Vaccines and the Prevention of
Biological Warfare and Bioterrorism
Max-Delbrück-Center for Molecular Medicine, 13092 Berlin-Buch, Germany
With the end of the nuclear confrontation the threat of biological (BW) and toxin warfare (TW) has increased and been complemented by the danger of bioterrorism. The perhaps still incomplete disclosure of Iraq's BTW programme; the 1992 admission of the Russian government that the USSR and its Russian successor state had run an offensive BTW programme for two decades after the adoption of the Biological and Toxin Weapons Convention (BTWC); the findings of the South African Truth and Reconciliation Commission that the apartheit regime had run a secret offensive BW programme which was halted by President de Klerk only in 1993[i]; and the disclosure of activities of the Japanese Aum Shinrikyo cult to produce and disseminate BTW agents demonstrate that fears of a conceivable hostile use of biological agents and toxins are justified.
President Clinton's speech at the 1998 US Naval Academy commencement may be an indication of present official assessments of the situation. Clinton announced three initiatives of the US administration against terrorism, one of which is explicitly directed against bioterrorism. "We will undertake a concerted effort", President Clinton said, "to prevent the spread and use of biological weapons, and to protect our people in the event these terrible weapons are ever unleashed by a rogue state, a terrorist group or an international criminal organization. [...] We must strengthen the international Biological Weapons Convention with a strong system of inspections"[ii].
The Biological Weapons Convention must be strengthened
The facts mentioned above demonstrate, indeed, that the BTWC is not sufficient to reduce the danger of BW and bioterrorism -- not to mention the fact that only 141 countries are States Parties to the Convention. It does not matter that the Holy See is not a States Party, although the Vatican is a States Party of the Geneva Protocol (since 1966), as is Israel (since 1969). But it is cause for concern that some important countries of the region where this meeting is taking place are not yet States Parties to the Convention.
Membership to the BTWC, however, does not automatically guarantee that a country does adhere to the provisions of the treaty. South Africa, for example, has been a States Party to the Convention since 1975. The USSR and its successor state is not only a States Party to the Convention, but even a depositary. And Iraq developed, produced and weaponized BTW agents although it was a signatory of the Convention and therefore politically bound to the international norm against biological weapons. Moreover, Japan's membership to the Convention did not prevent the clandestine bioterroristic activities of the Aum Shinrikyo cult within its territory.
These facts might impress countries that so far have refused to ratify or at least sign the BTWC. Some non-States Parties might also be concerned by the fact that the Convention does contain loopholes. One major loophole is the lack of a verification regime. Fortunately, activities have been in progress in Geneva since 1995 in the Ad Hoc Group convened to elaborate a Protocol to the BTWC which already exists as a draft rolling text[iii]. Members of the Ad Hoc Group group are optimistic that the protocol, which will deal with extensive verification procedures and national implementation measures, might be finalized by the end of 1999 for further action.
I doubt, however, whether such measures will be sufficient to prevent the future hostile use of biological agents and toxins. The experiences of the UNSCOM mission indicate that even the most intrusive verification measures are insufficient to reveal clandestine BTW preparations fully. But the intrusiveness of the verification measures applied in Iraq was rather unique. It was possible only under the special conditions of the cease-fire. And even today they cannot be fully implemented because of interference from the Iraqi government. It is hard to imagine that such measures could be applied to other situations to verify whether a rogue country is violating the Convention or not. Moreover, the Ad Hoc Group elaborating the Protocol to the BTWC received the mandate to consider "measures to promote compliance with the convention" which should be as "non-intrusive as possible"[iv].
Another major loophole in the Convention is that it only prohibits the development, production and stockpiling or otherwise procurement of biological agents, or toxins of types and in quantities "that have no justification for prophylactic, protective or other peaceful purposes"[v] [emphasis added]. That language implies that the development and production of BW and TW agents for ostensible prophylactic and protective purposes is explicitly allowed. The development and production of vaccines and other biologicals to protect against BW and TW agents or to counter their effects is legitimate, including also handling the agents in question, their production and their study.
This permission creates a severe weakness in the BTWC. One cannot but agree with the Permanent Select Committee on Intelligence of the US House of Representatives that these provisions "contain important gaps: it would be hard to name a biological agent that could not be produced under the rationale of 'prophylactic, protective or other peaceful purposes'. Even the production of quantities of anthrax might not necessarily be a breach of the Convention"[vi]. A leading expert has pointed out that "the great difficulty of separating what constitutes 'defensive research', particularly for biological weapons, from 'offensive research'" might raise suspicions: "To mount a program specifically for medical 'defense' against such [BW] agents would appear to others in the world to be simply a continuation of an arms race in these weapons"[vii]. Therefore, US congressman Owens concluded that "growing expenditures on biological defense programs will continue to provoke international suspicion and, in the process, escalate the proliferation of biological weapons"[viii].
The quadruple capability of vaccines against dual-threat agents
This is especially true with regard to the development and production of vaccines against putative BW and TW agents because of their very nature. BW and TW agents are not specifically designed and created as weapons agents for warfare and criminal purposes but are intrinsic components of our environment. They are naturally occurring pathogens and toxins endangering humans, animals and plants independent of any hostile activities. And they can also be used for hostile purposes as biological or toxin weapons agents. They are "dual-threat agents" (DTAs).
The development and production of vaccines against DTAs and their widespread use can generate suspicions, particularly if undertaken by the military or its contractors. Vaccines against DTAs can be described as having a "quadruple capability"[ix]. They can be used for quite different purposes, namely
* to protect both civilians and troops against natural infections and intoxinations in peacetime;
* to protect soldiers in conventional or other non-biological wars from natural in-fections and intoxinations caused by DTAs;
* to protect against biological attack (if applied well in advance of an attack with a known BTW agent);
* to prepare for biological and toxin warfare and to provide biological first-strike capability.
Moreover, vaccine development and production are dual-use activities, which depend on dual-use knowledge, technologies and equipment. That is especially true in the field of vector-based vaccines: one and the same technology can be used to construct efficient vaccines or highly contagious vector agents carrying multiple toxin genes. The latter recombinants can be described as "second-generation BTW agents" because they -- in contrast to DTAs -- are novel man-made products that cannot be found in nature .
Protection in peacetime
The necessity of protecting both civilians and troops against naturally occurring infections and intoxinations, including diseases caused by DTAs, by vaccination in peacetime, is evident and needs no further explanation. It should be taken into account, however, that the availability of vaccines and toxoids able to protect against DTAs is extremely limited. Owing to low profitability, most vaccine-manufacturing firms have no interest in developing and producing vaccines against such agents.
Protection of soldiers in non-biological wars
Regarding the protection of soldiers in non-biological wars it should be considered that infectious diseases have been the major cause of casualities among troops in all wars throughout history[x]. Therefore, military leaders have legitimate reasons to provide vaccines protecting their troops against naturally occurring infectious diseases and intoxinations. It is a must.
Protection against biological and toxin warfare agents
Most military leaders claim that vaccines must be developed and produced to protect troops against biological and toxin warfare. I share the view of many experts that it is impossible to protect even small contingents of troops by vaccination against a surprise attack involving BW or TW agents. Vaccines act specifically against only one or a few agents and they must be provided weeks or even months before they generate their protective effects[xi]. Moreover, in many cases it is uncertain whether licensed vaccines protect against agents disseminated as aerosols and inhaled by the respiratory system.
It has been asked, in addition, if a fundamental rethinking of the role of defence vaccines might be necessary because the number of BTW agents already in existence could be expanded by producing recombinant agents that can overcome the immune barriers established so far[xii].
Of course, if military leaders anticipate a biological threat well in advance and if vaccines are available they should be used. American and British troops, for example, were vaccinated during the Persian Gulf War against anthrax and botulism[xiii].
There are only a few agents, however, for which fully approved vaccines are available (tab. 1). Therefore, the US Department of Defense initiated in 1997 a "Joint Vaccine Acquisition Program" to develop, produce and stockpile licensed vaccines against "agents of most concern" for use by the military. The "agents of most concern" addressed by that programme are biological agents and toxins causing the following twelve infectious diseases and intoxinations: anthrax, brucellosis, plague, Q fever, tularemia; encephalitides caused by alphaviruses (Eastern equine encephalitis, Venezuelan equine encephalitis, Western equine encephalitis), smallpox; botulism, and intoxinations caused by ricin and Staphylococcal enterotoxins, respectively[xiv].
In November 1997 the Joint Vaccine Acquisition Program announced the award of a $322 million multi-year contract to DynPort LLC for the development and production of defence vaccines within that programme[xv]. In September 1998, DoD awarded a contract worth up to $29 million to BioPort Corporation to manufacture, test, bottle and store anthrax vaccine[xvi].
