity.” Article VI also requires each State Party “to cooperate in carrying out any investigation which the Security Council may initiate.” Although some attempts were made by the United Kingdom during negotiations to structure Article VI so that a permanent member of the Security Council could not veto an investigation (i.e., that investigations of alleged use be carried out under the auspices of the UN Secretary General), the final language of Article VI retained the right of veto by a permanent member of the Security Council. The implicit threat of a Soviet veto was no doubt why the United Kingdom and the United States refrained from requesting an investigation into the Sverdlovsk incident. For a more thorough discussion of these mechanisms, see Sims (2001) and BWPP (2004). In addition to the weaknesses of the BWC in the area of verification, implementation of the Convention has proceeded in a less than satisfactory manner. Implementation is “the process by which a State Party adopts appropriate and effective national measures to carry out and enforce the obligations to which it has committed when ratifying or acceding to a Treaty” (Woodward, Spence, and Escauriaza Leal 2009, 97). These measures include national regulatory and penal legislation to enforce the prohibitions of the treaty as well as enhance biosafety and biosecurity in dealing with biological materials of relevance to the Convention. Given the widely differing legal and constitutional structures of the States Parties to the Convention as well as their states of development, it is little wonder that implementation of the BWC has been quite diverse and in some cases decidedly insufficient or even lacking (Woodward 2003). One blatant deficiency of the BWC is that it lacks a treaty organization to aid in its implementation and to oversee its evolution and development, similar to the Organization for the Prohibition of Chemical Weapons (OPCW). Efforts to Strengthen the BWC The realization that the BWC needed strengthening, particularly in the areas of verification, implementation, and an established treaty organization to aid in implementation, led to several efforts over the years to deal with these deficiencies.

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Confidence-Building Measures The Second Review Conference of the BWC in 1986 coincided with the initial stages of the ending of the East-West Cold War, and there was some optimism about the possibility of introducing confidence-building measures (CBMs) into the Convention. Indeed, a series of CBMs (mainly annual information exchanges on past and present activities of States Parties relative to the BWC) were agreed on in 1986 at the Second Review Conference and were expanded and developed in 1991 at the Third Review Conference. Unfortunately, it was not possible to add these CBMs as legally binding measures to the BWC, so they remain only politically binding. Several analyses have documented the disappointing performance of States Parties in submitting CBMs over the years and how indeed “the limitations of these CBMs helped prompt treaty parties in 1994 to establish an Ad Hoc Group to negotiate a protocol to strengthen the Convention’s effectiveness” (Chevrier and Hunger 2000, 24). Significantly, CBMs were not a topic discussed during the intersessional processes (see below), but at the Sixth Review Conference it was agreed that they should be dealt with at the Seventh Review Conference in 2011. A joint initiative of the Geneva Forum with the governments of Germany, Norway, and Switzerland carried out a series of three workshops tasked with identifying problems with CBMs and offering proposals aimed at improving the CBM mechanism and increasing the participation in the annual information exchange, which are topics planned for consideration at the Seventh Review Conference. A review of the outcomes of these discussions, including proposals for improvements in the CBM regime in preparation for their consideration at the Seventh Review Conference, can be found in Lentzos (2011). None of these proposals has included one to make the CBMs in whole or in part legally binding (mandatory), which would help a great deal to ensure that the information provided would receive the collective scrutiny of the States Parties that would be most useful. Any action along these lines seems very unlikely at present, so it remains to be seen whether the efforts up to now will contribute substantively to improving participation in this information exchange. The Protocol Negotiations The Third Review Conference of the BWC took place just after the 1991 Gulf War amid great concern about the possible use of biological weapons by Iraq. Thus, a group of governmental experts was mandated to examine potential



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verification measures and to consider their technical feasibility. The VEREX 2 meetings of this group took place in 1992–1993 and the group submitted a positive report in 1993. A special Conference of States Parties examined the report in late 1994, and it then mandated the work of an Ad Hoc Group (AHG), which met in Geneva from 1995 until 2001. Though the mandate of the AHG was much broader than just the strengthening of the Convention through improved verification measures, it crucially was to consider appropriate measures, including possible verification measures, and draft proposals to strengthen the Convention, to be included, as appropriate, in a legally binding instrument. (United Nations 1994, 10)

So this marked a clear change in approach. States Parties agreed that there should be an attempt to agree on verification measures to be included in a legally binding instrument as part of the process of strengthening the BWC. The initial stage of the Ad Hoc Group’s work was devoted to building on the studies of VEREX in order to identify the elements required in a legally binding Protocol to the BWC. This initial stage of work lasted from 1995 through to mid-1997. It was only in the July–August session of 1997 that the group made a transition in its work to the consideration of a rolling text of the Protocol. The Fourth Review Conference of the Convention itself, in 1996, had called for an intensification of the work of the AHG (United Nations 1996) and, with the transition to a rolling text, more detailed provisions could be included in a systematic manner. According to the chairman of the AHG, Ambassador Tibor Toth of Hungary, a third stage of negotiations began in January 1999 with “the move to a final framework for the Protocol and the detailed negotiation on key elements” (Toth 1999, 1). Numerous statements made to the AHG by ministers from States Parties at the March 2000 session, which coincided with the twenty-fifth anniversary of the Convention, stressed that the text was at an advanced stage and that an agreement could be reached prior to the Fifth Review Conference of the BWC in late 2001 (Rissanen 2000). Ambassador Toth subsequently produced what is called the “chairman’s compromise text,” which is an impressively long and complex document, containing thirty Articles and numerous Annexes which extend to over 200 printed pages (United Nations 2001). However, it was clear at the same 2. The term VEREX is the name given to the meetings of the ad hoc group of governmental experts to identify and examine potential verification measures from a scientific and technical standpoint.

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time that numerous points of serious disagreement remained to be resolved (Pearson et al. 2000). For example, there were concerns that some states wished to use the Protocol definitions to limit the General Purpose Criterion of the Convention. There were also strong divisions between the developing and developed worlds over how export controls (Article III, BWC governing the transfer of “agents, toxins, weapons, equipment or means of delivery” and assistance and co-operation in biotechnology (Article X, BWC) should be handled in the future. Finally, there were differing views concerning crucial elements of the central compliance (verification) measures of the Protocol. At the last meeting of the Ad Hoc Group in July–August 2001 and after over six years of negotiations, an agreement on the chairman’s compromise text was supposed to be reached. However, at that session the U.S. government decidedly rejected not only the Protocol text but also the whole process of further negotiations over the Protocol (Mahley 2001). As a result, no agreement could be reached, and the meeting ended in disarray. For a comprehensive history of the Protocol negotiations, see Dando (2002) and Littlewood (2005). Following the Fifth Review Conference of the BWC in November– December 2001, strengthening the BWC with measures to allow demonstration of compliance became even more uncertain. Once again, the United States played a major role. Two hours before the Conference was to come to a close, the U.S. delegation proposed ending the mandate of the Ad Hoc Group, in order to crush any further attempts at negotiation over the Protocol and to prevent agreement on a Final Declaration of the Conference that would not be suitable to the U.S. government. To avoid total failure, there was a general agreement not to conclude the Conference but rather to adjourn it until November 2002 in order to achieve a “cooling off ” period (Butler 2001). The First Intersessional Process After resumption of the Fifth Review Conference later in November 2002, no Final Declaration with an article-by-article review of the BWC could be achieved. Nevertheless, a general sense prevailed that the weaknesses of the BWC, particularly in the areas of inadequate implementation, vulnerability to biological weapons attacks, and lack of prevention of the buildup of biological weapons programs still needed to be addressed. Accordingly, States Parties did adopt a new procedure of work for the coming years up to the Sixth Review Conference in 2006. The Conference agreed



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to hold three annual meetings of the States Parties of one week duration each year commencing in 2003 until the Sixth Review Conference, to be held not later than the end of 2006, to discuss, and promote common understanding and effective action on: i. the adoption of necessary national measures to implement the prohibitions set forth in the Convention, including the enactment of penal legislation; ii. national mechanisms to establish and maintain the security and oversight of pathogenic microorganisms and toxins; iii. enhancing international capabilities for responding to, investigating and mitigating the effects of cases of alleged use of biological or toxin weapons or suspicious outbreaks of disease; iv. strengthening and broadening national and international institutional efforts and existing mechanisms for the surveillance, detection, diagnosis and combating of infectious diseases affecting humans, animals, and plants; v. the content, promulgation and adoption of codes of conduct for scientists. (United Nations 2002, 3–4)

It was further agreed that each Meeting of States Parties would be prepared by a two-week meeting of experts. Items i and ii were considered in 2003, items iii and iv in 2004, and item v in 2005. It was made quite clear from the start that the States Parties had no mandate to negotiate on any of the issues to be discussed at these meetings. This points up the charged atmosphere under which the BWC was operating at that time, with the persistent fear that the Convention might break down at any time. In the eyes of many observers these discussions resulted in little substantive improvements or strengthening of the Convention. On the positive side, however, the States Parties continued talks in a multilateral arena, and some discussions have been useful. For example, more time than usual was devoted to discussions over implementation of the Convention, which, according to some, is a crucial topic that should have been addressed long ago (Kelle 2003a). Indeed, much can be achieved on the national level by enacting proper legislation and regulations to implement the BWC. Probably one of the most significant outcomes of these first intersessional process meetings was the decision by the chairman of the 2005 meetings, Ambassador John Freeman of the United Kingdom, to open up the proceedings (consideration of topic v above) to life scientists and

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representatives of professional and academic organizations to participate directly in the meetings and make contributions as additional expert advisers to the delegations. The Sixth Review Conference The Sixth Review Conference has been hailed by many observers as at least a partial success, especially in light of the chaos and near disaster that accompanied the Fifth Review Conference in 2001–2002, in which no article-by-article review of the Convention and no Final Declaration could be achieved. Also, there was no formal review and assessment of scientific and technological developments in relation to the BWC. The Sixth Review Conference on the other hand produced a Final Declaration, including an article-by-article review of the Convention. New developments in science and technology were reviewed and their relevance for the Convention was assessed. One event of considerable importance was the establishment of an Implementation Support Unit (ISU). This unit consists of three full-time staff members within the Geneva branch of the United Nations Department for Disarmament Affairs. It was given the mandate to provide administrative support, facilitate communication among States Parties and international organizations, and facilitate contacts with scientific and academic institutions and nongovernmental organizations as well. It also serves as a type of clearinghouse to receive and distribute the confidence-building measures (CBMs) submitted by the States Parties and to compile and distribute data on CBMs and to inform on participation (United Nations 2006a). A report on the activities of the ISU since its establishment can be viewed on its website (ISU 2007). Although the scope of the ISU is still a far cry from that of a permanent treaty organization, such as the Organization to Prohibit Chemical Weapons (OPCW) of the Chemical Weapons Convention, it might be seen as a first step in this direction. Indeed, the decision to establish the ISU was one of considerable significance. There has always been objection by some key States Parties to the establishment of a permanent treaty organization for the BWC, so the fact that consensus was reached on the ISU serves as a possible indication that the atmosphere for cooperation among the States Parties had changed to a more positive character since the Fifth Review Conference.



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The Second Intersessional Process One of the partial successes of the Sixth BWC Review Conference in 2006 was the agreement by the States Parties on a new work program for 2007–2010, to be carried out in a series of annual meetings up to the Seventh Review Conference in 2011. The stated purpose of these meetings was once again “to discuss, and promote common understanding and effective action” on the topics under consideration: i. Ways and means to enhance national implementation, including enforcement of national legislation, strengthening of national institutions and coordination among national law enforcement institutions; ii. Regional and sub-regional cooperation on implementation of the Convention; iii. National, regional and international measures to improve biosafety and biosecurity, including laboratory safety and security of pathogens and toxins; iv. Oversight, education, awareness raising, and adoption and/or development of codes of conduct with the aim of preventing misuse in the context of advances in bio-science and bio-technology research with the potential of use for purposes prohibited by the Convention; v. With a view to enhancing international cooperation, assistance and exchange in biological sciences and technology for peaceful purposes, promoting capacity building in the fields of disease surveillance, detection, diagnosis, and containment of infectious diseases: (1) for States Parties in need of assistance, identifying requirements and requests for capacity enhancement; and (2) from States Parties in a position to do so, and international organizations, opportunities for providing assistance related to these fields; vi. Provision of assistance and coordination with relevant organizations upon request by any State Party in the case of alleged use of biological or toxin weapons, including improving national capabilities for disease surveillance, detection and diagnosis and public health systems. (United Nations 2006, 21) Again, a different set of topics was to be covered each year during a one-week Meeting of Experts, followed by a one-week Meeting of States Parties. Items

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i and ii would be considered in 2007; items iii and iv in 2008; item v in 2009; and item vi in 2010. As at the previous intersessional process, the meetings continued to open up to greater participation of scientists, professional and academic organizations, and nongovernmental organizations. For example, the chairman of the 2007 meetings, Ambassador Masood Khan of Pakistan, introduced a new procedure at the Meeting of Experts to encourage and promote exchange between delegates and nongovernmental organizations (NGOs). For this purpose he had invited six NGOs to a roundtable discussion on the theme of “Practical contributions of civil society to national implementation and regional cooperation.” After an introductory statement by Ambassador Khan, each NGO representative gave a short statement on the perspectives of their organization in the way of practical suggestions for implementation of the Convention. This followed a question-and-answer session between the delegates and the NGOs. This roundtable was considered by many to be an innovative move on the part of Ambassador Khan in his capacity as chairman. However, he was obliged to dispel fears that NGOs might be given a new status by expressly assuring the States Parties that this procedure was not to be taken as a precedent and it did not change the status of anyone participating. Another method of interaction that proved to be quite effective was the introduction of a poster session by the 2008 chaiman, Ambassador Georgi Avramchev of the Republic of Macedonia. In addition, Ambassador Avramchev had “without creating a precedent” invited thirteen scientific, professional, academic, and industry bodies to participate in informal exchanges in the open sessions as guests of the Meeting of Experts. Allowing greater participation of a wider group of stakeholders has done much to encourage various professional organizations and individuals in the life sciences as well as the social sciences to actively address ways to strengthen the BWC by working from the bottom up. An example of these activities has been the participation of the BioWeapons Prevention Project (BWPP) in association with one of its member organizations, Verification Research, Training and Information Centre (VERTIC), in the first EU Joint Action program (EU 2006) to provide assistance to fully implement the BWC. Since that time, VERTIC has continued to provide legal advice to aid States Parties upon request in their implementation processes (Spence 2010). Further efforts of civil society include the promotion of codes of conduct and the drafting of education programs aimed at raising awareness among life scientists about



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dual-use issues relevant to the BWC (see chapter 6, subsection on “Awareness Raising among Life Scientists,” for a description of these efforts). A great deal of work has also been put into devising programs involving oversight of research in the life sciences by civil society actors (see chapter 6, subsection on “Research Oversight”). Science and Technology Developments Up to now all new developments in science and technology of relevance to the regime have been found to be covered by the BWC through the allencompassing formulation of prohibitions provided by the general purpose criterion in Article I of the Convention. At the First Review Conference in 1980, the relevance of the developments in genetic engineering, which began to be reported in the scientific literature of the mid-1970s, was not directly addressed in its final document (United Nations 1980a), although it was discussed in the background paper on scientific and technological developments submitted by the three depository nations (United Nations 1980b). The final declaration simply stated that all scientific and technological developments were covered: The Conference believes that Article I has proved sufficiently comprehensive to have covered recent scientific and technological developments relevant to the Convention. (United Nations 1980a)

Specific reference to the developments in genetic engineering first appeared in the final declaration of the Second Review Conference in 1986: The Conference, conscious of apprehensions arising from relevant scientific and technological developments, inter alia, in the fields of microbiology, genetic engineering and biotechnology, and the possibilities of their use for purposes inconsistent with the objectives and the provisions of the Convention, reaffirms that the undertaking given by the States Parties in Article I applies to all such developments. (United Nations 1986b, 3)

These reaffirmations were essentially repeated at the Fourth Review Conference in 1996, where the States Parties agreed that: The Conference, conscious of apprehensions arising from relevant scientific and technological developments, inter alia, in the fields of microbiology, biotechnology, molecular biology, genetic engineering, and any applications resulting from genome studies, and the possibilities of their use for purposes

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inconsistent with the objectives and the provisions of the Convention, reaffirms that the undertaking given by the States Parties in Article I applies to all such developments. (United Nations 1996, 15)

The next time an assessment of the relevance of developments in science and technology was undertaken was at the Sixth Review Conference in 2006. Instead of listing all the categories of development, the States Parties simply agreed that: The Conference reaffirms that Article I applies to all scientific and technological developments in the life sciences and in other fields of science relevant to the Convention. (United Nations 2006a, 9)

However, given the direction that nanotechnology, synthetic biology, and systems biology are taking, there are well-founded concerns that some future developments may pose a compounded threat. The UK Green Paper of 2002 stressed that the “accelerating pace of scientific developments now makes it quite unsafe only to have five-yearly technology reviews by the States Parties to support the five yearly Review Conferences” (Secretary of State UK 2002, 14) and proposed that “an open-ended body of government and non-government scientists should meet every one or two years to review the rate of change and assess their implications for the convention and measures being taken to strengthen it” (ibid., 3). Since that time the pace of technological change has been even more dramatic, making the call for more regular review of relevant science and technology developments all the more urgent. However, there is also a need for more structured assessment. Up to now the reviews of advances in science and technology have been carried out mainly by individual States Parties or the ISU and submitted as background papers. However, there has never been a formal assessment by the collective BWC body. “In the long term, scientific advice needs to be made a formal part of the BWC regime based on consensus because advice from outside organizations may be dismissed as politically motivated by some states” (Rhodes and Dando 2007). Other reports have also offered concrete proposals for consideration at the Seventh Review Conference that include both more frequent and more structured assessments of the developments in science and technology relevant for the BWC (Pearson 2010; Pearson 2011; Dando and Pearson 2010; Nixdorff and Dando 2011). While the risks are growing at an enormous pace, arms control developments to deal



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with these risks are lagging way behind. This is especially true considering the evolution of the BWC regime. The Fallacy of the Focus on Bioterrorism The events of September 11, 2001 were undoubtedly a deep shock for many Americans, underscoring the vulnerability of the United States to major terrorist attacks on its own soil. The anthrax letter assaults that followed close behind the 9/11 events drove this feeling of insecurity further toward a state of panic and made the possibility of bioterrorist attacks within its own territory, along with the prospect of inadequate protection from such assaults, seem suddenly very real. Thus, biosecurity became an imperative for the U.S. government, particularly in the context of protecting America against bioterrorism. The need for increasing security was seen as a national problem to be dealt with by national responses. This mindset resulted in the enactment of a series of very intrusive national legislative and regulatory measures aimed primarily at safeguarding dangerous biological agents and screening personnel working with such agents. Some of these regulations have proved to be cumbersome, have had negative effects on the research climate, and have driven up the cost of working with select agents beyond reason (Dias et al. 2010). But more than anything else, this focus on national regulations to protect against bioterrorist assaults has for almost a decade distracted from the need to address the “core business” (Kelle, Nixdorff, and Dando 2010) of the BWC—the growing threat posed by state-supported actors—by strengthening the deficit of the BWC in the area of compliance accountability. The assessment of bioterrorism as the primary bioweapons threat has proved to be fallacious. In his monograph titled Assessing the Biological Weapons and Bioterrorism Threat, Milton Leitenberg provided a systematic survey of the evolution of biological weapons programs of states and the efforts by nonstate actors to obtain, develop, and use biological agents. He concluded that “for the past decade the risk and immanence of the use of biological agents by nonstate actors/terrorist organizations—‘bioterrorism’— has been systematically and deliberately exaggerated. It became more so after the combination of the 9/11 events and the October–November 2001 anthrax distribution in the United States that followed immediately afterwards” (Leitenberg 2005, 88–89). The number and scale of actual bioterrorist events simply do not justify this focus.

