Ed. Note: From Bioterrorism to agroterrorism the threat can take many forms and in this paper, which was presented at the CBMTS-Industry IV, Professors Hincal explore the threat and the role of biotechnology.

GM Technology Offers Opportunities for Possible Bioterrorism

Filiz Hincal^1,3, A. Atilla Hincal²

University of Hacettepe, Faculty of Pharmacy, Department of Pharmaceutical Toxicology¹ and Department of Pharmaceutical Technology² , Hacettepe Drug and Poison Information Center³, ANKARA, 06100 — TURKEY

INTRODUCTION

          It was not long ago that a panel of outside experts told the CIA that advances in technology due to genetic research could produce the worst known disease and the most frightening biological weapons. The same CIA report said that the effects of some of these engineered biological agents could be worse than any disease known to man (1). Before going into the details of such possibilities, let’s have a short overview of the biotechnology which is pushed by genetic revolution into explosive growth phase.
          Biotechnology is defined as “techniques that use organisms or their cellular, subcellular, or molecular components to make products or modify plants, animals, and microorganisms to carry desired traits”. It traces its roots back to Sumerians who lived in Mesopothamia and discovered beer brewing four thousand years ago (2). The history of modern biotechnology, however, is rather new, and has gained tremendous momentum within the last three decades. It is the use of genetic engineering and recombinant technology to insert genes from one organism into a different organism with the aim of producing various products ranging from GM foods to rDNA products of therapeutic agents or vaccines, from intelligent weed killers to even the process of data storage in multiplying bacteria. Hence, this new era uses the many advantages of this development, and biotechnology now provides numerous benefits such as increased agricultural yields, improved methods of medical care, development of new materials and biopharmaceutical products, advances in industrial processes, besides lowering basic development costs. It seems that it will be a dominant technology in this new century.

MISUSE OF BIOTECHNOLOGY

          However, the science and technology which first lead to positive biotechnology and genetic engineering developments may also increase the chance of misuse. The dual use of biotechnology seems inevitable. Even without military applications in mind, research in biology may still contribute to the production of biological weapons, as the history demonstrated. The possibility of misuse for political reasons, for clandestine production, and for refinement and/or development of new biological weapons cannot be ignored. And hence, in spite of the potential benefits of biotechnology for health promotion and national defence, the same techniques may also be used to create a new generation of biological warfare (BW) agents by hostile governments and individuals. According to the before-mentioned CIA report (1), this may include “binary agents” that would consist of two separate and harmless agents (a mild pathogen and its antidote) and be deadly when combined; “designer” BW agents created to be antibiotic resistant or evade an immune response; weaponized gene therapy vectors that effect permanent change in the victims genetic make-up; a “stealth” virus which could lie dominant inside the victim for an extended period before being triggered by a signal.

BIOTERRORISM

          The possibility of misuse of biotechnology seems to be getting much higher with the fact that terrorist organisations have demonstrated an increasing interest in utilising biological weapons along with nuclear and chemical warfare agents for terrorist purposes. It was reported that Al Qaeda has manuals on preparations of biological warfare agents that were discovered at the group’s training camps in Afghanistan after the US invasion in late 2001 (3). Biological warfare and terror are not new; the fundamentalists, fanatics and extremists were always around. However, this is a more appealing time for various kind of terrorism, including bioterrorism, due to the facts such as lack of constrains; religious and cultural fervor; extensive urbanisation; more extensive global traveling; global mass food processing, production and shipping; and a much more interconnected world. Their goals are more strategic, they seek media attention to obtain recognition, tie up government resources, and make governments to overreact, discourage foreign investment, and expose government’s inability to provide security to its citizens. And of course, long term goals are to destroy existing social system, to replace existing government and use power to impose their will on their enemies. They do not differentiate the innocent from the enemy, hence, they cannot be negotiated. The evolving ways of terrorism started with conventional weapon use in a conventional way, continued with conventional weapon use in non-conventional way, followed by non-conventional weapon use in a conventional way. And, now, there seems to be a possibility of non-conventional weapon use in a non-conventional way by the rise of the possibilities offered by biotechnology. The face of terrorism is changing with new variety of actors and networked organisations, and may change more with WMD proliferation and more technology including biotechnology.