Early in 1998, Canada, the UK, and the USA decided to vaccinate their military personnel deployed in the Persian Gulf area against anthrax[xvii]. Earlier the US Defense Department had announced that it had plans to vaccinate all US military personnel against anthrax because there was concern that "a large number of potential enemies" might be able to produce, weaponize and deliver anthrax spores[xviii]. The cost of immunizing 2.4 million personnel over a 6-year period against Bacillus anthracis was estimated at about $130 million. In May 1998, US Defense Secretary William Cohen ordered the immunization of all active-duty personnel and selected reserves against anthrax[xix]. Until mid-August, shortly before Phase I of the Total Force Anthrax Vaccine Immunization Program began, already the vaccination of some 48,000 people had taken place[xx].
Preparation for use of biological and toxin weapons agents
On the other hand, vaccines and other specific biologicals might be used to protect personnel involved in offensive BW and TW research and development and the use of BTW agents and/or protect against an expected retaliation in kind. It is well known, for example, that the U.S "program on medical defense against biological warfare was initiated at [the U.S.Army Medical Research Institute of Infectious Diseases,] Fort Detrick, MD, in the 1950s primarily to protect the workers in the offensive program"[xxi] [emphasis given].
Moreover, vaccines might be used to protect troops prior an intended attack, thereby providing BW or TW first-strike capability, especially if vaccines are developed that are effective in protecting against a variant agent constructed secretly, in violation of the international norm against biological weapons.
Vaccines might also be used to protect troops in advance from retaliation in kind. As early as 1916, for example, German Oberstabsarzt Winter, Sanitation Officer of the 21st Army Corps, proposed using Yersinia pestis against England[xxii]. Liquid cultures of plague bacilli was to be disseminated from Zeppelins on the ports of England, 100 liters at a time, with the goal of infecting rats inhabiting the harbours, thereby initiating an epidemic. Winter considered British retaliation in kind and consequently proposed the secret production of sufficient amounts of anti-plague serum since only an amount of some 10,000 dosages of that serum was available in Germany at that time.
The danger of facilitating biological and toxin warfare preparedness by making vaccines available increased after the introduction of genetic engineering and other methods of molecular biotechnology. A panel of outstanding experts, among whom was Nobelprize winner Joshua Lederberg, that met in February 1981 "to advise the Departent of State on the foreign policy implications of genetic engineering" concluded, inter alia, that "we can develop better vaccine potential. An increased protection capability may be an inducement to use biological warfare, however, since the instigator has a decreased risk of being harmed by his own actions"[xxiii].
Military vaccine activities must be made transparent
Because it cannot be ruled out that military vaccine activities are performed with offensive intention the development and production of vaccines against dual-threat agents, as well as other bio-medical activities directly related to the BW Convention should be made more transparent.
The above mentioned Expert Panel convened by the Department of State recommended in 1981, "we should be collecting samples of every vaccine being devloped around the world for mass vaccination; we should know what other populations are being protected against"23. A group of experts participating in a study convened by SIPRI to evaluate the situation in the field of biological disarmament on the eve of the Second Review Conference of the States to the BTWC recommended, inter alia, that a BTWC Verification Agency should be established, and that each States Party as well as all other countries report to the Verification Agency "all vaccine development and vaccination programmes. [...] Registration of vaccine developments and of vaccination programmes (including military ones) should help to remove the suspicion that such vaccines have been developed and/or [used] solely in order to protect a possible attacker's troops"[xxiv] [emphasis added]. Corresponding proposals were re-emphasized by non-governmental groups before and during the Third Review Conference[xxv],[xxvi].
Similar recommendations were also made by States Parties to the BTWC. France proposed to invite countries to supply proof that the staff of high-containment facilities and military personnel had not been vaccinated against presumed BW agents[xxvii]. Austria, Finland, Ireland and several other countries suggested that States Parties provide information on the inoculation programmes of their armed forces[xxviii],[xxix].
At the Third Review Conference in 1991 several delegations proposed to agree on a confidence-building measure requesting reports on military vaccine activities. France, for example, recommended the "Declaration of regular military vaccination programmes: States Parties shall provide information on the regular pattern of military vaccination programmes for troops as predescribed by their military health authorities"[xxx] [emphasis given].
Likewise, Finland proposed that States Parties report on "Military Vaccination Programmes. Declarations should be provided for standard and/or regular peacetime vaccination programmes concerning active-duty military personnel, including conscripts, but excluding ad hoc, short-notice vaccinations for military personnel on special assignment (such as United Nations peace-keeping duties). Declarations would consist of lists of vaccines (agent/disease) used in implementing these programmes"[xxxi]. Hungary, too, recommended the declaration of military vaccination programmes[xxxii].
Vaccines and Confidence-Building Measures
When the Second Review Conference realized in 1986 that the Convention needed to be strengthened, the conference adopted a set of confidence-building measures (CBMs) designed to provide greater transparency with respect to activities directly related to the BTWC[xxxiii]. The Conference decided that the States Parties "are to implement [...] the following measures, in order to prevent or reduce the occurrence of ambiguities, doubts and suspicions, and in order to improve international co-operation in the field of peaceful bacteriological (biological) activities:
1. Exchange of data [...] on research centres and laboratories that meet very high [...] safety standards [...] or specialize in permitted biological activities directly related to the Convention.
2. Exchange of information on all outbreaks of infectious diseases and similar occurrences caused by toxins that seem to deviate from the normal pattern [...].
3. Encouragement of publication of results of biological research directly related to the Convention [...] as well as promotion of use for permitted purposes of knowledge gained in this research.
4. Active promotion of contacts between scientists engaged in biological research directly related to the Convention [...]."
The modalities for the information exchange were elaborated in 1987 by an Ad Hoc Meeting of experts convened by the Second Review Conference[xxxiv].
However, neither the recommendations of Non-Governmental Organizations and similar groups nor governmental proposals to provide information on military vaccine development and use were considered.
The Third Review Conference in 1991 modified and amended the CBMs. Some new measures were agreed on, including a "Declaration of vaccine production facilities" as confidence-building measure "G". "To further increase the transparency of biological research and development related to the Convention and to broaden scientific and technical knowledge as agreed in Article X", States Parties were requested to "declare all facilities, both governmental and non-governmental, within its territory or under its jurisdiction or control anywhere, producing vaccines licensed by the States party for the protection of humans. Information shall be provided on Form G attached"[xxxv]. Form G, entitled "Declaration of vaccine production facilities", asks for name of facility, location (mailing address) and "General description of the types of diseases covered".
Poposals to request information more directly related to the BTWC were discussed but not accepted by some delegations, however. Canada, for example, originally joined those States which called for more transparency in that field and suggested reports on vaccine production facilities which produce vaccines for protection of humans and animals. The original proposal, dated 13 September 1991, explicitly -- although in brackets -- referred to vaccines "[against those agents identified on the List of Concern]", i.e. against DTAs[xxxvi]. In a revised version of the Canadian proposal, submitted three days later, the reference to agents of concern was deleted[xxxvii].
The Fourth Review Conference in 1996 did not modify the CBMs. "Participants welcomed the continued contribution of the confidence-building measures established under [...] Article [V] to enhancing confidence in compliance with the Convention"[xxxviii]. It was also noted by the participants, "that, in accordance with its mandate, the Ad Hoc Group is considering the incorporation of existing and further enhanced confidence-building and transparency measures, as appropriate, into a future regime to strengthen the Convention".
The participants of the Fourth Review Conference noted, however, "that participation in the CBMs was not universal, and urged all States Parties who had not done so to meet their political obligation in this context". Participation in the information exchange was and is disappointing, indeed, both in quantitative and qualitative repects[xxxix]. Today, when most of the 1998 reports are available[xl], the situation is still unsatisfactory. Although the number of countries participating in the information exchange increased after the Third Review Conference, there are still 60 States Parties which did not participate in the CBMs at all.
Most participating States Parties took part only once or a few times. Only eight states participated in all rounds of the information exchange as requested by the Second Review Conference and emphasized by the Third Review Conference: Canada, Finland, the Netherlands, Norway, the Russian Federation (and the former USSR), Sweden, the United Kingdom and the United States of America.
Several countries de facto participated in the information exchange but merely submitted the nil declaration, "Declaration form on Nothing to Declare or Nothing New to Declare for use in the information exchange". Some of these states did not even mark any of the boxes of the nil declaration with a tick.
Availability of information on vaccine production
Of the 74 countries which participated in the information exchange since 1992, i.e. after the introduction of the request for information on vaccine production, only 34 States Parties provided data on vaccine production facilities (tab. 2) and vaccines and toxoids produced there (tabs. 3-5).
The number of facilities given in table 2 reflects the latest information. It should be mentioned, however, that there were changes in the number of facilities in many instances. In Canada, for example, three producers of vaccines were declared in 1994, whereas only one facility is still active in that field.