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From the analyses of the advances in the life sciences outlined in chapters 3 and 4 of this book and the scenario of the evolution of the BW threat spectrum offered by Petro, Plasse, and McNulty (2003), it is reasonable to conclude that the greatest danger of misuse would come from state-supported actors rather than substate actors and individuals, as state-supported actors would have the means to put sophisticated advances in biotechnology into practice. This has been very convincingly illustrated by the description of the numerous contingencies and sociotechnical factors that played a major role in the poliovirus (Cello et al. 2002) and the phiX bacteriophage (Smith et al. 2003) synthesis work as chronicled by Kathleen Vogel (2008). However, even much less demanding work would be difficult for substate actors to achieve. Frequent assertions that BW production is easy grossly underestimate the difficulties and time-consuming nature of biotechnology in practice. Indeed, several empirical studies have shown that “as biotechnology moves from the scientific bench to a more applied setting, it follows a well-established historical pattern of slow and incremental change and diffusion consistent with other major technologies” (Vogel 2008, 50). Focusing alone on such material aspects as safeguarding dangerous biological agents, screening personnel working with such agents, and regulating bioweapons research has been dubbed the “nuclearization” of biology, and some biosecurity experts themselves have contended that this policy actually represents a threat to health and security (Franz et al. 2009). Conclusions Efforts to strengthen the BWC in its effectiveness to prohibit and prevent the malign misuse of biological agents have been tedious and protracted. The mechanisms in Articles V and VI to deal with questions of compliance have proven to be ineffective, the Protocol negotiations over verification measures have failed, and the politically binding CBMs with the proposed improvements (Geneva Forum 2010) show little promise of achieving significant transparency goals. The intersessional processes can be scored as only partially successful in their aims to “promote common understanding and effective action” on important issues such as implementation of the Convention; biosafety and biosecurity; codes of conduct and awareness-raising education; and oversight of work in the life sciences. A great deal of effort has been expended by professional organizations and individuals working from the



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bottom up on awareness-raising, education, and oversight of work in the life sciences. However, these programs have proved very difficult to implement. Up to now, very little pressure has been applied by governments from the top down to help implement such programs, and this simply must be done if they are to be significantly successful in their aims. The main problem with the BWC still lies in the lack of compliance assurance, and addressing this problem has been neglected for almost a decade. Without adequate means of demonstrating compliance to the Convention, the security assurance that Article I should provide remains only partially realized. The United States rejected the Protocol to the BWC on the grounds that it believed that the verification measures contained therein would pose a risk to the protection of sensitive, confidential national security as well as commercial proprietary information (Mahley 2001). In contradiction of this view, a report on practice inspections carried out in consideration of what would be required in a militarily significant offensive biological weapons program, and how it might be detected, reached the conclusion: Provided the sites being inspected make preparation and use managed access, the risks to commercially sensitive information can be reduced. On many occasions, the amount of access that can be granted without unduly risking proprietary data can be extensive. (United Kingdom 1994, 3)

A more plausible explanation for the rejection of the Protocol by the United States appears to be connected with its long-held view that verification information sufficient to produce an unequivocal verdict of guilty on a proliferator would not be obtainable, and any verification regime would only provide a false sense of security (Bailey 1994; Mahley 2001). This position is also difficult to understand in light of the further evidence provided by the report on the inspection trials referred to above, which concluded that there was indeed a significant chance of a violation being detected and therefore deterred (United Kingdom 1994). The results of the United Nations Special Commission (UNSCOM) investigations in Iraq following the first Gulf War of 1990–1991 further attest to the feasibility of biological weapons verification. Although Iraq went to considerable lengths to prevent a comprehensive disclosure of its WMD programs, with particular efforts being made to conceal its BW programs, the results show quite clearly that a verification system with declarations, routine inspections, and challenge inspections would be

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adequate to detect any significant violations and therefore act as a deterrent (Pearson 2000; Pearson 2006). Even if the UNSCOM disclosure was far from a comprehensive declaration, evidence in several areas established the central proof of Iraq’s offensive program. This evidence included the collection of data on procurement of large quantities of growth media for which no credible explanation could be given; identification of facilities whose design was difficult to explain; evidence of the operation of large inhalation chambers as well as dryers and other processing equipment for anthrax production; the purchase of specialized munitions-filling equipment (Black 1999; Pearson 2000; Pearson 2006). It is important to realize that “unless a BWC violator is careless, the results of BWC inspections will not be instantaneous and conclusive. Instead, as UNSCOM’s experience illustrates, an incriminating case against a biological weapons proliferator will be made over time by diligently assembling pieces of evidence” (Smithson 1998, 110). In a speech delivered to the Meeting of States Parties in 2009, Undersecretary of State Ellen Tauscher made clear that the United States had not changed its position on the Protocol, stating that “[t]he Obama Administration will not seek to revive negotiations on a verification protocol to the Convention. We have carefully reviewed previous efforts to develop a verification protocol and have determined that a legally binding protocol would not achieve meaningful verification or greater security” (Tauscher 2009, 4). At the same time, Undersecretary Tauscher stated that the United States considered the BWC to be the “premier forum for dealing with biological threats” (ibid., 2) and that “we believe that confidence in BWC compliance should be promoted by enhanced transparency about activities and pursuing compliance diplomacy to address concerns” (ibid., 4). According to informed observers, this does indeed demonstrate a decided willingness by the United States to address the problem of compliance assurance within the BWC forum. However, explicit new approaches to tackling this task—beyond a generic endorsement of updating and strengthening CBMs (United States 2011)—have as yet not been offered by the United States.

8

Evolution of the CW Prohibition Regime Assessing Achievements and Weaknesses

Introduction The chemical weapons (CW) prohibition regime revolves around the CWC, which was negotiated over a period of more than twenty years, was opened for signature in January 1993, and entered into force on 29 April 1997. The CWC is the first international treaty that bans a whole category of weapons under international verification. The CWC also provides in Article VIII for the creation of a dedicated international organization—the Organisation for the Prohibition of Chemical Weapons (OPCW)—for the verification of treaty implementation by States Parties to the regime. As outlined in chapter 1, earliest attempts to ban the use of toxic chemicals that still have a bearing on the contemporary prohibition regime date back to the mid- to late nineteenth and early twentieth centuries. Most important in this respect is the 1925 Geneva Protocol. After the horrors of CW use during World War I, it sought to put an end to the use of chemical weapons in warfare, but given the many reservations that were added by states to their ratification, it only amounted to a no-first-use agreement among States Parties. Many countries reserved the right to retaliate against first CW use by other states. The Geneva Protocol’s effectiveness was further limited by the absence of some important states among its members, such as the United States, which only ratified the Protocol in 1975; and by the use of CW during the 1930s, such as by Italy in Abyssinia, which remained unsanctioned by the

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international community (SIPRI 1971a, 58–71; Tucker 2007a, 21f., 29). When chemical and biological weapons arms control regained some momentum during the 1960s, a political decision was made to separate the two and place greater emphasis on concluding an agreement to ban biological weapons: the 1972 BWC. Its Article IX contains an obligation to negotiate a separate agreement on chemical weapons. However, due to the ups and downs of the Cold War years, which conditioned the chances for success in a number of arms control arenas, negotiations on the CWC took around two decades to complete (Bernauer 1993; Robinson 1998). In chapter 6 we have discussed the wider web of responses to the threat of the misuse of biology and chemistry for hostile purposes into which the CWC is embedded and in which it takes center stage among the regulatory instruments against chemical weapons. Given the broad scope of the CWC, it overlaps with some of the elements of the web of responses discussed above. This is certainly the case for CW-related dual-use export controls of the Australia Group. Similar to the situation in the BW prohibition regime, implementation of the CWC has witnessed the ritualistic exchanges of wellrehearsed positions of both critics of such export controls and its proponents (Kelle 2006b). While critics regard them as violating Article XI of the CWC, according to which implementation of the Convention shall not hamper economic development, proponents of export control maintain that they are an essential tool for the implementation of one of the basic obligations under the CWC, that is, not to transfer to anybody materials, technology, or knowhow that can be used in the production of chemical weapons. More generally, CWC articles X and XI comprise the assistance and cooperation provisions of the CW prohibition regime. While Article XI calls for the promotion of technological development and international trade, Article X provides for emergency assistance in the event of deliberate use of chemical weapons. The provision of assistance can take three forms. States Parties can, firstly, contribute to a voluntary fund for assistance; secondly, enter into an agreement with the OPCW concerning their provision of assistance, should the need arise; and, thirdly, declare the kind of assistance they are willing to provide to the OPCW. Since entry-into-force of the CWC, the OPCW Technical Secretariat has divided its international cooperation and assistance (ICA) activities under Articles X and XI into three categories: first, to provide and coordinate assistance and protection in the event that a state party falls victim to chemical weapons; second, to promote economic and



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technological development in the peaceful uses of chemistry and cooperation with other international organizations with related mandates; and, third, to support the national authorities of member states in their efforts to implement the Convention at the national level—including through the provision of legal assistance in the drafting of implementing legislation. While these issues and activities are important, in order to assess the main achievements and shortcomings of the CW prohibition regime, the following subsections will focus on the regime’s two core goals of disarmament and nonproliferation before discussing two cross-cutting issues that are affecting several areas of the evolving regime. These are, on the one hand, universality and national implementation and, on the other, scientific and technological developments of relevance to the Convention. The concluding section will summarize the arguments presented in relation to these four sets of issues and begin discussing ways to address the challenges identified. Chemical Weapons Disarmament General Provisions As the overarching aim of the CWC is to rid the world of chemical weapons, the destruction of all CW stockpiles as well as CW production facilities is one of the key goals contained in the Convention. In order to allow for the verification of these destruction activities, Article III, paragraph 1 (a) of the CWC requires CW possessor states to inter alia declare their CW stockpiles and provide a general plan for destruction. Similar provisions apply to CW production facilities. Articles IV and V, together with Parts IV (a) and V of the Verification Annex, deal comprehensively with the modalities to be followed by States Parties possessing either CW or CW production facilities (CWPFs). Chemical weapons stockpiles must be destroyed, and CWPFs must be either destroyed or converted to be used for activities not prohibited under the Convention. Importantly, Articles IV and V provide for on-site inspection and monitoring of all locations at which chemical weapons are stored or destroyed. According to Article IV, paragraph 6, CW must be destroyed within ten years of the entry-into-force (EIF) of the Convention — by 29 April 2007 — and this destruction must begin within two years of the Convention entering into force for a given state party. Destruction or conversion activities at CW production facilities must begin within one year of the Convention entering

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into force for a state party, and they must be completed within ten years. On the way toward the total destruction of all CW holdings, intermediate destruction targets are established in Part IV (a), paragraph 17 of the Verification Annex to be achieved three, five, and seven years after the CWC’s EIF. In case a state party is unable to meet either any of the intermediate destruction deadlines or the ten-year deadline for complete CW destruction, the Verification Annex in Part IV (a), paragraphs 20 to 23 and 24 to 28, respectively, spells out the procedures to be followed for deciding on an extension of the original CW destruction deadlines. In case of complete CW destruction, a maximum extension of up to five years — until April 2012 — can be granted by the OPCW Conference of States Parties. Working Toward the 2007 Destruction Deadline Four CWC States Parties — India, Russia, South Korea, and the United States — initially declared possession of CW stockpiles, which were stored at thirtythree facilities in the four countries (OPCW 2000a, 20). These countries have declared a total of approximately 70,000 metric tons of chemical agents and about 8.6 million munitions and containers (Mills 2001, 13). Of these 70,000 tons the Russian Federation had declared some 40,000 metric tons, the United States 28,575 metric tons, India around 1,000 metric tons, and South Korea around 600 metric tons. In 2003 the number of CW possessor states increased to five when Albania declared in April of that year that it had discovered some 16 tons of chemical warfare agents on its territory (Tompkins 2009). In early 2004 Libya acceded to the CWC and became the sixth CW possessor state when it declared possession of 23.62 tons of CW (Hart and Kyle 2006). Due to the late discovery of CW stocks in Albania and the late accession of Libya to the CWC, both states had to apply for an extension of the intermediate destruction deadlines as stipulated in the Verification Annex to the CWC. Such decisions to extend in principle the phase 1, 2, and 3 destruction deadlines were taken by the Conference of States Parties at its Ninth Session in late 2004 (OPCW 2004a, 2004b). Already well before these requests had to be dealt with, delays in starting its CW destruction process led the Russian Federation to miss the first intermediate deadline for destroying 1 percent of its highest-risk (Category 1) chemical weapons stocks three years after the CWC’s EIF (Kelle 2007b). In November 1999, as permitted under the Convention, Russia applied to extend the intermediate destruction deadline (OPCW 2000b, 11). The Russian government argued that although the construction of CW destruction



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facilities had been impeded by economic difficulties, it intended to meet the next intermediate destruction deadline of 29 April 2002, when 20 percent of the Category 1 chemical weapons had to be destroyed (Feakes 1999, 13). The Conference of the States Parties, in addition to retaining the ten-year deadline for destruction of the entire stockpile, requested the Russian Federation to submit a revised destruction plan as early as possible. Moscow fulfilled this request in October 2000 (Mills 2001, 9). In 2001, the Russian government reassessed its plan for the destruction of its chemical weapons stockpiles, which led to significant changes, intended in part to comply with conditions set down by the U.S. Congress for the reinstatement of U.S. contributions to the Russian destruction program. In addition, the plan expected completion of the destruction effort in 2012. The new plan was formally presented to the OPCW Executive Council in September 2001 and then, in November, Russia submitted the required request for an extension of both the intermediate and final deadlines for the destruction of its Category 1 chemical weapons. Under the plan, 1 percent was to be destroyed by 2003, 20 percent by 2007, 45 percent by 2009, and complete destruction will be achieved by 29 April 2012. The request for the extension of the 1 percent deadline was approved by the Conference of States Parties at its Seventh Session in November 2002, as was the in-principle extension of the 20 percent intermediate deadline (OPCW 2002). The revised phase 2 deadline was set for 29 April 2007 by the subsequent Eighth Session of the Conference of States Parties, which also agreed in principle to extend the 45 and 100 percent deadlines for destruction of the Russian CW stockpiles (OPCW 2003a). The date for the destruction of 45 percent of Russian CW stockpiles was set by the Eleventh Session of the Conference of States Parties for 31 December 2009 (OPCW 2006a). Extending the 2007 Destruction Deadline It had become clear in the meantime that not only the Russian Federation but also most other CW possessor states would not be able to meet the April 2007 deadline for the complete destruction of their CW stockpiles. In late 2006 the United States had destroyed somewhat in excess of 40 percent of its category 1 CW, India around 70 percent, South Korea more than 80 percent, and the Russian Federation around 16 percent. Destruction in Libya had not yet begun. These delays required the extension of the final destruction deadline for practically all CW possessor states. In the case of India, the extension granted calls for all CW stockpiles to be destroyed by 28 April 2009 (OPCW 2006b), for South Korea the CSP set the deadline at 31 December

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2008 (OPCW 2006c), and for both the Russian Federation and the United States the deadline has been set at the latest possible date allowed under the CWC, that is, 29 April 2012 (OPCW 2006d, 2006e). A similar decision was made for Libya, with the deadline set for completion of destruction of its CW arsenal at 31 December 2010. This decision of the Conference also specifies the intermediate deadlines for Libyan CW destruction for earlier in 2010 (OPCW 2006f). Practically all of these decisions require the CW possessor states to report every ninety days on the progress made in the destruction process, as well as the continued submission of annual plans of destruction and annual reports on the destruction activities on their territories. In the case of Albania, which in spring of 2007 had destroyed almost 40 percent of its category 1 CW stockpiles, no extension request had been put forward before the deadline stipulated in the CWC, that is, one year before the destruction target should have been reached. Completion of the Albanian destruction process was expected sometime in summer 2007. However, as it is the prerogative of the Conference of States Parties to decide on such requests and the next available Session of the Conference took place only at the end of 2007, such a request would have been overtaken by events, that is, the completion of CW destruction. Instead, Albania was found to be in technical noncompliance and was tasked by the Executive Council to redress the situation and report back to the Council. This happened in July 2007 when Albania as the first CWC state party completed destruction of its stockpile of chemical warfare agents (OPCW 2008a, 4). In July 2008 South Korea completed destruction of its CW stockpile (OPCW 2008b), which was followed by India in March 2009 (OPCW 2009a). By contrast, the Libyan destruction effort has been beset by technical difficulties in reloading and transporting its chemical warfare agents to the destruction facility (OPCW 2008b). The country had thus to apply for another extension of intermediate and final destruction deadlines, which were granted by the Conference of the States Parties (CSP) to the CWC at its Fourteenth Session in late 2009 (OPCW 2009b). Increasing Doubts over the 2012 Deadline Given the significance of the completion of CW destruction activities by the last possible deadline stipulated in the CWC, the Executive Council has been tasked by the Conference of States Parties at its Eleventh Session in December 2006 to conduct additional visits in two of the CW possessor states, that is,



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the Russian Federation and the United States. The CSP’s decision emphasized the obligation of those two CWC States Parties to complete the destruction of their category 1 CW stockpiles by 29 April 2012 at the latest. This follows similar reminders contained in the abovementioned decisions to extend the final destruction deadline for the United States and Russia to the specified date and has to be seen in the context of (1) statements by former highranking members of the U.S. government, according to which the destruction of U.S. CW stockpiles might only be two-thirds accomplished by 2012 and take several more years to be completed (Army Times 2006); and (2) the fact that the construction of some of the Russian CW destruction facilities is not making the progress that would be required to meet the 2012 deadline. In line with this assessment, the decision stresses the “need for States Parties to take measures to overcome the problems in their chemical weapons destruction programmes” (OPCW 2006g, 1). Since then progress has been made by both Russia and the United States in destroying their CW stockpiles. According to U.S. predictions in 2006, only 66 percent of the U.S. arsenal was expected to be destroyed by the end of April 2012. More recent estimates put that figure in the range of 90 percent. However, there still remain the difficulties of the destruction sites in Pueblo (CO) and Blue Grass (KY), which, even under optimistic projections, will not complete destruction of the last remaining U.S. CW stockpiles before 2016 (USA 2009). A similar completion date has been suggested by observers in relation to the Russian CW destruction program, where the destruction facilities at Pochep and Kizner are still to open and commence operation (Walker 2010). However, as the Director General of the OPCW’s Technical Secretariat has reported in his opening statements to both the Thirteenth and Fourteenth Sessions of the Conference of States Parties, all CW possessor states have increased levels of transparency of their destruction efforts and have hosted visits under the chairmanship of the Executive Council that were mandated by the CSP decisions to extend their destruction deadlines (OPCW 2008b, 2009a). The course of action agreed upon by the CSP thus sets out to accomplish three goals. First, it serves as an additional reminder to the United States and the Russian Federation of their obligation under the Convention to completely destroy their category 1 CW stockpiles by 29 April 2012. Second, it allows the OPCW’s Executive Council to closely monitor the progress made by these two states in their destruction efforts and thereby to ascertain that all possible efforts are being undertaken to meet the extended deadline. In

