Silent Death
The possible abuse of genetic engineering for biological warfare
By Jan van Aken, Sunshine Project

Breathtaking developments in biotechnology and genetic engineering are dramatically increasing the threat of biological warfare. The necessary knowledge is now globally available. Genetic engineering enables the bioweapons makers to design even more destructive agents. The international community is not keeping pace with this rapid development and is missing its chance to strengthen the Biological Weapons’ Convention. Thirty years ago, when biotechnology was still in its infancy and only few countries had the know-how required to grow quantities of viruses or bacteria, the probability of biological warfare was low. Technical barriers appeared too high for most countries to develop, produce, store and apply deadly strains without risk of infecting their own scientists, soldiers and population. These technical barriers eased the way to an international consensus on biological weapons - 143 nations signed the 1972 Biological and Toxic Weapons Convention (BTWC). UN member states agreed not to develop, produce or stockpile biological weapons or toxins for offensive purposes. The convention has its weaknesses, however, and it contains no provisions for verification of compliance.

Since then, rapid technical developments have increased the threat of bio-warfare. The international community thus decided in 1994 to negotiate a protocol to strengthen the BTWC. The negotiations were fueled by Russia’s (1992) and Iraq’s (1995) admissions of offensive biological warfare programmes. After five years of negotiations in Geneva, however, few core issues have been resolved and the Protocol appears likely to fail.

Genetically engineered:
a new class of bioweapons

It sounds like science fiction, but it is already a deadly reality: lethal microbes, with no cure, invisible to detection systems, and able to overcome vaccines. In ‘defensive’ programmes, researchers in the USA, UK, Russia, Germany and other countries have genetically engineered biological weapons agents, building new deadly strains. And this is probably only the tip of the iceberg.

Disguising bacteria to cause unusual symptoms
Researchers from Obolensk near Moscow inserted a new gene into Francisella tularensis, a well-known microbial biological weapon agent that causes tularemia. The gene caused the bacteria to produce a drug, producing changes in the behaviour of mice infected with the bacteria1. If used as a weapon against humans, the genetic modification would disguise Francisella bacteria infection. Victims would not show the usual symptoms of tularemia, making diagnosis difficult and delaying treatment.

Photo: epd-bild / Gust

Photo: J. Maillard, ILO

Introducing a lethal gene into harmless bacteria
Genetic engineering can make previously harmless bacteria a deadly weapon if genes are introduced from a highly pathogenic organism. This was done by US researchers as early as 1986. Isolating the gene for the lethal factor in the causative agent of anthrax, the researchers introduced it into a harmless gut bacteria. The US team reported that the lethal gene was active in the new host, producing proteins that had the same deadly effects as they did in the anthrax bacteria2. Antibiotic resistant anthrax and tularemia Antibiotic resistance is often used as a marker gene in genetic engineering experiments. The very same genes, however, could render biological weapons more dangerous by making agents less treatable. Any experiment with biological weapons agents using antibiotic resistance genes has a strong offensive potential, even if in the context of so-called defensive research. Despite this obvious problem, there is a long list of questionable experiments:
  • Researchers at the main biological warfare research facility of the German Army in Munich cultured genetically engineered bacteria that are closely related to the causative agent of tularemia3. An antibiotic resistance marker gene was been inserted into these bacteria.
  • Recently, researchers at Porton Down in the UK used genes conferring resistance to antibiotics in fully virulent strains of anthrax4. In the late 1980s, a researcher at the University of Massachussetts in Amherst also introduced antibiotic resistance genes into anthrax, making it less treatable with antibiotics5. Similar research has been published by the Institut Pasteur in Paris6 and by a Russian laboratory in Obolensk7. All these studies are purportedly basic research, where antibiotic resistance is used as a marker gene. But the very same genetically engineered bacteria can be used to design more effective bioweapons compared to the natural anthrax strains, because bacteria that are resistant to antibiotics are more difficult to treat and will thus cause more harm if used as a weapon.

    Invisible anthrax
    In December 1997, the same Russian research group from Obolensk published a paper in a scientific journal on another effort to genetically engineer anthrax8. By putting new genes into fully pathoge-nic strains, they altered their outer surface, making existing anthrax vaccines ineffective against the new type. This modification also made existing detection systems unable to recognise these bacteria.