In 1998 the USA reported on nine vaccine facilities. The most interesting one concerning the BTWC, the Salk Institute, Biological Development Center, Swiftwater, PA, is not described on Form G in the 1998 report. It is, however, announced on Form A, part 28 (see below) as a facility involved in the US Biological Defence Research and Development Program. In the 1997 report the Salk Institute and its products were described in Form G.
Although numerous vaccines and toxoids declared are biologicals produced to protect against agents and toxins regarded not to be warfare agents (tab. 3), quite a lot of human vaccines announced are vaccines against dual-threat agents. A considerable number of States Parties informed on the production of vaccines and toxoids against those putative BTW agents which are listed in the most recent draft of the rolling text of a Protocol to the BTWC[xli] (tab. 4). Since the rolling text is subject to further revision, it is worth mentioning that numerous States Parties also reported on the production of vaccines and toxoids against several other biological agents and toxins, which had been regarded as DTAs by various experts, but which have not been included in the rolling text's lists so far (tab. 5).
Some states also provided information on military vaccine activities in connection with their reports on facilities and biological defence programmes. As far as such data were unequivocal regarding the type of vaccine developed, they were included in tables 4 and 5. Canada, for example, reported in 1997 on Form A, part 2, that research is carried out at the Defence Research Establishment, Suffield, "on new drugs and delivery systems, for example microencapsulated antibiotics and vaccines". The agents which have been used recently in the Canadian biological defence programme include F. tularensis, Brucella species (melitensis, suis and abortus), various influenza virus strains, as well as botulinum toxin, staphylococcal enterotoxin B and a variety of venoms from marine organisms, reptiles and insects. Furthermore, it is reported in the Canadian 1998 "list of contractors", that "production, characterization and in vivo efficacy evaluation of polymeric microcapsules and nanocapsules for the controlled release of antibiotics and vaccines", "development of therapies and experimental vaccines to P. pseudomallei and P. mallei", and "development of a mucosal vaccine vector for Y. pestis" is performed at several Canadian universities.
Canada also reported in the context of CBM F that "medical work in biological defence has covered research and development, and in some cases production of toxoids, antitoxins and vaccines for various potential BW agents including botulinum toxin, rinderpest virus, Newcastle disease virus, M. mallei, F. tularensis and diphtheriae toxin".
In 1998 the Netherlands declared on Form A, part 1, work done with genetically engineered vaccines without indicating the agent as well as the development of human vaccines by use of recombinant DNA techniques. Likewise, Romania, in 1998 on Form A, part 1 listed three facilities where vaccines are developed and produced without mentioning the agents.
Australia described in a Form A part 1 report that the work of the facility CSL Limited, Parkville, VIC, is directed, inter alia, to the production of vaccines and toxoid. "The diseases involved are cholera, brucellosis, tuberculosis, influenza, plague and typhus" as well as botulism and tetanus.
The United States report in 1998 on Form A , part1, that defence vaccines are developed at the US Army Medical Research Institute of Infectious Diseases without informing about the types of agents. On a Form A, part 2 18 DTAs are listed against which "medical countermeasures" are developed and "exploratory studies and advanced development of protective and therapeutic countermeasures" are performed.The agents mentioned include, inter alia, the following "agents of most concern": Bacillus anthracis, Brucella spp., Coxiella burnetti, Yersinia pestis, Eastern equine encephalitis, Venezuelan equine encephalitis, Western equine encephalitis, vaccinia virus, botulinum neurotoxins, ricin, and staphylococcal enterotoxins.
On other A/2 Forms it was reported in 1998 by the USA that the Walter Reed Army Institute of Research, Washington, DC, is involved, inter alia, in the "development of effective vaccines" and that the Armed Forces Institute of Pathology, Washington, DC, produces organisms for extraction of their components "to develop component vaccine products" and related purpose. The agents and toxins studied in both institutes are said to include Bacillus anthracis, Brucella abortus, Brucella melitensis, Brucella suis, Francisella tularensis, Vibrio cholera, Yersinia pestis, botulinum toxin and Staphylococcal enterotoxin B. Additional information about the vaccines under development can be taken from the extensive lists of publications attached to the US reports.
In 1998, as already mentioned, the Salk Institute, Biological Development Center, Swiftwater, PA, was not declared on Form G by the USA. Instead, it was reported on an A/2 Form as a facility involved in the Biological Defence Research and Development Program (BDRP) (see above). According to that report the Salk Institute "provides support to the medical portion of the BDRP in the form of pilot production of investigational vaccines, diagnostic materials, and antibodies". Agents studied are "Baculovirus/anthrax protective antigen; botulinum toxin, Western equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, vaccinia virus, Francisella tularensis, Coxiella burnetti antigens; Botulinum toxoids A & B, and ricin".
So far the USA has not declared the two facilities mentioned above, DynPort LLC and BioPort Corporation which have been requested to produce defence vaccines.
The United Kingdom in 1997 reported on Form A, part 2 , on the development defence vaccines against anthrax, plague, botulinum toxin, ricin, tularemia, VEE and glanders. It was also declared that a multivalent viral vaccine was being developed against a range of pathogens.
Future measures to strengthen the BTWC should include precise language on how to report on vaccine production facilities. Reports should not be restricted to human vaccines, since the BTWC also covers anti-animal BW agents. In addition, not only facilities where vaccines "licensed by the States Party" should be declared. Although "governments in the USA and European countries have decided not to make any large-scale use of unlicensed products for protection either of civil or military populations"[xlii], military vaccination strategies in other countries might well involve non-lincensed biologicals. The same might hold true even for Europe and the USA in times of crises.
Additionally, it is strongly recommended once again not only to report on vaccine production facilities, but also on vaccine R&D as well as on military vaccination programmes.
Given the incompleteness of the CBMs it is to be doubted, however, that even a significant improvement of Form G would create full confidence and would remove suspicions regarding military vaccine development and use. Other measures must therefore be considered. It might be unrealistic, moreover, to expect a significant improvement of Form G before conclusion of the additional protocol and its ratification, especially since the protocol itself will also involve measures destined to provide transparency in the vaccine field.
Coverage of vaccine activities by the anticipated additional protocol
The additional protocol to the BTWC, which is presently elaborated by an Ad Hoc Group, will include several paragraphs dealing with vaccine R&D and production and corresponding facilities. Since the obligations laid down in the Protocol will be legally binding after its ratification and enter into force, vaccine activities related to the BTWC will certainly become much more transparent. The draft protocol is still in progress and most of the items interesting in this context are still in brackets, i.e. are still subject to more or less extensive revision; it is nevertheless indicative to mention the anticipated measures.
There is already an agreement that States Parties to the Protocol submit "Initial Declarations". They will include declarations on past offensive and/or defensive programmes (3, pp. 31-32). If such activities have been performed in the past, it should be summarized whether any R&D performed as part of the programme involved prophylaxis, i.a. vaccine activities.
There is also agreement that "Annual declarations" will be requested to provide information on ongoing BTW defensive programmes (3, pp. 33-37). These declarations will include vaccine activities as part of defence programmes. Besides that, the envisaged annual declarations would also include declarations on vaccine production facilities (3, pp. 37-38). Information has to be provided on approved vaccines and toxoids -- in brackets: "[against listed agents and toxins]" -- that have been produced during the previous calender year, and under which conditions.
There is also an attempt to improve the forms to be used for declarations of vaccine production taking into account the deficiences in the reporting system used so far: in an appendix guidelines for completing the declaration format are given (3, pp. 281-310). Regarding reports on vaccine production, it is considered that work with listed agents and/or toxins has to be declared, as well as detailed information about the size and equipment of the facility and the means used to produce biological agents. It will presumably also be asked whether there were areas at the facility which could only be entered by vaccinated personnel, where these areas are located, and which vaccines were applied (3, pp. 290-96).
Moreover, vaccine activities will be requested also in some other measures. It is unclear, however, whether a "Multilateral information sharing" between States Parties and between the BTWC Organization and international organizations dealt with in the present draft of the rolling text will be part of the final version of the Protocol. The same holds true to the proposal, that the BTWC Organization "is to collect information from non-governmental organizations and programmes/ini-tiatives". "Areas which could be covered" by the information sharing are the "Confidence building reports (as agreed in 1991) and among them a "Declaration of vaccine production facilities" and "Information on pharmaceutical and vaccine production, good manufacturing pratices, biosafety capabilities and procedures" (3, pp. 255-58).
The Vaccines for Peace proposal
But even if an additional protocol to the BTWC can be agreed upon and enter finally into force, it is to be doubted whether enough transparency has been reached to remove all suspicions concerning military vaccine activities. Despite the efforts to agree on and ratify an additional Protocol, supplementary measures are necessary in the field of vaccines and toxoids against DTAs.