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such a scenario, and if the remaining time needed to complete the destruction process is measurable in months, not years, this decision and the resulting visits process might serve as the basis for the argument that both the United States and Russia have undertaken everything possible to meet the destruction deadline—which can be confirmed by the visits process established—but due to factors beyond their control have been unable to achieve the goal. In this case the state(s) of concern might be found to be in technical noncompliance with the provisions of the CWC—as was Albania in early 2007—and be tasked to redress the situation as quickly as possible. This would avoid undermining the wider validity of the Convention. Nonproliferation of Chemical Weapons Nonproliferation represents the second core goal of the CW prohibition regime. Although verification activities of the OPCW’s Technical Secretariat in the field of CW disarmament have taken up over three-quarters of the overall verification effort (both in terms of person days and money spent), verification of the absence of prohibited activities in the chemical industry of member states is equally important and will become even more so once CW destruction activities in member states will have been completed. Clearly, the CWC is not intended to stifle international trade or the development of the international chemical industry. Accordingly, in Article VI States Parties retain the right “to develop, produce, otherwise acquire, retain, transfer and use toxic chemicals and their precursors” for purposes not prohibited under the treaty. Generally, these are peaceful, non-chemical-weapon-related purposes, but they can also include some activities in the area of CW defense. States can pursue these kinds of activities within the parameters set by the Convention and the Verification Annex, which mandates declarations, data monitoring, and on-site verification of facilities in States Parties. In order to allow the OPCW Technical Secretariat to manage the verification activities with respect to the chemical industry, the CWC distinguishes between four different sets of chemicals and facilities dealing with these. The first three of these sets of chemicals are captured in the so-called Schedules that are contained in an Annex to the CWC. Schedule 1 chemicals pose a high risk to the Convention. Many have been developed, produced, stockpiled, or used as CW in the past and they have few if any peaceful uses. A chemical may also be listed in Schedule 1 if it is a final-stage



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precursor to another Schedule 1 chemical. These chemicals cannot be retained by States Parties except in small quantities for medical or defense research purposes. Schedule 2 chemicals pose a significant risk to the Convention either because they can be used themselves as chemical weapons or as a consequence of their role as precursors to Schedule 1 or 2 chemicals. Schedule 2 chemicals are also not produced commercially on a large scale. Finally, Schedule 3 chemicals are produced in large quantities commercially but pose a risk to the Convention due to their toxicity that makes them suitable as a CW or because of their role as precursors to either Schedule 1 or Schedule 2 chemicals. The detailed rules and procedures for putting into effect the CWC’s verification system related to facilities handling scheduled chemicals are contained in Parts VI to VIII of the CWC’s Verification Annex. Rules and procedures for the fourth category of chemicals that may pose a risk to the object and purpose of the convention, so-called discrete organic chemicals (DOCs) and the related “other chemical production facilities” (OCPFs), are detailed in Part IX of the VA. It is the verification of these OCPFs that has been a bone of contention among CWC States Parties during the past decade. By the end of 2007 seventy-eight States Parties had declared over 4,600 inspectable DOC-producing OCPFs. Of these facilities, 118 were inspected during 2007 (OPCW 2008a, 6ff.) and another 118 during 2008 (OPCW 2009c). This brought the overall number of OCPF inspections since entry-into-force of the CWC to approximately 720, or around 16 percent of inspectable facilities. Assuming the continuation of this rate of OCPF inspection activities, it would take the OPCW inspectors over thirty-three years to visit the remaining 3,900 facilities in this category. This is very problematic, as already before the first CWC Review Conference in 2003 from the point of view of the OPCW Technical Secretariat the OCPF inspections conducted had shown that there are . . . some [facilities] that are highly relevant to the object and purpose of the Convention. These facilities produce chemicals that are structurally related to Schedule 1 chemicals. Of particular relevance to the Convention are facilities that combine this kind of chemistry with production equipment and other hardware designed to provide flexibility and containment. (OPCW 2003b, 12)

The recognition of these new developments in the chemical industry lies at the heart of calls for an adaptation of the industry verification regime.

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However, that this assessment is not universally shared by States Parties became clear during the General Debate of the First Review Conference, when Pakistan demanded that an “[i]ncrease in emphasis on verification . . . of facilities producing relatively harmless discrete organic chemicals (DOCs) should not be at the expense of higher risk Schedule 1, 2 and 3 chemicals listed in the Annex to the CWC” (Pakistan 2003). In the Review Document that the Conference agreed on, the “need to ensure an adequate inspection frequency and intensity” for each category of Article VI facilities was confirmed. Proponents of expanded and more focused OCPF inspections could interpret this as allowing the redirection of industry inspection toward the group of OCPF that pose the greatest risk to the objects and purposes of the Convention. At the same time, this wording allowed those States Parties, like Pakistan—who see the CWC as containing a fixed risk-hierarchy with Schedule 1 chemicals and facilities topping this list and OCPFs being of a much lower concern—to claim victory. As a result, the debates about OCPF inspections continued and resurfaced during the Second CWC Review Conference in 2008. During the general debate, Cuba, on behalf of the Non-aligned Movement (NAM) and China, emphasized that the Convention clearly sets out the hierarchy of risks posed by different chemicals to its object and purpose. The verification regime under Article VI must therefore correspond to the hierarchy of risks inherent to the respective category of chemicals. Any shift in the distribution of inspections which is contrary to this hierarchy would signal a departure from the fundamental principles of the verification regime based on the Convention. (Cuba 2008, 4)

In other words, industry verification continues to be interpreted by the NAM and China as being based on a fixed definition of risks inherent in different types of chemicals and facilities. Given the disproportionately large numbers of OCPFs declared by China (1,400-plus) and India (500-plus), this position does not come as a surprise. The U.S. statement in contrast stressed the need to improve our approach to Other Chemical Production Facilities (OCPF), both by increasing the percentage of facilities that are inspected annually and by improving identification of the specific facilities that should be inspected. Some of these facilities incorporate technologies and features that are highly relevant to the Convention. . . . We believe that this Review Conference should request the Director-General to study and report on ways



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to focus declarations of the OCPF category . . . in order to focus our effort on facilities that are relevant. (USA 2008)

This call for focusing OCPF inspections on those facilities has been supported by a detailed Swiss national paper submitted to the Review Conference. In it, the case for a detailed risk assessment of OCPFs is made and a weighting mechanism for those facilities that pose the highest risk to the object and purpose of the CWC is introduced. Accordingly, multipurpose batch plants that produce unscheduled discrete organic chemicals containing the elements phosphorus, sulfur, or fluorine—so-called PSF chemicals—in excess of 200 tons annually pose the highest risk (Switzerland 2008, 15). In more general terms the Swiss paper concludes that “[t]he risk assessment of a plant site/facility consists not only of the assessment of the chemicals, but includes the process, as well as the engineering characteristics of a plant site/facility.” It continues that “[a] risk assessment which includes all three factors does not necessarily reflect the hierarchy of the Schedules, but identifies the plant sites/facilities of real relevance to the objective and purpose of the Convention” (ibid., 18). Given these widely diverging views as to the inspection modalities for OCPFs, it does not come as a surprise that the final document of the Second Review Conference contains only a very general comment on the effectiveness and efficiency gains still achievable in the context of Article VI inspections in general—without explicitly mentioning OCPF inspections—and the continued need for “early resumption of consultations on the OCPF site selection methodology with a view to reaching a decision by States Parties, in accordance with Part IX, paragraphs 11 and 25, of the Verification Annex to the Convention” (OPCW 2008c, 16). Universality and National Implementation CWC Universality Ridding the world of chemical weapons—by destroying CW arsenals and maintaining a CW-free world after comprehensive CW destruction has been achieved through implementation of the nonproliferation measures contained in the CWC—obviously depends on achieving a large membership of states with declared CW stockpiles, a CW-capable chemical infrastructure, or both. Against this background the drafters of the CWC decided that for the operation of the CW prohibition regime to be viable, at least sixty-five ratifications were required for the CWC’s entry-into-force. As a matter of

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fact, when the treaty became operational on 29 April 1997, there were already 87 states participating in the inaugural meeting of States Parties. Although this number grew to 151 by the time of the First CWC Review Conference in April 2003, member states decided that an action plan was required in order to speed up the process toward universality of the CW prohibition regime, thus drawing the then 25 signatory states, which had still to ratify the CWC, and, possibly, the 18 nonsignatories closer to the regime. As the Director General pointed out, it is especially the latter category of states that has been the target of the call for renewed efforts at universality: A number of States whose non-accession to the Convention is causing serious concern, however, remain outside its purview. Their CW capabilities remain undeclared and unverified, and are not eliminated under international verification. The international community should send a strong message to these States not party, stressing the need for [ . . . ] universal adherence to the Convention. (OPCW 2003c)

The Executive Council adopted an action plan for the universality of the CWC during its twenty-third meeting in October 2003, which requested the Technical Secretariat inter alia to report annually on progress made in this respect (OPCW 2004a). Beyond the mere reporting of up-to-date membership figures, the Technical Secretariat (TS) and several CWC States Parties have been involved in numerous outreach and technical assistance activities that led to a substantial increase in the number of member states in the years between the first and second Review Conferences. However, already in 2007 one could observe a much slower rate of increases in ratifications or accessions. This trend continued in 2008 and 2009 as well; 2010 has been the first year with a zero growth in membership since initiation of the action plan. Table 8.1 below provides an overview of the development of CWC membership since initiation of the action plan in 2003. At the time of writing there had not been a single new member for 2012. Eight states were remaining outside the regime—the two signatory states Israel and Myanmar, and the six nonsignatories Angola, Egypt, North Korea, Somalia, South Sudan, and Syria. Of these eight, there seems some possibility for drawing Myanmar, South Sudan, and Angola into the regime and in the case of Myanmar, there have been concrete indications that CWC ratification might be under way (Tint 2010) and may occur in the wake of recent general political developments in this country.



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TABLE 8.1. CWC universality and increase in

membership 2003–2011 Increase in membership

Total number of States Parties

April 2003 (First Review Conference)

—

151

End of 2003

7

158

End of 2004

9

167

End of 2005

8

175

End of 2006

6

181

End of 2007

2

183

End of 2008

2

185

End of 2009

3

188

End of 2010

0

188

End of 2011

0

188

Cutoff date

source: www.opcw.org (accessed 13 April 2012).

The underlying problems in relation to the remaining five states becoming members of the CW prohibition regime, although quite different from one another, are nevertheless very similar in that they clearly go beyond the scope of the CWC and its implementation. In the case of Somalia the basic difficulty lies in the impossibility to deal with a failed state that has had no viable state institutions for almost two decades and has been ravaged by a clan-driven civil war since the early 1990s (Blair 2008; Halden 2008). Even if a document of accession could be obtained from some political entity nominally in charge of government business, implementation of CWC provisions would be practically impossible given the lack of political authority and security across Somali territory. Although in terms of government control over state affairs the situation in North Korea is almost the opposite from that in Somalia, that is, excessive control exercised by North Korean authorities, the resulting lack of transparency and communication poses similar problems to OCPW efforts to engage the country with a view to facilitate its accession to the CW prohibition regime. Given the secretive nature of the North Korean political system and the absence of any authoritative statements by its leadership, any

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estimates of the country’s CW arsenal are highly speculative and impossible to independently verify. However, as the London-based International Institute for Strategic Studies (IISS) summarized in 2004: [S]ince the early 1990s, official US, Russian and South Korean government publications have all described North Korea as having an active chemical weapons (CW) programme that has gone beyond research and development and includes the actual production and stockpiling of chemical weapons. . . . Recent South Korean government reports estimate a range of between 2,500–5,000 tonnes. (IISS 2004, 49)

Regardless of the actual size of the North Korean CW stockpile, assuming the country’s eventual accession to the CWC, it will represent one of the cases for which the OPCW must maintain some CW-related knowhow and inspection skills once destruction of the current CW possessors’ arsenals will have been completed. The same may be the case for the other three remaining holdouts in the Middle East: Israel, Egypt, and Syria. Again, one of the main characteristics of the suspected CW programs is their opacity. However, suspicions and accusations over CW possession, and linkages to other forms of so-called weapons of mass destruction, have been dominating the discourse on making the region free of chemical weapons (Barak 2007). What clearly unites the remaining handful of holdouts discussed in this section are the required broader political developments to facilitate accession to the CW prohibition regime. These range from state-building in the case of Somalia to wider geopolitical considerations in the Middle East, and they go well beyond both scope of the CWC and mandate of the OPCW. Thus, continuation of the activities under the action plan is likely to be of limited utility in the “hard cases” just discussed and new “outside the box” thinking is required. One such “outside the box” impetus for achieving universality in the Middle East may be coming from the 2012 conference on a zone free of weapons of mass destruction. This conference has been agreed on as part of a package deal at the 2010 Review Conference of the Nuclear Non-proliferation Treaty (NPT). As part of the preparations for this conference, the OPCW has been requested to provide “background documentation . . . taking into account work previously undertaken and experience gained” (United Nations 2010, 30). National Implementation Most international agreements are not self-executing and thus membership in an international organization or treaty regime can only serve as a first



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indicator of the success in realizing a regime’s goals. What is also required is the internalization of the treaty provisions into the domestic sphere of its member states. With respect to the CW prohibition regime, the most relevant national measures are contained in Article VII of the Convention: each state party must ensure that nobody on its territory or anywhere under its jurisdiction is undertaking any of the activities prohibited by the CWC to States Parties. In addition, each state party must establish a National Authority to allow for effective and efficient communication with the OPCW and “shall inform the Organization of the legislative and administrative measures taken to implement this Convention” (Article VII [5]). Issues surrounding the implementation (or rather, the lack thereof) of the Convention’s key provisions, most notably the requirement to enact implementing legislation on the national level, have attracted increasing attention. Writing in 2004 Tabassi and Spence pointed out that [i]n the seven years since the CWC entered into force, the CWC’s policymaking organs have moved from benign lack of interest in CWC national implementing legislation to being fully engaged with the issue. (Tabassi and Spence 2004, 45)

A major step to build upon and enhance these initial Article VII activities was the adoption of the OPCW Action Plan on National Implementation. As in the case of the above-mentioned Action Plan on Universality, the First Review Conference served as the catalyst in relation to Article VII implementation as well. The Article VII action plan was adopted by the CSP at its eighth session in October 2003 (OPCW 2003c) and foresaw several measures that aimed to “incorporate the CWC’s prohibitions into the legal frameworks of its states parties” (Feakes 2007, 110). Initially scheduled to focus state and OPCW action in this area for a two-year period, the Action Plan optimistically called upon OPCW States Parties to accomplish: [T]he enactment of the necessary legislation, including penal legislation, and/ or the adoption of administrative measures to implement the Convention no later than the Tenth Session of the Conference of the States Parties, scheduled for November 2005. (OPCW 2003c, paragraph 11)

The action plan on national implementation also foresaw the regular reporting by the Technical Secretariat to both the Executive Council and Conference of States Parties on the progress achieved in relation to Article VII

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TABLE 8.2. Implementation of CWC Article VII Cutoff date

No. of States Parties

National authorities

Article VII (5) submission received

Legislation covering all key areas

2003

154

126 (82%)

94 (61%)

51 (33%)

2006

181

172 (95%)

112 (62%)

72 (40%)

2008

184

177 (96%)

126 (62%)

82 (45%)

19/08/2009

188

181 (96%)

128 (68%)

86 (46%)

30/07/2010

188

185 (98%)

135 (72%)

87 (46%)

source: OPCW 2009d, 7; OPCW 2010b, 3; OPCW 2010c, 2.

implementation. As the latest available reports show, there are still substantial gaps in the implementation record of a majority of OPCW States Parties, most importantly with respect to the comprehensive nature of the Article VII (5) data on national legislative measures. Table 8.2 below provides an overview of the situation with respect to Article VII implementation as of 30 July 2010 (OPCW 2009d, 2010b, 2010c). As these figures show, there are still seven States Parties who have not established or nominated their national authority for CWC implementation. Equally important, only 87 of 188 States Parties have enacted key national legislation to implement all the crucial provisions of the CW prohibition regime on their territory. This leaves the domestic coverage of key obligations undertaken by States Parties a goal still to be achieved by more than a hundred of them. Not surprisingly in light of the decreasing rate of improvements in national implementation, the Fourteenth Session of the CSP in late 2009 decided to extend once more many of the activities originally agreed upon in the 2003 action plan and also managed to put the assistance and reporting activities of the Technical Secretariat on a more permanent basis that does not necessarily require an annual decision of the Conference to this effect (OPCW 2009e). Scientific and Technological Developments Scientific and technological (S&T) developments of relevance to the object and purpose of the CWC can be addressed by both an organizational structure and procedures to address such S&T advances. In terms of procedures to deal with S&T issues the CWC is somewhat vague, and in Article VIII, paragraph 22 of the CWC merely stipulates that the CWC Review Conferences are to review such developments. It states that



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[t]he Conference shall no later than one year after the expiry of the fifth and the tenth year after entry into force of this Convention, and at such other times within that time as may be decided upon, convene in special sessions to undertake reviews of the operation of this Convention. Such reviews shall take into account any relevant scientific and technological developments . At intervals of five years thereafter, unless otherwise decided upon, further sessions of the Conference shall be convened with the same objective [emphasis added].

