This article has been edited from the orginal paper presented at CBMTS-III in Spiez, May 2000. The article has been edited for length and in doing so, some of the careful diplomatic language of the original may been shortened. The article summarizes the ideas presented at the AHG of the BTWC in 1999.The extensive tables, criteria and references are available at www.asanltr.com

POSSIBLE CRITERIA FOR SELECTING HUMAN, ANIMAL AND PLANT PATHOGENS AND TOXINS FOR THE BTWC

Slavko Bokan, M.D.
Croatian Military Academy
HR-10000 Zagreb, Ilica 256 b, Croatia

Introduction

Some of the critical parts of the BTWC that are being discussed are the lists of agents and toxins. All future work of the investigation of biological activities and all provisions of future Protocol of the BTWC will be based on these lists. These lists are discussed in the Rolling text of the Protocol of the BTWC, in the section "Definitions of Terms and Objective Criteria." They are for use with specific measures, particularly for Article III, Compliance Measures, section A. Lists and Criteria (Agents and Toxins), section D. Declaration, paragraph 15 (Work with listed agents and toxins), section F, subsection I (Initial declaration and annual declarations).

At the beginning of the negotiations, there were only 83 biological agents and toxins in the lists. There were 20 viruses, 9 bacteria, 3 rickettsia, two protozoa and one fungus in the list of human and zoonotic pathogens, 21 toxins, 19 animal and 18 plant pathogens. Many delegations submitted their Working papers during previous sessions for the evaluation and selection of agents and toxins according to current criteria, but the bulk of pathogens and toxins needed further negotiations and considerations.

Methodology

The delegation of the Republic of Croatia submitted WP No. 356/Rev.1 at the fifteenth session of the AHG (June - July 1999).(http://www.brad.ac.uk/acad/sbtwc/) It included some evaluation criteria to induce and accelerate discussions in the Definitions of Terms and Objective Criteria section. The intent was to show that currently all three lists (human pathogens, toxins, and animal and plant pathogens) were valid according to the existing criteria and how to apply some new additional criteria by which pathogens and toxins could be added. These criteria would also enable us to discriminate between pathogens and toxins.

Defining the human, animal and plant pathogens and toxin lists will be difficult and thus we proposed several tables of pathogens and toxins, along with important criteria for inclusion or exclusion. (See Tables 1-6. These are large tables and are available on the web) These evaluation or summary tables (1-6) can aid in comparing pathogens and toxins and in easing decisions to include or exclude an agent in the lists. (Editor's note: The tables can also be modified if there are changes in any of the criteria, such as evidence that a new agent has been weaponized.) In tables (1-5), the plus sign (+) signifies that pathogen or toxin satisfies the particular criterion for inclusion in the list, while the minus sign (-) signifies that pathogen or toxin does not. The final column is the total of positive and negative answers. The higher the number, the more dangerous the agent is as a weapon. Table 6, Toxins, is the opposite; the lower the total number, the more dangerous the toxin is as a toxin warfare agent.. These tables can serve as the basis for discussion and as an aid in defining the final list of agents and toxins.

Criteria and Explanations

We used eleven criteria for the evaluation of human and zoonotic pathogens. The criteria are shown in Tables A through D, below. It is very hard to find in available literature all the data for the most important criterion, criterion number 1 - agents or toxins known to have been developed, produced, stockpiled or used as weapons. Therefore, we have made our best estimate for this.

The key for producing large-scale respiratory infections is to generate an aerosol of suspended microscopic droplets, each droplet containing one to thousands of bacterial or virus particles. A high level of dissemination or large-scale contamination or coverage of a large area with aerosol for respiratory exposure plays the main role in evaluation of particular agent or toxin.

The existence of immunization and appropriate treatment against a particular agent is inversely proportional to the likelihood that the agent will be used. There are no effective prophylaxes or therapies for the majority of listed agents and toxins, if they are used as biological and toxin warfare agents. A full vaccination series for most diseases takes at least three months and in same cases up to one year. Hence, it is difficult to imagine how a mass-vaccination would be effective against more than one disease.

Our opinion is that if some pathogen or toxin satisfies the greater part of the criteria, it should be recommended for inclusion in the list. On the tables of human pathogens and toxins, some biological agents and toxins are not in the current BTWC list. These additional agents and toxins are not recommended as new agents for including in the list. However, more detailed risk assessments and comparisons with pathogens and toxins on the existing list may give us more information so these agents can either be added or dropped from consideration.