To make the development and production of vaccines and other biologicals by military institutions more transparent, a bill was proposed in the United States as long as ten years ago[xliii] stipulating that "any biological research that can be effectively conducted by a civilian agency should be removed from military supervision in order to defuse unnecessary suspicion about our [i.e. US] objectives" [xliv].
The implementation of this bill would go a long way for providing the transparency needed to inspire confidence in BTWC compliance. It would be a useful addition to the information released within the frame of the confidence-building information exchange. Such action, however, would enhance confidence-building in open societies only. Conversely, national civilian control might not provide confidence if exerted in those approximately ten countries, which are, according to American, British, Russian and other sources, suspect of, or known to be interested in having access to biological and toxin weapons[xlv]. Hence, international actions providing transparency in the field of vaccine R&D and production for military purposes are necessary.
For these and other reasons the establishment of an "International Program of Development and Use of Vaccines Against Dual-Threat Agents" was recommended[xlvi]. The proposal, which was later called "Vaccines for Peace" (VfP), was supported by the Third Review Conference. The participants welcomed the effort "to elaborate an international programme of vaccine development for the prevention of diseases involving scientific and technical personnel from developing countries which are States Parties to the Convention. The Conference recognizes that such a programme might not only enhance peaceful international cooperation in biotechnology but also will contribute to improving health care in developing countries and provide transparency in accordance with the Convention". The proposal was also welcomed by the Fourth Review Conference with similar language[xlvii].
The main intention of the proposal was to develop, produce, stockpile and distribute vaccines against the dual-threat agents not already covered by other international programmes under conditions of full transparency[xlviii]. The VfP programme would involve the participation of scientists and other personnel from developing countries that are States Parties to the BTWC in the development and production of vaccines thus implementing Article Xb by contributing to peaceful international cooperation and making the Convention more attractive to those developing countries which are not yet States Parties.
The vaccines produced by the VfP programme would be made available to all States Parties for civilian and permitted military purposes. They might also be provided at low cost to developing and underdeveloped countries, which are not yet States Parties -- on the condition that the vaccines are used for those purposes only which do not violate the BTWC..
It was also proposed that after adopting the VfP programme and an additional "Global Epidemiological Surveillance System" as proposed by Wheelis[xlix] -- now well known as "ProMED" -- the States Parties to the BTWC should refrain from all biological and medical research and development activities related to the Convention under national military control.
The VfP proposal was evaluated by experts in a series of private international meetings. These culminated in a meeting in Biesenthal near Berlin, Germany, in September 1992 involving experts in biotechnology, defence, diplomacy, international development, medicine, molecular biology and vaccinology from Australia, France, Germany, Hungary, India, Peru, Russia, Sweden, the United Kingdom and the United States as well as representatives or observers from the WHO, UNIDO and the United Nations Office for Disarmament Affairs.[l] Some participants argued that VfP might weaken and not strengthen the BTWC for several reasons (see below). The workshop agreed, therefore, that a modified VfP programme should be proposed, later designated as the "Biesenthal Vaccine Initiative" (BVI).[li] BVI did not request, in contrast to VfP, that military facilities so far involved in vaccine R&D and production become involved in the programme under conditions of full transparency.
Both VfP and BVI were further evaluated at seminars and conferences in 1993 and 1994. In December 1994 an in-depth analysis was carried out at the XVI Kühlungsborn Collouium on the Island of Vilm, Germany, by defence experts, epidemiologists, molecular bioogists, and virologists from Germany and the USA. Recognizing that changing political, economic, technical and military factors warranted further development of the proposal, participants recommended a modified version, the "Program for Controlling Emerging Inectious Diseases" (ProCEID), as a set of measures designed to facilitate the impleentation of Article X without weakening the international norm against biological and toxin weapons[lii]. ProCEID was thought to complement ProMED, not only with respect to the similarity of the acronyms. In contrast to ProMED, ProCEID would be directly related to the BTWC, however. Compared with BVI, it would not exclusively deal with vaccines, but with other biologicals, too, which are designed to counter DTAs[liii], .
Considering the present situation, however, it seems justified to reconsider a revival of the original Vaccines for Peace proposal.If this attempt is to be taken seriously, the criticisms expressed when the original VfP proposal was evaluated have to be reconsidered. In the following the three main criticisms will be addressed.
Civilians are increasingly threatened
One main part of the VfP proposal was that vaccines should be developed and produced for both and military purposes and that these activities should be funded at least in part by the ministries of defence. Funds used so far to support military vaccine activities should be redirected to support the VfP programme. The proposal to support VfP partly with defence money was critized in the early 1990s on the grounds that it is usually not permitted to spend defence and other military funds on civilian purposes. But that argument is not convincing, not only with respect to the threat posed by possible hostile usage of DTAs. One cannot but agree with Donald A. Henderson, former deputy White House Science Advisor, who concluded that, "if we can and are willing to spend tens of billions to deal with the threat of nuclear weapons, as it is now the case, we should be more than prepared to devote hundreds of millions to cope with the greater threat of new and emergent infections, whether naturally occurring or induced by man"[liv].
Military hostile activities do not harm troops preferably or even exclusively. Since World War II an estimated 23 million people have been killed in over 150 major wars, but now some 90% of all casualities are civilians compared to only 10% half a century ago[lv]. In fact, the attitudes toward civilian casualities have changed. In the 1930s, the bombing of civilians in Guernica, Spain and Ethiopia were universally condemned. World War II changed the ethos[lvi]. Massive civilian casualities were intentionally inflicted in many cities, including Coventry, Dresden, Hiroshima, Leningrad, and Nagasaki.
The argument to restrict the expenditure of defence money from measures geared toward protecting the civilian population is even less convincing with respect to the protection of the civilian population against DTAs. Since biological and toxin weapons may not be preferably used as battlefield weapons, losses among the civilian population after BTW attacks may be even higher. Protection of the civilian population from BTW agents is thus much more urgent than before. The same holds true with respect to bioterrorist attacks[lvii].
At least the US Administration is now well aware of that demand. In the speech mentioned in the introduction, President Clinton expressed his belief that more has to be done to protect the civilian population from the scourge of biological weapons. He announced that "we will train and equip local authorities throughout the nation to deal with an emergency involving weapons of mass destruction, creating stockpiles of medicines and vaccines to protect our civilian population against the kind of biological agents our adversaries are most likely to obtain or develop". Clinton proposed the creation of an unprecedented civilian medical stockpile of medicines and vaccines against such agents. Furthermore, he announced that "we will pursue research and development to create the next generation of vaccines, medicines and diagnostic tools"2.
In this context, the US President referred to a major advantage of biological defence programmes: because of the dual-threat nature of putative BTW agents, biological defence measures can also be effectively used to counter natural outbreaks of infectious diseases and intoxinations, including emerging diseases. Accordingly, President Clinton emphasized that the present activities of the administration will -- according to the press release -- "pay off in an enhanced ability to respond quickly and effectively to outbreaks of emerging infectious diseases". Some days earlier, Madam Minister of Justice, Janet Reno, informed that the President had requested to evaluate if substantial amounts of vaccines could be stockpiled over the whole country at strategic places that would be available for the civilian population if necessary[lviii].
But it is to be doubted whether bioterrorism can be effectively prevented and the effects of bioterroristic acts can be effectively countered by national measures alone. Michael Osterholm has estimated, for example, that "millions of doses of anthrax and smallpox vaccines and appropriate antibiotics must be readily available if we are to control such an outbreak"[lix]. International actions are necessary, therefore, to counter and contain bioterroristic attacks[lx]. VfP, ProCEID or similar programmes would represent powerful means to contribute to preparedness to counter such attacks on a global basis.
States have a national right to self-defence
Others criticised the VfP proposal with reference to the national right of states to self-defence. With respect to protection from BTW attacks, this right would be restricted by the establishment of a VfP programme.
Of course there is no reason to question the national right to self-defence. But it is well known, that for centuries states have formed alliances to join defence capacities. That was also true with respect to biological defence not only during the Cold War within NATO and the Warsaw Pact. During World War II, for example, Canada, the United Kingdom and the United States cooperated in the development of toxoids to protect against botulinus-toxin and to produce and weaponize Bacillus anthracis[lxi].
Moreover, although it is true that the right to self-defence is enshrined in the UN charter, one should take into account that this right was laid down half a century ago, at a time when BTW agents had only little military significance. In the meantime the problems involved in protection against DTAs have increasingly become global problems. First, biological agents do not respect national borderlines. This is well-known not only from studies on the spread of emerging diseases, but has also been known at least since the 14th century. At that time, Yersinia pestis, probably as a consequence of their hostile use, conquered all of Europe, eradicating large parts of the population. Yersinia pestis has remained a DTA "of most concern" even until today.