    Western military experts were alarmed by this work. The chief of the bacteriology division at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Fort Detrick, Md, Col. Arthur Friedlander, commented: This is the first indication we’re aware of in which genes are being put into a fully virulent strain. They genetically engineered a strain that’s resistant to their own vaccine, and one has to question why that was done.9 The Russian researchers also constructed a new vaccine against the new strain. This step is of particular importance, as it could enable an army to use such a genetically engineered bioweapon by vaccinating their soldiers against a specific strain, while the enemy remains vulnerable. This case is a particularly disturbing example of the offensive potential of genetic engineering.

  • Biological weapons that are targeted to specific human populations while leaving others unaffected, may become technically possible. Incredibly, some governments have been reported to have such an intent Selective weapons
    Another, still theoretical, use of genetic engineering gives bioweapons yet another very new quality. Biological weapons that are targeted to specific human populations while leaving others unaffected, may become technically possible. Incredibly, some governments have been reported to have such an intent. According to newspaper reports, the Israeli army is researching a biological weapon that will recognise a specific genetic structure that is Arab. During the former apartheid government in South Africa, the Rodeplaat Research Institute tried to develop bacteria that would only attack people of African origin with dark skin.

    It remains a controversial question as to whether or not selective bioweapons are technically possible. But ethnic conflicts leave little doubt that, if available, some would consider using them. Most established peace and disarmament researchers downplay the chances of selective genetic weapons; but concerned officials from several governments have publicly stressed the possibility. Based on current public knowledge it is impossible to rule out the possibility that genetic differences could be used to create weapons.

    The Bioweapons Convention and ongoing negotiations
    In 1994, a Special Conference of the Bioweapons Convention initiated negotiation of a legally binding document to strengthen the Convention. Since then, the member states convened 20 times, the last time in July 2000, but the outcome of the negotiations is still open.

    One key, and controversial, issue is compliance. The verification measures will be based on a system in which existing industry or military biological facilities must be declared by each state party. Geneva negotiators still dispute, however, which facilities will be subject to declaration. To enhance transparency between countries, declared facilities will be inspected in a non-challenging manner. If a declaration detailing activities at a facility is unclear or allegedly incomplete, a clarification process will be initiated. In case of suspicion being voiced, e.g. concerning the alleged production or use of bioweapons, an investigation will be launched.

    US drug producers repeatedly emphasize that they are reluctant to accept verification visits at manufacturing facilities Some countries strongly oppose randomly selected visits and have called for cursory and/or voluntary visits in which inspectors have very limited rights. The US government is heavily under pressure from US pharmaceutical industry interests opposed to any strong verification measures. US drug producers repeatedly emphasize that they are reluctant to accept verification visits at manufacturing facilities10. The threat is real: If US industry does not support the protocol, ratification by the US Congress is highly unlikely.

    To strengthen the Convention as much as possible, and send a clear message around the globe, the protocol should encompass broad triggers for declarations, mandatory random and clarification visits with extensive rights for the inspectors, the establishment of an extensive export notification system, and a mandatory approval process for genetic engineering of bioweapon agents. Projects to enhance virulence or to overcome defense measures of micro-organisms must be banned to prevent the unrestricted genetic engineering of bioweapon agents.

    It is now the responsibility of democratic groups worldwide to set clear standards to deter the production and use of biological weapons. A strong protocol will enhance transparency, making it much more difficult for countries to conceal a bioweapons’ programme. In light of recent advances in genetic engineering, and considering the discoveries of biowarfare programmes in the former USSR and Iraq, an update and strengthening of the global ban on biological weapons is urgently needed.

    Biological Weapons in the Drug War

    The United States is developing fungi that will kill opium poppy, marijuana, and coca plants. They are designed to have a high plant kill rate and to be deliberately sprayed in crop eradication programmes.

    Primarily intended for use in drug-producing areas of the Americas and Asia, some of the agents spread uncontrollably, are persistent in soils for decades, have questionable target-specificity and known health consequences for human beings and animals.

    In addition to serious environmental and social implications, the development of these agents undermines the global consensus against biological weapons. Aerial crop eradication is a government tool of choice for areas beyond state control. Arguing that there is a loophole in the Biological and Toxic Weapons Convention for narcotic crops, the US and the UK seek to apply these pathogens in countries like Colombia in which there are ongoing civil wars or with which it has unfriendly bilateral relations.

    These plans threaten to undermine international agreements prohibiting biological weapons. In an era of increasing biowarfare threats, any steps must be avoided that may lead to acceptance of biological weapons.

    The problem of biodefense research
    Many countries maintain a biodefense programme for the development of vaccines, detection systems, protection measures and treatments for bio-logical weapons agents. This research can be problematic, as in many cases defensive work involves the production, application or genetic alteration of a bioweapon agent. It can be very similar to offensive research. To test a cure for smallpox, mice and primates are infected with virulent strains of smallpox. To mimic real world scenarios, this is sometimes even done with weaponised agents applied as aerosols. In these cases, the difference between offensive and defensive research is solely a matter of intent.

