A report of the second meeting of the New Defence Agenda’s Bioterrorism Reporting Group Countering Bioterrorism:
With the Support of
BIBLIOTHÈQUE SOLVAY, BRUSSELS 18 OCTOBER 2004 Smallpox is a disease of the past. Let’s keep it that way. Countering Bioterrorism: Science, Technology and Oversight
How can smallpox, a disease declared eradicated more Through a partnership with Cangene, Acambis also than 20 years ago, still pose a threat today? offers vaccinia immune globulin (VIG), an investigational A report of the second meeting of the New Defence Agenda’s Although the World Health Organization declared product undergoing evaluation in clinical trials in the smallpox eradicated in 1980, it is suspected that the virus is treatment of rare severe reactions that may be brought on Bioterrorism Reporting Group held outside official repositories and, as such, could be by the administration of smallpox vaccine. used by bioterrorists. As a safeguard, governments around the world are establishing emergency-use stockpiles of smallpox Bibliothèque Solvay, 18 October 2004 vaccines with Acambis’ investigational smallpox vaccine. The US Government, for instance, is putting in place a stockpile sufficient to provide a dose for every man, woman and child in the US. The highest modern standards are being applied in the development and manufacture of Acambis’ investigational smallpox vaccine. It is the most advanced second-generation smallpox vaccine in development, with an extensive clinical trial programme well underway. Acambis is planning to apply to the US and European Co-organised by Acambis & Symphogen regulatory authorities in 2005 for licensure of the vaccine.
Acambis is committed to developing a portfolio of 191 203 products for governments looking to protect their citizens from the threat of smallpox.
www.acambis.com/smallpox www.acambis.com/vig Contents
INTRODUCTION ...... 5 Giles Merritt, Director, New Defence Agenda
RECOMMENDATIONS ...... 6 Three recommendations resulting from the 18 October debate
PROGRAMME ...... 9
LIST OF PARTICIPANTS ...... 11
AN OVERVIEW ...... 14 NDA Bio-Defence Consultant Jill Dekker-Bellamy distributed an introductory document to participants on 18 October, outlining the structure of the day’s debate
SUMMARY OF DEBATES ...... 19 A detailed summary of the day’s discussion, highlighting participant interventions
ANALYSIS ...... 31 Jill Dekker-Bellamy provides a deeper look into the debate of 18 October and highlights pressing topics for future discussions
SELECTION OF PARTICIPANT CONTRIBUTIONS Mick Garstang ...... 59 John Haurum ...... 63 Florin Paul ...... 69 Randall Hyer ...... 77
ABOUT THE NDA ...... 87 Giles Merritt
Introduction
Giles Merritt Director, New Defence Agenda
T he NDA is proud to present the first publication of the its Bioterrorism Reporting Group. It reflects the two meetings in June and October 2004 of an international group of experts on developments in the biological terrorism field.
The need for policies to counter the use of biological agents as weapons is not in question. The use of disease as a weapon of mass destruction (WMD) has to be considered as a low probability, high consequence instrument. For if such an event were to occur, the consequences would be so severe that preparatory action could attenuate its effects. Biological weapons have the capacity to infect thousands of people while initiating equally heavy economic disruption by destroying agriculture and infecting animal populations.
Of all WMDs, biological weapons remain the most vulnerable to diversion, and are also the most difficult to detect. It is therefore imperative governments should begin to address the threat biological terrorism poses.
The aim of this report is to make recommendations that could help accelerate the slow- moving political process governing responses to bioterrorism. The NDA plans to build upon its experience as the only regular forum in Brussels where the worlds of NATO and the EU, industry, think-tanks, academia, politics and the media gather to discuss security and defence - to deliver the expertise it sees in its meetings right to policymakers’ doorsteps. 3 Recommendations following the NDA These aims are supported by Bioterrorism Reporting Group Meeting the following persons: of October 18th 2004
1 Improved national defences against bioterrorist attacks are Ronald M. Atlas Cyril Klement needed – especially regarding laboratory resources and R&D. Co-director Head of Department of Microbiology Center for the Deterrence of Biowarfare and Regional Institute of Public Health, Slovakia Bioterrorism University of Louisville, USA 2 There is a need for international coordination of effective Marion Koopmans Martin Bishop Rijksinstituut voor Volksgezondheid, crisis response. UK HGMP Resource Centre The Netherlands 3 Tim Brooks A real-time reporting system needs to be developed. Director, Public Health Affairs Stanislaw Majcherczyk Health Protection Agency Porton Down Director Regional Center of Prevention of Bioterrorism in Jill Dekker-Bellamy Central and Eastern Europe, Poland Future meetings of the NDA Bioterrorism Reporting Group during 2005 will be Bio-Defence Consultant looking at how to translate these broad recommendations into detailed submissions New Defence Agenda Márta Melles to governments and relevant multilateral bodies. The Bioterrorism Reporting Group’s General Director Toon Digneffe National Center for Epidemiology, Hungary members will in each case be seeking to answer four questions. Government Affairs Manager Baxter Stephen A. Morse 1 Who will be in charge? Myron D. Fottler Associate Director for Science Professor - Editor Bioterrorism Preparedness and Texas Tech Bioterrorism Studies Group, USA Response Program National Centre 2 How long will it take? for Infectious Diseases, USA Lindsey Foulkes Marketing Manager Mircea Mudura Acambis Counsellor 3 What will it cost? Mission of Romania to the EU Henri Garrigue Deputy Head, WMD Centre North Atlantic Treaty Organisation (NATO) Sergey V. Netesov 4 Deputy Director, Research What can we build upon? John Haurum State Research Center of Virology Chief Scientific Officer and Biotechnology VECTOR, Symphogen Russian Federation
NEW DEFENCE AGENDA 7 Michael W. Oborne Maurice Sanciaume Director, Multidisciplinary Issues Director, European Affairs Programme for 18 October meeting Organisation for Economic Co-operation Agilent Technologies and Development (OECD) Lev Sandakhchiev Louis Réchaussat Director General Countering Bioterrorism: Chairman of OECD Task Force on BRC’s State Research Center of Virology Organisation for Economic Co-operation and Biotechnology VECTOR, and Development (OECD) Russian Federation Science, Technology and Oversight
Thomas Ries Eric Stephen Senior Researcher Coordinator Finish National Defence College Chemical and Biological Medical R& D Creating Viable Infrastructures Directorate for Science, Technology, Guy Roberts and Human Performance, Canada Surveillance and laboratory capacity play key roles in containing any outbreaks of disease. Principal Director Negotiations Policy Office of the Secretary of Defense, USA Lars Thomsen But the recent increase in ‘hot labs’ for working on highly infectious and dangerous CEO pathogens is controversial. Which diseases are under active surveillance, what role will Roger Roffey Thomsen Bioscience A/S Director of Research the EU Communicable Disease Centre play, what is the current state of EU collaboration Unit for International and Security Affairs Ted Whiteside Ministry of Defence, Sweden Head of the Weapons of Mass Destruction Centre Gita Rutina North Atlantic Treaty Organisation Smallpox Case Study Director of Public Health Department (NATO) Ministry of Health, Latvia Smallpox is often used as a model disease for bio-terrorism applications as it has been:
Juan Jose Sanchez Ramos Eradicated; [two repositories VECTOR Could cause massive logistical problems to and CDC still hold strains] manage and contain if an outbreak were Ministry of Health, Military, Spain to occur; It poses a serious communicable disease threat; If one state did not have enough stockpiles of vaccine, indicators suggest If it were released it would have large numbers of people could try to psychological effects associated with acquire it in other states causing civil bio- terrorism as it is the ultimate in disruption; feared diseases; If it takes ten minutes per person to Has been researched as a bio-weapon inoculate using bifurcated needles, and has naturally killed thousands of how will rapid and massive vaccination people across the world; programmes be conducted? The Soviet Union successfully developed and adapted smallpox virus for use in strategic weapons;
NEW DEFENCE AGENDA 9 efforts? Vaccine research is essential yet for many bio-terror agents there is no vaccine Participants 18 October 2004 available. Should the EU increase its own diagnostic capability or create greater capacities elsewhere? As regards the proposed Global Incident Analysis and Alerting System, where does the EU stand and where does it need to go?
Consensus building on a European vaccine policy for listed agents must be undertaken Sebastien Alauzet Mick Garstang not only in the event of a deliberate disease outbreak but for natural disease response. Project Manager Director of Marketing Is it possible for the EU to build consensus around smallpox vaccine? Should the EU set Antidote Pharma Acambis a minimum requirement for stockpiling and a comprehensive European level protocol for Licinio Bingre do Amaral Hazel Gulliver responding to an outbreak? If it takes ten minutes per person to inoculate using bifurcated Counsellor Consultant needles, how will rapid and massive vaccination programmes be conducted? Delegation of Portugal to NATO Agilent Technologies
Tim Brooks Richard Guthrie Director, Public Health Affairs Project Leader, Health Protection Agency Porton Down Chemical and Biological Warfare SIPRI Geert Cami Managing Director John Haurum New Defence Agenda Chief Scientific Officer Symphogen Finn Chemnitz UNC Jessica Henderson North Atlantic Treaty Organisation (NATO) Project Manager Bioterrorism Reporting Group New Defence Agenda Guy Collyer National Counter Terrorism Security Office, UK Brian Howat Head of Unit Jill S. Dekker-Bellamy National Counter Terrorism Security Bio-Defence Consultant Office, UK New Defence Agenda Cyril Klement Toon Digneffe Head of Department of Microbiology Government Affairs Manager Regional Institute of Public Health, Baxter Slovakia
Henri Garrigue Marion Koopmans Deputy Head, WMD Centre Rijksinstituut voor Volksgezondheid, North Atlantic Treaty Organisation (NATO) The Netherlands
NEW DEFENCE AGENDA 11 Victor Kulagin Michael W. Oborne Gita Rutina Catherine Verrier-Mary Conseiller Director, Multidisciplinary Issues Director of Public Health Department Freelance / Senior medical writer Embassy of the Russian Federation Organisation for Economic Co-operation Ministry of Health, Latvia Avicenne to Belgium and Development (OECD) Juan Jose Sanchez Ramos Ted Whiteside Jan Kyncl Magnus Ovilius Ministry of Health, Military, Spain Head of the Weapons of Mass Destruction Centre Deputy Head, Department of Epidemiology Senior Administrator North Atlantic Treaty Organisation (NATO) National Institute of Public Health, European Commission Maurice Sanciaume Czech Republic Director, European Affairs Ralf Wilken Florin N. Paul Agilent Technologies Policy Adviser Giles Merritt Representation of Bremen to the EU Deputy Surgeon General Director Ministry of Defence, Romania Robert Snoeck New Defence Agenda Observer for 18 October* Rega Institute for Medical Research Mircea Mudura Roger Roffey Katholieke Universiteit Leuven, Belgium Randall N. Hyer Counsellor Director of Research Medical Officer, Civil Military Liaison Activity Mission of Romania to the EU Unit for International and Security Affairs Istvan Szolnoki and Alert and Response Operations, United Ministry of Defence, Sweden Office of Chief Medical Officer Nations World Health Organisation (WHO) Daniel Nord Orszagos Epidemiologiai Központ, Hungary Desk Officer Hendrik Roggen *Observers will not be part of any Weapons of Mass Destruction Project Assistant Brooks Tigner recommendations made by the NDA Commission (WMDC) New Defence Agenda EU Correspondent Defense News Bioterrorism Reporting Group
NEW DEFENCE AGENDA 13 An Overview
Drs. Jill Dekker-Bellamy Bio-Defence Consultant, New Defence Agenda
Mick Garstang, Randall Hyer and Drs. Jill Dekker-Bellamy
uring our last Meeting, the need to raise public awareness and high containment facilities or are current There are several key issues I would like participants discussed improve communication and coordination facilities satisfactory? Is it possible for the participants to bear in mind throughout preventing the diversion between public and private actors Member States of the European Union to the ensuing debate: of dangerous pathogens including the interaction between civil and agree on guidelines for oversight in the Dand select agents in transport and how military authorities. These topics can be bio-sciences? Should these ‘guidelines’ be First, what type of policies should 1 to strengthen the EU’s Dual-Use Export found in the first report available on the voluntary or should we develop a system be developed and ultimately Control Regime. Participants agreed that NDA website. of minimum mandatory requirements? adopted to ensure the European Union the objective of preventing and combating How can this be best achieved? Clearly the is prepared for a major bio-terrorism bioterrorism cuts across a wide range October 18th’s sessions were developed role of the scientific community is critical event? Should policy planning occur at the of challenges. These include: stockpiling to more fully discuss the implications of to public health security, therefore how national or European level? Several nations and harmonizing sufficient quantities science, technology and the potential for can a system of oversight be constructed have run bio-terror drills and simulations of vaccines between nations; tracking oversight in the bio-sciences. Scientific to enable legitimate science to continue and have done so in collaboration with shipments of dangerous pathogens, advancement and work on bio-defence unhindered? Should there be a central other Member States, such simulations enforcing international sanctions; vaccines often require the use of highly agency charged with undertaking and often test infrastructure, communication, coordinating verification and information secure laboratories known as European overseeing these tasks? capacity, response and containment. exchanges among key stakeholders; P4 ‘Protection Level 4’ or US standard Coordination among two or three states reorienting research and development Biological Safety Level 4 laboratories. How or comprehensive collaboration on funds toward prevention; strengthening do we balance the needs of science against specific areas related to bio-terrorism bio-security at high containment facilities; the potential for abuse? Do we need more does not necessarily translate into a
NEW DEFENCE AGENDA 15 comprehensive or actionable policy of 3 I would like to turn to the recent This could mean the difference between of influenza vaccine has been cut in half, preparedness. If gaps exist what should be crisis in the United States over life and death for that 30% of the ‘at risk’ desperate people have been lining up in done to address potential inadequacies? influenza vaccine supply. During the population. what has been termed ‘vaccine lines.’ People Chiron crisis on the 14th of October, have been arrested in some instances as 2 Second. Who will lead during the Oklahoma State Department of 4 Within the European Union, the desperation has lead to civil unrest. a multi-state outbreak of a Health cancelled a mass immunization range for stockpiling is anywhere deliberate disease such as Smallpox? bio-terrorism exercise due to a lack of from 3% to 100% population coverage. 6 This particular on-going crisis Who will be in charge and in a position flu vaccinations which they were planning In the absence of adequate stockpiles should serve as a wake up call for of authority to consolidate information to use during what was supposed of both Smallpox and VIG (the current nations and their seemingly optimistic on bio-terrorism and rapidly coordinate to be a mock Smallpox vaccination standard is considered one dose per approach to emergency public health emergency public health response? exercise. The exercise was halted so person for Smallpox and one dose per policy in the securing of adequate Who will allocate resources and flu vaccinations could be diverted and 10,000 people for VIG although the US stockpiles of vaccines. Given that make difficult decisions, particularly if saved for those considered at risk or military recommends one dose of VIG Development of a new drug currently resource allocation may not be ‘immuno compromised.’ The Health per 8,000 people) - what needs to be takes more than a decade and costs possible due to lack of/or insufficient Department spokesman apologized for done? The CDC notes that the absence $800 million to one billion to produce, stockpiles of drugs and vaccines? Who the inconvenience and said they were of sufficient quantities of VIG to protect according to a recent study undertaken will be responsible for ensuring lab trying their best to deal with this surprise against adverse reactions during a mass on Bio-Shield, what must be done for capacity to process samples? Who situation. If a smallpox outbreak were immunization campaign would likely mean governments to offer incentives to drug will be responsible if deficiencies in to occur today instead of an impending some people with adverse reactions makers? Limited and inconsistent funding both the number and type of medical influenza epidemic nearly thirty percent would go untreated. We must decide for Bio-defence vaccine research, personal trained to handle potentially of the population who now fall into the if this ‘collateral damage’ is acceptable. development and stockpiling must be thousands of victims and casualties is ‘immuno compromised’ or critical category Would the general public whom many of urgently addressed at the policy level. inadequate? Thousands is a conservative would be put at immediate risk by receiving us represent find it ‘acceptable?’ Should the EU consider a system similar estimate... in many expert group a vaccination. I will remind participants to the Bio-Shield plan implemented in the meetings particularly within the US that not only do we not have mandatory 5 Moreover there would be no way United States? Although many nations in Department of Defense, they are regulations for the stockpiling of smallpox to secure a sufficient supply of the European Union do not feel perhaps discussing millions of casualties. Who vaccine although the international licensed vaccine on short notice. The United placed at immediate risk from a Class A will take responsibility if the current standard is moving toward the adoption States is in fact experiencing heightened or High consequence disease by an act of plans fall far short of our estimates of a total population coverage policy, we demand as moderate public panic over terrorism, by this I am talking about the and expectations? These are general also lack a standard for VIG which is used the lack of flu vaccine drives more people group of diseases considered the most questions for which we need clear and to counter adverse reactions to smallpox to ensure they are vaccinated. Every day deadly and having the potential to be concise answers. vaccinations (vaccinia immune globulin). since the announcement that the US stock used for bio-terrorism.