Second, the presumed increase of the bioterrorist threat parallels an increase in international terrorism[lxii]. Prevention of international bioterrorist activities and countering and containing bioterrorist attacks calls for joint international actions. Joint actions within political alliances such as NATO are not sufficient and must be complemented by joint activities in geographic regions and beyond.
Third, numerous difficulties12 in the development of vaccines, not to mention defence vaccines, including the problem of raising funds for the development and production of vaccines against DTAs, most of which lack an economically promising market, call for close international cooperation. The successful eradication of smallpox and other vaccine activities organized by WHO demonstrate the efficiency of international cooperation especially in that field. But WHO programmes concentrate on major diseases. VfP would supplement these programmes by provision of vaccines against infectious diseases and intoxinations against DTAs, which are less frequent but nevertheless pose serious health problems in certain geographic regions, including agents causing emerging diseases.
International cooperation would also allow the overcoming of a major obstacle caused by the fact that for many vaccines against DTAs the natural prevalence of the disease is restricted to exotic areas so that no conclusive field trials of efficacy can be carried out. The partnership of countries where DTAs against which vaccines are developed do occur in the VfP programme would enable the performance of field trials.
Transparent vaccine activities and deterrence
It has been criticized that VfP may unintentionally lead to BTW proliferation and might enable potential aggressors to circumvent BTW defence measures of the envisioned victim of their planned BTW attacks. One expert argued that "a defence that is freely available to the potential aggressor to examine and evaluate is no defence as he will seek to and be able to circument that defence. The objective of an effective defence is to increase the uncertainty of the aggressor as to whether his biological warfare capability will be effective in achieving his military objective as well as to what response the use of BW will provoke"[lxiii].
That argument sounds convincing. But first, knowledge about existing defence measures, especially of a global emergency defence system, might well act as a deterrent. Deterrence from the use of biological and toxin weapons can be achieved in different ways. The deterrence message may, inter alia, include the enemy's preparedness for retaliation in kind as well as his availability of protection measures.
Deterrence by the capacity for retaliation in kind
The impact of a capacity to retaliate in kind as a deterrent is indicated by the fact that Hitler was obviously concerned by the Anglo-American ability to retaliate[lxiv].
During the Cold War, the United States and their allies relied primarily on deterrence for the threat of retaliation in kind to a nuclear attack[lxv].One clearly defined enemy was the recipient of the deterrence message, the Soviet Union. After the Cold War, the situation changed in two important respects. Russia is no longer the perceived major enemy, and the nuclear threat has been reduced and complemented by the threat of the use of other weapons of mass destruction including biological and toxin weapons.
With respect to biological and toxin weapons, retaliation in kind today is not an option because the United States as most of its Allies -- except Isreal -- is a committed party to the Biological Weapons Convention62. Besides that, retaliation in kind is not an option to deter terrorist groups from using biological and toxin weapons.
Hence, deterrence by provision of efficient protective measures should become inreasingly important, so much the more so since there are examples from history that such measures did act as deterrence measures.
Deterrence by disclosure of protection capabilities
That knowledge about possible enemy defence capacities acts as deterrent, indeed, can be learned from history. When the feasibility of biological warfare was discussed in Germany as early as 1925, and the value of different biological agents as weapons agents was evaluated, a leading expert, Geheimer Medizinalrat Professor Richard Otto, came to the conclusion that "smallpox viruses are not suitable as BW agents, since vaccination provides an excellent defense measure"[lxvi]. The same conclusion was drawn nearly half a century later by a group of WHO experts: "Because of the effectiveness of the vaccine and the relative ease with which it can be produced and administered, it is unlikely that smallpox virus would be used as an agent for large-scale biological attack against countries systematically practising periodic vaccination"[lxvii]. Today, on the other hand, after the eradication of smallpox virus and the cessation of at least civilian vaccination, variola virus has not only become a "single-threat agent"[lxviii] but, according to the evaluation of the US Department of Defense, an "agent of most concern"14. This example clearly demonstrates how decisive knowledge about prophylaxis possibilities is for the evaluation of the military value of a biological agent or toxin.
Such evaluations have not been restricted to smallpox virus. Another leading German expert, Generalarzt Professor Riemer, concluded in 1925 that "infection of enemy [troops] will be only successful, if there was no vaccination against the BW agents used and", he added to the argument discussed above regarding the usfulness of vaccines for offensive purposes, "if the own troops are protected against"[lxix]. Knowledge about vaccination did act as deterrent.
Similar conclusions were drawn ten years later. Generaloberarzt Dr. Walter Kittel, Chief of Staff of the Sanitary Inspectorate, pointed out in 1934: "With respect to so called 'bacteriological weapons' the Sanitary Inspectorate [of the German army] still holds the view, that the dissemination of bacteria depends on an ample set of external factors. No practical results can be achieved, therefore, especially since every civilized country is equipped with measures to protect against infections"[lxx]. This judgement influenced German BTW policy until the beginning of World War II. Professors Fritz Wirth and Otto Muntsch. leading CBW experts, ascertained in both 1935 and 1940 that "hygienic and medical sciences are so developed today, that already by means of prophylactic measures (vaccination etc) the threat of biological warfare is greatly diminished"[lxxi].
The same notion was held by the US about 30 years later: when the requirements of biological weapons agents were compiled by the Departments of the Army and the Air Force, it was mentioned that it should be "possible for the using forces to protect against" but "difficult for a potential enemy to detect or to protect against"[lxxii].
Deterrence would be especially caused by the existence of a global biological defence system since an attacker state or group would not be threatening a single, more or less vulnerable state, but a community of states prepared to assist each other.
Conservatism in the selection of BTW agents
It is also highly unlikely that transparency in the vaccine field would increase the threat because it might induce an aggressor to select other BTW agents for a planned attack. A potential user of BTW agents would have to choose more rare BTW agents if he knows that the community of states participating in a common VfP programme is equipped with drugs and vaccines able to protect against "usual" BTW agents.
A study of the history of BTW reveals a remarkable conservatism in the choice of BTW agents. Even if it is doubtful whether the Tatars used Yersinia pestis in 1346 to attack Caffa, it is an established fact that British forces used smallpox against Amerindians in 1763[lxxiii]. Yersinia pestis and smallpox virus are still today top on the list of putative BW agents.
The Germans during World War I introduced Bacillus anthracis as a BW agent for sabotage acts performed in various countries[lxxiv]. Anthrax spores have since then been studied, produced and weaponized by numerous countries, including in Iraq and the former USSR and, remarkably, also by the Aum-Shinrikyo cult. The cultists sprayed in June 1993, for example, a slurry of anthrax bacilli from the roof of a building in Tokyo. The action failed like at least eight other bioterrorist attacks because of the selection of insufficently aggressive bacterial strains and/or technical inadequacies in the agent dissemination equipment[lxxv]. According to a paper distributed by the British government among the members of parliament early in 1998, "one hundred kilograms of anthrax released from the top of a tall building in a densely populated area could kill up to three million people"[lxxvi]. The civilians, again, would be the group affected the most by an attack.
A traditional TW agent is botulinus toxin. It was presumably first considered for warfare purposes by Russian BW researchers in 1928[lxxvii], and now is one of the DTAs "of most concern". It was also studied by the Aum-Shinrikyo terrorists56.
It is conceivable, of course, that a potential attacker will take into consideration the genetic modification of traditional BTW agents enabling them to overcome immune barriers (and to be resistant to common antibiotics). But that requires efforts, resources, manpower and equipment -- and can be likewise counteracted by joint defence activities, especially if they are performed on a multilateral basis.
Global actions are inevitable
In view of the increasing threat of the hostile dissemination of biological agents and toxins as well as the increasing threat of the natural occurrence of emerging infectious diseases, many more efforts have to be made to protect the population. Since neither the hostile use of DTAs nor their natural occurrence and evolution can be totally prevented -- except for very rare instances such as the eradication of smallpox and the envisaged eradication of polivirus -- countermeasures have to concentrate on protective and prophylactic measures as well as on contaiment activities once an outbreak of disease has occurred.
In the United States much effort is undertaken for this end. But local and national being measures are not sufficient to counter a global threat. The Vaccines for Peace Programm might well contribute to provide global security against DTAs as well as reduce the danger, that military vaccine activities are misinterpreted as offensive activities performed in violation of the international norm against the hostile use of biological agents and toxins.
A generous grant from the Volkswagen-Stiftung allowed the author to carry out his research. The author acknowledges with gratitude the helpful comments he received from Iris Hunger.
