Number 2001.2, November 2001

Disease by Design:
De-mystifying the Biological Weapons Debate

By Michael Crowley

Forward

Executive summary

What are bio-weapons?
Biological weapons (BW) spread disease among humans, animals or plants. These diseases occur when the target population is exposed to and infected by living micro-organisms. These micro-organisms multiply, and, after a short incubation period, the symptoms of the disease become apparent. In some cases, micro-organisms produce toxins – non-living toxic chemicals – that cause symptoms. Depending upon the biological agent chosen, the resulting disease can cause incapacitation or death. Possible biological agents include: bacteria such as those causing anthrax, plague or tularaemia; viruses causing smallpox and ebola; rickettsiae causing Q-fever and typhus; or toxins such as that from Clostridium botulinum, which causes botulism. There are also a number of fungal pathogens such as potato blight and cereal rust that can be used to destroy crops.

A short history of biological warfare
The use of disease as a weapon of war is nothing new. In 1346, for example, the bodies of Tartar soldiers who had died of the plague were thrown over the walls of the besieged city of Kaffa to infect the populace within. However, it was only after the discoveries of Koch, Pasteur and Lister into the microbial basis of infectious disease in the 19th Century, that bio-weapon research really began to become systematised.

Despite the signing of the Geneva Protocol in 1925 banning offensive use of bio-weapons, a number of European countries developed them during the 1930s and 1940s. However, to date the only fully documented modern use of biological weapons has been that of Japan’s attacks against China during the Second World War. In the immediate post war period at least three countries – the Soviet Union, the United Kingdom and the United States – are known to have continued large, ambitious programmes of biological weapons development, building on their war-time work.

On 25 November 1969, US President Nixon announced the unilateral and unconditional renunciation of biological weapons. The UK government had previously closed down its offensive bio-weapons programme in the early 1960s. Washington’s action led to the negotiation of the Biological and Toxin Weapons Convention (BTWC). The treaty did not prohibit defensive research and development programmes, and the United States and other countries have continued activities such as producing vaccines, antivirals and antibiotics to protect their citizens. However, the former Soviet Union continued to carry out a massive covert offensive biological weapons research and development programme, even after it ratified the BTWC. Though this programme officially ended in 1992, concerns about covert offensive Russian activities persist. During the 1990s evidence also came to light of the secret biological weapons programmes run by Iraq and the Apartheid regime in South Africa.

How great is the threat today?
Because the technology required for biological weapons production can be relatively easily obtained and camouflaged by states, the true number of bio-weapon producers and possessors and the extent of holdings is unknown. Publicly available information is scarce. However, unclassified US Central Intelligence Agency (CIA) reports released in 2001 state that Iran, Iraq, Libya, North Korea and Syria were among states suspected of possessing or seeking to possess offensive biological weapons.

As well as the potential danger from states, there is also growing concern about the possibility of bio-terrorism by non-state actors. Following a nerve gas attack on the Tokyo underground in 1995 by the Aum Shinrikyo religious cult and the discovery of its biological weapons programme, a number of governments, most notably the US administration, invested additional resources in fighting bio-terrorism and developing bio-defence capabilities.

Public fear of bio-terrorism, fuelled by ill-informed media reports, has grown following the 11 September 2001 events and the subsequent anthrax letter attacks in the United States. However, such public alarm, based upon inadequate risk and threat assessments, can lead to over-reaction and the development of counter-productive policies by governments put under pressure to act. This in turn can facilitate the growth of bio-hoaxes, fuelling further fear.

Building a web of re-assurance
To combat effectively the threat of biological weapons proliferation and use, whether by state or non-state actors, the international community must construct a web of re-assurance – an interconnecting network of national and international initiatives – to re-assure governments and their citizens that such weapons are totally prohibited and, if ever used, will have minimal effect.

At the heart of such a web of re-assurance lies a good national health care system and an effective disease detection and medical response programme. These should be coupled with resources for intelligence, anti-terrorism, civil bio-defence and emergency response programmes. However, no single government will be able, by itself, to totally protect its citizens from the nightmare of biological terrorism or warfare by these means alone. The best defence against biological weapons attack is to prevent terrorists, or more importantly states, from acquiring bio-weapons or their components in the first place.

Countries must exercise the political determination to establish and enforce stringent multilateral controls on the transfer of biotechnology and must protect the absolute international prohibition on the development and use of biological weapons as enunciated in the BTWC.