NEW DEFENCE AGENDA 17 7 Modern travel means no nation and we have a responsibility to ensure we Summary of Debates is safe or isolated from secondary will be ready to respond. outbreaks. While many of us may feel complacent or secure with the status-quo, The bottom line is that ensure public a mass casualty bio-terrorism event will health, governments need to provide quickly outstrip current resources even pharmaceutical firms with the incentive the most conservative estimates generate to develop vaccines for diseases such as Approximately 40 representatives from Commission and EU member states,” she this outcome. Unfortunately and unlike smallpox, anthrax, botulism, plague and national governments, industry and said. “How do we balance the needs of the Oklahoma Department of Health influenza as well as genetically modified EU institutions gathered in Brussels on 18 science against its potential for abuse? we will not be able to apologize for the diseases, which have the potential to October for the second meeting of the Do we need more high-containment inconvenience or simply state that we tried devastate the world’s populations. I would NDA’s Bioterrorism Reporting Group facilities, for example? Are the current to do our best with the surprise situation. venture to say that if the general public to review the increasing risks Europe ones adequate? Can EU member states Before a deliberate outbreak occurs actually knew how insecure our current faces, assess the adequacy of its current agree on guidelines? And should these be we have an opportunity and I believe a stockpiling system is they would demand response mechanisms, and formulate voluntary or mandatory?” responsibility to ensure we know who will regulations be immediately put in place. recommendations to EU policymakers. lead, we have a responsibility to ensure They would demand set standards for Noting that across the EU national vaccine stable and secure vaccine production, stockpiling and the secure production of NDA Bio-Defence Consultant and Mode- norms range from stockpiles sufficient to minimum and adequate standard stockpiles bio-defence vaccines. rator for the event Jill Dekker-Bellamy inoculate only 3 percent of a population opened the meeting by asking participants in one member state to 100 percent in to bear in mind the central issues to frame another, Dekker warned of the ensuing their debate, such as vaccine stockpiling, chaos were a serious biological outbreak harmonisation of alert-response systems, to strike the EU. tracking the shipments of dangerous pathogens, enforcing international sanctions “The recent public unrest in the United and coordination of national and EU-level States over flu vaccine shortages policy in the fight against bioterrorist threats should be a wake-up call to complacent – including tighter cooperation between governments on this side of the Atlantic,” military and civilian authorities. she said. “If the general public knew how inadequate the situation is, they would “The goal of this meeting is to present demand regulatory action.” policy recommendations to the European
NEW DEFENCE AGENDA 19 A long, successful history particularly difficult issues and problems. would be needed. The WHO estimates Hyer also briefly touched on the capacity of cooperation Using a wide range of formal and informal approximately a 7 month lag in mass of militaries to carry out impressive logistic networks, including UN sister agencies, production of a smallpox vaccine. case management and search capabilities During his opening talk, observer ministries of health, national disease and expertise which the WHO may want Randall Hyer, Medical Officer with the control centres, regional and country Risks involved in routine vaccination may be to partner with in the future. World Health Organization’s Communicable offices, and military health institutions, greater than the known risk of the disease Disease Surveillance and Response unit, the WHO has established the world’s first itself, however. Research and development gave an overview of the WHO’s success in network that could make a contribution of safer vaccines and anti-viral, anti-bacterial The case for smallpox wiping out smallpox. to global outbreaks. Over 200 institutions drugs must be continued and countries vaccines can compare resources and provide must be encouraged to have a “guarantee,” Though WHO triumphantly declared assistance if needed to a member state requiring continuous surveillance systems. Noting that the WHO takes smallpox smallpox’s eradication in the mid-1970s, its in crisis. This is mainly done through the vaccines seriously, Mick Garstang, existence in research labs remains a source Alert Response Operations Unit – “like The likelihood of man-made threats is more Director of Marketing at the pharmaceutical of concern he said. “Smallpox is a point of a 24 hour, 7 days a week, on call, global, appreciated. There is increased surveillance company Acambis and Co-Chair of the day’s focus for terrorism. Most clinicians today, kind of 911 center for disease outbreaks” and research, perhaps this making us debate, agreed. “Independently, both US after all, haven’t seen a smallpox attack and – for which Dr. Hyer works. more aware of their use. Biotechnology and Russian scientists agree that smallpox is there is a steady decrease in the number of continues its relentless search for good and the highest risk. It kills a third of the people people who are immune to it. The globe Hyer highlighted that the disappearance unfortunately also use for nefarious reasons. it infects, and we have a relatively ‘naive’ has more people and more mobility of of diseases such as smallpox is man-made, We all know that world tensions remain [vulnerable] population compared to the people across it than ever before. We have which does not rule out the fact that and that the possibility for such a release of situation 30 years ago,” he said. “There’s a a fix for smallpox but it remains one of the its reappearance could be man-made. a virus is not such a remote possibility as we virtual stockpile across world of only about most dreaded diseases—one suited for When eradicating disease, two steps are might want to think. 200 million doses.” spreading fear, which is a primary terrorist needed – an eradication step and then a objective,” said Hyer. guarantee. “What we’re here discussing, Hyer emphasised the importance of There is a great need for bioterrorism partly, is a guarantee.“ communications, both among and preparedness, when we look at issues An independent organization under between the scientific communities, such as alert response protocols, as well the umbrella of the United Nations, An international WHO smallpox vaccine policymakers and the public. Speaking as vaccine stockpiles. We should consider the WHO has two focal selling points: bank has been proposed. This is probably somewhat tongue-in-check, Hyer also what percentage of a population stockpiles neutral and privileged access to countries. needed because of the potentially long admitted that the element of good luck should cover – countries such as the US, Along with credibility, it has the ability incubation period of the virus – you would also tends to help – as in the case with France and the UK have a policy of 1 dose to convey a message in the public health need a vaccine to contain the disease. SARS, when no countries with very weak per citizen whereas other countries can arena - important when confronting Today, it is estimated that 500 million doses health systems were touched. have policies for 1 dose per 3 citizens.
NEW DEFENCE AGENDA 21 Garstang advocated persuading national and According to Haurum, the only active remedy treating adverse reactions to vacaccina He stressed the need to discuss further EU authorities to build up their stockpiles for most bioterror agents as well as emerg- vacinations which occur in about 1 per the possibilities of a vaccine pathway for of vaccines, prefaced by a white paper on ing infectious diseases is the natural immune 10,000 of the population vaccinated against polyclone antibodies where an existing bio-terrorism to identify shortfalls and system. The immune system has evolved over smallpox. Haurum pointed out that VIG compound is approved, allowing for emergency response deficiencies. the centuries to deal with emerging diseases works to treat side effects of the smallpox updates every two years on specificities – mostly viruses. This is also the mechanism of vaccine, especially in cases of pregnancy on new strains. Symphogen is developing “Different EU member states have different use for vaccines, using a modified weakened and underlining disease. Pathogen specific a second generation recombinant VIG. response protocols,” he observed. What version of pathogens prior to exposure, cre- polyclonal antibodies (pAbs) have also would happen if there was a smallpox ating an immune resistance towards future successfully been used for postexposure Haurum emphasized the importance of outbreak in Spain, and France proceeded exposure. Vaccination requires a certain time therapy against botulinum in animal government funding to finance projects immediately to vaccinate while Italy waited of activation. Effective immune response can models. This technology is believed to be of this kind, stating that Symphogen for an identifiable case? This would produce take up to a week to appear. But if it was pos- suitable for prophylactic and therapeutic is currently working with the Health potential panic, with Italian citizens crossing sible to administer the reaction that comes use agaisnt all CDC category A agents Protection Agency to develop a vaccinia the border to get black-market vaccines. from the natural immune response to vaccina- which could be used for bio-terrorism or hemoglobin to be used specifically for bio- It could very easily lead to a political crisis tion, you would have immediate protection. bio-warfare. The technology is also highly defence purposes. “What we would benefit and unrest. Consensus is needed here. But promising for developing counter measures from, however, is a clear statement from unfortunately, he noted, we are nowhere This natural immune response to against avian influenza and other possible governments about what they want from near a consensus in Europe. vaccination mimics what occurs in pandemic emerging diseases. industry and how they intend to fund it.” antibodies in natural infection – with the pathogen circulating freely around Most importantly for the day’s meeting The case for VIG the vaccinated person. Up to millions of perhaps, was Haurum’s statement that Smallpox, stockpiling antibodies can all recognize the pathogen unfortunately current VIG manufacturing and the difficulties of John Haurum, Chief Scientific Officer at differently, creating a significant diversity. is based on blood sampling from people consensus the Danish biotech company Symphogen, Previous developments to recognize these with a high vaccinia virus titer and spoke of new technology aims to produce pathogens were restricted since they could purification of immunoglobulin, making target specific recombinant human only recognize one aspect of the pathogen. VIG extremely expensive to produce. Marion Koopmans of the Rijks-instituut polyclonal antibodies. During research This means that if the pathogen manages Of each donor sample of blood used to voor Volksgezondheid, the Netherlands’ in drug development programmes for to develop different strains, it can very extract immunoglobulin, only 1% can be national public health authority, also called infectious diseases, Symphogen realised the quickly escape recognition. effectively used to protect against the for a more inflected approach. “There is application for their technologies are suited intended virus. All other antibodies are need for stockpiles but, just as importantly, to the biodefence sector as well as emerging Vaccina immune globulin (VIG), is the only defending against all the other infectious we need an EU approach to stockpiling. infectious disease areas. known agent reported to be effective in agents individuals have encountered. This is a public health issue. We need to
NEW DEFENCE AGENDA 23 build a bio-defence agenda into the public they are so difficult to deliver to the the most important factor, since reactions A serious problem brought up by participants debate - here I mean the European CDC intended target.” He pointed out that to any bioterror attack should be the same. is the lack of consensus among Member and its mandate.” luckily, there isn’t much expertise in the Are new member states’ facilities up to States who don’t necessarily consider that spread of deliberate disease around the date? What about third world countries? resources available can be shared, since Florin Paul, Deputy Surgeon General world. Indeed, it is dissemination of the How easy is it to get a hold of these agents this is a highly sensitive matter of national at the Romanian Ministry of Defence, material that is the main challenge. for illegal purposes? security. Even if they were shared, questions was of the opinion however, that how arise as to how vaccines are transported we manage and shift around supplies Tim Brooks, Director of Public Health Brooks concurred, but cautioned that from one state to another, where are they and capacity — sharing vaccines — is Affairs at the UK’s Health Protection it is important that Europe’s response kept, and how are they distributed evenly? more important than building up huge Agency at Porton Down, reminded the infrastructure not separate bioterrorism stockpiles of them. group, however, that smallpox transmits from the natural outbreak of other diseases. Giles Merritt, Director of the NDA, then very easily from one person to another. “If you have already established networks intervened to steer the debate’s emerging Not all participants were convinced that “One primary case will cause 6-8 and vaccines to cover all diseases, then you themes., noting the debate was throwing highly virulent agents such as smallpox or secondary cases. That is why everyone already have the infrastructure in place to out more questions than answers: anthrax pose the scale of risk commonly fears it so much. Case in point: in 1972 one deal with bioterrorism.” The reality is that assumed today. person came back to Yugoslavia with the natural disease is the most likely candidate Participants clearly stated the wheel disease and it infected over 100 people – for example, influenza. should not be reinvented in existing Guy Collyer, of the UK’s National in three waves before the situation was networks to deal with disease exist. Counter Terrorism Security Office in finally brought under control.” Paul supported that view, stating we have But are we talking about strengthening London expressed he was a bit sceptical to use what we have in place. We also these networks? Or of rationalizing a when he saw that smallpox is always sorted can’t forget about animal and agricultural whole set of overlapping networks? out as the main hazard. The changes needed impacts as well. Numbers in stockpiling address very specific areas – more of Funding is certainly a concern, especially In a similar vein, Richard Guthrie, Shifting discussion to prevention, regional and international concern. at the EU level. Are we talking simply Project Leader for Chemical and Magnus Ovilius, Senior Administrator at But the day’s discussions should focus about more money or about different Biological Warfare at the Stockholm the European Commission’s Directorate on how we can build up European and rules? Merritt heard talk during the International Peace Research Institute, General for Justice & Home Affairs, international support, such as drugs, debate of a billion euro proposal for opined that risk in general is difficult to insisted that whatever pathogen is used, vaccines or personnel among the 25 security research awaiting ratification speculate about. “Very few of these kind “the effects are the same. It is the events Member States, more than on how many by EU Member States, but noticed of diseases in the last 60 years have killed leading up to the crisis that we need to vaccines we should stockpile. We must that Jill Dekker-Bellamy mentioned the a lot of people at one blow. Access to address.” Ovilius pointed out that in the build more capabilities in terms of sharing creation of a new vaccine could cost up these pathogens is not the issue because event of a crisis, which agent is used is not vaccines between states. to a billion euros alone…