Table 1. Selected viral antipersonal DTAs
Vaccine Effectiveness of
Disease protection sero- or chemotherapy
Yellow fever + - -
Tick-borne encephalitis + - -
Japanese encephalitis + - -
Venezuelan equine encephalitis + - -
Eastern equine encephalitis + b - c -
Western equine encephalitis + b - c -
Chikungunya fever + b - c -
O'nyong-nyong + b - c -
Rift Valley fever + b - -
Smallpox + + +
Lassa fever + + -
Crimean-Congo hemorrhagic fever - + +
Ebola - + -
Marburg disease - + -
Dengue fever - - -
Korean hemorrhagic fever - - -
Table 2. Number of vaccine production facilities declared in most recent information
Argentina 2 Australia 1
Austria 1 Belgium 1
Brazil 7 Bulgaria 1
Canada 1 Chile 1
Cuba 2 Czech Republic 1
Denmark 1 Finland 1
France 2 Germany 4
Hungary 3 India 19
Italy 9 Iran 4
Japan 12 Mongolia 1
Netherlands 2 Norway 3
Poland 4 Republic of Korea 7
Romania 2 Russian Federation 16
South Africa 1 Spain 13
Sweden 1 Switzerland 1
Turkey 4 Ukraine 1
United Kingdom 2 United States 9
Table 3: Human vaccines and toxoids against agents and toxins not regarded to be putative BTW agents
Agent or disease Producer country
Hepatitis Austria, Spain, USA
Hepatitis A virus Belgium, Japan, Russia, Switzerland, USA
Hepatitis B virus Belgium, Cuba, France, Japan, Korea, Mongolia,
Herpes virus Bulgaria, Ukraine
Measles virus Belgium, Brazil, Bulgaria, Canada, Czechia, France, India, Iran, Japan, Korea, Netherlands, Romania, Switzerland, UK, USA
Mumps virus Belgium, Czechia, France, Iran, Japan, Korea, Netherlands, Switzerland, USA
Poliomyelitis virus Belgium, Brazil, Canada, Denmark, France, Germany, Iran, Japan, Korea, Netherlands, Russia, South Africa, Spain, Sweden, Switzerland, UK, USA
Rabies virus Argentina, Brazil, Bulgaria, Canada, Chile, Cuba, France, Germany, India, Japan, Mongolia,
(Netherlands), Romania, South Africa, Switzerland, Ukraine, USA
Rubella virus Belgium, Canada, Czechia, France, Iran, Japan, Korea, Netherlands, Spain, Switzerland, UK, USA
Bordetella pertussis Argentina, Australia, Belgium, Brazil, Bulgaria,
Canada, Chile, Czechia, Denmark, Finland, France, Germany, Hungary, India, Iran, Japan, Korea, Netherlands, Romania, Russia, South Africa, Spain, Switzerland, Turkey, UK, USA
Tab. 3, ctd.
Haemophilus influenzae Belgium, Canada, France, USA
Leptospira Japan, Korea, Romania
Meningococcus Belgium, Brazil, Cuba, France, Germany, Norway, Russia, USA
Mycobacterium Brazil, Canada, Denmark, France, Germany, Hungary, tuberculosis India, Iran, Japan, (Netherlands), Romania, Russia, South Africa, UK, USA
Pneumococcus France, USA
Table 4: Human vaccines and toxoids against listed agents and toxins
AgenT or disease Producer country
haemorrhagic fever virus Bulgaria
Eastern equine encephalitis USA
Hantaan virus Korea
with renal syndromec Korea
Haemorrhagic viral disease USAc
Smallpox virus Australia, Russia, USA
Tick-borne encephalitis Germany, Russia
Western equine encephalitis USA
Yellow fever virus Australia, Brazil, France, Germany, India, Russia, South Africa, UK, USA
Bacillus anthracis Netherlandsc, Russia, Turkey, UK, USA
Brucella Australiac, Romania, Russia
Tab. 4, ctd.
Burkholderia (Pseudomonas) mallei Canada
Burkholderia (Ps.) pseudomallei Canadah, Francec
Coxiella burnetti Australia, USA
Francisella tularensis Canada, Germanyh, Russia, Ukraine, USA
Yersinia pestis Australia, Canadah, Germanyh, Russia, Turkey, USA
Diphtheria Argentinia, Australia, Belgium, Brazil, Bulgaria, Canada, Cuba, Chile, Czechia, Denmark, Finland, France, Germany, Hungary, India, Iran, Japan, Korea, Netherlands, Poland, Romania, Russia, South Africa, Spain, Sweden, Switzerland, UK, Ukraine, USA
Botulinus toxin Australiac, Canada, Francec, Japan, Poland, UK, USA
Staphylococcal enterotoxins Hungary
Tetanus toxin Argentina, Australia, Belgium, Brazil, Bul- garia, Canada, Chile, Cuba, Czechia, Den- mark, Finland, France, Germany, Hungary, India, Iran, Japan, Korea, Netherlands, Poland, Romania, South Africa, Sweden, Spain, Switzerland, Turkey, USA
Table 5: Human vaccines and toxoids against putative BTW agents not listed in the Rolling Text
Agent or Disease Producer country
Dengue virus France, USA
Influenza virus Australia, Belgium, Bulgaria, Canada, France, Germany, Hungary, Japan, Korea, Netherlands, Romania, Russia, Spain, Switzerland, Ukraine, UK, USA
Japanese encephalitis virus India, Japan, Korea
Shigella dysenteriae Romania, USA
Typhoid fever Australia, Brazil, Bulgaria, Chile, France, Hungary, India, Iran, Korea, Mongolia, Romania, Russia, Switzerland, UK, USA
Vibrio cholerae Australia, Bulgaria, Canada, France, Germany, Hungary, India, Iran, Japan, Korea, Romania, Russia, Sweden, Switzerland, South Africa, Spain, USA
 Paper presented at the Third International Symposium on Science for Peace, Jerusalem 8-13 November 1998. Y. Becker et al. (ed.), Science for Peace 5, UNESCO, Venice Office, Venedig. Publication planned but not realized.
Winter's proposal was rejected by the supreme command for technical and ethical reasons.
 Article X of the BTWC requests State Parties to enhance peaceful cooperation by undertaking ”[...] to facilitate, and have the right to participate in, the fullest possible exchange of equipment, materials and scientific and technological information for the use of bacteriological (biological) agents and toxins for peaceful purposes [...]”, and to ”[...] avoid hampering the economic or technological development of State Parties [...] or international cooperation in the field of peaceful bacteriological (biological) activities [...]”.
 For 1998 only those 41 reports could be evaluated which reached the Department of Disarmament Affairs before 10 September 1998 and were disseminated thereafter among State Parties. Until the end of 1998, no additional reports were distributed by DDA, although it can be assumed that some additional reports were received by DDA after 10 September 1998.
 One signatory (Mali) and one non-State Party (Kyrgyzstan) also took part in the exchange once, although only declaring that they do not possess biological and toxin weapons.
 But see footnote c.
 It is a matter of opinion whether submission of an incomplete nil declaration can be regarded as "participation in the information exchange". Because the said states at least responded by provision of the incomplete form, they as well some other states have been regarded as participants
 This figure includes some 20 States Parties which submitted a general statement of nothing to declare.
 Confidence-building measure "A", part 2, was agreed by the Third Review Conference as "Exchange of information on national biological defence research and development programmes".
In addition, the production of veterinary vaccines including vaccines against the DTAs Bacillus anthracis, Brucella spp., foot-and-mouth disease virus, Newcastle disease virus and rinderpest virus, was reported by some countries.
 "Confidence-building measure 'F': Declaration of past activities in offensive and/or defensive biological research and development programmes".
 Confidence-building measure "A", part 1, was agreed by the Second Review Conference as "Exchange of data on research centres and laboratories" to be provided on Form 1. It was renamed CBM A, part 1, by the Third Review Conference in connection with the adoption of CBM A, part 2 (see footnote h).
ProCEID was additionally sligthly revised during the XVII Kühlungsborn Colloquium 30 June - 2 July, 1995, by experts from Germany, Russia, the United Kingdom, and the United States. The title was modified to "Programme for Countering Emerging Infectious Diseases" (emphasis added).
 Many authors claim that the Tatars have used plague-infected cadavers to attack the Genoese seaport Caffa on the Crimea in 1346, but it is nearly impossible to substantiate such claims (see Wheelis, note 64).
 Modified after J. Melling (note 12).
 Vaccine is experimental, used in humans.
 Passive protection for accidental laboratory exposure
 Production of rabies vaccine finished around 1996.
 Will bis or has already been ended.
 "Listed" agents as mentioned in the rolling text of a protocoll to the BTWC.
 In the lists only individual species are addressed. The faciliy Bunyaviridae includes more than 200 different viruses including the listed viruses Crimean-Congo haemorrhagic fever virus, [Hantaan virus], [Sin Nombre virus], and Rift Valley fever virus.