TERRORISM AND MIDDLE EAST

          To understand bioterrorism, one has to try to understand what terrorism means and the mindset of the terrorist. Terrorism is politically motivated violence deliberately targeted at civilians, and an instrument used for social and political change. It is the tactic of the weak against the strong, hence it is asymmetric. Terrorist’s main weapon is “fear”, and BW agents are much frightening of all. Over 20 countries exist in the Middle East and their combined GDP is smaller than that of a small country (e.g. Holland or Belgium) in Europe. There exist huge gaps between rich and poor, social status of women is very low. Birth rate is high, over _ of Arab world is under the age of 20 years which increases poverty, social gaps and cultural decline. All these facts are closely related to the rapid rise of suicide, homicide, freedom fighters and human bombers.
          Terror by suicide bombers is a very potent psychological weapon and no defence and no preventive measures can succeed against a determined suicide murderer. Suicide attacks throughout the history have taken various forms and have been encouraged by lionization of those who lay down their lives for a righteous cause. However, they are now, driven by money, power and cold blooded murderous incitement more than true fanatic religious beliefs or so-called freedom-fighting.

GLOBAL TERRORISM AND TURKEY

          After the September 11 tragedy in US, the spreading of attacks in Europe started with the bombings in Istanbul (11/20) in 2003, and in Madrid (3/11) in 2004. Then, continued with London events (7/7) in 2005. This short chronology shows us once more that terrorism can happen anywhere, anytime and there is no nation secure from that. Did the terrorist and the power behind them reach their ultimate goals? Except the human losses, they did not! Initial investor concern, for instance, was that Turkey’s tourism industry would be hurt by the November 2003 suicide bombs in Istanbul, which killed more than 60 people, proved unfounded. The same was true for the two consecutive bombing events in July 2005 in the most favourite tourist towns in the western part of the country.
Turkey has a delicate strategic position in the most unstable part of the world. It is a bridge from West to East, and the only secular and democratic country in the Muslim world. As noted by a former U.S. ambassador to Turkey in his article published in Miller Center Report, “Turkey is proof positive that there is no contradiction between being Muslim and modern . It is solidly rooted both in the Western democratic tradition and in the Islamic world, and is in the unique position to maintain positive relations with both Israel and its Arab neighbors. While it has suffered economic reversals and frequent political instability, Turkey is still poised to become a major economic hub in the Asia Minor region, and is making major investments to improve its infrastructure. These positive qualities, unfortunately, attracts opponents in the same political and religious environment” (4). Turkey has long borders with 9 countries most of which have important internal and external problems to be solved, level of development is not high, and some are thought to be the central for the international terrorist groups. Turkey has suffered a lot from terrorism since many years, and the threat is still continuing. It has been attacked by male and female suicide bombers many times, and it was fortunate that many unsuccessful attempts were discovered.
          With this picture before us, what kind of threats expectations we may have? We do not have natural immunity, we do not have any vaccine to immunize us for all possible types of biothreats, or we do not produce any vaccine that already exists in the stockpiles of some others. And what are the possibilities?
          Covered deployment of biothreat agents can be done by contamination of food and water supplies easily. Turkey’s reach water resources have been a center of interest since a long time, and it seems that this will continue unless another way of supply could be found. Bioattacks against agriculture and live stocks are substantially easier particularly in this geography through the long borders that are difficult to control. The needed delivery systems (plant or animal vectors) are nonsophisticated and readily available. Using bioweapons to attack livestock, crops, or ecosystem offers the means to wage a potentially subtle yet devastating form of warfare, and its impact on political, social, and economic sectors of a nation would be great in both developed and developing countries. Turkey is one of those countries having significant agricultural sector that provides important contribution of food and revenue to its economy. It is almost a self-sufficient country in terms of agricultural production and nutrition, and although the number of people and land involved in agriculture is gradually declining, almost half of the population’s income depends on agriculture. Hence, the overall agricultural productivity is vitally important for the country’s economy and social welfare.
          A bioterrorist attack employing suicide terrorists as human vectors is not far from the probability, as already cited by DeBell and Erlick (5). This is possible, for instance, with smallpox which is the most contagious disease known and spread through droplet aerosols by face-to-face contact. The variolation procedure that has been originated from Turkey and introduced to the western world by Lady Montagu in the 18th century can be used for bioterrorism to intentionally spread the disease (6). If the suicide terrorists readily available in this geography and are ready to give their lives voluntarily for their grand (!) purposes, this will not be impossible for them and the consequent destructions would be enormous. Influenza virus is also a good candidate for a deliberate spread with its structure suitable for genetic manipulations and highly contagious character. If the private terrorist groups such as Al Qaeda are capable of purchasing or developing infectious agents as reported, and if the acquisition of biotechnology and biological weapon capability is considerably easier than was the case in the 1940s and 1950s (7), then the threat of bioweapons is much higher with increased possibilities in terms of diversity, potency and quantity in design and production now.