NEW DEFENCE AGENDA 25 Decision making remains flux, both “What is needed is a syndronic, real He also brought up communication, traffic. The Commission needs to be in speed and in nature. The whole time surveillance system – with real time suggesting that the antidote to terror was able to bring in all the networks from the question of how Member States reporting, requiring a very significant most likely communication. A problem member states to circulate them within support each other is interesting since investment in infrastructure, as well as we’re seeing right now is the lack of the Union itself, working as a focal point we are dealing with very sensitive extensive training so that people know influenza vaccines in the United States, yet of communication for the 25 countries. matters of national security and more what to report and when. The challenges Hyer did not know of a serious influenza Bilateral relations are not enough. specifically, authority. Who has the are considerable, but the benefits are case in the US at that time. Yet people authority to transfer one sovereign enormous for any disease.” He called on are cueing for hours, paying ten times the How is an event of international nations’ pool of vaccines to another? the example of the UK’s influenza sentinel price. It’s a question of terror. consequence to be handled without a How far in advance do two leaders network – where general practitioners supranational body that has the public’s have to shake hands for the vaccines to report not true laboratory cases of Merritt brought the questions back to who’s confidence? As long as one event can be reach an infected country in time? To influenza, but system complexes that relate in charge of some of these different areas? isolated, fine. But what about something what extend do resources and logistics to it. These reports are used to plan health that takes place along a border or involving need a centralized mechanism? care provisions for any given current year. Koopmans stressed the need, along 3-4 Member States. A terrorist attack on with Richard Guthrie, for a current crisis the port of Rotterdam might kill only a few This provoked a lively exchange of views Dr. Hyer jumped in to make two key response system. When do you switch to people but the psychological impact would around the table. observations regarding public health a supranational system? Koopmans took shut down Europe. infrastructure and communication. Public the example of a situation such as the health infrastructure will face everything: SARS outbreak in China, what do you do Noting that the European Commission has What to recommend? from daily illness to a bio attack, and it if you know something is going on, but the just adopted a recommendation to set up is something the Commission can fund information is not being shared? What a new EU alert-crisis centre to coordinate There are different standards of biosafety and support. Looking at the American would have happened if that situation emergencies affecting two or more Member among European Member States. Several response after the anthrax attacks of 2001, took place in Europe. Can you impose States, Ovilius said the forthcoming centre participants, including Dr. Koopmans, Drs. the US government funded public health quarantine? When would procedures “doesn’t replace individual systems; it Dekker-Bellamy and Dr. Brooks, addressed infrastructure. People found out what switch from a national to European builds on them. There will be an interface the different standards of biosafety among the phone number was of the state lab authority? to channel the alerts so that all participants European Member States. next door, labs got more phone and fax are aware that an alert is there.” machines – what was missing was actually It was then suggested that perhaps the Brooks stressed the importance of remarkable. The WHO’s consistent European Council should take on the Brooks cautioned that whatever the pathogen results coming out of one message has been that investment, same structure as the Commission to be EU sets up, “it has to be credible. If you lab in a new Member State being the though difficult to sustain overtime as able to make these decisions – needing think there’s going to be a hand-over same as one from an old Member State. its not as visible as bioterrorism, is best. to be able to close borders or down air of sovereignty, well that is not going to
NEW DEFENCE AGENDA 27 happen. I think the WHO model is the one be European only – or global? Also, Agilent Technologies to follow: something voluntary, but with advocating some form of supra-national 2850 Centerville Road strong pressure for nations to respond to crisis response system seems evident. But Wilmington, DE 19808 its appeals.” this raises other questions: how to share Tel: 800-227-9770 Fax: 302-633-8953 Florin Paul warned that “it is important that resources; how authority is delegated, Web: www.agilent.com bioterrorism notification and prevention and the extent to which one country can be split into its scientific, technical and demand help from another,” he observed. political aspects.” PCR Based BWA Detection & Confirmation System As a final framing point, he asked: “Are Agilent Technologies Inc. and Invitrogen Corp have cooperated in the development of the Guthrie suggested a recommendation researchers doing the right things? If PathAlert™ Detection System, a complete screening and confirmatory detection system for infectious reminding Member States that despite the not, what incentives are needed to prod agents such as anthrax and smallpox. The PathAlert System features Invitrogen’s new PathAlert™ Detection Kit and the Agilent 2100 bioanalyzer. deeply sensitive nature of this subject, by them to move in the right direction— the time consensus on an issue is taken in a i.e., toward developing the right kind of Agilent 2100 Bioanalyzer The Agilent 2100 BioAnalyzer uses microfluidic lab-on-a-chip time of emergency, it may be too late. vaccines? If we can come up with just four technology to provide rapid (< 3 min/sample) qualitative and or five clear points that we can agree on, quantitative information on DNA, RNA, and proteins in biological samples. Biological pathogens can be detected and Merritt also pointed out existing entities then we have the beginning of a set of identified using the 2100 bioanalyzer after specific DNA that could help in a crisis situation that recommendations.” sequences from the chosen pathogens are amplified by polymerase chain reaction (PCR) using selective primers. might be overlooked. NATO, he alluded, is often associated with “hardware” and The primary advantage of the 2100 bioanalyzer relative to other PCR based detection methods, such as real time PCR, is that the things obviously military, rather than civil 2100 bioanalyzer allows for multiplex detection assays that can protection. This is a view Merritt was not simultaneously interrogate collected samples for many different types of bacteria and viruses. A multiplex assay enables a sure NATO would share. laboratory to routinely test for up to 16 PCR products in a single analysis vs. up to 4 products using Real Time PCR. This results in dramatically reduced operating costs as well as a more efficient Merritt wrapped up the session by workflow summarizing the broad recommen- dations that emerged from the workshop Invitrogen PathAlert Kit PathAlert�, a kit for detection of B. anthracis, Y. pestis, F. tularensis, and Orthopox, meets the debate, outlining three main aims for challenging requirements for sensitivity, specificity, throughput, and cost. Based on PCR technology recommendations. and proprietary novel modifications to reagents and primers, the kit includes a universal internal positive control for self diagnosis, selected dual target loci for sample detection, and corresponding engineered external positive controls for pathogen specific false positive readings when using the “It seems that our recommendations PathAlert system. Using the PathAlert multiplex-PCR kits with the Agilent 2100 bioanalyzer, the system can monitor multiple DNA targets and a series of internal controls in the same analysis should include the need for a real- without the multiplexing constraints imposed by conventional real-time PCR. time reporting system. But should this Analysis October 18
Drs. Jill Dekker-Bellamy Bio-Defence Consultant, New Defence Agenda Drs. Jill Dekker-Bellamy
Countering Bio-Terrorism: Science, Technology and Oversight
“Four points of view prevalent among enough organisms and dispersing them is national policy circles and the academic so difficult that it is within the reach of community at various times have served only the most sophisticated laboratories. to dismiss biological terrorism as nothing 4) Like the concept of a “nuclear winter,” more than a theoretical possibility. the potential destructiveness of bio- 1) Biological weapons have so seldom been weapons is essentially unthinkable and so deployed that precedent would suggest to be dismissed. Each of these arguments they will not be used. 2) Their use is so is without validity.” morally repugnant that no one would deign to use them. 3) The science of producing D.A.Hendersen, the Johns Hopkins University
1 Henderson, D.A., “Bioterrorism as a Public Health Threat”, Emerging Infectious Diseases, Vol. 4, No.3. Centers for Disease Control and Prevention, Atlanta, July-September 1998.
NEW DEFENCE AGENDA 31 Preface Introduction capacity, bio-security and the problems of have the highest priority because of their variation in standards, practice, regulation ability to spread rapidly, cause high On 18 October, the New Defence Agenda The last New Defence Agenda Bio- and technology. The original Member mortality and for which many have no presented the second in its new series of Terrorism Reporting Group on 21 June States which comprise the European vaccine or prophylactic intervention quarterly Expert Group Meetings on Bio- discussed the need to strengthen our Union have largely enjoyed advanced available. Many Class A3 diseases initially Terrorism. The Brainstorming session on ability to identify diseases. In our latest capability and capacity to conduct rapid, present with symptoms associated with 21 June opened the debate on the use of meeting, disease surveillance was sighted accurate diagnostic and reference testing influenza. It is therefore essential we disease as a weapon of mass destruction. as a crucial component of any national even for select biologic agents likely to be train medical professionals to identify This latest meeting saw the official launch public health security system. However used in a bio-terror attack. New Member potential cases of smallpox, anthrax, of the Bio-Terrorism Reporting Group. one of the newer challenges of disease States still face tremendous challenges in plague, botulism and tularemia among While the primary intention of the session surveillance in the post 911 environment building their infrastructure for disease other highly infectious diseases which was to follow on the recommendations is to determine if an outbreak is natural or surveillance, capacity and collaboration. could be suitable for bio-terrorism. At and suggestions developed from the if it is deliberate. Should a deliberate attack It is important to remember that wide the same time it is important to have the Brainstorming Meeting, new areas for be prepared for and responded too in the variation exists and to account for this in technical and scientific capacity to conduct debate were opened up; deepening the same way as a natural outbreak? Or does preparing for a regulatory approach to accurate diagnostics on possible agents. content and our understanding of the many the nature of bio-terrorism, the fact that counter bio-terrorism. facets of public health protection, security there is a well thought out planning period, It was deemed important to develop and defence, intrinsic components for the potential for greater spread due to standard diagnostic tests so results in one preparing to counter biological terrorism. either advanced dispersal techniques, or Designating and state can be interpreted in another. At the Participants were reminded that the goal the potential for a simultaneous release, detecting the intentional European level developing a “common” of the Bio-Terrorism Reporting Group is to mean that in countering a deliberate use of disease list of select agents should be undertaken. make policy recommendations to decision disease we may be required to engage in Many Member States have lists which makers. This report therefore presents more extensive rapid assessments and are variable even among the national the key policy recommendations experts interventions? Should we place more In 2002, the Chief Medical Officer of the UK institutes; listed select agents can vary agreed formed the critical areas vital to diseases under active surveillance? Should reported that anthrax, botulism, bubonic from one laboratory to another. While preparing for and addressing mass casualty we build in a system embedded within plague, smallpox and tularaemia are the most list the above select agents, some bio-terrorism. our existing capacity to identify and agents that have been most extensively laboratories drop botulinium toxin for their respond to deliberate disease outbreak? studied and used in scenario plans2. These lists and do not include viral haemorrhagic
Building upon the last Bio-Terrorism Report 2 The Select Committee on Science and Technology, “The Scientific Response to Terrorism”, The United Kingdom Parliament, House of Commons, Session we take a deeper look into the issues and 2002-2003, Science and Technology Committee Publications, 6 November 2003. URL: http://www.publications.parliament.uk/pa/cm200203/cmselect/cmsctech/415/41502.htm the structure of European surveillance, 3 See table 1. Charles Kemp, Infectious Diseases, 2001-2004.
NEW DEFENCE AGENDA 33 Disease & Agent Probable BW Incubation Signs & Symptoms Treatment of Prophylaxis Vaccine Type Route (days) (incomplete) mass casualties used to prevent (prophylactic) and treat Bio-shield post exposure casualties of a bio-terror Anthrax: Aerosol; 1-7 days Febrile flu-like; then Ciprofloxacin or Ciprofloxacin Available, but Spore-forming no person- (or more) severe respiratory Doxycycline or, if susceptible, short supply attack. As there is no way to estimate Bio-Shield is a 10 year, 6 billion dollar plan bacteria to person distress Doxycycline return on research and development costs to increase research and drug development Smallpox: Aerosol; 7-17 days High fever, prostration; Supportive only None Available but Virus then person- then rash & pustules short supply for producing ‘orphan’ drugs , participants for bio-defence vaccines. A number of to person
Plague: Aerosol; 1-6 days Fulminate pneumonia; Doxycycline or Doxycycline or Not now discussed ways to encourage incentives bio-defence analysts and industry experts Bacteria then person- then sepsis Ciprofloxacin Ciprofloxacin available to person and the potential for setting minimum polled on Bio-Shield were less optimistic
Botulism: Aerosol; 2 hours Bulbar nerve palsies; Passive immuni- Passive im- Antitoxin in standards for government support. about the ability of governments to offer Toxin from no person- to 8 days descending flaccid zation (antitoxin); munization short supplyv bacteria to person paralysis supportive care (antitoxin) incentives for the pharmaceutical industry
Tularemia: Aerosol; 1-14 days Febrile, flu-like; respi- Doxycycline or Doxycycline or Not widely On a similar front legislation to increase to continue research and development into Bacteria no person- ratory; sepsis Ciprofloxacin Ciprofloxacin available & to person incomplete bio-defence vaccine research was orphan drugs. This they concluded could protection designated as a significant function of have significant and detrimental effects Table 1. Summary of Selected Class A Biological Warfare Agent preparing to meet emergency public when coping with large scale epidemics health challenges into the 21st Century. such as SARS or influenza, and would Experts opened the discussion on not be enough to induce development problematic areas related to orphan of counter measures nations need for fevers. A system which rates factors such health security for the prevention and drugs4, government support for research effective bio-defence. Moreover the lack as likelihood for weaponization, ease of containment of deliberate disease? Is the into drug development on diseases of stockpiling of bio-defence vaccines and delivery and the threat of mass casualty focus on public health security missing the for which there can be no projection vaccines for naturally occurring diseases is probably a more accurate reflection of point? Should we also strive to balance of return. How can we maintain our could compromise not only public health probable threat agents. However given the the strengthening of emergency public defensive bio-tech edge without sacrificing but civil order; as nations with 1 dose per potential outcome of a Class A agent and/ health policy and the current health highly advanced research into some of the person smallpox stockpiled, verses nations or smallpox strike, while the probability infrastructure with security, intelligence and most devastating diseases which have the with no or low smallpox vaccine stockpiles may be low, the outcome of such an attack military infrastructures to create a more potential to kill millions of people? We may try to acquire vaccines in other states.5 would be so devastating we cannot fail comprehensive approach to bio-defence? touched upon the Bio-Shield legislation The point was made that it is easy to be to account for the most deadly diseases. in the United States where governmental moderate when your nation has 100% What should be done at the policy Stockpiling and Vaccine guarantees for drugs which may not return coverage. Many east European states only level to encourage harmonizing a list Research the investment might be considered have a virtual stockpile of smallpox and VIG6 of select agents, strengthen laboratory within a European framework. (Vaccinia Immune Globulin), if smallpox capacity, increase disease surveillance A central theme in the discussions was
4 The term “orphan drug” refers to a product that treats a rare disease affecting fewer than 200,000 people. The Orphan Drug act was adopted in the United and standardize tests? How best can we the need to ensure Member States have States as a means to encourage research and development of counter-measures for rare diseases. Regulation (EC) No 141/2000 of 16 December 1999, sets out a Community procedure for designating drugs as orphan medicinal products. The Regulation establishes the Committee for Orphan Medicinal Products achieve these crucial components of public adequate and consistent stockpiles of drugs (COMP), within the EMEA, which is responsible for examining applications for orphan medicinal product designation.