The CWC in Article VIII, paragraph 21 (h) also establishes a Scientific Advisory Board (SAB) so as to enable the Director General of the OPCW’s Technical Secretariat “to render specialized advice in areas of science and technology relevant to this Convention, to the Conference, the Executive Council, or States Parties.” Experts are appointed to the SAB mainly on the basis of their expertise and reputation, and only then to achieve an equitable geographical distribution. As one of the very few studies on the SAB has noted, the idea of establishing such an advisory body was first proposed by France during the negotiations for the CWC (Lawand 1998). Its author correctly pointed out that “it is precisely this ambiguity of science that makes the independence of a scientific advisory body, acting at arms’ length from governments and the political organs of international institutions, all the more critical” (ibid., 1). Since CWC entry-into-force the activities of the SAB have developed as low-key events with initially annual meetings being held at the seat of the OPCW and some temporary SAB working groups meeting additionally to discuss specific technical matters of relevance to implementing the CWC. Such temporary working groups have been addressing questions relating to inspection equipment and verification methodologies, or chemical weapons destruction technologies (OPCW 1998), or, more recently, issues related to sampling and analysis during on-site inspections (OPCW 2007a) or the relevance for the CWC of developments in nanotechnology (OPCW 2009f). Activities of the SAB have been lifted from their relative obscurity only in the run-up to the two Review Conferences on the CWC’s operation in 2003 and 2008, respectively. It has been during these two events, but not the regular meeting of the Conference of States Parties, that member states have addressed S&T developments of relevance to the CWC. But even then the attention that S&T issues received, both by organs of the OPCW, such as the SAB, and by NGOs were only widespread in the preparatory phase of the Review Conferences. The SAB, for example, liaised with the International

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Union of Pure and Applied Chemistry (IUPAC), which held a workshop and produced a technical report on S&T issues of relevance to the CWC (Parshall et al. 2002). This report was subsequently discussed by the SAB, which produced its own report, which in turn was then submitted by the OPCW’s Director General to the Review Conference (OPCW 2003d). With the opening of the First Review Conference, however, the S&T issues identified by IUPAC and SAB were fed into a number of different aspects of reviewing the CWC’s operation instead of being treated as a set of issues in their own right (Kelle 2003b). However, S&T issues—more specifically the SAB Report as submitted to the Conference by the Director General—resurfaced in the Review Document both in the sections on general verification provisions and on activities not prohibited under the CWC. In paragraph 7.30, for example, the Review Conference “requested the Council, assisted by the Secretariat and members of the SAB, as appropriate, to study these recommendations and observations with a view to preparing recommendations to the Conference on them” (OPCW 2003e, 9). With a view to improving the work of the SAB, the Director General pointed out that “improvements can be made by providing for more interaction and feedback between the SAB and member states” (OPCW 2003b, 20). However, one state party, Pakistan, in this context cautioned that “technical bodies, such as the Scientific Advisory Board, in which developing countries lack adequate trained participation, should not attempt to suggest lines of action which would have the effect of amending the provisions of the Convention” (Pakistan 2003). In the run-up to the second CWC Review Conference in 2008, the pattern of interaction between the SAB and IUPAC repeated itself with IUPAC holding a meeting in Zagreb in April 2007, which led to another IUPAC Technical Report being published (Balali-Mood et al. 2008). This report in turn was utilized by the SAB for its own report that was submitted by the Director General of the OPCW’s Secretariat to the Conference (OPCW 2008d). As remarked in the SAB report of its tenth session, the IUPAC workshop reached “two high-level conclusions”: that, with respect to advances in science, there was an increasing convergence between chemistry and biology; and that, with respect to technological advances, there was an increasing shift of chemical production towards what are known as non-traditional chemical-producing countries. (OPCW 2007b, 3)



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In addition to the involvement of IUPAC, participation of the NGO community was even broader than it had been in the run-up to the first CWC Review Conference. Many NGOs followed the call of the chairman of the Open-Ended Working Group (OEWG) and submitted papers on different aspects of CWC implementation, including S&T issues (Kelle 2007c). Statements on S&T issues have been inserted into the final document of the Second Review Conference in a number of different places. Among them is the recognition that the scope of the CWC’s prohibitions extends to recent S&T developments, that such developments have an impact on the industry verification regime (see above), and that staff of the OPCW’s Technical Secretariat needs to keep abreast of S&T developments of relevance to the treaty’s implementation (OPCW 2008c). The Review Conference also agreed to support the work of the SAB with increased funds so that two annual meetings plus two meetings of temporary working groups can be financed from the regular OPCW budget. Furthermore, the Review Conference took note of the SAB report as submitted by the Director General and “requested the [Executive] Council to consider these issues” (OPCW 2008c, 15). To this end a meeting of governmental experts was convened in February 2009 to consider the SAB report and the recommendations contained therein, as well as to “prepare a report for submission to the Council” (OPCW 2008e, 1). Given the diverging political assessments in this area and sometimes contradictory views among States Parties on how best to address S&T developments—such as the issue of OCPF inspections mentioned above— it was unlikely that this governmental experts meeting would lead to a breakthrough in relation to any of the issues discussed in the SAB report submitted by the Director General to the Second Review Conference. While the general tone of the report is appreciative of the work and recommendations of the SAB, some issues such as the above-mentioned OCPF inspections were effectively removed from the purview of the SAB by the experts meeting by reference to the political discussions on the question that had taken place during the Review Conference and discussions since then in the OPCW’s policymaking organs (OPCW 2009g). Among the issues identified by the experts meeting for further work are, first, issues that should be kept under SAB review, such as the discovery of new chemicals; advances in drug delivery; and “developments in the chemical industry, including new manufacturing technologies, and related verification issues” (OPCW 2009g, 10). Secondly, the governmental experts identified issues where

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additional advice and information from the SAB was regarded as helpful, such as the convergence of chemistry and biology or the analysis of toxins. Not completely unexpectedly, given the composition of the experts group, a third category of issues that should be reviewed by the Technical Secretariat includes the creation of opportunities for the more developmental aspects of the CWC’s provisions, such as in the fields of international cooperation and assistance and protection. What both this last point and the above-mentioned point dealing with the question of OCPF inspections demonstrate is that care needs to be taken that the independence of the scientific advice rendered by the SAB will not be compromised by having its recommendations filtered through such an ad hoc body of governmental experts that are not selected on the basis of their expertise but on government affiliation. This selection criterion clearly lends itself to the politicization of the SAB’s work. This would be limiting this body’s usefulness, for as Lawand has rightly pointed out more than a decade ago: Past experience shows that it is clearly to the advantage of an international organisation to have a scientific advisory body which is as de-politicised as possible, and at a minimum this requires, firstly, a membership composed of persons acting in a personal capacity [ . . . ] and secondly, a functional structure which shields the body and its members from the influence of the international organisation’s political organs and its member States. (Lawand 1998, 5)

Although different organizational arrangements are being implemented in other contexts, such as UNESCO’s operation of two international bioethics committees—one nongovernmental, the other intergovernmental (Rhodes and Dando 2007)—the SAB’s functional structure and operational practice are following the principles summarized by Lawand above. As there is no clear-cut division of labor and competences, activities such as the convening of the governmental expert group and especially its formulation of issues for the SAB to address in its future work can potentially undermine its depoliticized position, which it derives from being appointed by and answerable to the Director General of the OPCW’s Technical Secretariat. Summary and Conclusions In summary, as the preceding pages have shown, the CW prohibition regime is clearly much further developed than the one on BW. This applies across



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the different dimensions of regime implementation discussed. However, both achievements and weaknesses in treaty implementation have been identified in all of these areas. In the field of disarmament the majority of declared CW stockpiles have been verifiably destroyed by CW possessor states. Three of the seven declared CW possessors are free of chemical weapons. However, as analyzed above, none of them was able to accomplish this goal in the initially foreseen time period, and for both Russia and the United States it is increasingly unlikely that they will manage by 29 April 2012, the extended date the legal treaty regime of the CWCV specifies. Thus, what is needed is a political solution that manages to both hold the two largest CW possessor states to their commitments undertaken, and at the same time does not lead CWC States Parties into the trap of declaring the disarmament dimension of the regime a failure. The currently conducted additional visits under Executive Council leadership are pointing in the direction of a possible solution to this quandary. In addition, as the OPCW Advisory Panel on the Future Priorities of the OPCW has pointed out, the “Technical Secretariat must retain the competence and resources needed to provide the necessary verification” (OPCW 2011, 7). Another fundamental question in relation to CW disarmament is related to the broader issue of reorienting the work of the OPCW once CW destruction will have been completed. Already, the jockeying for position has gotten under way with some arguing that all “pillars” of the CWC, including nonproliferation, international cooperation, and assistance and protection, need to be equally strengthened in this reorientation once the resources that are now being spent on the verification of CW destruction will become available. Others, who regard the CW prohibition regime more in security than development terms, tend to emphasize the nonproliferation dimension over the other two. In any event, this will require a broad-ranging and transparent dialogue of all interested States Parties and should also involve additional stakeholders. Again, the OPCW Advisory Panel has provided some useful hints in this respect. In the area of nonproliferation one of the biggest challenges remains the adaptation of the OCPF inspection regime, which is still operating on a provisional basis and at the current inspection rate will require over thirty years to complete the inspection of all OCPF facilities at least once. Here the focusing of inspections to the most relevant facilities, that is, those with the highest potential for being misused by states for the production of chemical

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warfare agents, needs to be combined with an increase in annual inspection numbers up to the maximum allowed under the terms of the CWC. The main obstacle to overcome in this respect is best exemplified by the mantra-like, and erroneous, statements of some NAM-states according to which the CWC contains a strict hierarchy of risks with OCPF facilities representing the lowest one. Here, scientifically backed explanations of the actual risk presented by individual facilities combined with some political pressure will be needed to convince those opposed to adequate verification of OPCW facilities that represent a real danger to the object and purpose of the Convention. As the discussion on universality of the CW prohibition regime has revealed, there are likely to be five hard cases of states that will not ratify or accede to the CWC unless major political changes occur that go well beyond the scope of the regime. This has led some to raise the “uncomfortable questions” about whether “CWC universality [is] really achievable” and, if not, what the consequences of an “NPT-like stage, with countries such as North Korea and a few in the Middle East” remaining outside the regime would be (Wilson 2007, 168f.). Although such a scenario would prevent the CW prohibition regime to be declared truly global in scope and 100 percent effective in achieving its aims, as in the case of the destruction deadlines discussed above it would only be a partial setback that could still be reversed. For such a reversal to occur, at a minimum the OPCW and its member states would have to continue the efforts already begun to engage the holdout states and thus achieve universality. As the efforts to entice those states into the regime on normative grounds are not likely to be successful, additional, wider political initiatives at “convincing” them of the utility of joining the CW prohibition regime need to be developed. However, such initiatives are likely to carry costs for those pursuing such a policy: it is therefore a cost-benefit calculation both for the regime members and for the handful of states at the receiving end of such policies. For regime members, the cost-benefit calculus can only be expected to tilt toward a more costly policy, such as by suffering from lost trade due to export restrictions vis-à-vis one or more of the holdout states, when there is a clear perception that the increase in insecurity (by not having a truly global regime) outweighs the cost involved in changing the holdouts’ cost-benefit calculation. Once that tipping point is reached for regime members, a decision will need to be made as to the most appropriate tools from the web of responses discussed in chapter 6 to actively pursue the ratification/accession of the last holdouts to the regime.



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National implementation of CWC obligations can be expected to be one of the factors influencing the understanding reached by regime members in this respect. Only with most, if not all, loopholes within the regime closed and States Parties fully implementing the CWC domestically should we expect to see a willingness emerge to tackle the hard cases of nonadherence head-on. Until full implementation is achieved—and based on the above discussion of some of the issues to be overcome in terms of national implementation, this is still to be attained some time in the future—improving the qualitative dimension of CWC adherence will carry a smaller pricetag than pressing the last remaining holdouts to join the regime. Such qualitative improvements can also be achieved in the area of scientific and technological developments, where more could be made of the expertise of the SAB without running the risk of undermining its unpolitical character. Increasing the frequency of its meetings will only serve to improve the way in which its member states can address risks to the object and purpose of the regime emanating from such S&T developments, when at least part of the SAB’s activities are more forward-looking and less focused on the minutiae of treaty implementation. Such a more systematic monitoring of S&T developments could also be complemented by the establishment of a dedicated unit or a Science Adviser for this purpose within the OPCW Technical Secretariat (OPCW 2011, 19). While some such forward-looking issues have been identified in the areas of the convergence of chemistry and biology, others, such as an S&T-based solution to the OCPF inspection issue or the question of toxic incapacitants, have been removed from the purview of the SAB and either subjected to the play of political forces among member states (OCPF) or not addressed at all, due to the political sensitivities of some regime members (incapacitants). However, in order to future-proof the CW prohibition regime, it is essential to subject all S&T issues of relevance to the CWC to the scrutiny of the SAB or a new S&T unit within the Secretariat, not only a politically opportune subset thereof.

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Introduction In late 2010 James F. Hoge Jr. completed eighteen years of editing Foreign Affairs with a special issue titled The World Ahead (Hoge 2010a). In addition to a set of essays, the edition contained a section of book reviews introduced by an essay written by Richard Betts that was intended to set the stage for the forward-looking review “by looking backwards at three seminal books that defined in different ways the post–Cold War era” (Betts 2010). These books were Francis Fukuyama’s The End of History and the Last Man, Samuel Huntington’s The Clash of Civilizations and the Remaking of the World Order, and John Mearsheimer’s The Tragedy of Great Power Politics. Betts’s review was titled “Conflict or Cooperation? Three Visions Revisited.” He argued that in the interval between the end of the Cold War and 9/11 many people understood that they were in a time of change and wondered rather more consciously than normally about how the world worked. He suggests that the three authors he chose for his review stood out in presenting “a bold and sweeping vision that struck a chord with certain readers” (ibid., 187). And while none of the three won the argument, [e]ach outlines a course towards peace and stability if statesmen make the right choices—but none offers any confidence that the wrong choices will be avoided. (Ibid.)

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when one peels away the top layers of the three arguments and gets down to the conditions the three authors set for their forecasts, it turns out that they all point in a remarkably similar—and pessimistic—direction ” [emphasis added].

Fukuyama, on Betts’s reading, is not convinced that people will be content to be equal and that strivings for superiority will reignite violence. Mearsheimer may not be alarmed by the rise of China and the development of a new bipolar system, but hegemonic transitions, many scholars have argued, are rarely peaceful. And Huntington’s prescription for the West to make a clear choice of concentrating on its own problems and allowing others to develop as they wish seems an unlikely outcome. Not surprisingly, against that kind of background, Hoge wrote, as editor to the issue: Today, unlike 20 years ago, there is widespread recognition of a long list of simmering conflicts, unsettling trends, and mounting global problems. (Hoge 2010b, i)

As Betts pointed out in his review, there are certainly darker visions of our future in which, for example, scientific advances in biotechnology and weapons of mass destruction could “trigger apocalyptic results,” but what surely is clear is that a stable peace is unlikely to come about soon. We probably face decades of conflict, terrorism, and wars. Against this background it is imperative to prevent a resurgence of interest in developing new and/or using known chemical and biological warfare agents in the evolving, but still conflict-ridden, international system. In this book we have therefore sought to examine how pressures from three kinds of developments can best be prevented from being applied to new generations of chemical and biological weapons or the utilization of existing ones, so as to prevent a biochemical arms race from occurring. Based on the analysis in chapter 2, we have come to conclude that the nature of warfare is changing and that “wars amongst the people” remain a much more likely characteristic of coming decades rather than the largescale force-on-force clashes that characterized the wars of the twentieth century. However, it is not necessary to accept that argument to see that some of the wars of coming decades will be amongst the people and that they will give reason for some participants to reconsider the utility of chemical and biological weapons. This applies not only to “rogue” states

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striving for regional hegemony or facing a conventionally superior Western intervention force but also to states forming part of such a coalition of the willing, and to actors in a new war situation more generally when toxic industrial chemicals or CW precursors are available in the context of diminished or absent state authority. The latter is comparatively less serious than the first two scenarios, as it is less likely to spur an offense-defense arms competition. Furthermore, it cannot possibly be argued that the ongoing advances in science and technology are likely to favor the defense for many decades to come. Quite to the contrary, as chapter 3 has shown, advances in systems biology will provide an increasingly better understanding of complex biological systems, in the process revealing possible targets to attack and ways to attack them. Synthetic biology does already allow the resurrection of extinct viruses and will most likely enable rogue actors to construct novel pathogens from scratch. Adding to this, advances in the delivery of biological agents and the problems of rapidly finding means of safe defense (Bender 2011) must favor the offense if an offense/defense arms race is allowed to break out.

Policy Proposals It is against that background of the probability of continuing conflict and armed violence—in our opinion characteristically as “war amongst the people” and associated substate violence in areas of diminished or absent state authority—that proposals for minimizing the application of the modern life sciences to new forms of warfare and terrorism have to be considered. We have divided our discussion into three main sections dealing with biodefense, the BWC, and the CWC. Finally, we have to consider how, in the longer term, new CB weaponry might be dealt with by better coordination between the BWC and the CWC. So the policy questions of importance are: 1. How can reasonable biodefense be made less likely to be misperceived and avoid triggering an offense-defense arms dynamic? 2. How can the CWC and BWC regimes be strengthened—particularly to cope with the extremely rapid developments in relevant science and technology? 3. How can the political-psychological gap between CWC and BWC be closed with respect to mid-spectrum agents?



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4. What are the options for strengthening the wider web of responses to the dangers outlined in this book?

Biodefense Transparency It is becoming ever clearer that there are, in fact, no easy technical solutions to biodefense (Bender 2011). Yet it is also to be expected that states will continue to invest in biodefense and in doing so will risk their efforts being misperceived by other states if they are not zealous in trying to ensure this does not happen. The exposure of projects like Clear Vision—replication of a Soviet BW bomblet—as part of the U.S. biodefense program at the turn of the millennium, when the future of the BWC was in doubt, can hardly have increased confidence in compliance (Miller, Engelberg and Broad 2001b). Yet biodefense necessarily will involve activities that could be misperceived, as they are addressing potential threats in a way that lacks full transparency. The general problem of transparency in chemical and biological defense programs was considered at a meeting in Washington, D.C., in 2008 in which government and nongovernment experts discussed how Australia, Canada, Germany, the United Kingdom, and the United States went about ensuring compliance and transparency of their increasing biodefense activities. The summary of the discussion made clear, first, that the mechanisms in place to ensure compliance with the Convention varied, for example, in such aspects as their degree of formality; whether they assess individual projects, programs, or both; the primary locus for such assessment; and the degree to which independent oversight is exercised. (Center for Arms Control and Nonproliferation 2009, 16)

However, all were based on the assumption that “such activities can and sometimes do raise compliance concerns amongst outside observers, both at home and abroad” (ibid.). The discussion focused on two distinct issues: 1. how to develop oversight and review processes that can ensure that one’s own biodefense activities are and remain BWC compliant; and 2. whether and how compliance processes can be designed so as to gain external legitimacy and provide outside observers (other nations, civil society, the general public) with assurance of Treaty compliance. (Ibid.)