The evaluation of agents and toxins according to existing criteria assumes all criteria have equal status. It may be that the criteria should be weighted. The criteria we used for evaluating these biological agents and toxins are based on the characteristic outbreaks of infectious diseases in "natural" forms. Genetically engineered and modified bacteria and viruses present a difficult problem. New criteria reflecting new characteristics of bacterial and viral strains enhanced for infectivity, transmissibility, virulence and antibiotic resistance should be inserted.

We also prepared a new list of toxins and criteria for them to help in final discussions. (Tables 6 and B ) In the additional list of criteria for toxins, we can see at a glance which criterion is unimportant: ease of decontamination. For toxins in general, decontamination is unimportant, except for fungal toxins. Fungal or myco-toxins are extremely difficult to decontaminate and it can take years of hard cleaning to eliminate the toxins, especially if delivered with fungal spores.

Lethality alone is not an appropriate criterion on which to base a toxin's potential as an agent. Therefore, we included those toxins that act primarily as incapacitating agents, because these toxins have high potencies and represent a significant trend for the future. For example, Staphylococcal enterotoxin B (SEB), a so-called super-antigen, is one of the most potent agents for incapacitating because it can cause illness at extremely low doses (although lethal doses are relatively high). Trichothecene-Mycotoxins, Batrachotoxins and Brevetoxins can be included in this list. If we included only those lethal toxins, we would be underestimating the number and potential of toxins as agents.

Results And Discussions

The results of negotiations on the twentieth session of AD-Hoc Group are presented in the tables that follow.

The list of viruses, as a part of list of human pathogens, consists of the15 viruses listed above. The list of human pathogens includes bacterial agents. I think that Brucella suis and Brucella abortus will be deleted during further negotiations. Also, two protozoa, Naegleria fowleri and Naegleria australiensis, will be deleted. The final list of toxins consists of 11 toxins.

In the list of animal pathogens, two agents Rinderpest virus and African swine fever virus, have been already resolved. Eventually, Blue Tongue Disease virus was returned in the list. All the others are in square brackets and need further negotiations and considerations. My opinion is that: Classical swine fever virus, Newcastle disease virus, Avian influenza virus, Foot and mouth virus, Vesicular stomatitis virus, African horse sickness virus and Porcine enterovirus type 1 should be kept in the list. The Croatian delegation proposed inclusion of Nipah virus in the list of animal pathogens and this was kept in the list about one year. However, it was deleted on the nineteenth session. The reason for the deletion of this agent was because the outbreak of Nipah encephalitis covered only a small part of the world and, for the time being, does not satisfy the criteria for inclusion in the list.

In the list of plant pathogens you can see Tilletia indica, Xathomonas albilineans and Colletotrichum coffeanum var. virulans that are resolved, but all other pathogens need further negotiations and considerations. In my view, Puccinia graminis, Erwinia amylovora, Ralstonia solenecearum, Xanthomonas compestris citri and Dothistroma pini (Schirria pini) should be kept in the list.

CONCLUSIONS

It is very hard to make a final decision on criteria, and, hence, on the final list of agents and toxins for the future needs of Protocol to the BTWC based on the current criteria. We propose that the lists and criteria for agents and toxins should be well studied. The lists are not exhaustive; they do not exclude those unlisted microbial or other biological agents or toxins, which potentially can be used as weapons or vectors (such as pests, arthropods and helminthes). The lists of human, animal and plant pathogens do not include live-attenuated strains, which have been registered in official culture collections or are internationally recognized as such. Progress in modern genetics presents newer possibilities that have not been included, such as microorganisms carrying nucleic acid sequences coding for pathogenic properties of listed agents and toxins and nucleic acid sequences coding for toxins.

Any State Parties of the BTWC may propose modifications to the lists. The Executive Council of the OPBTW shall review such proposed modifications to the list of agents and toxins. Any changes to the list shall be made in accordance with Articles III. and XIV. of the Protocol. In reviewing the lists of agents and toxins the Executive Council shall consider current criteria, as well as:

  • Scientific and technological developments that may affect the potential of individual agents and toxins for use as weapons.
  • Effects of potential inclusion or exclusion of an agent or toxin in the list on scientific and technical research and development.

And finally, the main goal of this presentation is to induce discussions among and from scientists and experts who are involved with biological and toxin warfare agents or weapons as part of their job. It seems that our group of scientist and experts in the CBMTS members are not sufficiently included in negotiations in Ad-Hoc Group of the BTWC within their delegations.

References are available.

From ASA Newsletter, # 83, 01-2, April 12, 2001

Tables 1-6. Evaluation Tables

Tables A-H. Criteria Tables

References

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