NEW DEFENCE AGENDA 35 were to break out the populations in these public health crisis is therefore an essential of infectious diseases (see: MEMO/03/155) reference labs, it is essential to strengthen states would probably not take a moderate tool in preventing and reducing panic which cooperation on investigating and controlling the ability of the new Member States to approach and there exists the real risk of could result during smallpox or naturally disease is largely ad hoc.10 For example, participate in such programmes. This can civil breakdown. Discussions then focused occurring epidemic for which there are the small EU team sent to help the WHO best be achieved through strengthening on vaccine availability to nations who limited supplies of vaccine available. investigate avian influenza in Vietnam (see technical and scientific capacity throughout can not stockpile. The sharing of vaccine IP/04/165) is part of an EU project to train the new Member States. The new Member stockpiles and the potential for the World disease investigation experts11. The EU States were invited to participate for Health Organization to moderate in such a The European expert group on SARS created during the example in Enter-Net prior to Accession. crisis would be highly advantageous. Communicable Disease outbreak in spring 2003 was put together At that time several eastern national Center and Wider under the European Communicable reference labs lacked the computer An area often overlooked but key to Disease Network.12 While these have systems needed to collaborate; in a few any pubic health emergency is the Collaboration been good short term solutions, they are labs test results were still being written communication of the risk. Public not sustainable in the long term.13 The on paper. While an ECDC will hopefully perceptions and opinions often determine The Reporting Group discussed the ECDC is on course to become operational support surveillance programmes across the resolution of high concern, high stress European Communicable Disease in 2005. The EU summit in December the EU, participation by all Member or emotionally charged issues.7 The Center (ECDC) as a possible choice 2003 decided that the ECDC will be based States must be addressed. When a lab intentional or unintentional introduction in leading during a deliberate disease in Stockholm, Sweden. struggles to identify salmonella, a common of a pathogen in an urban setting presents strike.9 However given that intelligence and foodborne disease; advanced technologies severe communication challenges.8 Public security sector agencies from a number of required to rapidly processes and confirm perception can have a profound impact on Member States would likely be involved, Epidemiology samples in the event of unusual clusters or the successful outcome of a public health it was unclear how such agencies would Surveillance multiple mass outbreaks, may mean some emergency. The media can play a positive liaise with the ECDC. Moreover although labs would not be able to successfully and central role in how the threat is the European Union has a system for the As appeared in the first Bio-Terrorism identify or rapidly process samples. This managed. Risk communication during a Europe-wide epidemiological surveillance Reporting Group report, the European could mean the difference between Union has many well established rapid containment or mass casualties programmes for detecting and reporting from widespread communicable disease. 5 The halving of the US supply of influenza vaccine with the closure of Chiron production in the UK, has lead to civil unrest in some US states. US citizens are now crossing the boarder to Canada to receive vaccines. Some people have died waiting all night for inoculations and the US reports several arrests due to civil outbreaks of disease.14 While the disorder. Aventis Pasteur the only other US supplier has recently found another 2.4 million doses but this continues to leave the US short of approximately 50 million doses. European CDC will likely increase disease Participants identified a number of gaps 6 The European Union Commission recommends access to VIG to supplement smallpox stockpiling programmes. In the US the Centers for Disease Control and Prevention (CDC) is supplementing its smallpox stockpiling strategy through the stocking of Vaccinia Immune Globulin (Human) Injection (C-VIG). Recom- mended stockpiling is at a rate of 1 dose of C-VIG per 10,000 doses of stockpiled vaccine. Acambis URL: http://www.acambis.com/default.asp?id=622 surveillance capacity in states with existing and lack of infrastructure. It was noted 7-8 Covello, Vincent, T., Richard G. Peters, Joseph G. Wojtecki and Richard C. Hyde, “Risk Communication, the West Nile Virus Epidemic and Bioterrorism: Respond- ing to the Communication Challenges posed by the Intentional or Unintentional Release of a Pathogen in an Urban Setting”, Journal of Urban Health: Bulletin of collaboration such as among the 8 P4 improved surveillance efforts should the New York Academic of Medicine, Vol. 78, No.2. June 2001, p382-392. 9 The Council of Ministers agreed on the Commission’s proposal to create a new European Centre for Disease Prevention and Control (ECDC European Commission Press Release, “New EU Centre for Disease Prevention and Control adopted”, Ref.: IP/04/427; 31/03/2004. 10-14 European Commission Press Release, “New EU Centre for Disease Prevention and Control adopted”, Ref.: IP/04/427; 31/03/2004. Accessed at: http://europa.eu.int/rapid/pressReleasesAction.do?reference=IP/04/427&format=HTML&aged=0&language=EN&guiLanguage=en Accessed at: http://europa.eu.int/rapid/pressReleasesAction.do?reference=IP/04/427&format=HTML&aged=0&language=EN&guiLanguage=en
NEW DEFENCE AGENDA 37 be instituted with as close to real-time reemerging diseases occur. Should we also (P3/P4) are highly specialized facilities.20 Research on the basic biology and data gathering as possible.15 All facets of be working toward a stronger response The potential to increase capacity in new mechanisms of disease causation in surveillance should be used, to include capability? Strengthening the infrastructure states of the European Union was discussed select pathogens; emergency visits, laboratory data, of coordination and leadership in areas within the wider framework of capacity pharmacy use, school absenteeism, or any critical to identifying and containing an strengthening. Policy recommendations Identification of intervention into other data that correlate with an increase emergency public health crisis? Who for standardizing bio-safety regulations as human immune responses to toxicity in infectious disease.16 Robust surveillance should lead? Should the Ministries of well as the number of available P3 facilities and infection; systems are essential to detecting any Public Health from each Member State were areas considered to be significant for emerging or reemerging disease; quick agree on a rotation of leadership? Should increasing preparedness. Creation of systems to rapidly detect recognition of any change in disease simulations be routinely conducted to test the presence of select agents in the patterns will facilitate determining the the preparedness of this leadership? The ability to diagnose Class A or select environment; source and preventing further exposure, agents requires the use of advanced which should be the key driving force laboratories. As mentioned in our previous Development of methods for more behind any epidemiologic investigation.17 Hot labs: Why the Report, P4 laboratories are rare. There effectively diagnosing human exposure to Through strong epidemiologic training, a Controversy? are 8 within the European Union. P3 and infection from bio-terrorism agents; close attention to disease patterns, and a concepts and considerations laboratories are more common yet the healthy respect for the threat of biological challenges to undertake diagnostics on a Creation of new therapeutic inter- terrorism, potential problems can be The meeting touched upon the issue of high potentially unknown pathogen make the use ventions for specific as well as broad discovered rapidly, and actions can be containment facilities or what are commonly of such facilities imperative. Concurrently, categories of pathogens; and taken to decrease the impact of disease, referred too as ‘hot’ labs. National Reference while accidents in these labs are rare, regardless of its origin.18 and bio-defence laboratories are critical they do occur. P4 in many Member States Production of vaccines against specific aspect of public health infrastructure and are associated with or conduct research agents.21 Within the Member States it is important bio-defence. Bio-safety labs are categorized in collaboration with defence. Biological to build upon existing assets. To increase into four levels based on the level of danger defense laboratories study organisms Controversy over bio-defence research result disease surveillance capacity particularly associated with the diseases they conduct categorized as potential agents of bio- from both the secrecy associated with these in states which lack this, while structuring research, analysis and diagnostics upon.19 terrorism. Much of the work in these facilities facilities and the often dual-use nature of the an approach which takes bio-terrorism The US Bio-Safety Level (BSL) 3 and 4 or falls into one of the following six categories: research. As previously mentioned it can be into consideration when emerging or European standard Protection 3 or 4
20 Bacterial usually include: tularaemia, pulmonary and nonpulmonary tuberculosis, glanders, melioidosis, typhoid fever, paratyphoid fever, plague (bubonic, pneumonic, and septicaemic), Q fever, typhus (scrub and epidemic), and Rocky Mountain Spotted Fever. Viral agents usually include over 160 arboroviruses such as West Nile, Yellow fever, encephalitis (Dengue fever, Hantavirus various others); lymphocytic choriomeningitis(LCM) (neurotrophic strains), Hepatitis B and C, HIV, and Rift Vally Fever. Fungal agents in BSL3 include: Coccidioides immitis (causes pulmonary disease), pulmonary histoplasmosis, and North American 15-18 Pavlin, Julie Col., “Epidemiology of Bioterrorism”, Emerging Infectious Diseases, Centers for Disease Control and Prevention, Vol.5 No.4, July-August 1999, Blastomycosis. BSL 4 covers a more limited group of exotic pathogens that pose a high risk of exposure and infection ratio to personel, the community and the Accessed at: http://www.cdc.gov/ncidod/EID/vol5no4/pavlin.htm environment if released. Includes” filoviruses, arenaviruses, arboroviruses such as Junin, Marburg, Congo-Crimean, hemorrhagic fever, Omsk Hemorrhagic fever, Lassa, Machupo, Ebola, Sabia and Encephalmomyltis. 19 Labs that deal with organisms that would not typically cause disease in a healthy human, such as E. coli, are given a Biosafety Level 1 designation. Biosafety Level 3 includes viruses, bacteria, and fungal agents. 21 Boston University Biodefence, A project of the Council for Responsible Genetics. Cambridge, Mass. 2003.
NEW DEFENCE AGENDA 39 difficult to distinguish between offensive and P3 are the result of accidents which Should the Member States of the “The shipping of deadly, live bacteria is defensive applications.22 Almost all of the heightened public awareness to the risk European Union move toward a system in theory controlled by regulations and requirements of Level 4 facilities deal with of bio-defence research. Four cases of of laboratory accreditation to standardize permits and it might typically be handled preventing accidents; and then the focus are SARS-CoV were laboratory acquired.23 bio-safety and bio-security? Should we by courier rather than sent through the almost exclusively on accidents from within While the last case of endemic Smallpox build consensus on bio-safety and set mails. These safety provisions should the Lab (preventing infections) not from occurred in Somalia in 1977, the last recorded minimum criteria which each lab must work. In June 2004, it was discovered that outside forces. For example, what happens case in humans occurred in England in 1978; demonstrate in order to transport, researchers at the Children’s Hospital in case of massive power failure, fire, and this case was a Laboratory Acquired Disease hold and conduct research on high Oakland Research Institute in Oakland, explosion? Although there are a number of (LAD). Should we be concerned not only consequence Class A and B pathogens? California, were working with deadly, live examples of laboratory accidents involving about the protection level under which such anthrax bacteria when they thought they select agents, the increased investment in high consequence diseases are held24 but The following example noted by the were using only a non-hazardous, dead bio-defense funding has created many more the bio-safety standards and practices which Massachusetts Institute of Technology, bacterium. Six researchers, who were research sites. The present complexity of can vary widely from one lab to the next? Security Studies Programme reflects the involved in a project on anthrax vaccine, shipping, handling, and research has increased The four confirmed laboratory acquired growing public concern of laboratories handled the deadly bacteria and others the risks of accidents that can pose harm within SARS outbreaks reflect the dangers to engaged in bio-defence research and may have been exposed.”26 and beyond the laboratory. These are all areas public health security that arise from the potential need for a system of which the European Union Member States accidental laboratory acquired disease and certification. While this incident occurred “That a deadly strain had been sent was must consider when developing regulations to the potential release of biological pathogens in the United States such ‘accidents’ have not immediately reported. Researcher’s prevent accidental and deliberate exposure. which may only exist in a laboratory setting. happened in a number of facilities. A injected mice with what they thought were In 1977 an influenza virus not reported European approach which standardizes dead anthrax bacteria. It was only after for 27 years inexplicably reappeared and procedures and requires laboratory several days, when all the mice in the Accidents do happen circulated worldwide this too may have been certification on a wider set of criteria than experiment died, that the lead researchers a laboratory release or LAD.25 How safe are currently employed may reduce the risk were told there might be a problem. Then The concern and controversy surrounding the most dangerous pathogens held in high of such accidents. It may also help reduce a second batch of mice was inoculated P4 facilities and to a more limited extent containment facilities? the risk of diversion and the potential for and cultures obtained from a dead mouse bio-terrorism. The following is an account revealed virulent anthrax.”27 22 Boston University Biodefence, A project of the Council for Responsible Genetics. Cambridge, Mass. 2003. of one such accident. 23 On 17, December 2003, a 44 year-old male researcher was confirmed to have SARS in Taiwan. The patient is a senior scientist in the Institute of Preventive Medicine, National Defense University in Taipei, conducting SARS Co-V research. He was working on the SARS study in a Level 4 Laboratory in Taiwan. On the fifth of May 2004, WHO reported two researchers working at the National Institute of Virology in Beijing contracted SARS although they were not working directly on active SARS. On 8 September Singapore confirmed a laboratory acquired SARS case. The patient was conducting research on the West Nile virus in a laboratory that was also conducting research using active SARS-CoV (coronavirus). 24 There is a significant difference between fist and secondary barrier methods for a P3 compared to those of a P4. 25 Unintentional release of extinct human-adapted viruses arguably poses a serious threat to global health as bioterrorism or a natural outbreak. Again an example from influenza is instructive: Genetic sequencing of the global pandemic 1977 H1N1 influenza virus has shown it to be identical to an H1N1 strain that became extinct outside laboratories in the 1950’s. The most plausible scenario is that the 1977 virus was one stored for decades in a laboratory freezer and thawed for experimental study during the 1976 swine influenza scare. See: Donald S. Burke, “Ignoring Deadly Viruses”, Johns Hopkins Bloomburg School of Public Health, 26-27 Massachusetts Institute of Technology, Security Studies Programme, Level Four Bio-Safety Laboratories: Public Information and Risk Analysis Baltimore, January 2004. URL: http://www.jhsph.edu/Press_Room/Press_Releases/PR_2004/Burke_WSJ_viruses.html (High Risk Scenarios). Accessed at: http://web.mit.edu/ssp/twg/level4/scenarios.html on 20, October 2004
NEW DEFENCE AGENDA 41 “The source of the virulent bacterium the reporting of accidents which occur Should regulations be established to the type of biological pathogen (disease) was the Southern Research Institute of in these facilities. On May fifth of 2004 certify P3 and P4 laboratories on an most likely to be deployed or used in Frederick, Maryland, an affiliate of Fort a senior researcher at the State Research annual basis using standard criteria and material or weapon form. While Class Detrick. This company maintains two Centre of Virology and Biotechnology independent audits? B diseases and emerging disease pose a “hot labs,” one in Frederick and another known as Vector died after a sharps Should the EU require the reporting tremendous challenge to public health, the in Birmingham, Alabama. Thomas Voss, accident involving hemorrhagic Ebola. of accidents in P3 and P4 laboratories bio-terror potential of such organisms is in charge of the company’s emerging There is no requirement to report such which could result in Laboratory considered within the European Union’s infectious disease program, initially said accidents so World Health Organization Acquired Diseases such as SARS? RAS-BICHAT programme.29 Although that “We receive [select] agents on a was not informed until nearly two weeks emerging and multi-resistant strains of routine basis. But on our end, we ship very later. They could not therefore provide Should the EU set standards on what salmonella and e-coli may pose a significant infrequently. I don’t even recall shipping treatment which may have saved her life. constitutes a P3 and limit application of health risk if released and their natural live agents.” The deadly agent was The secrecy surrounding select agent plus practices? occurrence greatly impacts public health shipped via FedEx, double-boxed. The research continues to be controversial. and economic sectors annually, lab capacity California Department of Health Services Should the EU require and standardize to identify foodborne pathogens such as e- was called in, as were the FBI and the security screening for personnel coli, salmonella, listeria and campylobacter CDC. Samples of the anthrax bacterium Policy Options and working on select agents? is fairly well established both within the were sent to CDC in Atlanta for testing. Considerations EU under the Enter-Net30 programme The local community was not informed and Salm-Gene.31 While the public may about research on anthrax vaccine. The Should we be concerned? Each of these The Bio-Terror Debate have cause to be concerned about an act institute is not registered for work on live statements and examples may help to of terrorism using foodborne or Class B select agents. Before the 2001 anthrax better define a European approach to bio- The meeting witnessed debate on whether diseases, the focus of this reporting group, letters, there were around 12 facilities defence, how we conceive of ‘acceptable or not bio-terrorism actually poses the similar to other bio-defence forums is to working with the anthrax bacterium. Now risk’ in the bio-sciences and ultimately threat some believe it does; or whether discuss the more widely feared Class A group it appears that there are 350.”28 the regulatory approach to encourage this threat was more marginal and should for which there are fewer interventions bio-defence research while reducing be considered to have a low probability and for which the human and economic A wider concern to both the European the risk associated with this research. and low priority. There was also debate on costs would most certainly be higher. Union and international community Mediating the threat posed either by as a whole is the reporting not only of naturally occurring or deliberate disease 29 Rapid Alert System for Biological and Chemical Attacks and Threats. research on dangerous pathogens but is a delicate issue. 30 Enter-net is the international surveillance network for human gastrointestinal infections. The participants in the network are the microbiologist in charge of the national reference laboratory for salmonella and E. coli infections, and the epidemiologist responsible the national surveillance of these diseases. The network involves all 15 countries of the European Union (EU), plus Australia, Canada, Japan, South Africa, Switzerland and Norway. The newly associated states of Eastern Europe will formally be able to join the network in 2003, although an informal working relationship already exists with the Czech Republic, Hungary, Latvia and Poland. The network is funded by the European Commission (EC) DG Health and Consumer Protection, and conducts international surveillance of salmonellosis and verocytotoxin producing Escherichia coli (VTEC) O157, including antimicrobial resistance. 28 Massachusetts Institute of Technology, Security Studies Programme, Level Four Bio-Safety Laboratories: Public Information and Risk Analysis 31 Salm-Gene is a project funded by the European Commission (DG-RESEARCH) aiming to strengthen international Salmonella surveillance through molecular (High Risk Scenarios). Accessed at: http://web.mit.edu/ssp/twg/level4/scenarios.html on 20, October 2004 strain typing and differentiation