It is clear from the summary that both questions aroused differing viewpoints and that answers that are widely accepted will not be easily found. In

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regard to the second question, the summary notes that it is a “formidable challenge” and that it requires not just that a compliance review process be in place but also that the context—of the rule of law, for example—is also providing reassurance that the process is effectively implemented. On the first question, a range of different possibilities was examined but it was clear that even among these closely aligned states there was no consensus as to how best to proceed. Clearly, increasing transparency in biodefense is a problem that will not be rapidly solved, and while it may be possible to somewhat improve the annual BWC Confidence Building Measures in this regard (see the next section) this seems unlikely to provide a solution. Perhaps the best interim measure would be widespread replication of Canada’s Biological and Chemical Defence Review Committee (FBCDRC), which is mandated to review annually the research, development and training activities in biological and chemical defence (BCD) undertaken by the Department of National Defence (DND) to ensure that they are defensive in nature. (Biological and Chemical Defence Review Committee 2011, 1)

Its members are drawn from, for example, the Royal Society of Canada and the Canadian Federation of Biological Societies and it produces an annual report available on the Internet. Here, though the review process is internal to the State, it is not carried out by the organization that is doing the work or by other government agencies. Given this relative degree of independence of the assessment, replication of this process by all other BWC States Parties and posting annual reports in one of the official UN languages on an easily accessible Internet site—or submitting them to the ISU for posting on its website—would already constitute a substantial step forward in achieving a higher level of transparency in relation to biodefense activities. Strengthening the BWC Of course, the problem of the transparency of biodefense activities is but part of the core weakness of the BWC—the lack of any effective mechanism for assuring States Parties that other States are living up to their obligations under the Convention (Kelle, Nixdorff, and Dando 2010). However, in a statement to the BWC meeting in Geneva in December 2009, the United States made it very clear that, as one astute commentator put it, the United States was “seeking biosecurity without verification” (Tucker 2010). Given the continued opposition of the United States to developing an effective mechanism of verification,



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what can be done to strengthen the Convention by more modest means at the Seventh Review Conference in December 2011 and whatever Intersessional Process can be agreed on through to the Eighth Review Conference in 2016? As Littlewood noted in his consideration of why verification should not and will not be a major focus of the Seventh Review Conference: Incrementalism in the form of an intersessional work programme has however, reached the end of its useful life. Discussion on a discrete topic that seeks only to establish common understandings and promote effective action at the national level is no longer sufficient, something more substantive will be required for the BTWC after 2011. (Littlewood 2010, 15)

Littlewood, in fact, fears that differences over international cooperation (Article X) are more likely than verification to disrupt the Review Conference as there are numerous signs suggesting that differences over verification could be finessed. With this background, the question is: What positive progress can be made? In the hopeful absence of any major hostile use of chemical or biological agents, it has to be accepted that there will be little high-level political (or media) attention focused on the Review Conference to enable or encourage far-reaching change. Clearly, the first necessity is for a continuation of the Intersessional Process (ISP) to be agreed on for 2012–2015 but in a modified, more effective, form. This should surely include a requirement for analysis of the implications of advances in science and technology to become a regular annual agenda item and for the ISP to be able to make decisions—where there is a clear consensus—rather than having to wait for the next Review Conference to decide (Sims 2010a). Within that context it would then be possible to agree upon how ideas such as Canada’s accountability framework (Sims 2010b) and proposals for improved submission and discussions of the annual confidence-building measures (Lentzos 2010) could be regularly addressed. Should such agreement prove possible, then the much-needed modest expansion of the Implementation Support Unit should inevitably follow. So it is possible to imagine a positive outcome from the Seventh Review Conference of the BWC. This would include: · the continuation of annual meetings, redesigned to a more effective form; confidence in compliance being advanced through the introduction of the accountability framework, national reporting and improved CBMs, opening up an eventual reopening of the question of verification; and,

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· a resolution to the differences over Article X, building on the progress made on disease surveillance in the ISP and the United States’ emphasis on allowing “the BWC to make major contributions to building global capacity to combat infectious diseases” in its opening statement to the Conference on Disarmament in January 2011. (United States 2011)

However, that would be to ignore the concerns that this book has raised about the difficulties of dealing with the ongoing advances in the life and associated sciences. No one can read the background document on science and technology developments relevant to the Convention for the Sixth Review Conference without being aware of the scope and pace of technological change and the worldwide spread of countries where this change is occurring (United Nations 2006b). What may be far less obvious, as the Lemon-Relman Report of the U.S. National Academies emphasized, is the unpredictability of developments. Few, if any, specialists anticipated the phenomenon of interfering RNA, or that neurons had more than one chemical transmitter each, or that tens of new neuropeptides would be discovered since 1990. Moreover, it is almost impossible to envisage how a new scientific or technological development will interact with ongoing progress in other fields: consider, for example, how recent advances in functional brain imaging have impacted on other aspects of neuroscience such as neuropharmacology (Robbins 2011). So how might a reinvigorated ISP be able to handle the assessment of such changes and provide input to an annual meeting of States Parties? One possibility is that the preceding annual meeting would designate an area such as synthetic biology and ask a Meeting of Scientific and Technical Experts (MSTE) to consider the relevance of developments in that area and provide a report to the annual meeting (Dando and Pearson 2011). The meeting could be open to experts from all States Parties and to qualified representatives from civil society groups such as the National Academies. The meeting could also be tasked with considering the impact of advances on all relevant Articles of the Convention: that is, Article X, Article III, and Article V as well as compliance in Article I. Such a process would allow key issues to be explored and acted upon as necessary without affecting the role of the Review Conference to carry out its oversight of the scientific and technological developments. There is, of course, one obvious flaw in that scenario. Given the scope and pace of change, it will be necessary to incorporate a very wide range of scientific expertise in these assessments. However, very few of the practicing life scientists involved in those cutting-edge developments have



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any knowledge of the Convention or of the potential danger if the life sciences are deliberately applied in a major way for malign purposes. In order to correct this deficiency and obtain the breadth of in-depth knowledge needed, it is clear also that the Seventh Review Conference will need to take effective decisions to implement the sensible list of educational initiatives agreed on at the meeting of States Parties in 2008 (Whitby and Dando 2010). Without that element, a major lacuna will persist in the policies needed in coming decades to minimize the possible malign misuse of the life sciences. Strengthening the CWC In order to ensure the viability of the CWC and to not allow a CWC nonstate party or other “rogue” state to use the continued existence of small CW stockpiles in the United States and Russia as a pretext to trigger a negative CW arms dynamic, the complete destruction of remaining CW arsenals needs to be accomplished as quickly and safely as possible. While many acknowledge the positive impact of the confidence-building visits conducted by the OPCW Executive Council in ascertaining that these delays are not driven by the desire of either state to maintain a CW capability, it remains of crucial importance to complete CW destruction as close to the April 2012 deadline as possible. Along these lines the Advisory Panel on future priorities of the OPCW stressed that determined and relentless efforts needed to be made by the possessor States Parties to rectify the situation at the earliest possible date. (OPCW 2011, 8)

Another key task for strengthening the CWC is the management of a smooth transition from an era of OPCW activities with the focus on the verification of destruction activities to a new phase in the life of the organization for which the priorities of its activities still need to be determined. Deliberations with a view to establishing these priorities have been initiated by the OPCW Director General through the appointment of the above-mentioned Advisory Panel, but it remains to be seen whether the different priorities by member states that have manifested themselves in relation to issues as diverse as export controls, assistance measures, or the role of scientific advice for the implementation of the Convention can be fed into a transparent process of organizational change and bridged in a way so as to allow the organization to adapt to the changing political and S&T environment it has to operate in. A further priority area for maintaining the effectiveness of the CW prohibition regime and its ability to prevent the misuse of chemical facilities

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for offensive military purposes lies in the strengthening of the OPCW’s capabilities in the nonproliferation field. As discussed in chapter 8, the role of other chemical production facilities (OCPF) will be of crucial importance in this context, with some convincing to be done of those who erroneously maintain that the CWC contains a fixed hierarchy of risks. While some promising proposals—such as the one by Switzerland in 2008—have been put forward, there is still no political consensus discernible to substantially increase the number of OCPF inspections and increasingly focus them on those facilities that pose the greatest danger to the Convention. This overprotectiveness of so-perceived national commercial interests is supplemented by continued deficiencies in national implementation measures in a large number of CWC States Parties. Addressing these is crucial in enabling States Parties to comply with the obligations they have undertaken by signing up to the CWC and thus for enhancing confidence in compliance by other member states. In substantive terms, scientific and technological advances of relevance to the CW prohibition regime overlap to a large and growing extent with the issues addressed under the BWC heading above. One particularly relevant issue—related to so-called mid-spectrum agents—will be discussed separately below. In principle, the possibilities to address S&T issues are markedly different in the CWC context: with the Scientific Advisory Board (SAB) at the disposal of the Director General of the OPCW’s Technical Secretariat, the organizational context is a much stronger one. Given the recent increases in funding for SAB activities, if so instructed by the new Director General this expert body could assume a more active role in the forward-looking monitoring of S&T advances of relevance to the CWC. This would allow for a more regular review of such trends than the current review pattern that has been tied to the five-yearly review Conferences of the CWC. As in the BW context, the accelerating speed of S&T advances lets such long intervals between reviews appear more and more out of step with scientific and technological realities. Closing the Gap between the CWC and BWC: Addressing Mid-Spectrum Agents In legal terms, the international prohibition of the misuse of mid-spectrum agents is very explicit since both the BWC and the CWC cover these agents. In addition, mid-spectrum agents have come to be subject to export controls developed by the Australia Group (AG) of countries (and increasingly by



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many other countries following this lead). Writing in 2004, Robert Mathews, of the Australian Defence Science and Technology Organisation, reviewed the history of the group’s biological control system. As he pointed out: The most recent review has led to the addition of 14 biological agents (human pathogens) and 8 new toxins to the List of Biological Agents for Export Control , which raises the total number of human pathogens controlled to 51 (32 viruses, 4 rickettsiae and 15 bacteria), and the total number of toxins controlled to 19. (Mathews 2004, 2)

Unlike the situation in regard to chemical weapons, since less information was available about which pathogens and toxins were being sought by proliferators, a major reason for inclusion of a pathogen or toxin on the BW export control list was the judgment made by experts of its intrinsic risk. And, as Mathews also pointed out, adjustments to the BW lists have often been made on the basis of ongoing developments in biology and biotechnology. Yet, despite the existing international legal provisions, there is a politicalpsychological gap observable that is partially caused by the absence of verification measures in the BW prohibition regime. In addition, an expectation seems to have developed over time among participants in both of the regimes that the “sister regime” would somehow address this area of overlap. Given the large overlap of member states in both regimes, this expectation is all the more puzzling. However, one way in which the gap between the CWC and BWC in the area of mid-spectrum agents might be closed would be through improvements in verification or transparency measures for the BWC. But, as we have seen, any such developments—if there are indeed any—will not happen until agreement on new measures is reached at the 2011 Seventh Review Conference. Furthermore, if any such improvements are agreed on, they will only come into force after more detailed follow-on negotiations that will have to take place after the review. If the history of the 1990s is anything to go by, these negotiations could take many years. Therefore, if we want to see the gap in coverage of mid-spectrum agents being dealt with in the relatively near future it will have to come in developments in the operation of the Chemical Weapons Convention. The problem in regard to the CWC was set out very clearly by Jonathan Tucker in a wide-ranging article (Tucker 2007c), “Verifying the Chemical Weapons Ban: Missing Elements.” As he argues, the General Purpose

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Criterion of the CWC comprehensively bans all nonpeaceful purposes in the use of toxic chemicals but, as a practical matter, it was obviously not possible for the Organization for the Prohibition of Chemical Weapons (OPCW) to monitor all possible chemicals so those of most concern at the time of the negotiations were listed in agreed-upon schedules and the international monitoring system applied to the chemicals in these schedules. Even then, however, choices had to be made and, Tucker says, several types of chemicals such as the novichok family of binary nerve agents and other chemicals designed to penetrate gas masks were not included in the schedules, despite their known dangers. Also not included were long-lasting incapacitating and “calmative” agents, such as the anesthetic fentanyl and related compounds, which both the United States and Russia have developed under the CWC’s exemption for “law enforcement including domestic riot control”

and many toxins (toxic molecules produced by living organisms) and bioregulators (natural body chemicals that have potent effects on the nervous and immune systems). (Tucker 2007c, 8)

Only two such agents—the toxins ricin and saxitoxin—are included in Schedule 1 of the CWC and thus subjected to regular verification measures. Tucker suggests that the negotiators of the Convention tried to get around this problem by a number of different means. Most particularly, he notes that they agreed on “a provision for routine inspections of ‘other’ chemical production facilities” (Tucker 2007c). These OCPFs were defined in the Verification Annex to the Convention as plant sites that produce by synthesis more than 200 metric tons per year of discrete organic chemicals (DOCs) which are not listed in the schedules. This definition also encompasses one or more plants that manufacture more than 30 metric tons of an unscheduled DOC containing phosphorus, sulphur, or fluorine (PSF) which are common constituents of blister and nerve gases. (Tucker 2007c, 9)

It has to be understood here, as Robert Mathews wrote, that the term “Other Chemical Production Facilities” was agreed on as a “politically acceptable descriptor for ‘CW-capable facilities’” (2009, 5) and, of course, the ongoing



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revolution in the life sciences and its technological application is likely to increase the number of such facilities around the world. As Tucker argued in his paper, a seemingly straightforward way of dealing with the gap would be to increase such inspections still further as the OPCW’s task changes from monitoring the destruction of chemical weapons stocks to preventing proliferation. However, that may not be a simple matter as both he and Mathews note. One complication comes in the wording “production by synthesis.” Mathews, in reviewing the negotiation history, points out: Agreement could not be obtained on whether production should be limited to chemical synthesis or to also include biochemical reaction processes. Thus the term “production by synthesis” was devised because it could be interpreted either way. (Mathews 2009, 7)

With biochemical reaction processes being increasingly used by industry, agreement on this crucial point would be needed to move forward with a major increase in inspections to cover the gap between the two Conventions. In addition, it is not difficult to find informed commentators who raise numerous other questions about how OCPF facilities should be monitored (Männing 2008). Of course, that does not mean that the CWC-BWC (mid-spectrum agent) gap cannot be closed to a significant degree by further development of the OCPF verification regime, but in light of the above discussion it does mean that States Parties and civil society need to give considerably more attention to how this can be accomplished than they have done to date.

A Checklist on Progress to the Next Review Conferences The Biological Weapons Convention A first indicator for a successful Seventh Review Conference will be an article-by-article review and arrival at a consensus final declaration that will set out a constructive way forward for the strengthening of the BWC and its implementation by States Parties. In the period between the Seventh and Eighth Review Conferences to be convened in 2016 the following steps need to be taken:

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States Parties should decide upon and engage in a reinvigorated intersessional process (ISP). This can build upon practices established previously (such as the involvement of civil society organizations), but needs to be expanded to include some regular items on the agenda (such as a review of relevant science and technology) and the ability to take some decisions. Especially this last point requires urgent attention as past practice amounts to States Parties’ self-curtailment to being the masters of their own treaty regime. This has become somewhat of an oddity in comparison to the annual meetings of States Parties in the CWC or even the Comprehensive Test Ban Treaty Organisation context, where in the latter case, the underlying treaty has not even formally entered into force!

· States Parties should agree upon and support throughout the ISP a modest expansion of the ISU. Again, in light of support in different areas of BWC implementation that States Parties could derive from such an increased organizational unit, its nonexistence until a few years ago and small size up to now look somewhat out of place in relation to organizational structures available in the chemical or nuclear weapons’ sphere. Especially in light of the changing nature of warfare that could well lead to a resurgence of interest in biochemical weapons, BWC States Parties would be well advised to establish stronger organizational support in good time, before such trends materialize. ·

A continuing effort to improve transparency and confidence in compliance, for example, through the development of Confidence Building Measures (CBMs) and other forms of accountability. As verification measures along the lines of other prohibition and nonproliferation regimes are not likely to receive substantial support, improved CBMs and other, creative ways of demonstrating compliance will need to be employed in order to strengthen trust on a state’s compliance with the regime.

· Development of means of strengthening Article X, for example, through the ISU operating an Internet-based clearinghouse. · Much improved national implementation of the BWC in States Parties. A particular focus in this area should be a major initiative to improve the dual-use education of relevant scientists and engineers around the world. · Intensification of efforts to universalize the Convention and to have all reservations removed from the Geneva Protocol. · A major effort to help civil society to take a more informed interest in the Convention, particularly civil society in the developing world.



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The Chemical Weapons Convention A successful Third CWC Review Conference in 2013 will to a considerable degree depend on preparations for the transition from a so far mostly CW-disarmament-focused prohibition regime to one in which the nonproliferation dimension will play a much more crucial role in ensuring the continued effectiveness of the regime. Thus the top priority in the run-up to the 2013 Review Conference needs to be on a political solution to the issue of the United States and Russia not meeting the final CW destruction deadline of 29 April 2012. This needs to be complemented by an as inclusive as possible process of change management toward the OPCW’s post-CW-destruction phase of operations. It is unlikely that such a process can be completed before the review, but every effort should be made to prepare the ground in a way that will enable the Review Conference to make the necessary decisions that will not only ensure the OPCW’s and the regime’s survival but also adapt to the changing political, military, and S&T environments that we have analyzed earlier in this volume. In particular, preparations for the crucial April 2013 gathering of CWC States Parties have to enable the Review Conference to decide and take action with a view to the following: · Continuation of both verification and enhanced transparency measures in relation to continuing CW-destruction activities. · Arrival at a consensus on the shift to nonproliferation as the major focus of OPCW activities, without losing sight of the balance to be achieved in realizing goals related to international cooperation and assistance. ·

Intensification of efforts to achieve much higher levels of compliance with national implementation provisions of the CWC. Over time these should shift from a focus on key areas of legislation and implementation to a comprehensive coverage.

· Improved usage of a depoliticized Scientific Advisory Board, to address on a more regular basis forward-looking questions of S&T of relevance to the Convention. · Pursuing a public debate among all stakeholders and seeking to foster a consensus on so-called nonlethal CW, including linking up to the BWC in regard to mid-spectrum agents discussed above. · Inviting and enabling civil society involvement in the more effective implementation and adaptation of the CW prohibition regime to changed environmental conditions brought about by changes in the

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nature of warfare and S&T progress. Although the establishment of a CSO coalition in support of the CWC and the wider web marks an important first step, the limited funds available especially to CSOs from developing countries represents a serious limitation that CWC States Parties should seek to address individually or through appropriate international institutions.