    The critical question is where to draw a line. It is neither feasible nor desirable to ban all biodefense research, because this would include any drug or vaccination development. All bioweapon agents are natural pathogens that cause illness and death and thus require medical research.

    One line to draw relates to genetic engineering of bioweapon agents - the addition of genetic elements to any pathogen that could be used as a bioweapon. The application of genetic engineering to makemicrobes more dangerous or less susceptible to treatment cannot be justified for medical or biodefense purposes and must be strictly prohibited. Other bans could relate to the use of BW agents in aerosols, inhalation experiments, or the loading of mock grenades with simulant microbes.

    Public awareness about the dangers of biodefense research is next to zero. Participation is made difficult by the scarcity of publicly available information about biodefense programmes. An open, broad discussion about the current state and future strategies of biodefense research is urgently needed.

    Jan van Aken is co-founder of the Sunshine Project, an international non-profit organisation that gathers information on the potential harmful military use of biotechnology. The Project is concerned that abuse of some scientific advances may undermine international agreements on peace, disarmament and the environment. Through research, awareness building and advocacy, the Sunshine Project stands for the promotion of the internatio-nal consensus to reject biological weapons.


    A short history of biological weapons

    Ancient Times: Neanderthals poison arrows with animal feces.
    Roman Empire: Soldiers throw animal cadavers into their enemies’ wells.
    1346: Tartarian leader Khan Janibeg throws plague corpses into the city of Kaffa to infect the inhabitants.
    18th century: British soldiers deliberately distribute smallpox-infected blankets to Native Americans.
    World War I: German soldiers infect horses with glanders and cattle with anthrax in sabotage acts.
    1933-45: Japan conducts experiments on Chinese prisoners-of-war and uses biological weapons in attacks on Chinese towns in World War II.
    1942/43: British military researchers perform tests with anthrax bombs on the small island of Gruinard near Scotland. For 50 years the island was out of bounds for all human beings.
    1950s: North Korea alleges the US Army used plague and anthrax-infected insects, fleas and spiders in the Korean conflict.
    1992: Boris Yeltsin admits to an offensive BW programme in the former Soviet Union. In 1979, an accident with anthrax bacteria near Sverdlosk caused 100 fatalities.
    1995: UNSCOM finds final proof for an offensive biowarfare programme in Iraq.
    Future?: Genetically targeted "ethnic weapons" designed to only attack specific populations may become possible.

    1. Borzenkov VM, Pomerantsev AP, Ashmarin IP (1993) The additive synthesis of a regulatory peptide in vivo: the administration of a vaccinal Francisella tularensis strain that produces beta-endorphin Biull Eksp Biol Med 116(8):151-3 (Article in Russian)
    2. Robertson DL, Leppla SH (1986) Molecular cloning and expression in Escherichia coli of the lethal factor gene of Bacillus anthracis. Gene 44(1):71-8
    3. According to the public register of genetic engineering experiments at the Bavarian State Authority for Environmental Protection, in a letter dated March 27, 2000
    4. Bowen JE, Quinn CP The native virulence plasmid combination affects the segregational stability of a theta-replicating shuttle vector in Bacillus anthracis var. New Hampshire. J Appl Microbiol 1999 Aug;87(2):270-8
    5. Nass M (1991), The labyrinth of biological defense. The PSR Quarterly, March 1991, Vol.1, page 24
    6. C. Pezard, E. Duflot, M. Mock from the Laboratoire de Genetique Moleculaire des Toxines, Institut Pasteur, Paris: Constructing of Bacillus anthracis mutant strains producing a single toxin component. J. Gen. Microbiol. 139:2459-2463 (1993)
    7. A.P. Pomerantsev, N.A. Staritsyn (1996) Behaviour of heterologous recombinant plasmid pCET in cells of Bacillus anthracis. Genetika 32:500-509
    8. Vaccine 15(17-18):1846-1850, Dec 1997, Pomerantsev AP. Staritsin NA. Mockov YV. Marinin LI., Expression of cereolysine ab genes in Bacillus anthracis vaccine strain ensures protection against experimental hemolytic anthrax infection
    9. New York Times, Feb. 14, 1998, Gene-engineered anthrax: is it a weapon?
    10. Compliance Protocol to the Biological Weapons Convention, a joint position of European, United States and Japanese Industry, published in July 2000, downloaded on August 28, 2000.

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