NEW DEFENCE AGENDA 43 World Health Organization among other It is quantifiable and it is on-going. While Medicine in 1974 and obtained a masters communications equipment to Chechnya and major health centers such as the Centers public health security is vital to this degree in surgery. He is an optical surgeon. Algeria. Six of the previous detentions involved for Disease Control and Prevention in equation so too is an understanding of His father was a professor of pharmacology. suspected members of the Salafist Group for Atlanta list the specific diseases associated the nature of the threat and the vital role He has lived in Denmark and Switzerland. Call and Combat, which formed in 1998 as with bio-terrorism as: anthrax, botulism, security, defence and intelligence agencies a faction of Groupe Islamique Armé (GIA). plague, smallpox, tularaemia.32 The World play toward preventing bio-terrorism. Within the EU several cases have come Health Organization has recognized to light which would appear to support Four Islamic terror suspects arrested in threats to food safety in it’s “Terrorist The potential for al Qaeda to use biological intelligence claims that al Qaeda is seeking 2003 in France identified as Merouane Threats to Food: Guidance for Establishing weapons has and continues to be a focus biological capability. In December 2002, Benahmed, Mourredine Merabet, Menad and Strengthening Prevention and of concern within expert defence and French counter-terror agents arrested Benchellali and Ahmed Belhout had lived Response Systems.” While discussions on intelligence circles. It has been documented four suspected terrorists and seized two in Spain and was closely associated with probability of a Class A event are relevant that al Qaeda training camp (abu-Khabab) phials of substance (unidentified) along the suspects arrested in Italy. Merouane and the potential of a Class B or foodborne outside Jalalabad, Afghanistan, named after with “Hazmat” (hazardous materials) suits. Benahmed is an expert in bio-chem and pathogen attack may be more likely, this al-Qaeda’s Egyptian born chemical and The four suspects were thought to have explosives. Common denominators among forum is designed to address Class A biological expert Midhat Mursi who goes spent time in Chechnya. Terrorist factions these men and their associates include: major biological attacks. Class B may be by the alias Abu Khabab, ran chemical and from the Groupe Islamique Armé34 (GIA) Training in chemical and biological weapons better served within a special focus on biological training programmes. Moreover have been notably involved in Albanian at a camp in the Transcaucus (Pankisi and agro-industrial threats with public health al-Qaeda’s manual “Encyclopedia of organized crime and have strong ties to Korda Gorges); training in Afghanistan and consequences. Afghan Resistance” distributed on CD- the Chechen conflict with the Russian Pakistan. At the time of the London arrests ROM includes sections on making chemical Federation. Chechnya is viewed as a it is believed the Ricin found at a London flat and biological weapons.33 Al Qaeda poses training ground for Muslim terrorists. was partially refined in the Pankisi Gorge. Loosing sight of a threat as their top leadership not only In January 2003, Spain arrested 16 Islamic Terrorism? actively recruits from within European terrorists with connections to the four Preventing terrorism and in particular bio- states but many of their top leadership French suspects and the British suspects terrorism requires security and intelligence Often when discussing “bio-terrorism” hold Ph.D., d.Phil. and M.D. degrees. found in possession of Ricin. The Spanish cooperation with those responsible for and the need to implement policies to For example Ayman Al-Zawahri comes authorities believe the suspects, of mainly ensuring public health security. Both prevent it, we loose sight of the terrorist from a family of doctors and scholars. He Algerian decent, were preparing to send aspects must be brought into the equation component. It is not abstract or unknown. graduated from Cairo University School of
34 Previous conventional GIA terrorist attacks in France has led to the exposure of an extensive GIA infrastructure in various European countries, particularly in France, Belgium, the U.K., Germany, Italy, Sweden, and Spain. Logistics, financial and operational ties were found to exist between the members of the small ter- ror cells operating in these countries. The main objective of this European network is to smuggle funds and weapons to their comrades in Algeria and support 32 For more information see: World Health Organization, Communicable Disease Surveillance and Response (CSR), “Specific Diseases Associated with Biological Chechen Islamic terrorism. The later is partially funded through the massive heroin trade run through Albania. Other Muslim organizations helping the Chechens Weapons”, World Health Organization, Geneva, 2004. URL: http://www.who.int/csr/delibepidemics/disease/en/ are affiliated with the Saudi Wahabi Movement and Al Qeada. Moreover ranks of Chechen terrorists have increased with foreign fighters. Some from Afganistan, headed by Ibn-ul-Khattab, whose extensive combat and leadership skills, acquired in Afghanistan and Tajikistan, have proved of great service to the Chechens. 33 de Rugy, Veronique and Charles V. Pena, “Responding to the Threat of Smallpox Bio-terrorism”, No. 434, Cato Institute, Washington D.C., 18 April 2002. p.2. See: Shaul Shay and Yorum Schweitzer, “The Afghan Alumni Terrorism”, International Policy Institute for Counter Terrorism, Herzlia, Israel. 6, November, 2000. URL: http://www.ict.org.il/
NEW DEFENCE AGENDA 45 in order to prevent and deter acts of What role should Member States policy framework which may serve to reduce for the Prevention Terrorism, hosted deliberate disease. A European orientation counter-terrorism organization play? the risk. How can the European Union the senior-level war game examining the to preventing bio-terrorism must therefore apply some aspects presented to create a national security, intergovernmental, and carefully center regulations on criminal law How can we strengthen the moderate policy on bio-terrorism which suits information challenges of a biological attack as well as health protection and emergency existing infrastructure and increase a broader European level consensus? How on the American homeland. public health regulations. communication to prepare for a deli- can we bring together science and security berate public health emergency? to develop policies which fill the gaps and In July 2001 “Dark Winter” was enacted to strengthen our bio-defence posture? “Over demonstrate the roles of the US President Policy Options Should we structure a European a period of at least three millennia smallpox and other officials who would have to approach to criminalizing the possession was second to none in inflicting human pain, respond to a bioterrorist attack by Iraqi As with planning for any other type of and development of select agents into suffering and death; by some estimates, agents. The presumption was made that potential attack nations generally don’t biological weapons?35 smallpox killed as many as 500 million people Iraq either had the smallpox virus or could wait until they have an ample number of during the twentieth century alone.”38 obtain it from Russia. One of the political such events occurring before they begin Clearly a key challenge appears to be to As recently as 30 years ago, smallpox was goals of the scenario was to underscore the preparing for it. For example although build an infrastructure which balances endemic in 31 countries, and of the 10 to 15 need for national stockpiles of smallpox.40 there has not been a mass casualty the science of bio-defence with the million people who contracted the disease strike against the European Union using need for a wider security agenda. each year, it killed two million.39 advanced tactical weapons, national Dark Winter security planners still invest billions to Drawing on concerns about possible 36 prepare for such an attack. Is the EU Scenario bioterrorism, consultants from four The following scenario was drawn from prepared today to cope with a major different organizations devised a fictional Tara O’Toole, Michael Mair, and Thomas mass casualty bio-terrorism event? Several fictitious scenarios have been created contagion scenario called “Dark Winter” V. Inglesby, “Shining Light on Dark Winter” to explore the ways in which the public may which described three U.S. states being from the Center of Civilian Bio-defence Should we create a bio-defence team be better protected from both bioterrorism attacked. The Center for Strategic and Strategies, Johns Hopkins University: that can liaise between security and the and accidents involving infectious diseases.37 International Studies, the Johns Hopkins scientific community during an emergency A couple examples are provided to help Center for Civilian Bio-defense Studies, the In Dark Winter world supply of smallpox and conduct contingency planning? conceptualize the risk, outcome, and basic ANSER Institute for Homeland Security, and vaccine doses is estimated at 60 million, the Oklahoma National Memorial Institute with half in South Africa. There are
35 For example French public health legislation effectively criminalizes non-authorized persons from possessing and transferring select agents may provide a roadmap for general EU guidelines as it comprehensive and concise. 36 This scenario is provided to better understand the threat a biological attack may pose. It is based on The Plague Makers: The Secret World of Biological Warfare 38 Koplow, Daniel, A., “Smallpox: the Fight to Eradicate a Global Scourge”,University of California Press, Berkeley, CA 2003, p. 1 by Wendy Barnaby. While this scenario reflects the potential of deliberate disease it must be noted that experts who attended the Reporting Group in general 39 Acambis. “The History of Smallpox and Vaccination”, URL: http://www.acambis.com opted for a moderate approach to bio-terrorism and the current risk was generally perceived as low. 40 The ANSER Institute for Homeland Security, “Dark Winter”, Arlington, VA, http://www.homelandsecurity.org/darkwinter/index.cfm 37 Massachusetts Institute of Technology, Security Studies Programme, Level Four Bio-Safety Laboratories: Public Information and Risk Analysis (High Risk Sce- narios). Accessed at: http://web.mit.edu/ssp/twg/level4/scenarios.html on 20, October 2004.
NEW DEFENCE AGENDA 47 concerns that some non-U.S. vaccine may couple of days. The NSC develops a plan to two to three weeks, according to medical outside the framework of a malicious be ineffective, and may also have a higher use private pharmaceutical facilities in the experts. Continuing this grim calculation, actor....If you’re going against someone rate of side effects41 which would require U.S. to produce about 12 million doses of that would mean 30 million cases, with who is using a tool that you’re not used to intervention such as VIG. an unlicensed smallpox vaccine per month. 10 million deaths in the fifth wave. And having him use disease and using it toward But first delivery would be 5 weeks from then, two to three weeks later, a final quite rationally and craftily an entirely Initially 100,000 doses of vaccine are the current time. wave sweeping the nation and killing off unreasonable and god-awful end we are released for Oklahoma, with the same nearly one out of every three citizens. in a world we haven’t ever really been in amounts prepared to be sent to Pennsylvania Near the end of the role-playing exercise, Of the smallpox importations analyzed, before” (James Woolsey). and Georgia, pending lab confirmation of about three weeks after the fictional the importation into Yugoslavia in 1972 suspected cases in those states. Because bioterrorism attack, a second generation is particularly instructive because that The ‘learning points’ presented by of the limited vaccine stock, the decision is of cases begins to appear. During the outbreak encompassed many of the ANSER (Analytic Services) developed made to ration vaccine. The only civilians past 48 hours, the number of cases has attributes that would be expected if a for the Dark Winter scenario reflect to be vaccinated are close contacts, skyrocketed with 14,000 new smallpox smallpox outbreak occurred today (e.g., wider issues which are applicable to the healthcare personnel and investigators in patients confirmed in 25 states, among a large number of susceptible people, European Communities and developed case states. 2.5 million doses are reserved them the large population centers of New delayed diagnosis, both hospital and nations alike. In summary these ‘points’ for the military and the National Guard. As York, California and Florida. community transmission, wide geographic have been adapted for consideration the scenario progresses, two weeks after dispersion of cases, difficulty in contact in their application to the more general the presumed attack there are 2000 cases Smallpox is an extremely contagious tracing). Given the low level of herd issues which would immediately face most in 15 states, with 300 deaths. A total of disease. A single case can infect 10 to 20 immunity to smallpox and the high developed nations: three million doses of smallpox vaccine others, and this can go on for generation likelihood of delayed diagnosis and public have been sent to Oklahoma, Pennsylvania after generation (or wave after wave), with health intervention, the authors of this An attack on a western nation with and Georgia. Shipments of 500,000 doses a rapidly increasing number of infections exercise used a 1:10 transmission rate for biological weapons could threaten delivered to each of 12 affected states. Five at each step. The second generation, Dark Winter and judged that an exercise vital national security interests. days after the first case was diagnosed only outlined in this exercise, would be that used a lower rate of transmission Massive civilian casualties, breakdown 1.25 million doses of vaccine remain. followed by a third, a fourth and so on. would be unreasonably optimistic, might in essential institutions, violation of result in false planning assumptions, and, democratic processes, civil disorder, By day six of the crisis, vaccine supplies With a vaccine supply enough to therefore, would be irresponsible. loss of confidence in government and are dwindling. An additional supply, from immunize less than 5 percent of the reduced strategic flexibility abroad are the United Kingdom (500,000 doses) and population (2001), the infection rate “We are used to thinking about health among the ways a biological attack Russia (4 million doses), last for only a would continue to increase tenfold every problems as naturally occurring problems might compromise national security; 42
41 BioHazard “Smallpox Scenario”, URL: http://www.biohazardnews.net/scen_smallpox.shtml 42 The ANSER Institute for Homeland Security, “Dark Winter”, Arlington, VA, http://www.homelandsecurity.org/darkwinter/index.cfm
NEW DEFENCE AGENDA 49 vs. voluntary isolation and vaccination) Current organizational structures and levels of government. Information lessons of Dark Winter48 may be applicable what can be applied to European vs. capabilities are not well suited for the management and communication to policy issues on both the international national jurisdiction issues? 51 management of a BW attack. Major “fault (e.g., dealing with the press effectively, and European front. lines” exist between different levels of communication with citizens, Leaders in states most affected by government, between government maintaining the information flows smallpox wanted immediate access and the private sector, among different necessary for command and control Points and Observations to smallpox vaccine for all citizens institutions and agencies, and within at all institutional levels) will be a to Consider: of their states, but the federal the public and private sector. These critical element in crisis/consequence government had to balance these “disconnects” could impede situational management; 45 “It isn’t just [a matter of] buying requests against military and other awareness and compromise the ability more vaccine. It’s a question of how national priorities; to limit loss of life, suffering, and Should a contagious bio-weapon we integrate these [public health and economic damage; 43 pathogen be used, containing the national security communities] in ways How will nations holding a 1:1 ratio spread of disease will present that allow us to deal with various facets of vaccine respond when demand There is no limited surge capability in significant ethical, political, cultural, of the problem.” (James Woolsey).49 in another Member State with no health care and public health systems, operational and legal challenges; 46 stockpile occurs? Will they protect or the pharmaceutical and vaccine Federal and state priorities may be their own population or share their industries. This institutionally limited unclear, differ, or conflict; authorities stockpile? surge capacity could result in hospitals Confronting gaps may be uncertain; and national- being overwhelmed and becoming in policy regulatory issues may arise; 50 There were problems cited over inoperable; could impede public health jurisdiction on both quarantine, agencies’ analysis of the scope, source After a bioterrorist attack, leaders’ decisions In Dark Winter, tensions rapidly transport, closing airports and borders; and progress of the epidemic, the ability would depend on data and expertise from developed between state and federal to educate and reassure the public, and the medical and public health sectors. In authorities in several contexts. State Will Member States be inclined to the capacity to limit causalities and the Dark Winter, even after the smallpox leaders wanted control of decisions go against European level regulations spread of disease; 44 attack was recognized, decision makers regarding the imposition of disease- as has happened in the past with were confronted with many uncertainties containment measures (e.g., mandatory emergency animal disease outbreaks? Dealing with the media will be a and wanted information that was not major, immediate challenge for all immediately available.47 The general 48 Criticisms of “Dark Winter” emerged. Experts thought that the high rate of contagion in the scenario, which allowed each one person infected to infect another 12 to 15 other people, was an exaggeration of what would happen in real life. They also criticized the way in which the scenario left out the active role an informed public could take in preventing the spread of the disease, by hand washing, staying at home, and wearing a simple mask. In the 1947 smallpox outbreak that threatened New York City, the public and the media worked together to allow vaccinations to take place with great efficiency and without the public panic and violence that were part of “Dark Winter.” These criticisms and other criticisms are found in journal articles by scientists and physicians in Emerging Infectious Diseases, volume 7, number 1, (2001); Nature, volume 414, number 13 (2001) and New England Journal of Medicine volume 348, number 5 (2003). It is important 43-46 The ANSER Institute for Homeland Security, “Dark Winter”, Arlington, VA, http://www.homelandsecurity.org/darkwinter/index.cfm to emphasize that the purpose of the Dark Winter exercise was not to make the case that smallpox is the weapon most likely to be used in a bioterrorist attack (it is impossible to make such predictions) but to demonstrate that the use of a contagious pathogen as a weapon of bioterrorism can have devastating effects. 47 O’Toole, Tara, Mair, Michael, and Inglesby, Thomas V., “Shining Light on Dark Winter”, in Clinical Infectious Diseases Confronting Biological Weapons, Donald A. Henderson, Thomas V. Inglesby, Jr., and Tara O’Toole, (eds.), Vol. 34:972-983, 2002. 49-51 O’Toole, Tara, Mair, Michael, and Inglesby, Thomas V., “Shining Light on Dark Winter”, in Clinical Infectious Diseases Confronting Biological Weapons, Donald A.