Strengthening the Wider Web of Responses As with the efforts to increase the effectiveness of the CW and BW prohibition regimes, any measures to strengthen the wider web of responses would have to be pursued in the context of the changing threat environment, which is largely driven by the changing nature of warfare as well as the ongoing revolution in the life sciences. Practically all the elements of the web that we have discussed in chapter 6 have been prompted by changes in the threat environment, be they the establishment and continued existence of the Australia Group in response to the procurements activities of state proliferators, the setting up of the 1540 Committee as a reaction to the perceived threat of increased terrorist interest in CBW, or the “drafting” of public health infrastructures following the realization that responding to a CBW event would require a substantial reliance on said infrastructures. As the CBW prohibition regimes have not yet evolved into a comprehensive tool to address state-level procurement activities, the dominant threat perception in relation to substate actors has not changed dramatically and public health infrastructures in many countries would be overwhelmed by having to deal with a CBW event, we do expect these activities to continue for some extended time. Given the continued side-by-side existence of a large number of these elements of the web of responses at various levels from the global to the individual, it will become increasingly important to ensure the compatibility and increase coherence of these regulatory and governance mechanisms. Catherine Rhodes’s (2009, 2010) assessment of the closely related issue area of international biotechnology governance is largely applicable to the wider web of responses to the proliferation and use of CBW: The international biotechnology regulations largely developed separately from each other, at different times, for different purposes and based on different principles. . . . Comparison of the regulations to the model of coherent international regulatory sets clearly demonstrates that they display



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few of its characteristics and they still are a long way from meeting the model. (Rhodes 2010, 177)

In addition to the harmonization of already existing measures in the web of responses, the changing nature of warfare and the resulting new utilities for chemical and biological warfare agents require us to revisit the body of international humanitarian law and analyze whether this needs strengthening. Already in September 2002 the International Committee of the Red Cross (ICRC) launched its appeal on “Biotechnology, Weapons and Humanity.” While this focused predominantly on the biotechnology revolution, the ICRC also is acknowledged “as the ‘guardian’ of the Geneva Conventions and the various other treaties that constitute international humanitarian law [IHL]” (ICRC 2010a). A recent ICRC expert workshop on Incapacitating Chemical Agents: Implications for International Law (2010b) clearly highlights the problematic character of such agents for international humanitarian and other bodies of international law. A more detailed analysis of current weaknesses and means to strengthen or supplement IHL is beyond the scope of this concluding chapter and will need to be pursued in future research. Continued Centrality of the CBW Prohibition Regimes Looking to the longer term it will be necessary to shield the CBW prohibition regimes from erosion caused by the major challenges we have discussed in this volume. For this to be achieved, benefits derived from the revolution in the life sciences will need to be protected from hostile misuse by thoroughly embedding an understanding of biosecurity among life scientists from their schooling, through university, and on through their continuing professional development. We do not expect that there will be many examples of very dangerous experiments of dual-use concern, but we think that life scientists should be able to spot such an experiment in their field and that their workplaces should have mechanisms in place so that such concerns can be brought to the attention of higher management and, if necessary, to national authorities. It will also be necessary that life scientists are kept aware of the development of the international and national elements of the prohibition regime through their professional associations so that their expertise is available when required to help with the further elaboration of the regime and its better implementation. There can be no doubt that effecting such a

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cultural change will take a great deal of effort over many years, but it will have to be done if the hostile misuse of the life sciences is to be effectively prevented. Over the same period, and for the same reason, we think that there will need to be radical improvements in the CWC and the BWC. We do not expect that the two CBW prohibition regimes will be amalgamated over the next couple of decades, but we do expect that through informal, and increasingly formal, arrangements their operations will become more coordinated. For example, as we suspect that there is a similar degree of ignorance about the CWC among chemists as we have found among life scientists in regard to the BWC, it will clearly be necessary to change the culture of chemists in the same way as for life scientists. Moreover, this will have to be seen as part of a broader strategy of developing an informed support for the Convention in civil society because such support is sorely lacking at present and this could leave the regime vulnerable in the future. As the high-level Advisory Panel on future priorities of the OPCW reported, there are a number of adjustments that should be considered now in order to improve implementation of the CWC and thereby strengthen the CW prohibition regime (OPCW 2011). However, the most important of these is the need to make a major change in the verification system so that it is focused on the problem of preventing proliferation as soon as the Cold War period stocks of CW are totally destroyed. Within that process of adjustment the scientific and technical problem of dealing with production by synthesis will have to be faced and a solution found. Moreover, that will have to be part of a continuous process of adjustment of the Convention in a period of very rapid change in both chemistry and biology and the convergence of the two with respect to scientific understandings and methods (Tucker 2012). The most important long-term problem facing the States Parties to the BWC is how to greatly improve the means of assuring compliance. That is unlikely to be possible through the agreement to implement a comprehensive system in the near future. Yet it is important, in our opinion, that efforts are made to move toward that objective (Kelle, Nixdorff, and Dando 2010). In that regard, building on the good work of the first two intersessionals seems to be the best way forward. Short of the establishment of a formal international organization with a permanent secretariat, means have to be found to make the succeeding intersessional processes more systematic and effective, for example, in considering the impacts of scientific advances. The most likely



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route to a successful strengthening of the verification system would appear to be through the use of an enhanced intersessional process to investigate the utility of different subsystems that could be integrated at a later stage into a complete system (Lennane 2010). Likely subsystems that should be explored are improved CBMs and disease monitoring via Article X (Pearson, Sims, and Dando 2011). It is important to stress that States Parties need to view the development of these subsystems as part of a process of producing an integrated verification system, not just for the continued validity of the Convention but also because they will need the same kind of informed civil society support for the Convention in the difficult decades ahead as the States Parties to the CWC need—and without effective verification in either of the two regimes, that informed support seems most unlikely to be forthcoming.

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Index

Aas, Pal, 56–58 ABW (advanced biological warfare), 5–6, 9 Abyssinia, CW by Italy in, 157–58 Ackerman, G. A., 99–100 Adams, Gordon, 98 Adams, V., 4 advanced biological warfare (ABW), 5–6, 9 aerobiology, 3 aerosol delivery, 48, 59; biochemical therapeutics, 50–52; nasal delivery, 50, 51, 52, 55–56, 59; respiratory routes, 55–56, 59; traditional biological agents, 48–49; vaccination, 49–50; viral vectors, 55–56, 59 Afghanistan, 29, 96 agonists, 45 AIDS, 53, 125 AK-47s, 29 Albania, CW stockpiles, 160, 162, 164 American Journal of Psychiatry, 61 American Type Culture Collection, 120 amygdala, anxiety and fear, 83–84 Andreasen, Nancy, 61–62, 62table, 64–66, 69–70

Anfal campaign, CW, 20 Angola, and CWC, 168 animals: global health concerns, 124; insecticide control, 48–49; research with, 69, 74–78 antagonists, 45 anthrax, 22, 56, 133; aerosol vaccination, 49; attacks in U.S., 8, 90, 94, 102–3, 117, 119, 121, 125, 153; biodefense against, 8, 90, 91, 121; inhalational, 21; Iraq, 156; pulmonary, 91; Sverdlovsk outbreak, 142, 143 antibiotics, 5, 35 Antiterrorism and Effective Death Penalty Act (1996), U.S., 120 antitoxins, 5 antiviral drugs, 5, 35 anxiety and fear, oxytocin and, 83–84 Aplysia sea slug, 69, 74–75 “arms competition,” 182; between arms racing and maintenance, 2; Cold War, 2–3, 18, 21, 26; defensive measures inducing, 87 arms control: BW, 37, 111, 119, 125, 138; Center for Arms Control and Non-Proliferation, 89–90, 91; CW, 229

230

Index

19, 111, 138, 158; developments in science and technology, 152–53; nuclear, 3, 138; U.S. Arms Control and Disarmament Agency, 137. See also biodefense; deterrence; disarmament; web of responses arms dynamic, 1–2. See also “arms competition”; arms race arms race (most extreme arms dynamic), biochemical, 2, 99, 110, 181 army type, 15 arsenic, 17 Aryan Nations, 120 Asperger’s syndrome, 86 assassination and sabotage, BW, 21, 23, 24 Assessing the Biological Weapons and Bioterrorism Threat (Leitenberg), 153 Associated Press, on disarmament talks, 104 Australia: biodefense, 183; BWC Meeting of Experts (2005), 128–29; life science courses’ biosecurity awareness, 131 Australia Group (AG), 135–36, 194; export controls, 112, 113–15, 135–36, 158, 188–89 Australian Defence Science and Technology Organisation, 189 autism, 86–87; oxytocin and, 82, 86 Avramchev, Georgi, 150 Axel, Richard, 66, 67 Bacilus anthracis. See anthrax bacteria, 20; Bacillus thuringiensis, 48–49; bacterial virus, 38, 154; Escherichia coli, 39; Mycoplasma capricolum, 40; Mycoplasma genitalium, 40; Mycoplasma mycoides, 40. See also anthrax BEM (Biosecurity Educational Module), 132–35 Betts, Richard, “Conflict or

Cooperation? Three Visions Revisited,” 180–81 biodefense, 1, 4–9, 88–109, 182; vs. bioterrorism, 90–92, 95, 98, 117, 120–21, 125, 153–54; funding, 8, 90–108, 121–22; missions, 94; “next generation” approaches, 6–7, 95; sensible, 88; transparency, 183–84; U.S., 4, 7–8, 9, 89–109, 117, 120–21, 183, 184–85. See also arms control; biosafety; biosecurity; danger; life sciences research misuse and biosecurity; medical countermeasures Biodefense Research Supporting the DoD: A New Strategic Vision (Martinez), 100–101 bioengineering. See molecular biology; synthetic biology bioethics, 131, 134, 176 Biological and Toxin Weapons Convention (BWC, 1972), 1–12, 22, 60, 87, 110, 137–56, 182, 191–92; Ad Hoc Group (AHG, 1995–2001), 117, 124, 125, 145–46; Article I, 47, 103, 128, 140, 151–52, 155, 186; Article III, 112, 146, 186; Article IV, 128; Article V, 141–42, 154, 186; Article VI, 141, 142–43, 154; Article X, 146, 185–86, 192, 197; BEM, 134; biosafety and biosecurity, 117–19, 121, 123; “chairman’s compromise text,” 145–46; Conference of States Parties (1994), 145; confidencebuilding measures (CBMs), 144, 148, 156, 184, 185, 192, 197; “core business,” 153; Depositary States, 138; Final Declaration of the Conference, 128, 146, 148, 151, 191; General Purpose Criterion, 47, 140; Implementation Support Unit (ISU), 148, 184, 185, 192; inspections, 22–23, 104–6, 139, 155–56; intersessional processes (ISP), 106, 117–18, 123–25, 128–29, 140,



144, 146–51, 154, 185–86, 192, 196–97; layers of undertakings, 141fig; legally binding obligations, 117, 141fig, 144, 145; and life scientists’ awareness of biosecurity, 107, 128, 129, 132–34, 135, 154–55, 196; Meeting of Experts, 128–29, 149–50, 186; Meeting of Scientific and Technical Experts (MSTE), 186; Meeting of States Parties, 43, 132–33, 134, 141fig, 142, 147, 149–50, 156, 186–87; microbial forensics, 38; nanotechnology, 47, 152; national implementation, 125, 134, 143, 146, 147, 149, 155, 192; nongovernmental organizations (NGOs), 150; politically (as opposed to legally) binding, 140, 141fig; poster session, 150; preamble, 137; Protocol negotiations, 103, 105, 117, 124–25, 145–46, 154–56; scientific and technological (S&T) developments, 1, 60, 151–53, 182, 185; sensible biodefense, 88; strengthening, 124–26, 143–53, 184–87, 191–92, 196–97; strengths and weaknesses, 140–43; transfer provisions, 112–14, 146; twenty-fifth anniversary, 145; UN Security Council (UNSC) Resolution 1540 (2004), 135, 194; U.S., 3, 4, 95–96, 99, 103–9, 139, 141–43, 146, 155, 156, 183–86; VEREX, 145; verification of compliance, 103, 139– 46, 154–56, 184–85, 189, 192, 196–97; WHO’s neutrality and, 127, 128 Biological and Toxin Weapons Convention (BWC, 1972) Review Conferences, 139–40, 141fig, 144–49; First (1980), 139, 151; Second (1986), 128, 139, 144; Third (1991), 139, 144–45; Fourth (1996), 137, 139, 145, 151–52; Fifth (2001–2002), 117–18, 139, 145, 146, 148; Sixth (2006), 117–18, 129, 139, 146–47, 148, 149, 152, 186; Seventh

Index

231

(2011), 10, 106, 117–18, 144, 149, 152, 185–87, 191; Eighth (2016), 185, 191 Biological Research Security System, 123 Biological Threat Reduction Program, 108 The Biological Threat Reduction Program of the Department of Defense (National Academies), 98 biological weapons (BW), 1, 7, 93, 137–56; ABW agents, 5–6, 9; arms control, 37, 111, 119, 125, 138; Australia Group (AG) and, 135–36; Clear Vision, 103, 183; CW separated from, 3, 138–39, 158; evolution, 4–8, 6fig, 137–56; “experiments of concern,” 35, 122; experiments on humans, 21; export control list, 189; four categories, 20; Iraq, 21, 22–23, 138, 144, 155; largescale attacks, 21–22, 34; old wars, 20–24; PATRIOT Act (USA 2001) and, 119–20; perceived utility, 11, 22; for sabotage and assassination, 21, 23, 24; traditional agents, 4–5, 7, 48–49, 56; UN Security Council (UNSC) Resolution 1540 (2004), 115, 194; U.S., 3, 4, 21, 22, 103, 139; WHO and, 127, 128, 135; WMD, 89, 138. See also biodefense; Biological and Toxin Weapons Convention (BWC, 1972); biotechnology; bioterrorism; chemical and biological weapons (CBW); medical countermeasures; mid-spectrum agents; toxins biology: circadian, 64; DNA discovery and status of, 71; molecular, 38, 71, 75, 76–78; “nuclearization” of, 154; sociobiology, 76–78. See also biological weapons (BW); synthetic biology; systems biology Biomedical Advanced Research and Development Authority (BARDA), 7–8, 92 bioreactors, “protocells” and, 41

232

Index

bioregulators, 20, 23–24, 57table, 133; CWC and, 190; Lemon-Relman Report and, 36, 56; misuse potential, 44, 46–47, 56–58, 79; peptides, 46, 57, 58. See also mid-spectrum agents; neurotransmitters biosafety, 42, 117–23, 149; defined, 118; life sciences education in, 131; risk groups, 118table; in “web of prevention,” 111 biosecurity, 117–23, 149; Biosecurity and Bioterrorism (Franco), 98; defined, 119; 5P-strategy of biosecurity, 44; global issue, 123; prohibition of research rejected for, 122. See also biodefense; life sciences research misuse and biosecurity; oversight; public health security; surveillance biotechnology: “apocalyptic results” triggered by, 181; biodefense and, 4, 5, 6, 92, 153–54; biotech era, 1, 6fig; Biotechnology Research in an Age of Terrorism (Fink Committee Report, NRC 2004), 9, 35, 122, 134; BWC and, 105–6, 146, 151, 154; developments in, 5–6, 92, 151–52, 154, 196; genetic engineering, 5, 24, 151–52; governance, 42–44, 59, 194–95. See also synthetic biology bioterrorism, 34–35, 89, 96, 194; anthrax attacks, 8, 90, 94, 102–3, 117, 119, 121, 125, 153; biodefense vs., 90–92, 95, 98, 117, 120–21, 125, 153–54; Bioterrorism Risk Assessment (BTRA), 91–92; counterterrorism, 91, 111; fallacy of focus on, 153–54; perceived threat, 1, 125, 127–28; primary bioweapons threat, 9, 153; U.S. vs., 90–92, 95, 117, 120–21, 153 Bioterrorism and Threat Assessment (Ackerman and Moran), 99–100 Bioterrorism Preparedness Act (2002), U.S., 121

Bioterrorism Risk Assessment (BTRA), DHS, 91–92 BioWeapons Prevention Project (BWPP), 150 blood agents, 17, 56 blood-brain barrier, 51, 58, 59 bombing: Clear Vision, 103, 183; suicide, 29. See also 9/11; nuclear weapons Boot, M., 13 Bosnia-Herzegovina war (1992 to 1995), 25 botulinum, 22, 56, 133 Bradford University, 129; Biosecurity Educational Module (BEM), 132–35 brain: blood-brain barrier, 51, 58, 59; direct delivery to, 58; “mind and brain are inseparable,” 71–73, 73table; social attachment circuits, 64. See also mental illnesses; neuro... Brave New Brain: Conquering Mental Illness in the Era of the Genome (Andreasen), 61, 64, 65–66 “A Brave New World in the Life Sciences” (Choffnes, Lemon, and Relman), 36 Brenner, Sydney, 77 British troops: pox-infested blankets to Native Americans, 20. See also United Kingdom The Broken Brain: the Biological Revolution in Psychiatry (Andreasen), 61 Brussels Treaty (1954), 3 BSL-3 and BSL-4 laboratories, 93–94 BTWC. See Biological and Toxin Weapons Convention (BWC, 1972) Buck, Linda, 66 Bulletin of the Atomic Scientists, 94 Bush administration: biodefense, 90; nuclear disarmament, 104; PATRIOT Act (USA 2001), 119–20 Buzan, B., 2 BW. See biological weapons (BW)



BWC. See Biological and Toxin Weapons Convention (BWC, 1972) BZ (3-quinuclidinyl benzilate), 23, 73 Caenorhabditis elegans, nematode worm, 76–77 calmatives, 33, 190; fentanyl, 23, 31, 52, 190 Canada: aircraft spray of Foray 48B, 49; biodefense, 183, 184, 185; Biological and Chemical Defence Review Committee (FBCDRC), 184; BW, 21 cancer therapy, viral vectors, 52–53, 54–55, 59 Carlsson, Arvid, 68, 73 CBMs (confidence-building measures), BWC, 144, 148, 156, 184, 185, 192, 197 CDC (Centers for Disease Control and Prevention), 92, 120 cell division, Nobel prize, 77 Center for Arms Control and NonProliferation, 89–90, 91 Center for International Security Studies at Maryland (CISSM), Project on Controlling Dangerous Pathogens, 123 Centers for Disease Control and Prevention (CDC): Category A, B, and C agents, 92; Laboratory Registration/Select Agent Transfer of Regulations, 120 Center for Strategic and International Studies (CSIS), 42 Chechen insurgents, Moscow theater hostage crisis (2002), 31 chemical and biological weapons (CBW), 1, 2, 7, 11–179; arms race, 2, 99, 110, 181; changing nature of warfare and, 1, 11–34, 87, 181, 192, 193–95; between classical CW and BW agents, 23; disarmament, 138, 159–64, 176, 193; export controls, 112– 17, 135, 146, 158, 188–89; new utilities,

Index

233

9, 12, 26, 30–32; new wars, 26, 30–32, 181–82; old wars, 13, 16–24; perceived utility, 11, 22, 34, 87; Pugwash movement on, 3; separation of, 3, 138–39, 158; “web of deterrence” with, 110–11. See also biological weapons (BW); chemical weapons (CW); mid-spectrum agents; web of responses; WMD chemical weapons (CW), 1, 3, 7, 17–20, 157–79; Australia Group (AG) and, 135–36, 158; binary, 18–19, 24, 190; BW separated from, 3, 138–39, 158; classical, 23, 56; Cold War, 2, 12, 18, 23, 158, 196; cyanides, 17, 56; dual-use precursors, 31–32, 32table, 158; Iraq, 17, 19, 20, 24, 30–31, 33, 115; mustard gas, 17, 20, 56; new utilities, 9, 12; nonlethal, 31, 104, 193; old wars, 16–20, 23–24; opacity of programs, 170; riot-control, 139, 190; terrorists, 96, 194; UN Security Council (UNSC) Resolution 1540 (2004), 115, 194; U.S., 3–4, 18–19, 31, 33, 139, 160, 161–64, 177, 187; WMD, 138, 170; World War I, 1, 3, 11–12, 17, 24, 138, 157; World War II not using, 3, 17–18. See also chemical and biological weapons (CBW); Chemical Weapons Convention (CWC, 1993); mid-spectrum agents; nerve agents Chemical Weapons Convention (CWC, 1993), 2, 10, 12, 60, 87, 110, 182, 193–94; Article I, 113; Article III, 159; Article IV, 159; Article V, 159; Article VI, 113, 164, 166, 167; Article VII, 171–72, 172table; Article VIII, 157, 172–73; Article IX, 158; Article X, 158–59; Article XI, 158–59; assistance and cooperation provisions, 158–59; CW production facilities (CWPFs), 159; disarmament, 159–64, 176, 193; discrete organic chemicals (DOCs),