Biological weapons prohibition endangered
The BTWC, which was opened for signature in 1972, prohibits the development, production and stockpiling of bio-weapons by States Parties. It was the first ever arms control convention to completely ban a whole class of weapons. But it had no mechanisms for monitoring or verifying compliance.

Seeking to address this omission, States Parties began to negotiate a legally binding Protocol to the BTWC in 1995. Over the next six years, the international deliberations focused on concrete measures to ensure that states comply with and respect the BTWC. Yet on 25 July 2001 the US Government not only rejected the draft Protocol text, but went further by also rejecting the entire ‘approach’ of the Protocol. The US announcement was the precursor to the complete collapse of the negotiations and effectively stalled the Protocol process.

From 19 November until 7 December 2001, States Parties to the BTWC will meet in Geneva at the Fifth Review Conference to assess the health of the BTWC, address potential weaknesses of interpretation of the Convention and review scientific and biotechnological developments. This is a critical time for arms control advocates who should act now to protect the biological weapons control regime.

Reinforcing the bio-weapon prohibition:  the way forward
BASIC calls on the international community to:

• Use the forthcoming BTWC Review Conference to reaffirm its determination to maintain and rigorously enforce the existing norm prohibiting possession of bio-weapons, and press for universal adherence to the BTWC.
  
  

• Establish an interim BTWC Oversight Committee and secretariat to promote adherence to the BTWC and to aid implementation of the politically binding Confidence Building Measures (CBMs) agreed at previous Review Conferences.
  
  

• Continue the Protocol negotiations, utilising the existing draft text as the basis for talks. Such negotiations must have a clear timeframe for completion.
  
  

• Develop a legal framework to ensure that breaches of the BTWC by individuals or groups are treated as an international crime.

Acronyms and Abbreviations:

AG: Australia Group
AHG: Ad Hoc Group
BTWC: Biological and Toxin Weapons Convention
CBM: Confidence Building Measures
CBW: Chemical and Biological Weapons
CDC: Centers for Disease Control and Prevention
CIA: Central Intelligence Agency
CONPLAN: Interagency Domestic Terrorism Concept of Operations Plan
CTR: Cooperative Threat Reduction Programme
CWC: Chemical Weapons Convention
DNA: Deoxyribo-Nucleic Acid
DoD: Department of  Defense
DoJ: Department of Justice
EU: European Union
FAO: Swedish Defence Research Establishment
FBI: Federal Bureau of Investigation
FDA: Food and Drug Administration
FEMA: Federal Emergency Management Agency
GAO: General Accounting Office
HGP: Human Genome Project
HHS: Department of Health and Human Services
IAEA: International Atomic Energy Agency
NAC: North Atlantic Council
NAM: Non-aligned Movement
NATO: North Atlantic Treaty Organisation
NGO: Non-Governmental Organisation
NPT: Nuclear Non-Proliferation Treaty
OPBW: Organisation for the Prohibition of Bacteriological (Biological) and Toxin Weapons
OPCW: Organisation for the Prohibition of Chemical Weapons
PhRMA: Pharmaceutical Research and Manufacturers Association of America
TRC: Truth and Reconciliation Commission
UN: United Nations
UNMOVIC: United Nations Monitoring and Inspection Commission
UNSCOM: United Nations Special Commission in Iraq
VEREX: Ad Hoc Group of Governmental Experts to examine verification measures
WHO: World Health Organisation
WMD: Weapons of Mass Destruction

Part I:
The Threat of Biological Weapon Proliferation and Use

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Section 1:  Introduction

The terrible events of 11 September 2001, which resulted in the death of over 6,000 men, women and children in New York, Washington and Pennsylvania, have stunned the world. In the shadow of those dreadful acts, we are now trying to come to terms with a world that we view as much less safe than it seemed two months ago – a world where determined terrorists can take the lives of thousands of people in an instant.

In the weeks that followed, public shock and sadness subsequently turned to widespread alarm in the United States and elsewhere following the discovery that letters containing anthrax had been delivered to US politicians and media workers. The source of this biological attack is to date, unknown. But the fear it has engendered around the world is palpable. Reports are multiplying that terrorists might be able to obtain even more deadly biological weapons, such as plague or smallpox, or that ‘rogue states’ might be mass producing such material in secret laboratories. How true are these reports? What is the real danger of terrorists killing the population of a city with anthrax or of a state unleashing germ warfare upon the world? What can the international community do to prevent such catastrophes?