NEW DEFENCE AGENDA 51 The Dark Winter exercise offers Smallpox Case Study Smallpox infects only humans and does not shock.59 He died before a definitive diagnosis instructive insights and lessons for those exist in a carrier state. In the 20th Century was made and buried 2 days before the first with responsibility for bioterrorism The smallpox virus is specific for humans approximately 110 million people died in case of smallpox was recognized.60 preparedness in the medical, public and non-pathogenic in animals. Smallpox war. An estimated 300 to 500 million people health, policy, and national security is one of the two most dangerous BW died of smallpox; several times the number The first cases were positively diagnosed 4 communities and, accordingly, offers agents (the other being anthrax) because of deaths from all wars combined.56 weeks after the first patient became ill, but insights on future options. of its high case-fatality rate (>30%), ready by then, 150 persons were already infected; person-to-person transmission, lack of The Yugoslavia outbreak of Smallpox in of these, 38 (including two physicians, The consequences of an attack with population immunity (possibly including February 1972 reflects the chaos that a two nurses, and four other hospital staff) smallpox are potentially catastrophic. persons immunized 25+ years ago), few cases can create. Yugoslavia’s last case were infected by the second patient.61 The Therefore, even if the likelihood cannot and lack of treatment54 As a result of a of smallpox occurred in 1927. In 1972, cases occurred in widely separated areas be established, the effects of smallpox worldwide eradication campaign, the last a man returning from Mecca became of the country. By the time of diagnosis, as a weapon of bioterrorism warrant endemic case of smallpox was reported ill with an undiagnosed febrile disease. the 150 secondary cases had already begun taking the threat seriously in order to in 1977. Russia and the U.S. are the last Friends and relatives visited from a to expose yet another generation, and, understand the efficacy of potential two known repositories of smallpox virus number of different areas; 2 weeks later, inevitably, questions arose as to how many response options.52 Also, preventive (with Russia having virus at several sites). 11 of them became ill with high fever and other yet undetected cases there might be.62 measures, which might act as a potential Plans to destroy the virus by 1999 were rash.57 The patient’s physicians (few of deterrent, reduce the risk, and mitigate delayed and it is not known when or if they whom had ever seen a case of smallpox) Health authorities launched a nationwide the consequences of an attack, need to will be destroyed.55 failed to make a correct diagnosis.58 vaccination campaign. Mass vaccination be examined and evaluated. 53 Should we clinics were held, and checkpoints along decide on a limited system of indicators Smallpox is the result of infection by the One of the 11 patients quickly became roads were established to examine and warnings? Well constructed scenarios variola virus, which belongs to the genus critically ill with the hemorrhagic form, a vaccination certificates. Twenty million and simulations can indicate how well Orthopoxvirus in the family Poxviridae. The form not readily diagnosed even by experts. persons were vaccinated. Hotels and or ill prepared public health institutions, variola virus is a large brick-shaped double- The patient was first given penicillin at a local residential apartments were taken over, security infrastructure and civil defences stranded DNA virus that serologically cross- clinic, but as he became increasingly ill, he cordoned off by the military, and all known are for a major biological attack. We can reacts with other members of the poxvirus was transferred to a dermatology ward in contacts of cases were forced into these then better assess the gaps and coordinate family, including ectromelia, cowpox, a city hospital, then to a similar ward in the centers under military guard.63 Some 10,000 a policy response. monkeypox, vaccinia, and camelpox. capital city, and finally to a critical care unit persons spent 2 weeks or more in isolation. because he was bleeding profusely and in Meanwhile, neighboring countries closed 52-53 de Rugy, Veronique and Charles V. Pena, “Responding to the Threat of Smallpox Bio-terrorism”,No. 434, Cato Institute, Washington D.C., 18 April 2002. p.4. 54 Henderson, D.A., “Smallpox: Clinical and epidemiological features”, Emerging Infectious Diseases, Vol.5, No.4, Centers for Disease Control and Prevention, Atlanta, 1999. 56 Shepard, H.R., and Peter J. Hotez, “The First Great Terror of the 21st Century”, Sabin Vaccine Report 3, No.2 (Winter 2001). 55 Henderson, D.A., Inglesby, T.V., Bartlett, J.G., Ascher, M.S., Eitzen, E., Jahrling, P.B., Hauer, J., Layton, M., McDade, J., Osterhoim, M.T., O’Toole, T., Parker, G., Perl, T., Russell, P.K., & Tonat, K., (1999). “Smallpox as a biological weapon: Medical and public health management”, JAMA, The Journal of the American Medical 57-63 Henderson, D.A., “Bioterrorism as a Public Health Threat”, Emerging Infectious Diseases, Vol. 4, No.3. Centers for Disease Control and Prevention, Atlanta, Association, Vol. 281, No. 22, 1999. July-September 1998.
NEW DEFENCE AGENDA 53 their borders. Nine weeks after the first flu in the initial stages. Training, for first on select agents for counter-measures On the immediate horizon, we cannot delay the patient became ill, the outbreak stopped. responders and medical practitioners could to prevent and treat deliberate dis- development and implementation of strategic In all, 175 patients contracted smallpox, increase vigilance. Moreover educating and eases receives priority as a prepared- plans for coping with civilian bioterrorism. and 35 died.64 informing the public of the potential for ness option? The needed stocking of vaccines and drugs as unusual disease outbreaks may reduce the well as the training and mobilization of health risk of panic or civil unrest during an attack. In the event of a bio-terrorism attack workers, both public and private, at state, city, What might happen if While most Member States as well as the should national governments offer the and local levels will require time. Knowing well smallpox were released US government have decided upon a ring public vaccination on demand? what little has been done.68 today? vaccination strategy, the public should be informed of what this means, why it is the What needs to be done to ensure dominant policy and what steps to take new Member States are prepared Summary The current ring containment strategy of during an emergency public health crisis. (sufficient vaccine stockpiles, adequate administering smallpox vaccinations only and standard laboratory capacity and A range of proposals were presented after an outbreak in the hope of containing the ability to participate in surveillance as advantageous to European policy for the spread of the virus favored by the US Points to Consider: programmes) to counter a major bio- increasing public health security, improving Federal Government and some European terrorism event? our preparedness and response to bio- Member States is appropriate for dealing Should the EU develop a separate terrorism. The vexing questions which with a natural outbreak of smallpox, but public health response plan to bio- We need to be as prepared to detect, remain are who should lead? Who will take it is likely to be woefully inadequate for terrorism than its current reliance on diagnose, characterize epidemiologically, and responsibility during an actual attack? Which countering a direct attack by a thinking the natural disease outbreak paradigm? respond appropriately to biological weapons institution will coordinate these efforts and enemy intent on inflicting mass infection, use as to the threat of new and reemerging delegate specific activities to be undertaken death and panic.65 If smallpox were Flexible and responsive bio-manufac- infections. In fact, the needs are convergent. rapidly? Who will be in charge of both released today across several member turing infrastructures are an essen- We need at international, state, and local the security and public health response? states simultaneously or staggered with tial part of an effective overall strat- levels a greater capacity for surveillance; One example of the problem and possible interval releases every few days the egy for bio-terrorism preparedness66 ; a far better network of laboratories and solution is reflected in the Select Committee outcome could be devastating. As with the what role can national and European better diagnostic instruments; and a more on Science and Technology Eighth Report index case in Yugoslavia, few practitioners level policies play toward ensur- adequate cadre of trained epidemiologists, to the United Kingdom Parliament. Herein could differentiate smallpox from the ing the research and development clinicians, and researchers. 67 the Select Committee stated:
64 Henderson, D.A., “Bioterrorism as a Public Health Threat”, Emerging Infectious Diseases, Vol. 4, No.3. Centers for Disease Control and Prevention, Atlanta, July-September 1998. 65 de Rugy, Veronique and Charles V. Pena, “Responding to the Threat of Smallpox Bio-terrorism”, No. 434, Cato Institute, Washington D.C., 18 April 2002. p.4. 66 Kocik, Janusz, “Preparedness against bioterrorism and reemerging infectious diseases: regional capabilities, needs and expectations in Central and Eastern European Countries”, NATO Advanced Research Workshop, Warsaw, Poland, January 15-18 2003. p.12. URL:http://www.onrglobal.navy.mil/reports/csp/2003/ 67-68 Henderson, D.A., “Bioterrorism as a Public Health Threat”, Emerging Infectious Diseases, Vol. 4, No.3. Centers for Disease Control and Prevention, Atlanta, 2003CSP1011.doc. July-September 1998
NEW DEFENCE AGENDA 55 “There seems to be a range of risk Key Points and epidemiology support to national limited or culturally pre-conceived concept. assessments, particularly within the and European level efforts to stamp out We must be careful not to transfer how we Department of Health (DoH). It is not It was difficult to determine who a disease caused by bio-terrorism. WHO think governments or individuals will act clear who in Government is responsible for should and would lead during a major could also assist in rapidly obtaining onto the potential actions of the enemy. determining what threats the UK should be bio-terrorism attack; vaccines, bifurcated needles and VIG in responding to, and with what priorities. We the event of a smallpox outbreak. A new approach is critical because terrorism have not established how risk assessments Fragmented infrastructure was sighted is just one of many, non-traditional security are informing Government policy and thus as obstructive to strengthening WHO recommends each country challenges.73 Such threats - where conflict the scientific response. There should be a collaboration: prepare a Smallpox Preparedness Plan; and crime often merge - respect no single assessment, informed by science and as Europe is now an open border area boundaries; all too often, there are no intelligence, which is communicated clearly Standardizing a range of bio-safety and should we prepare a European Plan to leaders or legions against which to focus to all those who need to make strategic bio-security measures was promoted counter the threat of Smallpox? attention or target a response.74 Given decisions on funding allocations. We hope as advantageous; advances in science and technology and that the Joint Terrorism Analysis Centre can the potential for biological pathogens to fulfill this function.“ 69 Variation in bio-defence vaccine Conclusion rapidly cross borders and infect thousands stockpiling could pose a serious problem of people, how can we best prepare This statement would seem to reflect the and lead to civil unrest if standards Contemporary threats are of an entirely for biological terrorism and the possible very basic dilemma which faced experts are not set to harmonize policies on different nature and scale than hitherto.70 use of Weapons of Mass Destruction? at the Bio-Terrorism Reporting Group. If stockpiling and production; Moreover the current responses to such each Member State cannot answer such threats appear increasingly inadequate. Facing ‘next generation’ challenges will questions then there could be problems The ability to conduct research on Class A Weapons developed to counter threats require wider thinking both in terms of which would lead to breakdown in response select agents is necessary and increasing at the end of the last millennium will not the potential for biological terrorism and and preparedness. A breakdown during a P3 level capacity could strengthen the sufficiently meet the challenges of the 21st increasing our ability to respond from major bio-terror event could devastate existing laboratory capacity; Century.71 Yet beyond specific technologies, multiple platforms i.e. regulatory, scientific, populations not only in Europe but fresh thinking is required to cope with the technical and security levels. Despite compromise international health security. The World Health Organization could new environment.72 We must be careful current emphasis on non-state actors, it It is therefore imperative we determine play a key role in communication of when considering the nature and type of is important to remain cognoscente of the exactly where the gaps are and what needs disease outbreak in real-time; provide threats likely to occur in the future that we threat posed by state actors as well. The to be done to close those gaps now. expertise on containment and control do not position such threats based on a so-called ‘listed’ states still pose a real threat
69 Henderson, D.A., “Bioterrorism as a Public Health Threat”, Emerging Infectious Diseases, Vol. 4, No.3. Centers for Disease Control and Prevention, Atlanta, July- September 1998 70-74 Hall, Robert and Carl Fox, “Rethinking Security”, NATO Review, Vol. 49, No.4, Winter 2001, pp. 9-11. URL: http://www.nato.int/docu/review/2001/0104-02.htm
NEW DEFENCE AGENDA 57 to international security. A recent report face mass casualty bio-terrorism, or we The need for EU on biological weapons by the National can fail to prepare and accept the risks that Intelligence Council stated that more than come with this decision. Given the possible consensus to deal a dozen states are known to possess or outcome, a moderate approach would be are actively pursuing offensive biological to hope for the best and prepare for the with a bioterrorist capabilities.75 The European Union is at a worst. We must now put policies in place very definitive crossroads. We can choose to ensure proper response and reduce the attack to prepare to respond and hope to never risk of bio-terrorism.