234

Index

165–66; entry-into-force (EIF), 159, 160, 165, 167–68, 173; future of, 104; general provisions, 159–60; inspections, 159, 165–67, 170, 173, 175–79, 188, 190–91; life scientists’ awareness of biosecurity, 130, 133, 135; Meeting of States Parties, 168, 192; membership development, 168–69, 169table; mid-spectrum agents, 182, 188, 189–91, 193; national implementation, 113, 167, 170–77, 172table, 179, 193, 196; no-first-use agreement, 157; nonproliferation, 159, 164–67, 177–78, 187–88, 191, 193, 196; Open-Ended Working Group (OEWG), 175; “other chemical production facilities” (OCPFs), 165–67, 175–79, 188, 190–91; PSF (phosphorus, sulfur, fluorine) chemicals, 167, 190; Review Conferences, 10, 130, 165–67, 168, 171, 172–75, 188, 193; Schedules (categories of chemicals), 164–67; Scientific Advisory Board (SAB), 173–76, 179, 188, 193; scientific and technological (S&T) developments, 172–76, 179, 182, 188, 193–94, 196; sensible biodefense, 88; strengthening, 187–88, 196; transfer provisions, 112–14, 158; universality, 167–71, 169table, 178; UN Security Council (UNSC) Resolution 1540 (2004), 135; U.S. and, 104, 105, 108–9, 160, 161–64, 177, 187, 193; verification/Verification Annex, 113, 157, 159, 160, 164–67, 187, 190, 193, 196, 197. See also Organisation for the Prohibition of Chemical Weapons (OPCW) China: CWC, 166; Japanese BW, 138; life science courses’ biosecurity awareness, 131; Mearsheimer book and, 181 chitosan, 51, 54

chlorine, 17, 33 Church, George, 42 circadian biology, 64 Clear Vision, 103, 183 Clinical Neuropsychiatry (Cummings), 72 Clostridium botulinum toxin, 22 Cold War, 15; “arms competition,” 2–3, 18, 21, 26; BW, 2, 21–22, 23, 24; CW, 2, 12, 18, 23, 158, 196; end, 144; export controls, 112; nuclear weapons, 11, 26; weapons since, 29 commercial uses: bioreactors, 41; BWC and, 105–6, 155; CW, 17, 31–32, 32table, 158, 164–65; CWC and, 164–65, 188; “statization of war” and, 14–15 Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare Threats, 35–36 Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology (Fink Committee), 9, 35, 122, 134 Comprehensive Test Ban Treaty Organisation, 192 computerized tomography (CT) scans, 70 cosmopolitanism, vs. particularist identities, 25, 30 costs: dangerous-pathogen research, 121; medical countermeasures, 92–93; sequencing, 37. See also financing counterinsurgency operations, 25, 30, 33 countermeasures. See biodefense; medical countermeasures counterterrorist operations, 12, 30, 91, 111 Crick, Francis, 71 crimes: acts of war distinguished from, 14; BW sabotage and assassination, 21, 23, 24. See also misuse; terrorists CSIS-MIT-Venter group, 42



CT scans, 70 Cuba: BWC, 142–43; CWC, 166 Cummings, Jeffrey: Clinical Neuropsychiatry, 72; Neuropsychiatry and Behavioral Neuroscience (Cummings and Mega), 72–73, 73table CW. See chemical weapons (CW) CWC. See Chemical Weapons Convention (CWC, 1993) cyanides, 17, 56 cystic fibrosis, 55 Dando, M., 21, 22, 23, 146 danger: biodefense projects, 102–3; life sciences research, 93–94, 106, 130, 186–87. See also biosafety; dualuse agents; misuse; risk/threat assessment Daschle, Tom, 90–91 Declaration of Paris (1856), 14 defense. See biodefense dendritic cells, 45 deoxyribonucleic acid. See DNA Department of Defense (DoD): Annual Report to Congress on the Chemical and Biological Defense Program “Doctrine, Training, Leadership, and Education Strategic Plan” (2009), 97, 104; biodefense, 90, 94, 96–98, 100–101, 107, 108–9; The Biological Threat Reduction Program of the Department of Defense (National Academies), 98; Chemical and Biological Defense Program, 94; Chemical Biological Program Strategic Plan, 96; Chemical Demilitarization Program, 94; Defense Inspector General, 98; funding, 90, 96–98, 103–4; organizational structure, 101; WMD defense missions, 94 Department of Health and Human

Index

235

Services. See HHS Department of Homeland Security (DHS): biodefense funding, 90; Bioterrorism Risk Assessment (BTRA), 91–92; Project Bioshield, 90 deterrence: logic of deterrence and retaliation in kind, 24; “web of deterrence,” 88, 110–11. See also arms control; biodefense DHS. See Department of Homeland Security (DHS) diabetes, 52 Dias, M. B., 121 disarmament: CBW, 138, 159–64, 176, 193; nuclear, 104; UN Department for Disarmament Affairs Geneva branch, 148; U.S. Arms Control and Disarmament Agency, 137 diseases. See infectious diseases; medical countermeasures; mental illnesses DNA (deoxyribonucleic acid), 37, 38, 46; artificial viruses, 54–55; discovery of structure of, 71; polymerase chain reaction (PCR), 67–68; synthetic, 40–41, 42, 43–44, 59; vaccines based on, 50 DoD. See Department of Defense (DoD) dopamine, 68, 73 Drosophila melanogaster, fruit fly, 77–78 dual-use agents, 1, 35–37, 121, 195; CW precursors, 31–32, 32table, 158; Fink Committee Report on, 35, 122, 134; Lemon-Relman Report and, 35–36, 134; life scientists’ awareness of, 107, 128–35, 150–51, 192, 195; NSABB oversight recommendations, 107, 122–23, 132; systems biology and, 46; transfer provisions, 114–15; viral vectors, 53, 59. See also midspectrum agents Ebola virus, 55, 121

236

Index

economics: CWC and, 158; neuroeconomics, 84–86; war economy, 14–15, 25, 32. See also commercial uses; costs; financing; funding Egypt, 24; and CWC, 168, 170; CW against Yemen, 19, 30–31, 33 emotion: oxytocin and, 83–84; study of, 63. See also fear; mental illnesses; stress; trust endorphins, 58 engineering. See genetic engineering; synthetic biology enkephalins, 58 environmental stress, viral vectors, 55–56 Escherichia coli, 39 ethics, bioethics, 131, 134, 176 European gypsy moth, 48–49 European life science courses, biosecurity awareness, 130–31 European Union (EU): Joint Action program (2006), 150; Seventh Framework Programme (2007–2013), 79; Verification Research, Training and Information Centre (VERTIC), 150 Evans, D. H., 38 Exeter University, 129 “experiments of concern,” BW, 35, 122 export controls, CBW, 112–17, 135, 146, 158, 188–89 “Exubera,” 52 “FANTOM” (Functional Annotation of the Mammalian Genome), 45 FBI, 94, 102–3 fear: oxytocin and, 83–84; spreading “fear and hatred,” 25, 30 fentanyl, 23, 31, 52, 190 Fidler, D. P., 125 financing: biology research, 79; war, 14–15, 25. See also costs; funding

Fink, Gerald R., 35 Fink Committee Report, 9, 35, 122, 134 “fishing expedition,” 68 “Foliant,” 18, 19 food: terrorist contamination of, 34. See also animals; plants Food and Agriculture Organization (FAO), Plant Protection Service, 124 Food and Drug Administration (FDA), medical countermeasures, 100 Foray 48B, 49 Foreign Affairs, The World Ahead, 180–81 France: BW, 20–21, 24, 138; BWC, 124, 140–41; BW not needed along with nuclear weapons, 11, 22, 24; CW, 19; CWC, 173; Napoleonic Wars, 15; UN Security Council (UNSC) Resolution 1540 (2004), 116 Freeman, John, 147–48 fruit fly, Drosophila melanogaster, 77–78 Fukuyama, Francis, The End of History and the Last Man, 180–81 functional genomics, 36–39, 40 functional magnetic resonance imaging (fMRI), 70–71 funding: biodefense, 8, 90–108, 121–22; Gulf War illness research, 102; mental illnesses research, 63. See also financing fungi, 20 Furmanski, M., 23 Gage, Phineas, 73 Gates, Robert M., 96–98 genes, 37; “switch,” 78 gene synthesis, 39–44 gene therapy, viral vectors, 52–55, 59 genetic engineering, 5, 24, 151–52 Geneva Convention (1925), Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous, or Other Gases, and of Bacteriological Methods of Warfare, 12, 14, 133, 192;



vs. BW, 22, 138; vs. CW, 19, 20, 138, 157; and export controls, 112; ICRC and, 195; Iraq and, 19, 20, 22; and life sciences education in biosecurity, 128 genomics, 38, 59; Brave New Brain: Conquering Mental Illness in the Era of the Genome (Andreasen), 61, 64, 65–66; “FANTOM,” 45; functional, 36–39, 40; human genome, 37, 79; metagenomes, 37; and neuroscience, 65–67 Germany: biodefense, 118, 119, 120–21, 183; biosafety, 118, 120–21; Brussels Treaty (1954) prohibiting BW by, 3; BW, 20–21, 138; CW by Nazi Germany, 17–18; life sciences research with dual-use agents, 129; UN Security Council (UNSC) Resolution 1540 (2004), 116 Gilman, A. G., 66–67 Giving Full Measure to Countermeasures (National Academies), 100 Globalization, Biosecurity, and the Future of the Life Sciences (Lemon-Relman Report, NRC 2006), 9, 35–36, 56, 111–12, 134, 186 goals, war: force preservation, 28, 31, 32–33; new wars, 25–33; old wars, 15 governance: self-governance, 42, 44; synthetic biology/biotechnology, 42–44, 59, 194–95. See also oversight G-protein coupled receptors, 66–68, 77 Greengard, Paul, 68, 69 Gronvall, Gigi Kwik, 95–96 guerrilla warfare, 25–29 Gulf War, 100; first (1990–1991), 88, 102, 144, 155; illness, 102, 108; second, 23 Gulf War Illness and the Health of Gulf War Veterans: Scientific Findings and Recommendations (Research Advisory Committee on Gulf War Veterans’ Illness), 102 gunpowder revolution, 13

Index

237

gypsy moth, insecticide, 48–49 Hague Conferences (1899 and 1907), 11–12, 14 Halabja, CW use, 17, 20 Hansen, John-Erik Stig, 128 Harvard University, 42 health: global concerns, 124, 125–27, 128, 135; NIH/NIMH, 63–64, 82–83, 122– 23; separate from security, 125, 126. See also HHS; infectious diseases; medical countermeasures; mental illnesses; public health security “hearts and minds,” capturing, 25, 27, 30 herbicides, Vietnam, 139 Herring, E., 2 HHS (Department of Health and Human Services): biodefense, 7–8, 90, 92–93; synthetic biology, 43–44 Hitler, Adolf, 17 HIV/AIDS, 53, 125 Hoge, James F. Jr., 180, 181 Homeland Security. See Department of Homeland Security (DHS) hormones, 46; neuro-hormones, 56; peptide, 51, 82 Horvitz, Robert, 77 human genome, 37, 79 humanitarian law, international, 195 Huntington, Samuel, The Clash of Civilizations and the Remaking of the World Order, 180–81 Hussein, Saddam, 17 ICRC. See International Committee of the Red Cross (ICRC) identity politics, 25, 30 imaging, neuroimaging, 64, 70–71, 76, 186 immune system: “immuno-stealth” proteins, 53; innate/adaptive immunity, 45; malign interference, 1; reconstituted, 54; viral vectors and, 52

238

Index

Implementation Support Unit (ISU), BWC, 148, 184, 185 India: CW stockpiles, 160, 161, 162, 166; life science courses’ biosecurity awareness, 131 Indochina, “wars amongst the people” (1950s), 26 industrial revolution, 1, 13 infectious diseases: deliberate spread of, 1, 126–27, 135; global efforts, 124, 125– 26, 186; historical knowledge of, 34, 138; HIV/AIDS, 53, 125; surveillance, 92, 111, 124–28, 149; swift and timely reporting of outbreaks, 125; threat from non-bioweapons agents, 121–22. See also medical countermeasures; plague; pox; viruses influenza virus, Spanish (1918), 38–39 information technology, 1, 13, 38 insect toxin, 48–49 Insel, Thomas, 83 Institute of Medicine, 35–36 Institutional Biosafety Committee (IBC), 35, 42 insulin, 51–52, 58 insurgents, enemy, 27, 28, 29, 31; counterinsurgency operations, 25, 30, 33 interleukins, 46, 51 International Association of Synthetic Biology (IASB), 43–44 International Committee of the Red Cross (ICRC), 19, 111, 195; Incapacitating Chemical Agents. Implications for International Law, 195 International Consortium for Polynucleotide Synthesis (ICPS), 42–43 International Gene Synthesis Consortium (IGSC), 43–44 International Genetically Engineered Machine (iGEM), 40

International Health Regulations (IHR), 125–27 International Institute for Strategic Studies (IISS), 170 internationalism, 2, 10; infectious disease surveillance, 124, 125–26, 186; U.S. biodefense and, 95–96, 108–9. See also Biological and Toxin Weapons Convention (BWC, 1972); Chemical Weapons Convention (CWC, 1993); Geneva Convention (1925); NATO; United Nations international law. See laws/legislation International Sanitary Regulations (1951), 125 International Union of Pure and Applied Chemistry (IUPAC), 130, 173–75 Internet: BEM, 134; Canadian Biological and Chemical Defence Review Committee (FBCDRC) report, 184; education and outreach about biosecurity, 132, 134; ISU operating through, 192; survey on biosecurity education in life science courses, 130–31 ion channel, 68 Iran, Iraqi war against, 19, 20, 24, 30–31 Iraq, 24; BW, 21, 22–23, 138, 144, 155; CW, 17, 19, 20, 24, 30–31, 33, 115; multinational intervention forces, 29; Saddam Hussein, 17; UNSCOM investigations, 155–56; war against Iran, 19, 20, 24, 30–31; war against Kurds, 19, 20; “wars amongst the people,” 28 ISG (Iraq Survey Group), 23 Israel: and CWC, 168, 170; life science courses’ biosecurity awareness, 131 Italy, CW in Abyssinia, 157–58 Ivins, Bruce, 94, 102–3 Japan: BW, 21, 138; life science courses’



biosecurity awareness, 130–31 Jelzin, Boris, 22 Kaldor, M., 9, 13, 15–16, 25, 30 Kandel, Eric, 68–70, 72, 74–78; “A New Science of Mind,” 71–72, 73–74, 75, 76; Principles of Neural Science, 69–70 Kelle, Alexander, 5P-strategy of biosecurity, 44 Khan, Masood, 150 Korea. See North Korea; South Korea Kurds, Iraqi CW used against, 19, 20 Lauterbur, Paul, 70 Lawand, K., 176 laws/legislation: BWC legally binding obligations, 117, 141fig, 144, 145; BWC national legislation, 117, 119–21, 128, 143, 147, 149; CWC national legislation, 158, 171–72, 172table, 193; international Geneva Protocol law, 138; international humanitarian law, 195; international war-conduct law, 14, 138, 195; UNSC Resolution 1540-related, 115, 116, 117; U.S. bioterrorism, 153 L-DOPA, 68, 73 Lederberg, Joshua, 137 legislation. See laws/legislation Leitenberg, Milton, 153 Lemon, Stanley M., 35–36, 111 Lemon-Relman Report (Globalization, Biosecurity, and the Future of the Life Sciences, NRC 2006), 9, 35–36, 56, 111–12, 134, 186 lentiviral vectors, 53–54, 55 Lentzos, F., 144 Libya, CW stockpiles, 160, 161, 162 life sciences research, 154, 186; BWC involvement by participants, 149–50; revolution in, 1, 9, 32, 33, 34–61, 190–91, 195. See also biology;

Index

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biotechnology; neuroscience; scientific and technological (S&T) developments life sciences research misuse and biosecurity, 1, 4, 61, 93–94, 107–8, 128–35, 186–87, 195–96; danger, 93–94, 106, 130, 186–87; dual-use agents, 107, 128–35, 150–51, 192, 195; education and outreach, 128–35, 154–55, 187, 192; late nineteenth century, 133; medical countermeasures, 122; mid-spectrum agents, 56–60; neuroscience, 64–65, 79, 81–82, 86–87; oversight, 94, 122–23, 136, 152, 154–55; scientists’ awareness, 93–94, 107, 128–35, 150–51, 186–87, 192, 195– 96; state-supported actors as greatest threat, 60, 154; substate groups, 60, 106, 111, 153, 154; war crimes, 21; “web of deterrence,” 110; “web of prevention,” 111, 134, 135. See also web of responses Lind, W. S., 13 Liquid Trust, 52 Littlewood, J., 185 Littlewood, Jez, 146 Lorenz, K., 78 Lugar, Richard, 95 Luongo, Kenneth, 95 Macedonia, BWC, 150 machetes, 29 macrophages, 45, 51 magnetic resonance imaging (MRI), 70–71 malign manipulation. See misuse Malta, UN Security Council (UNSC) Resolution 1540 (2004), 116 Mansfield, Peter, 70 Martinez, Coleen K., 100–101 Massachusetts Institute of Technology (MIT), 40, 42 Mathews, Robert, 189, 190–91

240

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Mauroni, A. J., 99 McNulty, J.A., 5–10, 87, 88, 99, 154 Mearsheimer, John, The Tragedy of Great Power Politics, 180–81 medical countermeasures, 5, 7–8, 92–93, 100–102, 108, 121–22; antibiotics, 5, 35; antitoxins, 5; antiviral drugs, 5, 35. See also cancer therapy; gene therapy; vaccines Mega, Michael, Neuropsychiatry and Behavioral Neuroscience (Cummings and Mega), 72–73 melanocortin, 58 memory, 68–70, 74, 75 mental illnesses, 61–62, 62table; biochemistry, 69; NIMH, 63–64; oxytocin and, 83–84, 86. See also emotion; psychiatry Meselson, Mathew, 4, 5 Mexico, aerosol vaccination, 49 microbial forensics, 38 microbiology, developments in, 151–52 Middle Ages: BW, 20; new wars compared, 25; war economies, 14 mid-spectrum agents, 20, 23–24, 56–58; BWC and CWC and, 133, 182, 188, 189–91, 193; examples, 57table; misuse potential, 37, 56–60, 188–91. See also bioregulators; chemical and biological weapons (CBW); dual-use agents; toxins military-industrial complex, 15 military technology, 1, 13, 15, 27, 29. See also biological weapons (BW); chemical and biological weapons (CBW); chemical weapons (CW); nuclear weapons “mirror” neurons, 78–79 misuse: CW, 158; mid-spectrum agents, 56–60, 188–91. See also dual-use agents; life sciences research misuse and biosecurity; web of responses molecular biology, 38, 71, 75, 76–78

