File:Weaponisation of Mycotoxins.pdf

 paper  by Robert Russell Monteith Paterson, Nelson Lima

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Subjects: Mycotoxins
Source: Unknown

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The Weaponisation of Mycotoxins

Robert Russell Monteith Paterson and Nelson Lima

Introduction

Mycotoxins as weapons is a serious issue. The word “weaponisation” in the title of this chapter is poor grammatically, although it is useful as it is generally understood. Crucially, access to accurate information is required to enable appropriate responses for potential threats. The high interest created by a recent review of fungi and toxins as weapons indicated that further publications in the field are desirable: Paterson (2006a) remained at number 1 in Science Direct’s “Top 25 Hottest 10 Articles” (Mycological Research) for a year. Citation numbers put it fourth since 2006: Holstege et al. (2007) is instructive as it indicates just how seriously the threat is taken in the United States of America. The authors focus on trichothecene mycotoxins and particularly T-2 toxin. Of course, the reasons for the topicality were the mass attacks on citizens which have occurred this century, and the claim that aflatoxins had the potential to be used by Iraq. The recent attacks in the USA using anthrax spores via internal post also caused a great deal of concern: massive casualties have been predicted from anthrax released into very large cites. Dohnal et al. (2007) are also concerned with T-2 toxin. Latxague et al. (2007) focuses on anticrop bioterrorism and bioweapons against the agricultural sector. They appear to be more concerned with whole organisms, rather than purified mycotoxins per se. However, it is difficult to obtain a list of the fungi with which Latxague et al. are concerned, no doubt for security reasons. Mycotoxin-producing fungi need to be on the list, as do plant pathogens. Also, countries where crops are developed almost as a monoculture are at particular risk from natural pathogens [e.g. the fungus Ganoderma and the oil palm crop (Paterson et al. 2009)]. Pohanka et al. (2007) considered the issue of developing bioassays to detect mycotoxins. Finally, Casadevall and Pirofski (2006) provide a well-argued assessment concerning why human pathogenic fungi could usefully be given greater consideration as biowarfare and bioterrorism agents.

A recent example of a biosecurity lapse in Egham, UK demonstrates why complacency cannot be permitted: poor infrastructure and inadequate funding led to accidental release of the foot and mouth disease virus. Possible causes of the breach may have involved misaligned effluent pipes and tree-root damage to the pipes, compounded by an increase in water caused by floods (HSE 2007). Obviously, those working with toxigenic fungi and fungal toxins need to exercise appropriate care. It is now absolutely necessary to consider the issue as it relates to the field of weapons.

The topic of fungal toxins as weapons is no longer taboo as it has changed to one of public interest and media attention. The remainder of this chapter discusses the toxins and not the fungi per se (i.e. the biochemical rather than the biological) although this tends to overlap when the problems with the taxonomy of the producing fungi are considered (Paterson et al. 2004, 2006). One might expect that the fungi which produce the toxins are well characterised. However, this is not the case. Conversely, this lack of knowledge may work as an advantage in terms of security as it is not always straightforward to select toxin-producing isolates on the basis of current taxonomies. It makes more difficult (a) the application of legal restrictions on the use or export of the fungi, and (b) tracing particular strains used in toxin production.

Public pressure exists on authorities to assess if occurrences of food contamination are nefarious acts (Elad 2005). The economic consequences of simply reacting to a potential attack can be huge, if what was experienced after the recent attacks in the USA is an example (Lenain et al. 2002). Furthermore, a sombre assessment of the dangers of bioweapons to the United States of America is provided by Bailey (2001). It is much more appropriate to focus on prevention, followed by readiness and response. The balance is to declassify essential information with a view to preventing aggressive acts. A compromise has to be drawn: it is self-defeating to ignore the subject given the large amount of public information already available. Biosecurity guidelines are essential reading for those working with toxigenic fungi (Tucker 2003). They have highly significant implications which could limit research in the field, including determining which individuals do the work. However, just how representative the views are of this publication is unclear when the disclaimer states, “The views expressed in this report are those of the author alone. They do not necessarily reflect the views of the United States Institute of Peace”. A public debate is required. Some well-known reports have claimed recently that aflatoxins were placed in warheads for use by Iraqis, although the effect of such a limited amount of aflatoxins dispersed in this manner would be minimal (Paterson 2006a). On the other hand, Aspergillus flavus may be more dangerous as a human pathogen than is generally realised (Hedayati et al. 2007).

There is nothing to be gained from being coy about discussing this issue. There is a great deal of information in scientific papers, published journals, newspapers, and the World Wide Web. The most comprehensive, and well considered source of information/best practices is the Australia Group (http://www.australiagroup. net). This is a body which meets every year and represents numerous nations whose aim is, inter alia, to control the spread of chemical and biological weapons. For example, it is used by the UK Department of Trade and Industry for export control of a wide range of potentially and obviously dangerous material with possible utility as weapons. The web site is essential reading for anyone involved in the field. The mycotoxins considered are diacetoxyscirpenol, T-2 toxin, HT-2 toxin, and aflatoxin B1. Information is becoming increasingly available on these bioweapons (Bennet and Klich 2003; Miller et al. 2005; Paterson and Lima 2005; Stark 2005; Paterson 2006a); in addition to the dubious mixture of the informative (Locasto et al. 2004) and illegitimate material on the World Wide Web. A great deal is known about botulinin from Clostridium botulinum which is the most toxic compound in the world (human lethal dose 0.2–2.0 mg kg ^-1), and so there is little point in not discussing fungal toxins as weapons which are, after all, less toxic. To obtain some level of calibration at the extremes, mycotoxins are (a) not as dangerous as nuclear weapons and (b) more dangerous than teargas. Ease of conversion to a weapon is a crucial factor (i.e. “weaponization”). It is crucial that rational discussion appears in reputable journals, books and media. This chapter does not concern primarily fungi that cause disease per se. Obvious growth of fungi on animals is called mycosis and they are primary pathogens e.g. Histoplasma capsulatum (Bennet and Klich 2003). An excellent overview of fungi as weapons is provided in Casadevall and Pirofski (2006). Dietary, respiratory, dermal and other exposures to mycotoxins are called myco-toxicosis, and this area is more relevant to the creation of weapons. However, Hedayati et al. (2007) reported the aflatoxin-producing fungus A. flavus at the second most serious Aspergillus for causing human and animal infections (Aspergillus fumigatus is the first). The importance of this fungus increases in regions with a dry and hot climate. Consequently, the potential as a bioweapon may have been underestimated. Furthermore, the use of fungi in technologies (e.g. biocontrol) requires revision because of the current heightened security awareness. There is an apparent similarity between fungal biocontrol agents (FBCA) and weapons, in that toxin- producing fungi are mass-produced and, for example, sprayed onto crops. (This also has ramifications for the health and safety of those who use these organisms for mass production and/or in non-sterile conditions.) Which raises the question, what are the natural levels of fungi (Goncalves et al. 2006) and toxins (Paterson 2007a) in the environment? Interestingly, Bucheli et al. (2008) describe the occurrence of deoxynivalenol and zearalenone in river water which is of relevance to this topic.

Pharmaceuticals from fungi are also relevant to the discussion. The difference between a compound being a toxin or a drug may be a shift in a decimal point of concentration and/or a change in a simple moiety. How these compounds are classified depends to some extent on the prevailing “climate”. For example, mycophenolic acid, ergot alkaloids, penicillin and perhaps patulin, can be either. [[Category:Weapons]