Mick Garstang Director Of Marketing, Acambis Mick Garstang
The experts participating in the NDA the two, smallpox is considered to be the meeting on October 18th are in a unique more complex to deal with because it is position to be able to influence and facilitate transmissible from person to person, there the development of a consensus view on is no proven treatment and it is difficult to bioterrorism preparedness within the EU. distinguish from less serious diseases such It is essential that there is agreement within as chickenpox. However, there is a vaccine the EU on policies such as alert response known to prevent the disease and the protocols and stockpiling of vaccines to vaccine can be used up to four days after counteract a bioterrorist attack. Without exposure to the virus. a co-ordinated plan, an attack or even a suspected attack could lead to civil unrest. The basic outbreak control response for bioterror agents where there is no The scenario of a smallpox attack provides vaccine or treatment is simply detection a good model to outline the potential and isolation of cases. For smallpox and problems of an uncoordinated approach anthrax, this basic control response within Europe. Smallpox and anthrax is required but there is the additional are the only two Category A bioterror control option of vaccination available. 75 Cilluff, Frank J., and Daniel Rankin, “Fighting Terrorism”, NATO Review, Vol. 49.No.4, Winter 2001, pp.12-15. URL: http://www.nato.int/docu/review/2001/0104-03.htm agents for which there is a vaccine. Of At present, EU Member States appear to
NEW DEFENCE AGENDA 59 have different alert response protocols Example scenario: Scenario: This scenario is likely to be much worse in place. Recent international exercises if we were to consider the situation such as Global Mercury highlighted Country A has sufficient smallpox 1 There is a confirmed case of small- where one country moves to implement some of the difficulties in co-ordinating a vaccine to provide a dose per citizen. pox in neighbouring Country C a policy of mass vaccination rather than response. Member States have different The preparedness response plans state ring vaccination during an outbreak. The approaches to stockpiling of smallpox that it will begin vaccination of first Country A begins to vaccinate first response needs to be coordinated across vaccine, ranging from stockpiles of one responders once there is a confirmed responders EU to prevent civil unrest. dose per citizen through to stockpiles case of smallpox anywhere in the world. of one dose per 30 citizens. There are Country B does not begin to vaccinate In summary, the EU needs to act as one also difference in the type of vaccine Country B has only a limited stockpile first responders to deal with a bioterror attack. For this to held, with some countries stockpiling of smallpox vaccine, insufficient to happen, there needs to be consensus on modern, licensable cell culture provide a dose per citizen. The policy in 2 There is public concern and de- when to move to the next alert level, what vaccines and others stockpiling old Country B is not to start vaccinating first mand for vaccination in Country B the response protocol should be and, in animal lymph derived vaccine which is responders until there is a confirmed the case of smallpox, when vaccination will not now licensable. case of smallpox in their country. The public in Country B are aware begin. With specific regard to smallpox, if that there is only enough vaccine for countries within the EU have an agreed a small percentage of the population stockpiling strategy, even just an agreed base level coverage of the population, this It is known that Country A has a should provide more public reassurance in stockpile large enough to provide a the event of a smallpox release. dose of vaccine per citizen
Citizens start to cross from Country B to Country A
NEW DEFENCE AGENDA 61 Recombinant Vaccinia immune globulin (VIG) for biodefense use
Dr. John Haurum CSO, Symphogen Dr. John Haurum
Although smallpox was eradicated in 1980, 10,000 vaccinated, and this is too high a bioterrorism has reintroduced smallpox as frequency to allow mass vaccination of a potential threat to public health. The US the general population. Anti-Vaccinia virus and some of the European governments serum has previously been reported to are for this reason ordering large quantities be efficient in treating the vaccine-related of vaccines for stockpiling with the aim of adverse effects and the protective effect having up to one dose per citizen. of neutralizing pAb against Vaccinia virus has been established in mice. Monoclonal Smallpox is caused by airway infection antibodies have also been shown to block with the orthopox virus Variola. Serum Vaccinia virus infectivity in vitro and in vivo. from Smallpox convalescents have used to treat smallpox infection. Endemic Given the antigen complexity of Vaccinia smallpox has been eradicated as a virus a polyclonal antibody would likely be consequence of worldwide prophylactic superior to mAb in mediating protection vaccination programs using the related in a natural out-bred population. Thus, we orthopox Vaccinia virus. propose that a recombinant polyclonal Vaccinia virus-specific antibody for Unfortunately, Vaccinia virus vaccination treatment of vaccine-associated adverse results in moderate to severe adverse reactions would facilitate general reactions in approximately one in every and safe mass vaccination programs.
NEW DEFENCE AGENDA 63 Importantly, such a Vaccinia virus- as a biodefense agent for post-exposure the procedure, since antibodies are active it has been described for rabies and specific recombinant polyclonal antibody prophylactic or therapeutic use against immediately after injection. Vaccines on hepatitis B virus. In addition, polyclonal might also be effective as pre- or post- smallpox virus. The project is fully funded the other hand have a lag period of over a antibodies can be used in combination exposure prophylaxis against smallpox. by Symphogen and the Company retains all week before the appearance of protective with antibiotics to afford broad-spectrum commercial rights to the results from the levels of antibodies. Also, vaccines are less microbial neutralization following Current VIG manufacturing is based on collaboration. The Company intends to apply efficient in immune compromised individuals exposure to hard-to-treat pathogens. blood sampling from individuals exhibiting for US and EU government research funding such as elderly people and vaccines may be Collectively, their pharmacology and the a high Vaccinia virus titer, and purification for manufacturing and clinical development. associated with adverse reactions, such as spectrum of potential prophylactic and of the immunoglobulin fraction. This it has been observed with Vaccinia virus therapeutic uses make pathogen-specific product is in short supply, very expensive vaccination against smallpox. polyclonal antibodies attractive remedies to produce, of low titer, associated with Immunological in both military and civilian defense against inherent risks of transmission of human biodefense agents Biodefense agents for use against biological biowarfare agents. donor-derived pathogens, and problems weapons of mass destruction such as with batch-to-batch variability. The only countermeasure which is active viruses, bacteria or bacterial toxins needs Many existing hyperimmune immuno- against most human viral infections or to be fast-acting and broadly reactive, globulin -based antibody products are Symphogen is developing a second bacterial toxins is the human immune which is a key characteristic of antigen- relatively low titered and therefore have generation recombinant VIG based on the system. This is the basis for the victorious specific polyclonal antibodies. Human to be administered by slow intravenous Company proprietary antibody discovery entry of vaccines in the history of human polyclonal antibodies has a serum half-life of infusion. This is clearly not compatible with and polyclonal antibody manufacturing medicine. Thus, vaccines act to induce novel approximately 25 days upon administration, efficient mass prophylaxis after pathogen platforms. Biological proof of concept is or boost preexisting immunity resulting in thus offering an opportunity for the exposure. For this purpose, high titered expected in 2005. a subsequent increased state of immunity prophylactic use of neutralizing pathogen- polyclonal antibodies formulated for small- against the corresponding pathogen in specific pAb in high-risk groups such as volume parenteral (intramuscular) injection The project is performed in collaboration the form of circulating, pathogen-specific military personnel and healthcare workers and even single-use self-administration with Health Protection Agency (HPA) polyclonal antibodies (pAb). during an imminent threat of exposure systems may be warranted. However, the who is responsible for delivering blood or as post-exposure prophylaxis. Due to combination of recombinant polyclonal samples from recently vaccinated donors The appearance in the body of such the immediate immunopharmacological antibody technology and modern and conducting the preclinical proof of circulating pathogen-specific antibodies can efficacy, pathogen-specific pAb may also be mammalian expression technologies concept studies. The aim is to replace obviously also be brought about by direct applicable for use in post-exposure therapy. may be able to offer such high titered existing anti-Vaccinia virus hyperimmune administration of therapeutic antibody Pathogen-specific polyclonal antibodies therapeutics. Also, this approach might immunoglobulins (VIG) for treatment of compositions, either therapeutically or can also be administered in combination potentially eliminate the problem with adverse effects in connection with Vaccinia prophylactically. The major advantage of with vaccines to combine immediate limited supplies of existing plasma-based virus vaccination against smallpox and this approach is the immediate efficacy of protection with long term immunity, as polyclonal antibody products.
NEW DEFENCE AGENDA 65 Design of antibodies for eradication of a bacterial pathogen. In first generation of therapeutic antibodies, The so-called SympressTM manufacturing use in biodefense addition, several bacterial toxins and and carry the natural diversity of human technology eliminates any cellular growth superantigens exist in multiple variant antibody responses as an inborn strength. biases in the polyclonal manufacturing To offer broad protection against forms and antibody mixtures have Such products have been on the market cell bank, thereby producing a technology biowarfare agents such as viruses or been shown to be more efficient than for decades, and represent a market for robust industrial manufacturing of bacteria in a large population, pathogen- mAb’s in mediating botulinum toxin of USD 3-4 billion today. The second recombinant polyclonal antibodies. specific polyclonal antibodies ideally should neutralization. generation of therapeutic antibodies is encompass a broad range of reactivities manufactured as recombinant monoclonal The first project of the Company is against the given pathogen, in order to In addition, microbial mutations could antibodies (mAb) and is characterized by currently undergoing cGMP manufacturing counter that the microorganism may be intentionally induced, by genetic high specificity towards a single, well- with a contract manufacturer and the first escape neutralizing antibodies through manipulation for example, in order described antigen. The introduction of drug development program (a replacement mutations in the epitopes recognized, as to make pathogens more lethal for new technologies which make it possible of donor blood-derived rhesus D-specific has been described for a number of viruses biowarfare use. Such mutations may to humanize animal-derived antibodies hyperimmune immunoglobulin used to after antibody treatment. The therapeutic make the pathogen less sensitive to has made monoclonal antibodies the most prevent hemolytic disease of the newborn) implication is that pAb reacting with several known mAb therapeutics, but might not important drug class in the pharmaceutical is expected to move into the clinic in 2006. epitopes on the same viral protein should be able to afford escape of recognition industry with estimated total sales around be superior to a mAb which inherently by polyclonal antibodies. USD 20 billion by 2010. Symphogen’s technology is also useful only reacts with a single viral epitope. Thus, for the generation of novel biodefense it is much less likely that individual viral Symphogen provides a totally new class of agents. Thus, for most of the biowarfare particles should fortuitously accumulate Pathogen-specific therapeutic antibodies which capture both agents listed by NIH as category A sufficient mutations to simultaneously Recombinant Polyclonal aspects of the immune system, namely the biowarfare pathogens, antibodies are a escape neutralization of all the antibody Antibodies natural diversity and the specificity. Thus, strong immune correlate of survival. specificities in a polyclonal antibody through its proprietary technologies, composition targeting multiple epitopes. the Company aims to produce target- The use of passive immunotherapy against Also, several viruses exist naturally in a Currently existing therapeutic antibodies specific recombinant human polyclonal anthrax, hemorrhagic viruses, botulinum range of strain subtypes, with obvious can be grouped into two different antibody preparations. Such recombinant neurotoxins, plaque, tularemia, smallpox implications for the need of a carefully generations of antibodies, each displaying polyclonal antibodies (rpAb) will virus has shown promises in animal models designed, broadly reactive reagent. one of the two unique features of the prove superior to existing antibody or in humans. Symphogen proposes immune system, diversity and specificity. preparations against complex antigens to develop high-titered recombinant Similar considerations hold true for such as infectious disease agents, toxins, antibody products, which are efficient bacterial pathogens; a diverse antibody Antibodies derived from human plasma, and bacteria since they mirror the natural both in preventing and treating several response should lead to more efficacious so-called immunoglobulin, represent the antibody-response produced by humans. of these pathogens.
NEW DEFENCE AGENDA 67 Advantages over immunoglobulin-derived Involvement of the Particularities of Acquisition in products of rpAb include the ability to biopharmaceutical produce rpAb in unlimited supply against industry Medical Research: any target of choice, while eliminating the dependency on unstable blood donor Pharmaceutical Product for NBC supply and the complicated logistics of The business model of the biopharmaceutical blood collection. Also, the composition can industry and especially of the smaller, Medical Protection as Orphan Products be manipulated beyond what is possible innovative biotech industry in development with immunoglobulins, including the ability of novel biodefense agents hinges upon to ensure coverage against several microbial clarifying the potential product market. Thus, Dr. Florin Paul serotypes, and the elimination of unwanted for investor-backed companies to choose MD, PhD, MPH, Deputy Surgeon General, reactivities through negative selection. to enter into research and development Romanian Ministry of National Defence Medical Directorate Finally, there is no risk of transmission of of biodefense agents, for which there is donor-derived pathogens, minimized lot-to- commonly no conventional market for the lot variability, and absence of irrelevant, non- product, alternative business opportunities specific antibodies, leading to high specific must be made clearly available by governments activity and an expected manufacturing and governmental organizations. One way to cost which is comparable to mAb. ensure this is to issue calls for tender in the Introduction form of e.g. EU Commission proposals which Advantages of rpAb over mAb include the define clear characteristics to be met by Recent worldwide terrorist acts and antitoxins, and other pharmaceuticals, in ability to deliver a product which maintains the development of novel products. If such hoaxes have heightened awareness large amount and have the capability for heterogeneity in the reactivity towards characteristics can be met then the issued that incidents involving weapons of prompt procurement. There is no doubts the target (broad-spectrum reactivity) contract should guarantee procurement of mass destruction (WMD) may occur that both physicians and pharmacists as well as heterogeneity in isotype and a certain amount of that product from the everywhere. This fact requires the should became knowledgeable in drug effector functions, if desired. Thus, activity biotech drug development company. Such development of preparedness programs therapy of NBC threats with respect to is maintained against complex antigens a novel funding structure through public to train and equip emergency services and nerve agents, cyanides, pulmonary irritants, including microorganisms of multiple tender for acquisition of specific biodefense emergency department personnel in the radionucleotides, biological agents as antrax serovariants. In addition, immune escape products would allow companies to assess management of large numbers of casualties or botulism, and other possible WMD. is less likely, thus making these drugs the potential market directly from the call and exposed to nuclear, biological, or chemical potentially more efficient in the face of thus eliminate the commercial risk attached (NBC) agents. Hospital pharmacies and Protection against nuclear, bacteriological natural microbial variation, or against to the project portfolio decisions stemming national pharmaceutical stockpiles will be and chemical hazards and emergency microbial variation induced by terrorists. from the unknown market size. required to provide antidotes, antibiotics, treatment of induced toxic effects is based
NEW DEFENCE AGENDA 69 on antidotes and special pharmaceutical and to long delays in obtaining the approval situations” (war, natural or technological lack of adverse effects after long term products, other than current drugs. These for registration and industrial production. disaster, terrorist attack etc.). Practically all and many administrations; pharmaceutical products should be included NBC-OD, with very few exceptions, like in the “orphan drugs” group that includes Mass casualty in NBC disasters, require anthrax vaccine, have no “civil” use, as drugs. longer biological half-life after also the medicines used in more than 3000 immediate availability of antidotes and Another serious difficulty arises administration. rare and very rare diseases. Antidotes and special pharmaceutical products that can from the assimilation of NBC-OD other pharmaceutical products as vaccines save the live of affected population. with common drugs. The requirements for vaccines, immune treat- or antitoxins are called “orphan drugs”, in ment prophylaxis products and antibiotic are: the sense that, following their sporadic use In respect to this issue in USA and Almost all NBC-OD do not fulfill the in normal times, their production is not European Union special legal provisions requirements for registration as drugs; their rapid efficacy and high profitable for pharmaceutical companies. were released to facilitate the production registration must be leaded by other rules. immunogenesis effects; and use of orphan drugs. availability and long shelve time; The development of drugs for these diseases, The technical difficulties in research, intended for a limited number of patients, These stipulations would provide to society production and use of NBC-OD are less stability of microbial strain used in vaccine; often require considerable research, and a tool for imposing on pharmaceutical known. These difficulties come first from subsequently, cost. A particular approach of companies to support an important part special requirements imposed to NBC-OD. covering the entire antigenic profile ethical, political and economical problems of these expenses for production of of the targeted pathogen; relevant for development and disposal of “less profitable” orphan drugs, especially The requirements for treatment of chemi- orphan drugs is also required. that are for NBC medical protection of cal and antitoxin NBC-OD are: wide spectrum for antibiotics and no the population. special condition for preservation; The registration of this special means increased stability; appropriate conditions for storage, encounters high difficulties in almost self-administration; all countries, following their inclusion transportation and usage for large areas; Particularities of NBC universal action; in the category of usual drugs. A lot of orphan drug research high efficiency; quality control for immune serum in requirements concerning a very wide, and production instantaneous onset of action. order to avoid transmission of other preclinical and clinical investigation, which practically hinders registration of antidotes diseases, as hepatitis B and C, HIV and makes no sense in case of these special The lack of financial profit of the production Preventive antidotes, protectors and de- infection etc. pharmaceutical products. of orphan drug production is the main corporators must have: obstacle in achievement of the protection All these requirements are difficult to Complying with such requirements can task. NBC orphan drugs (NBC-OD) are lack of incapacitating effects; be achieved, some of them being rather lead to drastic reduction of the availability necessary in large amount, only in “critical oral or percutaneous administration; contradictory.