In the past much governmental and journalistic discourse on biological weapons and warfare has been ill-informed, often apocalyptic hype based on scant data. This report attempts to present the basic facts, while acknowledging the substantial uncertainties that continue to cloud the subject.

It is intended to be an introduction for policy makers, journalists, non-governmental organisations (NGOs) and the public into the realities of biological weapons – assessing the true dangers of the proliferation and possible use of such weapons and analysing existing control mechanisms and current initiatives by the international community to deal with this threat.

By providing this report, BASIC is hoping to open up the policy debate around biological weapons which at present is restricted to a trusted circle of government officials, academics and policy analysts. BASIC believes that the issues of biological warfare, bio-terrorism and strategies for the effective enforcement of the prohibition against possession of biological weapons are vitally important ones for our times.

The report is divided into two parts. The first part outlines the history of biological weapons and attempts to give an indication of the threat today from biological weapons proliferation and possible use by state or non-state actors. The second part is concerned with the mechanisms the international community employs (or should in future employ) to combat biological weapons proliferation and prevent use. Although this part contains a brief overview of disease detection and bio-defence, it is primarily concerned with the international control architecture for the existing ban on bio-weapons development, stockpiling or use. In particular, the report examines opportunities and challenges for the international community at the Fifth Review Conference of the Biological and Toxin Weapon Convention, which takes place in November and December 2001.

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Section 2:  Historical perspectives

Biological warfare is commonly defined as the deliberate spreading of disease amongst humans, animals or plants. These diseases occur when the target population is exposed to an infection by living micro-organisms. The micro-organisms multiply, and after a short incubation period, the symptoms of the disease become apparent. In some cases, micro-organisms produce toxins – non-living toxic chemicals – that cause symptoms. Such toxins, e.g. botulinum toxin, can be used directly as weapons agents, in which case the producing micro-organism, Clostridium botulinum, does not have to come into contact with the target population. Depending upon the biological agent, the resulting disease can cause incapacitation or death of the target population.

Biological warfare is not new.[1]  Its use dates back as far as the 6th Century BC when Solon of Athens used the herb hellebore to poison the enemy water supply during the siege of Krissa. Similarly in 1346, the bodies of Tartar soldiers who had died of the plague were thrown over the walls of the besieged city of Kaffa (now Fedossia in the Crimea) to infect the populace within. The Russians were also said to have used the bodies of plague victims to provoke an outbreak of the disease among the enemy during their 1710 war with Sweden. And in the 1767 French and Indian War in North America, both the English and French forces used blankets infected with the smallpox virus to spread the disease amongst the native population.

It was only after the discoveries of Koch, Pasteur and Lister on the microbial basis of infectious disease in the 19th Century, that bio-weapon research really began in earnest. And research led to at least one substantial instance of use. Detailed evidence exists of a Japanese biological weapons programme between 1937 and 1945. The Japanese Military Unit 731 at Ping Fang in Manchuria experimented extensively with bio-weapons, allegedly killing thousands of prisoners of war with anthrax, cholera, plague, dysentery and other infectious agents. They also released plague on the Chinese civilian population of Chekiang Province on several occasions by dropping laboratory grown infected fleas from airplanes.[2]  There have also been unconfirmed allegations that during World War II, Tularaemia was used by Soviet troops against German forces in the Battle of Stalingrad.[3] 

History shows that as the technology around microbiology, genetics and biotechnology has advanced and spread so has the capacity for biological weapon development. In this regard, the practioners of the biological sciences seem to be following their colleagues in other fields.

"Every major technology – metallurgy, explosives, internal combustion, aviation, electronics, nuclear energy – has been intensively exploited, not only for peaceful purposes but also for hostile ones. Must this also happen with biotechnology, certain to be a dominant technology of the twenty-first century?….At present, we appear to be approaching a crossroads – a time that will test whether biotechnology, like all major predecessor technologies, will come to be intensively exploited for hostile purposes or whether instead our species will find the collective wisdom to take a different course."[4]

The dangers of proliferation and possible use of biological weapons by both states and non-state actors will be addressed in subsequent sections. First, we examine the processes for manufacturing such weapons; in effect how bombs are grown.

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Section 3:  Growing a bomb

There are five essential requirements that must be mastered in order to produce biological agents. These are:

• Obtaining an appropriate strain of the disease pathogen;

• Knowing how to handle the strain correctly and safely;

• Knowing how to grow the strain in a way that will produce the appropriate

• characteristics;

• Knowing how to store the strain, and to scale-up production properly; and

• Knowing how to disperse the strain properly.[5] 

None of these requirements is easily met, even with substantial resources and highly trained personnel.