 Not reported on Form G but on Form A (1).
 Production of vaccine against EEE by the Salk Institute was mentioned in 1997 on Form G. In 1998 the Salk Institute and its products are no longer declared on Form G but on Form A, Part 2.
 Usually it is understood that Haemorrhagic fever with renal syndrome is caused by Hantaan virus. Nevertheless the Republic of Korea reports separately on the production of vaccines against Hantaan virus and Haemorrhagic fever with renal syndrome. Hantaan virus is listed in brackets.
 Production of vaccine against WEE by the Salk Institute was mentioned in 1997 on Form G. In 1998 the Salk Institute and its products are no longer declared on Form G but on Form A, Part 2.
 Not reported on Form G but on Form A (2).
 Not reported on Form G but on Form A (2) and Form F.
9 Burkholderia (Ps.) pseudomallei is listed in brackets.
 Not reported on Form G but on Form F.
 "Toxins of Corynebacterium diphtheriae" are listed in brackets.
 Tetanus toxins is listed in brackets.
 Compiled in Geissler, E., "Arms control, health care and technology transfer under the'Vaccines ofr Peace programme", in: Geissler, E. and J.P. Woodall (eds.), Control of Dual-Threat Agents: The Vaccines for Peace Programme. Oxford University Press, 1994, pp. 10-37, Table 3.3., p. 29.
 Not reported on Form G but on Form A (1).
[i] Tucker, J. B. (1997) "The Biological Weapons Threat", Current History 96 (April), pp. 167-192.
[ii] [Clinton, W.J.] (1998) "Preparedness for a Biological Weapons Attack". Fact Sheet. The White House, Office of the Press Secretary, Annapolis, Maryland (22 May). See also: The CBW Conventions Bulletin, no. 40 (June), p. 38.
[iii] United Nations (1999) Procedural Report of the Ad Hoc Group of States Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction,. PART I. ANNEX I, "Rolling Text of a Protocol to the Convention on the Prohibition of the Development, Production and Stockpiling Bacteriological (Biological) and Toxin Weapons and on their Destruction" (29 January). BWC/AD HOC GROUP/44 (Part I), pp. 6-326.
[iv] United Nations (1994) Final Report, Special Conference of the States Parties to the Convention on the Prohibition of the Development, Production and Stockpiling Bacteriological (Biological) and Toxin Weapons and on their Destruction, 19-30 September. BWC/SPCONF/1, 1994, p. 10.
[v] Convention on the Prohibition of the Development, Production and Stockpiling Bacteriological (Biological) and Toxin Weapons and on their Destruction, reprinted in E. Geissler (ed., 1986), Biological and Toxin Weapons Today, Oxford University Press, Oxford, pp. 135-37.
[vi] USA (1980) Soviet Biological Warfare Activities, Permanent Select Committee on Intelligence, US House of Representatives, June, p. 2, quoted by M. Leitenberg (1991) "Soviet activities related to biological weapons", Arms Control 12, no. 2 (September), pp. 161-190, see p. 168.
[vii] Sidel, V. (1989) Testimony on "Germ wars: Biological weapons proliferation and the new genetics", in Global Spread of Chemical and Biological Weapons. Hearings before the Committee on Governmental Affairs and its Permanent Subcommittee on Investigations, United States Senate, U.S. Goverment Printing Office, Washington (1990), pp. 512-518.
[viii] Owens, W. (1989) Testimony ... (note 7), pp. 180-182.
[ix] Geissler, E. (1991) "Contribution of confidence-building measures to greater transparency in activities directly related to the Biological Weapons Convention", in S.J. Lundin (ed.. 1991), Views on Possible Verification Measures for the Biological Weapons Convention. Oxford University Press, Oxford, pp. 10-25, see p. 12.
[x] Poindexter, J.S. (1988) "Responsible uses of microorganisms and microbiological products", in P. DeForest, M.S. Frankel, J.S. Poindexter and V. Weil (eds.), Biotechnology, Professional Issues and Social Concerns, AAAS, Washington, DC, pp. 51-71.
[xi] Strauss, H. and King, J. (1986) "The fallacy of defensive biological weapon programmes", in Geissler (note 5), 66-73; Yamamoto, K.R. (1989) Testimony .... (note 7), pp. 485-497.
[xii] Melling, J. (1999) "Vaccine Production", in A. Kelle, M. Dando, and K. Nixdorff (eds.), The Role of Biotechnology in Countering BTW Agents, Kluwer Academic Publishers, Dordrecht, forthcoming.
[xiii] USA (1991) Biological Warfare. Role of Salk institute in Army's Research Program. Report to the Chairman, Committee on Governmental Affairs (December), United States General Accounting Office. GAO/NSIAD-92-33. U.S. Senate, Washington, D.C.
[xiv] Quoted by Melling (note 12).
[xv] The CBW Convention Bulletin, no. 39 (March 1998), p. 25.
[xvi] UPI from Lansing, 25 September 1998, quoted in The CBW Conventions Bulletin, no. 42 (December), p. 32.
[xvii] The CBW Conventions Bulletin, no. 40 (June), p. 27. See also: Nass, M. (1998) "Anthrax vaccine and the´prevention of biological warfare?", The ASA Newsletter, no. 92-2 (April), pp. 1, 23-25.
[xviii] The CBW Conventions Bulletin, no. 39 (March), pp. 31-32.
[xix] USA (1998) DoD release, 22 May. The CBW Conventions Bulletin, no. 41 (September), p. 24.
[xx] USA (1998) DoD news release, 14 August. The CBW Conventions Bulletin, no. 42 (December), p. 24.
[xxi] Huxsoll, D.L., Patrick III, W.C., and Parrott, C.D. (1987) "Veterinary services in biological disasters". Journal of the American Veterinary Association, 190, no. 6, pp. 714-22.
[xxii] Geißler, E. (1999) Biologische Waffen - nicht in Hitlers, Arsenalen, Biologische und Toxin-Kampfmittel in Deutschland vor 1915 bis 1945. 2nd ed. LIT Verlag, Münster.
[xxiii] Brill, W., Lederberg, J., Mayer, J., Rutter, W., Schneidermann, H., Singer, M., and Young, F. (1981) "Summary of the Genetic Engineering Expert Panel" (5 May). Unpublished, partly quoted in Genetic Engineering Letter 1 no. 10 (24 May), p. 4.
[xxiv] Geissler, E., Blackaby, F., Falk, R.A., King, J., Lohs, Kh., Mechtersheimer, A., Strauss, H., Zilinskas, R.A., and Trapp, R. (endorsed by D. Baltimore et al.) (1986) "Conclusions and recomendations" in Geissler (note 5), pp. 121-29, see p. 128
[xxv] Geissler, E., Brunius, G., Levin, A.L., Lundin, S.J., Marcovich, H., and Woodall, J.P. (1990) "Conclusions and recommendations" in E. Geissler (ed.), Strengthening the Biological Weapons Convention by Confidence-Building Measures. Oxford University Press, Oxford, pp. 147-53, see p. 152.
[xxvi] FAS Working Group on Biological and Toxin Weapons Verification (1991) "Proposals for the Third Review Conference" in E. Geissler. and R.H. Haynes (eds.), Prevention of a Biological and Toxin Arms Race and the Responsibility of Scientists, Akademie-Verlag, Berlin, pp. 485-505, see p. 498.
[xxvii] United Nations (1986), Summary Record of the 8th Meeting. Second Review Conference of the Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction. BWC/CONF.II/SR.8, 22 September, p. 2.
[xxviii] United Nations (1986), Summary Record of the 5th Meeting. Second Review Conference (note 25). BWC/CONF.II/SR.5, 19 September, p. 5.
[xxix] Ireland and Austria (1987), Proposal on agenda item 4 (a), in United Nations (1987), Report, Ad Hoc Meeting of Scientific and Technical Experts from States Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction. BWC/CONF.II/EX/2. 21 April. Attachment, p. 30.
[xxx] France (1991) "Confidence-building measures proposed by France", in United Nations (1991) Final Document. PART III. Report of the Committee of the Whole, Third Review Conference of the Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction. BWC/CONF.III/23/Part III. Geneva, 9-27 September, p. 79.
[xxxi] Finland (1991) "Proposal for a confidence-building measure. Military vaccination programmes", in United Nations (1991, note 30), p. 93.
[xxxii] Hungary (1991) "Suggestions for revising the data exchange", in United Nations (1991, note 30), p. 95-96.
[xxxiii] United Nations (1986) Final Document. PART II. Final Declaration. Second Review Conference (note 25), BWC/CONF.II/13/II. 30 September, p. 6.
[xxxiv] United Nations (1987) Report (note 27). BWC/CONF.II/EX/2. 21 April.