NEW DEFENCE AGENDA 71 Particularities in areas: scientific and economical, regulatory Important is that procedure for Reliable information on the epidemiology, acquisition of antidotes and administrative requirements, and authorization to be simplified. disease severity, and effect on public – registration, delivery managing distribution in crisis. Authorities need to accept similar health is essential to sustain the need for a criteria for registration of a new vaccine. The authorities must develop the and usage Governments and chemical industries are antidote (less comprehensive that than policy to prevent infectious diseases and responsible for ensuring comprehensive for normal drug) as, for example, for in the same time countermeasures against Antidotes are listed and classified in scientific studies for regulatory authorities anticancer or anti AIDS agents because effects of biological weapons attack. accordance with their effectiveness and to accept registration of effective antidotes. of the special conditions of their use. availability (Table 1). Antidotes reduce Development of orphan vaccines is the overall burden of health service in In the same time pharmaceutical guided by the limited need for or markets managing of poisoning cases. companies involved in production of Particularities of potential of the product, with the antidotes must be encouraged to register acquisition of vaccines accompanying regulations, as well as the In developing countries that lack adequate their products in their own countries. specific characteristics of the vaccine and facilities for intensive therapy of poisoned The development of vaccine against rare those who need it. After September 11th, people, antidotes may be more essential in In this respect, is very helpful that emergent infectious diseases is hampered 2001, the threats of biological attack open the prevention and treatment of poisoning. administrative procedures of registration by many disincentives. perspectives for acquisition of new vaccines But availability of antidotes is different and disposal of an antidote, for example, to and immune-prophylaxis products. from one country to another. In developing comply with international rules regarding Vaccine development involves a sub- countries, physicians reported difficulties the orphan drugs. stantial investment in time, effort, and However, research for new effective in obtaining even common antidotes. resources. Any public or private research products needs long time, and the Even in industrialized countries, could Pharmaceutical companies will and producing facility should allocate development of any orphan vaccine should be noticed administrative difficulties and manufacture and supply antidotes only huge financial and human rescues when be broadly supported by measures to the lack of suitable drugs (pharmaceutical if they are encouraged by adequate development of vaccine is decided. The increase the awareness of immunization formulation, concentration etc.). economic refunds for their investment cost from research to licensure, the risks benefits at three levels – the decision- and by simple registration procedures. inherent in vaccine development (e.g. makers, the care-givers, and the patients. A very important issue is that technological constraints, regulatory pharmaceutical companies may hinder the Particular aspect regards common approval) and short- or long-term Developments in biotechnology have access to certain antidotes from different drugs (active substance) used in evaluations of scientific and financial created the promise of prevention for reasons. therapy that could be used successfully results may constrain this activity. In many more infectious diseases and chronic as antidotes, but in different formula the developing world, price has been a diseases and build the confidence in Difficulties in obtaining of adequate or concentration. In that condition major impediment to the introduction of acquiring new effective measures against availability arose from three interrelated additional authorization is required. new vaccines. biological warfare agents.
NEW DEFENCE AGENDA 73 Particularities in there are two alternative solutions: to Conclusions stockpiling and delivering establish a manufacturing facility (or a of pharmaceutical pharmacy laboratory) supported with international and regional consensus government funds or the establishment of in fighting against WMD threats and products a central agency for import and distribution elaboration of common strategy of of antidotes, under governmental control. intervention in crisis situation; The availability of an NBC-OD is highly The decision depends on the economical dependent on its manufacturing, delivery and technological capabilities. governmental support for developing procedures, and economic power of the facilities for production, import society. Storage facilities for NBC-OD require and storage of NBC-OD; specific conditions: The costs of procurement of NBC-OD simplifying the methodology of is a sensitive issue, looking to developing distance from medical facilities and registration and approval for NBC- countries that can not afford high transportation facilities (airport, roads); OD, and special legal provisions in this respect is mandatory; expenditures even in crisis situation. inside temperature and humidity;
communications; By the other hand it is practically impossible development of international and that all countries to develop production building safety in case of WMD attack, regional programs for scientific natural or technological disaster; facilities for the whole range of NBC-OD. research, production and distribution capacity of storage; of NBC-OD appear as an urgent In circumstances of increasing the threat real time of intervention. requirement in fighting the NBC of international terrorism, and attack with threats and international terrorism. WMD, the regional and international The amount and the type of NBC-OD cooperation become mandatory. A part of reserve depend on: this cooperation is the availability of NBC- OD for affected population. In same cases, size and geographical profile of the like biological attack, the affected area could exposed area to WMD attack; be larger, pathogens crossing the political or nature of potential NBC hazard; administrative borders. number and density of population in the affected area; If certain NBC-OD are not available from distances to medical care facilities local manufactures and must be imported from theater, communications etc.
NEW DEFENCE AGENDA 75 References WHO
1. Burda AM, Sigg T. Pharmacy preparedness for incidents involving weapons of mass Presentation destruction. Am J Health Syst Pharm 2001, Dec, 1, 58(23): 2274-84;
2. Food and Drug Administration, USA. Improving Public Health through Human Drugs. Report 2001. http:/www.fda.gov/cder/cder.org.htm; Dr. Randall Hyer Medical Officer, Civil Military Liaison 3. Lang J, Wood SC; Development of Orphan Vaccines. An Industry Perspective. Activity and Alert and Response Operations, Emerging Infectious Diseases, 1999, 5(6): 749-755. World Health Organisation (WHO) Dr. Randall Hyer
4. Matherlee K. The Public Stake in Biomedical Research: a Policy Perspective. National Health Policy Forum, November 1999, USA. http:/www.cdc.gov/nih; The following slides are part of an introductory presentation 5. Mircioiu C., Voicu V. Self protection of pharmaceutical companies against terrorist given by Dr. Hyer at the 18 October meeting. attacks as core of large area population protection. Proceedings of CB Medical Treatment Symposium Industry I, 151-153, 1998, Dubrovnik, Croatia;
6. Schwartz B., Rabinovich NR; Stimulating the Development of Orphan (and Other) Vaccines. Emerging Infectious Diseases, 1999, 5(6):832;
7. Shah ND; Vermeulen LC; Santell JP and all. Projecting future drug expenditures. Am J Health Syst Pharm, 2002, 59(2):131-140;
8. Voicu V., Mircioiu C. Antidotes – Individual protection means: drugs and special means. Proceedings of CB Medical Treatment Symposium Industry I, 315-326, 1998, Dubrovnik, Croatia;
9. Watson R. Health ministers to help orphan drugs. British Medical Journal, 1995; 310:1557-1558;
10. Wong SH; Challenges of toxicology for the millennium. Ther Drug Monit, 2000, 22(1):52-57.
NEW DEFENCE AGENDA 77 NEW DEFENCE AGENDA 79 NEW DEFENCE AGENDA 81 NEW DEFENCE AGENDA 83 About the New Defence Agenda (NDA)
The New Defence Agenda was launched in 2002 under the Presidency of Eduardo Serra, former Spanish defence minister, and under the co-patronage of Lord Robertson, Javier Solana and Chris Patten. Under this patronage and with the close collaboration of prominent defence experts drawn from a cross-section of government, politics and industry, the NDA quickly established itself as the only regular forum in Brussels devoted to debating the future of defence and security policies.
NDA is also a networking centre of defence-related think-tanks around Europe, and has strong contacts with the Brussels-based press corps – the largest international press corps of the world. The NDA’s success is based on the support of a wide-range of institutions, industries, government representations and think tanks. Because of their continued support, the New Defence Agenda brings clarity and new ideas to the rapidly-changing defence policy scene through its monthly roundtables and regular international conferences, press dinners and publications.
Bringing clarity and new ideas to the fast-changing defence policy scene has been the NDA’s aim from the start. We see ourselves as a builder of partnerships with nationally-based defence think-tanks whose expertise needs to be more widely shared with other analysts and with European-level decision-takers.
NDA brings together a wide range of actors in the security and defence world and its activities range from monthly roundtables, international conference, press dinners, reports and discussion papers, which attract high-level speakers and industry support.
One of our prime objectives is to raise the profile of defence and security issues among the Brussels-based international press. To encourage more in-depth coverage of defence and security topics holds regular, informal dinners for journalists.
Its patrons Javier Solana and Chris Patten have backed the initiative from the start along with NDA’s president, Eduardo Serra, former Spanish defence minister. The NDA’s Advisory Board is made of some 20 prominent defence experts drawn from a cross-section of government, politics and industry.
NEW DEFENCE AGENDA 85 Recent NDA Events 2004
DOES EUROPE NEED A BLACK SEA SECURITY POLICY? DEFENDING GLOBAL SECURITY: Roundtable, 20 September 2004 THE NEW POLITICS OF TRANSATLANTIC DEFENCE COOPERATION Annual Security and Defence Conference, 17 May 2004 Speakers included Speakers included Oksana Antonenko Programme Director (Russia and Eurasia), Jaap de Hoop Scheffer International Institute for Strategic Studies (IISS) NATO Secretary General Sergei Konoplyov Director, Harvard Black Sea Security Program Vecdi Gönül Ovidiu Dranga Minister of Defence, Turkey Director General, Department for Defence Policy and Euro-Atlantic Integration, Ministry of National Defence, Romania Paulo Portas Minister of Defence, Portugal Yannis N. Papanicolaou Director General, International Center for Black Sea Studies, Greece Cristian George Maior Rear Admiral Serdar Dülger State Secretary for Defence Policy, Romania Chief of Plans and Policy Department, Ministry of National Defence, Turkey Sir Peter Ricketts VIP Lunch with Ambassador Turan Morali, Director General for International Security, UK Ambassador to NATO Ministry of Foreign Affairs, Turkey
HOPES AND AMBITIONS OF THE NEW EUROPEAN DEFENCE AGENCY Press Dinner 28 April 2004 with ON THE EVE OF ISTANBIL: CAN NATO BECOME A MOTOR FOR REFORM? Roundtable, 21 June 2004 Nick Witney Speakers included Head of the European Defence Agency Establishment Team Julian Lindley-French ETC Course Director, Geneva Centre for Security Policy (GCSP) Press included Alessandro Minuto Rizzo Deputy Secretary General, NATO The Guardian Time Magazine Ergin Saygun Reuters Defense News Military Representative, Delegation of Turkey to NATO Financial Times Die Zeit John Koenig Le Monde Knack Magazine Deputy Head of Mission, Delegation of the United States of America to NATO VIP Lunch with Ambassador Nicholas R. Burns, US Ambassador to NATO Armed Forces Journal Zweites Deutsches Fernsehen (ZDF)
NEW DEFENCE AGENDA 87 The views expressed in this Report are the personal opinions and not necessarily the views of the organisations they represent, nor of the New Defence Agenda, its Board of Trustees, its members or sponsors. Natural human antibodies for the treatment and Reproduction in whole or in part is permitted, providing that full attribution is made to the New prevention of human disease Defence Agenda and to the source(s) in question, and provided that any such reproduction, whether in whole or in part, is not sold unless incorporated in other works. Using proprietary technologies, Symphobodies offer a number of Symphogen develops recombinant advantages over plasma-derived polyclonal antibody-based products that immunoglobulins and monoclonal mimic the diversity, affinity, and antibodies for treatment of diseases specificity of the natural human immune caused by complex targets such as in system. infectious disease and cancer. We generate antibodies using the Likewise, recombinant polyclonal Symplex™ technology and the lead drug antibodies are an obvious choice against candidate may be polyclonal or the microbial agents causing anthrax, monoclonal, depending on the nature of botulism, plague, smallpox, tularemia and the target. viral hemorrhagic fevers. Manufacturing of recombinant polyclonal Symphogen actively seeks partnerships antibody drugs (symphobodies) is with biotech and pharmaceutical performed using the proprietary companies, as well as relevant SympressTM expression technology, which government organizations within allows consistent manufacturing of biodefence and welcomes any contact recombinant polyclonal antibody concerning future collaborations. compositions.
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Symphogen A/S Elektrovej, Building 375 EDITOR: Giles Merritt DK-2800 Lyngby RAPPORTEURS: Brooks Tigner and Jessica Henderson Denmark
PHOTOS: Frédéric Remouchamps, Keops Telephone: +45 4526 5050 Fax: +45 4526 5060 DESIGN & PRODUCTION: , www.aovo.net AOVO DESIGN E-mail: [email protected] PRINTING: UPO Web site: www.symphogen.com FOLLOWING THE INTEREST GENERATED IN PAST NDA EVENTS AND THE ENCOURAGEMENT OF THEIR PARTICIPANTS, THE NDA DECIDED TO CREATE A VENUE FOR MORE FOCUSED DISCUSSIONS ON THE AREA OF BIOTERRORISM. THE BIOTERRORISM REPORTING GROUP WILL ALLOW THE DISCUSSIONS NOT ONLY TO BE TAILORED TO THE EVOLVING DEVELOPMENTS IN THE BIOLOGICAL FIELD BUT MOST OF ALL, THE RESULTING REPORT WILL ACT AS A CATALYST FOR THE POLITICAL WORLD.
There is no question of the need for policies directly focused against the use of biological agents as weapons. The use of disease as a weapon of mass destruction (WMD) is considered a low probability, high consequence event. However, if such an event were to occur, the consequences would be so severe that preparatory action must be undertaken to prevent it. Although biological weapons are often grouped together as agents of mass destruction, biological weapons vary significantly from chemical and nuclear munitions. Biological weapons and materials have the capacity to silently infect thousands of people, destroy agriculture and infect animal populations.
Of all the classes of WMDs, biological weapons remain the most vulnerable to diversion while also being the most difficult to detect. Unlike the Chemical Weapons Convention and the nuclear Non-Proliferation Treaty, which have full verification regimes, the Biological and Toxin Weapons Convention does not. This leaves the development and potential use of bio-agents entirely unchecked. It is therefore imperative governments begin to address the serious threat biological terrorism poses to the EU and the international community.
NEW DEFENCE AGENDA FORUM EUROPE TEL: +32 (0)2 737 91 48 Bibliothèque Solvay Fax: +32 (0)2 736 32 16 137 rue Belliard [email protected] B-1040, Brussels, Belgium www.newdefenceagenda.org