ACCESS TO KNOWLEDGE

          The information to conduct genetic engineering research and advanced technologies are easily accessible on the Internet. Scientific journals are also rich sources for the information that has the dual-use nature. Inadvertent discovery of Australian scientists that the virulence of mousepox virus can be significantly enhanced by the incorporation of a standard immunoregulatory gene (8); the in vitro creation of a polio virus (9); and the synthesis of smallpox viral proteins which can block the critical aspects of the human immune system (10) are the most cited examples of those type. Equipment and expertise are globally available. And hence the possibilities for more lethal bioweapons have increased in the post-genomic era. Hundreds of viral sequences are already available. Information on antibiotic and drug resistance, virulence and toxins may increase the possibilities of creating new more deadly recombinants to attack humans and crops. There is also increasing potential for manipulating the immune system. An article in Nature highlights the danger of many partially effective vaccines, which may lead to increased virulence of the pathogens as more people are vaccinated (11).
          During the past decades, however, the world has experienced two opposite eras in respect to existence of CBRN information. Before and during the first Gulf crisis, there was almost no information accessible even for an academic health institute that needed to establish an infrastructure for preparedness against possible chemical attacks of Saddam by his Scud missiles (12). But, then all kinds of information, from simple explosive bomb production to lethal chemical agent synthesis and “how to use manuals” become available for everybody on the Internet. Hopefully, by foreseeing the dangers of the availability of know-how to develop new generation of bioweapons, and the dual-use nature of the biotechnology and GM techniques and research, a new era is now coming. Where to draw the line is difficult, however, new initiatives to restrict and control the scientific research and publications are underway in the US (7). But much more is needed: as terrorism becoming an increasingly global phenomenon the response must be global as well. One last thing that has to be considered more seriously is that terrorism has political and economical roots. Without eradication of those roots global terrorism cannot be prevented.

REFERENCES

1. Central Intelligence Agency. The darker bioweapons future, 3 November 2003. http://www.fas.org/irp /cia/product/bw1103.pdf
   
2. Biotechnology Industry Organization. “BIO Editors’ and Reporters Guide to Biotechnology 2000-2001” Washington, D.C. Feb 2000
   
3. Mike Boettcher. Evidence suggests al Qaeda pursuit of biological, chemical weapons. Nov 14 2001. http://archives.cnn.com/2001/WORLD/asiapcf/central/11/14/chemical.bio
   
4. Parris M. The U.S. and Turkey after September 11. Miller Center Report, 18, 1, 17-22, 2002
   
5. DeBell RM, Sappington J, Erlick B. The human vector: A potential new terrorism threat. In “Proceedings-CBMTS Industry III-Second World Congress on Chemical, Biological and Radiological Terrorism” Dubrovnik, 6-12 September 2003. pp. 88
   
6. Encyclopedia Britannica Online. Montagu, Lady Mary Wortley. http://www.britannica.com/eb/article-9053471
   
7. Committee on Research Standards and Practices to Prevent the Destructive Applications of Biotechnology. Biotechnology research in an age of Terrorism: Confronting the Dual Use Dilemma. National Research Council of the National Academies. The National Academic Press Washington, D.C. www.nap.edu. Prepublication Copy, 2003
   
8. Jackson RJ, Ramsay AJ, Christensen CD, Beaton S, Hall DF, Ramshaw IA. Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. J Virol. 75:1205-10, 2001
   
9. Cello J, Paul AV, Wimmer E. Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Science Online, July11. http://www.sciencemag.org/cgi/content/abstract/1072266
   
10. Rosengard AM, Liu Y, Nie YZ, Jimenez R. Variola virus immune evasion design. Expression of a highly efficient inhibitor of human complement. Proc Natl Acad. Sci 99, 8808-8813, 2002
    
11. Gandon S, Mackinnon MJ, Nee S. read AF. Imperfect vaccines and the evolution of pathogen virulence. Nature, 414, 751-755, 2001
    
12. Hincal, F., Çeliker, A., Hincal, A. A. Are the civilians prepared for chemical, biological or nuclear warfare? The need of a cooperative effort for a simple guideline. In “NBC Risks — Current Capabilities and Future Perspectives for Protection” NATO Science Series- Disarmament Technologies-Vol.25. Kluwer Academic Publishers, Dordrecht, The
    Netherlands, 1999. pp. 39-42