[xxxv] United Nations (1991, note 30), PART II, Final Declaration, BWC/CONF.III/23, Part II (1991), pp. 46-47
[xxxvi] Canada (1991) [Proposal for CBMs] in United Nations (1991, note 30), p. 93.
[xxxvii] Canada (1991) "CBM (new): Declaration of vaccine production facilities", in United Nations (1991, note 30), pp. 86-87.
[xxxviii] United Nations (1996) Final Document. PART II, Final Declaration, Fourth Review Conference of the Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biologial) and Toxin Weapons and on their Destruction. BWC/CONF.IV/9, p. 19.
[xxxix] Chevrier, M.I. and Hunger, I. (in preparation) "Doubts about confidence: the potential and limits of confidence-building measures for the Biological and Toxin Weapons Convention"; Geissler (notes 9, 28); Geissler, E. (1994) "Confidence-building information from the parties to the Biological Weapons Convention" in J. Altmann, T. Stock and J.P. Stroot (eds.): Verification after the Cold War, V.U. Press, Amsterdam, pp. 171-177; Geissler, E. and Woodall, J.P. (in press) "Reporting of outbreaks of disease under BTWC Confidence-Building Measures" in M. Dando and Pearson, G.S.(eds.) Scientific and Technical Means of Distinguishing Between Natural and Other Outbreaks of Disease, Kluwer, Dordrecht; and Hunger, I. (1996), "Article V: Confidence building measures" in Pearson, G.S. and Dando, M. (eds.), Strengthening the Biological Weapons Convention: Key Points for the Fourth Review Conference. Quaker United Nations Office, Geneva.
[xl] United Nations (1991-98) BWC/CONF.III/2 and Add.1, 2 and 3; DDA/4-92/BWIII and Add.1, 2, 3, 4 and Report of Romania; ODA/9-93/BWIII and Add.1 and 2; CDA/16-94/BWIII and Add.1 and 2; CDA/14-95/BW-III and Add.1 and 2; CDA/11-96/BW-III and Add.1 and 2; CDA/BWC/1997/CBM and Add.1; DDA/BWC/1998/CBM and Add.1.
[xli] United Nations (1999, note 3), pp. 152-54.
[xlii] Melling (note 12).
[xliii] USA (1988) "A Bill to require that all Federal research, development, testing, and evaluation of the use of biological agents in the development of defenses against biological warfare be conducted by the Director of the National Institutes of Health, and for other purposes". H.R.5241. Introduced in the House of Representatives by W. Owens. Washington, DC, 11 August.
[xliv] Owens (note 8).
[xlv] Geissler, E. (1994) "Biological weapon and arms control developments", SIPRI Yearbook 1994, Oxford University Press, Oxford, pp. 713-38, see especially pp. 715-16.
[xlvi] Geissler, E. (1989) '"Biological and toxin weapons: the renewed threat", NGO Committee on Disarmament Forum at the UN Headquarters, New York (2 February), transcript; Geissler, E. (1989) "The international control of biological weapons" (interview), geneWATCH, 6, no. 1 (August), pp. 1-4.
[xlvii] United Nations (1991, note 30), p. 23; United Nations (1996, note 38), p. 13.
[xlviii] Geissler, E. (1992) "Vaccines for Peace. an international program of development and use of vaccines against dual-threat agents", Politics and the Life Sciences 11, no. 2 (August), pp. 231-43.
[xlix] Wheelis, M. (1990) "The role of epidemiology in strengthening the Biological Weapons Convention". In: Geissler and Haynes (note 29), pp. 277-83.
[l] Geissler, E and Woodall, J.P. (eds., 1994), Control of Dual-Threat Agents: The Vaccines for Peace Programme, Oxford University Press, Oxford.
[li] "The Biesenthal Vaccine Initiative (Vaccines for Peace). Biesenthal Consensus". In: Geissler and Woodall (note 49), pp. 255-257. "The Biesenthal Vaccine Initiative Mission Statement", in Geissler and Woodall (note 49), p. 258.
[lii] ProCEID Steering Committee (1995), "ProCEID--Program for controlling emerging infectious diseases: Mission Statement", Politics and the Life Sciences 14, no. 1 (February), pp. 89-92.
[liii] Meeting Report (1996) "Programme for countering emerging infectious diseases (ProCEID) by prophylactic, diagnostic and therapeutic measures. Mission Statement, revised", Biologicals 24, pp. 71-74 .
[liv] Henderson, D.A. (1998) [speech at an international conference on emerging infectious diseases], Atlanta, Georgia, 8-11 March, quoted in Chemical and Biological Weapons Convention Bulletin, no. 40 (June), p. 28.
[lv] Levy, B.S. and Sidel, W.V. (eds., 1997), War and Public Health, New York, Oxford University Press, p. 149.
[lvi] Levy and Sidel (note 55), p. 40.
[lvii] Tucker, J.B. (1996) "Chemical/biological terrorism: coping with a new threat" and roundtable commentaries by K.C. Bailey et al., Politics and the Life Sciences 15, no. 2, pp. 167-247.
[lviii] Reuters (1998), "USA erwägen Impfstofflager gegen B-Waffen". 16 April.
[lix] Osterholm, M. (1998) New York Times, 14 August, quoted in Chemical and Biological Weapons Convention Bulletin, no. 42 (December), p. 23.
[lx] Hunger, E. und Geißler, E. (1997) "ProCEID. Der Gefahr des Bioterrorismus international begegnen". S+F. Vierteljahresschrift für Sicherheit und Frieden 15, no. 4 , pp. 250-55.
[lxi] Geissler, E. and van Courtland Moon, J.E. (eds., 1999), Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945. SIPRI, Oxford University Press, Oxford.
[lxii] Alexander, Y., this volume; Falkenrath, R.A. (1998) "Confronting nuclear, biological and chemical terrorism". Survival 40, no. 3. 43-65; Tucker (note 57).
[lxiii] Pearson, G.S. (1994) "Vaccines for biological defence: defence considerations" in Geissler and Woodall (note 50), pp. 151-62, see especially p. 157.
[lxiv] Geißler, E. (1998) Hitler und die Biowaffen, LIT-Verlag, Münster.
[lxv] Moodie, M. (1998) Chemical and Biological Weapons: Will Deterrence Work? The Deterrence Series. CBACI Policy Report. Alexandria; VA.
[lxvi] Otto, R. (1925) "Die Verwendung von Krankheitskeimen als Kampfmittel im Kriege", Wissenschaftlicher Senat für das Heeressanitätswesen, Berlin, 19 February. Bundesarchiv Militärarchiv, Freiburg, Brsg., RH 12-9/27, pp. 17-22.
[lxvii] United Nations (1969) Chemical and Bacteriological (Biological) Weapons and the Effects of their Possible Use. UN Report S/9292/Rev.1. New York.
[lxviii] Fenner, F. (1994) "The WHO global smallpox eradication programme: vaccine supply and variola virus stocks". In Geissler and Woodall (note 50), pp. 185-202.
[lxix] Riemer (1925) "Die Verwendung von Krankheitskeimen als Kampfmittel im Kriege", Wissenschaftlicher Senat für das Heeressanitätswesen, Berlin, 19 February. Bundesarchiv Militärarchiv, Freiburg, Brsg., RH 12-9/27, pp. 22-32.
[lxx] Kittel, [W.] (1934) Letter to departments T 3, T V, Ausl. of High Command. Secret. 6 November. Bundesarchiv Militärarchiv, Freiburg, Brsg., RW 5/345.
[lxxi] Wirth, F. und Muntsch, O. (1935, 1940) Die Gefahren der Luft und ihre Bekämpfung, Georg Stilke Verlag, Berlin, 2nd ed., p. 208, 3rd ed., p. 220.
[lxxii] [US] Departments of the Army and the Air Force (1964) Military Biology and Biological Agents, Technical Manual TM 3-216/Air Force Manual AFM 355-6, March, p. 25.
[lxxiii] Wheelis, M. (1999) "Biological warfare before 1914" in Geissler and van Courtland Moon (note 61), pp. 8-34.
[lxxiv] Geissler, E. (1997) "Anwendung von Seuchenmitteln gegen Menschen nicht erwünscht". Dokumente zum Einsatz biologischer Kampfmittel im Ersten Weltkrieg. Dokumentation. Militärgeschichtliche Mitteilungen, 56, pp. 107-55.
[lxxv] New York Times, 26 May 1998, quoted in The CBW Conventions Bulletin, no. 41 (September), p. 25.
[lxxvi] UK document, 4 February 1998, quoted in The CBW Convention Bulletin, no. 40 (June), p. 25.
[lxxvii] Boijtzov, V. and Geissler, E. (1999) "Military biology in the USSR: 1920-45". In: Geissler and van Courtland Moon (note 61). Pp. 153-67.