Moran, K. S., 99–100 Moscow theater hostage crisis (2002), 23, 31, 33, 63 Münkler, H., 9, 14, 15, 25 mustard gas, 17, 20, 56 Myanmar, and CWC, 168 Mycoplasma capricolum, 40 Mycoplasma genitalium, 40 Mycoplasma mycoides, 40 nanoparticles, 47, 50, 51, 59 nanotechnology, 36–37, 47, 152 Napoleonic Wars, 15 nasal delivery: aerosol delivery, 50, 51, 52, 55–56, 59; smell mechanism, 66 National Academies: anthrax attack review, 102–3; The Biological Threat Reduction Program of the Department of Defense, 98; dual-use awareness, 130; Giving Full Measure to Countermeasures, 100. See also Institute of Medicine; National Research Council (NRC) National Advisory Group, 42 National Biodefense Analysis and Countermeasures Center, 99 National Institutes of Health (NIH): Guidelines for Research Involving Recombinant DNA, 122–23; National Institute of Mental Health (NIMH), 63–64, 82–83 nationalism, citizens motivated by, 13 National Research Council (NRC), 35–36, 91; Fink Committee Report, 9, 35, 122, 134; Lemon-Relman Report, 9, 35–36, 56, 111–12, 134, 186. See also National Academies National Science Advisory Board for Biosecurity (NSABB), 107, 122–23; Strategic Plan for Outreach and Education on Dual Use Research Issues, 132 Native Americans, pox-infested blankets



from British troops, 20 NATO: Advanced Research Workshop in Bucharest (June 1999), 124; nuclear rearmament decision, 19 Nature: IASB, 43; “Oxytocin Increases Trust in Humans,” 79–81, 83 Nature Biotechnology, 92 Navy, U.S., 98 Nazi Germany, CW, 17–18 Neher, E., 68 nematode worm, Caenorhabditis elegans, 76–77 nerve agents, 3, 17–18, 20, 56; A-230, 18, 19; A-232, 18, 19; binary, 190; “Foliant,” 18, 19; Gulf War illness and, 102; malfunctions, 73; novichok, 190; VX, 18, 19 neurobiology, 63 neuroeconomics, 84–86 neuroimaging, 64, 70–71, 76, 186 neurokinin A, 56 neuropeptides, 46, 186; amygdala, 83–84; neuropeptide Y, 58. See also oxytocin; peptides neuropsychiatry, 61, 72–73, 73table, 75 Neuropsychiatry and Behavioral Neuroscience (Cummings and Mega), 72–73, 73table neuroscience, 61–87; future of, 74–79; golden age, 62; misuse, 64–65, 79, 81–82, 86–87; Nobel Prizes in Physiology or Medicine, 65–71, 65table, 72, 75–76, 77; research priorities, 63–65 neurotransmitters, 23, 46, 56, 58, 66–68, 73, 186 “A New Science of Mind” (Kandel), 71–72, 73–74, 75, 76 new wars/”wars amongst the people,” 9, 15–16, 25–34, 181–82. See also substate groups “next generation” approaches, 6–7, 37, 95 NIH Guidelines, 122–23

Index

241

NIMH (National Institute of Mental Health), 63–64, 82–83 9/11: biodefense after, 8, 97, 101; insecurity and vulnerability felt after, 117, 153 Nixon administration, BW abandoned by, 3, 22, 139 Nobel Prizes in Physiology or Medicine, in neuroscience, 65–71, 65table, 72, 75–76, 77 Non-Aligned Movement (NAM), 114, 166, 178 nongovernmental organizations (NGOs): and BWC, 150; and CWC, 173–74, 175 nonlethal agents, 31, 59, 104, 193 nonproliferation: Center for Arms Control and Non-Proliferation, 89–90, 91; CWC, 159, 164–67, 177–78, 187–88, 191, 193, 196; next-generation Global Proliferation Prevention Initiative, 95; nuclear, 170, 178; WMD, 89 North Korea, and CWC, 168, 169–70, 178 Norwegian Defence Research Establishment, 56 Novichok agents, 19 NRC. See National Research Council (NRC) Nuclear Non-proliferation Treaty (NPT), 170, 178 nuclear weapons, 15; “arms competition,” 26; arms control, 3, 138; BW phased out in preference for, 11, 22, 24; Cold War, 11, 26; disarmament talks, 104; nuclear age, 3, 16; Nuclear Non-proliferation Treaty (NPT), 170, 178; Pugwash Conferences on Science and World Affairs, 130; UN Security Council (UNSC) Resolution 1540 (2004), 115; WMD, 138 nucleic acids, 46. See also DNA

242

Index

(deoxyribonucleic acid); RNA (ribonucleic acid) nucleotides: sequencing technologies, 37–38. See also nucleic acids Nunn-Lugar Cooperative Threat Reduction Program, 95 Obama administration: biodefense, 8, 95, 98; BWC verification protocol, 156; disarmament talks, 104 Office Internationale des Epizooties (OIE), 124 old wars, 13–16; CBW, 16–24; evolution of, 15–25, 16table Organisation for the Prohibition of Chemical Weapons (OPCW), 2, 113, 143, 148, 157, 193; Action Plan on National Implementation, 171–72; Action Plan on Universality, 168, 170, 171; Advisory Panel on the Future Priorities of the OPCW, 177, 187, 196; Conference of States Parties (CSP), 160, 161, 162–64, 171–72, 173; Director General, 168, 173, 174, 175, 176, 187; Executive Council, 161, 162–64, 168, 171–72, 173, 175, 177, 187; mid-spectrum agents, 190–91; and North Korea, 169– 70, 178; Technical Secretariat (TS), 113, 158, 163, 164–65, 168, 171–72, 173, 175, 176, 177, 179; transfer provisions, 113, 115 “other chemical production facilities” (OCPFs), CWC, 165–67, 175–79, 188, 190–91 O’Toole, Tara, 90–91 oversight, biosecurity, 42, 43, 183; life sciences research, 94, 122–23, 136, 152, 154–55 oxytocin, 82; aerosol delivery, 52; anxiety and stress decreased by, 83–84; trust increased by, 52, 79–86, 81fig “Oxytocin Increases Trust in Humans” (Nature), 79–81, 83

Pakistan: BWC, 150; CWC, 166, 174 Parkinson’s disease, 68, 73 Parnell, G. S., 91–92 particularist identities, 25, 30–31 Partnership for Global Security, 95 PATRIOT Act (USA 2001), 119–20, 121 Pearson, Graham, 88, 110–11 peptides, 51; bioregulators, 46, 57, 58; hormones, 51, 82; vasopressin, 58, 83–84, 86. See also neuropeptides pesticides, 49, 56, 102, 139 Petro, J. B., 5–10, 87, 88, 99, 154 PET scans, 70 pharmaceutical industry: and BWC, 105–6; medical countermeasures, 8, 93, 101 phiX bacteriophage, 154 phosgene, 17 plague, 56; aerosol vaccination, 49; biosecurity, 120 Plant Protection Service, Food and Agriculture Organization (FAO), 124 plants: antiplant CW, 3; global health concerns, 124 Plasse, T. R., 5–10, 87, 88, 99, 154 “plastic antibodies,” 47 poliovirus, 38, 154 polycationic substances, 51, 54 polyethylenegylcol, 54–55 polymerase chain reaction (PCR), 67–68, 69 positron emission tomography (PET) scans, 70 Poste, George, 4 pox: pox-infested blankets from British troops to Native Americans, 20; poxviruses, 38. See also smallpox Prehospital and Disaster Medicine, “Terrorism Special Report,” 56–58 prevention: biodefense, 94–95; “web of prevention,” 111, 134, 135. See also biosecurity; deterrence; medical countermeasures; nonproliferation



Principles of Neural Science (Kandel), 69–70 “Principles of Neuropsychiatry” (Cummings and Mega), 72–73 prohibition regimes. See biodefense; Biological and Toxin Weapons Convention (BWC, 1972); Chemical Weapons Convention (CWC, 1993); web of responses Project Bioshield, Homeland Security, 90 Project Clear Vision, 103, 183 proteomics, 45–46 “protocells,” 41 pseudotyping, 53, 55 psychiatry, 61; neuropsychiatry, 61, 72–73, 73table, 75 psychopathologies. See mental illnesses psychotropic drug action, 64 public health security, 120, 124–28, 194; disease surveillance, 92, 111, 124–28, 149 Public Health Security and Bioterrorism Response Act (2002), 120 Pugwash Conferences on Science and World Affairs, 3, 130 Ratta, R. D., 95 Reagan administration, CW, 3, 18–19 receptors: G-protein coupled, 66–68, 77; olfactory receptor cells, 66; Toll-like receptor (TLR) functions, 45 Reed, Jean, 94 Relman, David A., 35, 111; “A Brave New World in the Life Sciences” (Choffnes, Lemon, and Relman), 36. See also Lemon-Relman Report reproduction, oxytocin and, 82 Research Advisory Committee on Gulf War Veterans’ Illness, 102, 108 reserpine, 68 respiratory routes, aerosol delivery, 55–56, 59

Index

243

responses. See web of responses retroviral vectors, 54, 59 revolutionary wars, 15, 25–26 Rhodes, Catherine, 194–95 ribonucleic acid. See RNA ricin, 56, 190 rickettsiae, 20 riot-control agents, CW, 139, 190 risk/threat assessment, 6, 91–94, 99–100, 123, 152–53, 167. See also danger; misuse; security “risk-transfer war,” 28, 31 Rizzolatti, Giacomo, 78 RNA (ribonucleic acid), 37, 38, 46; RNA interference (RNAi), 45, 54, 186; synthetic, 41 Robb, J., 13 Robinson, Julian Perry, 3, 9, 12, 30, 32 Rodbell, M., 66–67 Romania, UN Security Council (UNSC) Resolution 1540 (2004), 116 Roosevelt, F. D., 18 Russia: BW, 22; BWC, 142; CW stockpiles, 160–64, 177, 187, 193; fentanyl calmative, 23, 31, 33, 52, 190; Moscow theater hostage crisis (2002), 23, 31, 33, 52; and North Korea, 170. See also Soviet Union sabotage and assassination, BW, 21, 23, 24 Saddam Hussein, 17 safety. See biosafety; danger St. Petersburg Declaration (1868), 14 Sakmann, B., 68 Sarin, 17 saxitoxin, 56, 190 Scientific American Mind, 71, 75, 76 scientific and technological (S&T) developments, 182, 186; BW, 1, 35–36, 60, 151–53, 182, 185; CW, 1, 172–76, 179, 182, 188, 193–94, 196. See also biotechnology; life sciences research;

244

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systems biology; technology sea slug, Aplysia, 69, 74–75 security: health kept separate from, 125, 126. See also biosecurity; public health security Seevaratnam, J. I., 114–15 September 11, 2001. See 9/11 sequencing technologies, 37–38 Setting Priorities for Basic Brain and Behavioral Science Research at NIMH, 63 sexual behavior, “switch” genes, 78 Shaw, Martin, 28 Shoyele, S. A., 51 sleep research, 64 Slowey, A., 51 smallpox, 38, 49, 133 smell, basic mechanism of, 66 Smith, Rupert, 9, 15, 25–30 social processes and behaviors, research in, 63–64 social recognition, oxytocin and, 84 sociobiology, molecular, 76–78 Somalia, and CWC, 168, 169 Soman, 17 South Africa, 24; BW, 21, 23, 138 South Korea: CW stockpiles, 160, 161–62; life science courses’ biosecurity awareness, 131; and North Korea, 170 Soviet Union: aerosol vaccination, 49; BW, 21, 22–23, 24, 137–38, 183; BWC, 3, 139, 141, 142, 143; CW, 3, 18, 19; separate BW and CW negotiations, 3. See also Cold War; Russia Spence, S., 171 states, 1; absolutist, 15; borders, 14; establishment of nation-states, 13–14, 15; “inside,” 14; interstate war, 25–26, 27, 29, 32–33; life sciences misuse, 60, 153, 154; multinational intervention forces vs., 29; national biosecurity policies, 120, 136; “outside,” 14; “rogue,” 9, 137, 182, 187; “statization

of war,” 14–15, 25, 32; UN Security Council (UNSC) Resolution 1540 (2004), 115–16; “web of deterrence,” 111; WMD used by, 96. See also laws/ legislation; substate groups Steinbruner, J., 123 Strategic Plan for Outreach and Education on Dual Use Research Issues (National Science Advisory Board for Biosecurity), 107 stress: NIMH research, 64; oxytocin and, 83–84 “substance 33,” 19 substance P, 56, 58 substate groups, 1, 9, 13, 136, 194; guerrilla warfare, 25–29; life sciences misuse, 60, 106, 111, 153, 154; NBC treaties not focused on, 115; “wars amongst the people,” 29–30, 182. See also insurgents; terrorists Sudan, and CWC, 168 suicide missions, 28, 29 Sulston, John, 77 surveillance, disease, 92, 111, 124–28, 149 Sverdlovsk, anthrax outbreak, 142, 143 Sweden, BWC, 140–41 Switzerland: CWC, 167, 188. See also Geneva Convention (1925) synthetic biology, 36–44, 59, 182; biosecurity risks, 42–44, 59, 152; governance, 42–44, 59, 194–95. See also biotechnology Syria, and CWC, 168, 170 systems biology, 36–37, 44–47, 182 Tabassi, L., 171 Tabun, 17 targeted delivery systems, 36–37, 48–52 Tauscher, Ellen, 156 technology: information, 1, 13, 38; medical, 101, 108; nanotechnology, 36–37, 47, 152; sequencing, 37–38. See also biotechnology; military



technology; scientific and technological (S&T) developments terrorists: Commission on the Prevention of WMD Proliferation and, 89; counterterrorist operations, 12, 30, 91, 111; CW, 96, 194; new wars, 27, 29, 30; “Terrorism Special Report” (Prehospital and Disaster Medicine), 56–58. See also bioterrorism threat. See danger; misuse; risk/threat assessment; security “The Threat of Mid-Spectrum Chemical Warfare Agents” (Aas), 56–58 Tinbergen, N., 78 Toll-like receptor (TLR) functions, 45 Toth, Tibor, 145 toxins, 20, 34–35, 56–58, 133, 190; Aflatoxin, 22; antitoxins, 5; biotoxins, 56, 57table; botulinum, 22, 56, 133; diversity of, 57; insect, 48–49; pesticides, 49, 56, 102, 139; ricin, 56, 190; saxitoxin, 56, 190; U.S. list, 43, 44 “transcriptome profiling,” 45 Transformational Medical Technologies Initiative, 101, 108 trust: neuroeconomics and, 84–86; oxytocin increasing, 52, 79–86, 81fig Tucker, Jonathan, 99, 120; “Verifying the Chemical Weapons Ban: Missing Elements,” 189–91 United Kingdom: biodefense, 120, 183; biosafety, 120; BW, 3, 20–21, 24, 138; BWC, 105, 138–39, 143, 147–48; BW not needed along with nuclear weapons, 11, 22, 24; Chemical and Biological Defence Establishment at Porton Down, 88; CW, 19; Institute for Public Policy Research (IPPR) Commission on National Security for the 21st Century, 90; International Institute for Strategic

Index

245

Studies (IISS), 170; life sciences research with dual-use agents, 129; mid-spectrum agents, 23. See also British troops United Nations: Department for Disarmament Affairs Geneva branch, 148; Secretary General’s investigations of alleged use, 20, 143; UNESCO, 176; UNMOVIC (United Nations Monitoring, Verification, and Inspection Commission), 23; UNSCOM (United Nations Special Commission), 23, 155–56. See also UN Security Council (UNSC) United States: anthrax attacks, 8, 90, 94, 102–3, 117, 119, 121, 125, 153; Arms Control and Disarmament Agency, 137; biodefense, 4, 7–8, 9, 89–109, 117, 120–21, 183, 184–85; vs. bioterrorism, 90–92, 95, 117, 120–21, 153; Bush administration, 90, 104, 119–20; BW, 3, 4, 21, 22, 103, 139; BWC, 3, 4, 95–96, 99, 103–9, 139, 141–43, 146, 155, 156, 183–86; BZ program, 23; Civil War, 15; CW, 3–4, 18–19, 31, 33, 139, 160, 161–64, 177, 187, 190; CWC, 104, 105, 108–9, 160, 161–64, 177, 187, 193; CW stockpiles, 160, 161–64, 177, 187, 193; “Decade of the Brain,” 61; Geneva Protocol, 157; NIMH, 63–64, 82–83; 9/11, 8, 97, 101, 117, 153; Nixon administration abandoning BW, 3, 22, 139; and North Korea, 170; Obama administration, 8, 95, 98, 104, 156; PATRIOT Act (2001), 119–20, 121; Reagan administration and CW, 3, 18–19; Russian CW destruction program, 161; Select Agent Rule, 120– 21; UN Security Council (UNSC) Resolution 1540 (2004), 116; Vietnam War, 27, 31, 33, 96, 139. See also Cold War; Department...; National... Uniting and Strengthening America

246

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by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act (PATRIOT Act, USA 2001), 119–20, 121 University of California at Berkeley, governance recommendation, 42 University of Pittsburgh Medical Center, Center for Biosecurity, 92 UN Security Council (UNSC), 128; BWC complaint, 142–43; Cease-Fire Resolution (1991), 23; legally binding obligations, 117; Resolution 1540 (2004), 112, 115–17, 135, 194; Resolution 1673 (2006), 116; Resolution 1810 (2008), 116–17; Resolution 1977 (2011), 116 vaccines, 5, 35, 37; aerosol delivery, 49–50; biodefense, 92, 100, 101; DNAbased, 50; for infectious diseases, 122; viral vectors, 52 vaccinia virus, 53 vasopressin, 58, 83–84, 86 Venter Institute, 40, 42 VEREX, BWC, 145 verification of compliance, BWC, 103, 139–46, 154–56, 184–85, 189, 192, 196–97 Verification Research, Training and Information Centre (VERTIC), 150 verification/Verification Annex, CWC, 113, 157, 159, 160, 164–67, 187, 190, 193, 196, 197 Vero Labs, 52 Vietnam War, 27, 31, 33, 96, 139 viral vectors, 48, 52–56; aerosol delivery, 55–56, 59; gene therapy, 52–55, 59; injection, 55; nonviral vectors, 54–55 virulence factor information repository (VIREP), 43 viruses, 20, 38–39; adenoviruses and adeno-associated viruses, 53, 55; antiviral drugs, 5, 35; artificial,

54–55; bacterial, 38, 154; Ebola, 55, 121; HIV/AIDS, 53, 125; lentiviral vectors, 53–54, 55; poliovirus, 38, 154; retroviral vectors, 54, 59; vaccinia, 53. See also viral vectors Vogel, Kathleen, 154 war economy, 14–15, 25, 32 warfare: changing nature of, 1, 11–34, 87, 181, 192, 193–95; fourth generation warfare (1995 to the present), 99; “low-intensity conflicts,” 25; new wars/”wars amongst the people,” 9, 15–16, 25–34, 181–82; “small wars,” 25. See also goals, war; military technology; old wars; states; substate groups Warsaw Pact, 29 Watson, James, 71 weapons of mass destruction. See WMD web of responses, 10, 89, 110–36, 158, 178, 183; export controls, 112–17, 135, 146, 158, 178, 188–89; mass casualty response, 92; strengthening, 194–95; U.S. biodefense and, 106–9, 117, 120–21; “web of deterrence,” 88, 110–11; “web of prevention,” 111, 134, 135; “web of protection,” 111. See also biodefense; deterrence; laws/ legislation; nonproliferation Western military forces, force preservation goal, 28, 32–33 Wheelis, Mark, 124 WHO, 124, 125–27, 135; neutrality of, 127, 128, 135; Preparedness for Deliberate Epidemics, 126–27 WMD (weapons of mass destruction): “apocalyptic results” triggered by, 181; Commission on the Prevention of WMD Proliferation, 89; CW linkages to, 138, 170; DOD missions vs., 94; Iraq, 155; states using, 96; Weapons of Mass Destruction



Commission, 99–100. See also military technology World Health Assembly (WHA), 125–26 World at Risk (Commission on the Prevention of WMD Proliferation), 89 World War I: BW, 20; CW, 1, 3, 11–12, 17, 24, 138, 157 World War II: CW not used, 3, 17–18;

Index

247

technology of maneuver vs. firepower and mass, 13; “wars amongst the people” following, 26 Wright, Susan, 91 Yao, X.-D., 38 Yemen, Egyptian war against, 19, 30–31, 33