3.1 Types of agents
Biological agents which potentially may be used as weapons can be classified as follows: [6] 

(i)Bacteria are single-cell organisms that cause diseases such as anthrax, plague, and tularaemia. Bacteria vary greatly in their level of lethality and infectivity. Although many pathogenic bacteria are susceptible to antibiotic drugs, strains can be selected by classical (non-genetic engineering) methods that are resistant to antibiotics and occur naturally. Bacteria can be readily grown in artificial media using facilities similar to those found in the brewery industry.

(ii)Viruses are organisms which require living cells in which to replicate utilising many of the host cells biosynthetic process. They must therefore be grown on living tissue. Viruses can infect animals, crops and humans. They produce diseases which do not respond to antibiotics. Some antiviral compounds are available, though of limited use. Among the disease-producing viruses are smallpox, ebola, foot-and-mouth disease and venezuelan equine encephalitis.

(iii) Rickettsiae are similar to bacteria in structure and form possessing metabolic enzymes and cell membranes, but like viruses are intracellular parasites, requiring host cells in order to replicate. They are susceptible to broad-spectrum antibiotics. Diseases caused by rickettsiae include Q-fever, typhus and Rocky Mountain spotted fever.

(iv) Fungi occur in great variety in nature. Relatively few species appear to have potential for deliberate use against humans. Allegations however do persist over the use of Trichothecene (T2) Mycotoxin Yellow Rain’ as a biological weapon by Soviet forces in South East Asia, although these are unconfirmed and are disputed by independent scientific research. Many fungal pathogens can be used to destroy crops, e.g. potato blight and cereal rust.

(v) Chlamydia are obligatory intracellular parasites incapable of generating their own energy source. Originally classified as viruses and now as a form of bacteria, they are responsive to broad-spectrum antibiotics. Like viruses, they require living cells for multiplication. Diseases caused by chlamydia include trachoma and forms of pneumonia and venereal disease.

(vi) Toxins are the non-living products of micro-organisms (e.g. botulinum toxin and Staphylococcal enterotoxin B), plants (e.g. ricin from castor beans) or living creatures (e.g. saxitoxin from shellfish). Toxins can also be produced by chemical synthesis. Toxins, like chemical warfare agents, can only affect those directly exposed to the toxin and cannot produce transmissible diseases. Because they are not living organisms, producing a large quantity of toxins requires more time than would be needed to make a similar quantity of other biological agents. However, toxins may be produced in militarily significant quantities by the new genetic engineering technologies. Toxins may be countered by specific anti-sera and selected pharmacological agents.

3.2 Agent production
When compared to the cost of a nuclear weapons program, biological weapons are in theory extremely cheap. In one analysis, the comparative cost to incur civilian (unprotected) casualties is "$2,000 per square kilometre with conventional weapons, $800 with nuclear weapons, $600 with nerve-gas weapons, and $1 with biological weapons".[7] The costs of establishing a biological weapons program are being reduced further by advances in microbiology and biotechnology.

Analysts have long asserted that certain forms of biological and toxin weapons are also easier to produce than either chemical or nuclear weapons. Certain biological agents can be found in nature, for example in the carcasses of animals that have died from disease or in soil or contaminated food. However, isolation and growth of such agents are not without dangers and difficulties. For states, the facilities and technical knowledge needed for producing biological and toxin agents are relatively simple and inexpensive – fermenters and an understanding of growth media – and relatively few people would be required to run a small biological weapons agent plant. Moreover, the technology and know-how needed to manufacture biological weapons agents is almost entirely dual-use, with legitimate application in fields such as medicine, cosmetics, brewing and biotechnology.

However, there has been a tendency in the media and by certain government officials to underestimate the resources and skills needed to manufacture an effective bio-weapon.

For example, in seminar presentations a few years ago, former CIA Director James Woolsey asserted that "a B-plus high school chemistry student" could produce biological agents, and at a January 2000 meeting described producing biological agents as being "about as difficult as producing beer".[8] 

Bio-warfare agents are deadly, but they are also labile and difficult to deliver to their intended target. It took years of experimentation and huge financial investment before the US and Soviet programmes succeeded in developing effective means of stabilisation and delivery. Whilst such processes may be well within the means of states, the likelihood of non-state actors weaponising biological agents on any large scale is small.

At a meeting on ‘Bio-terrorism in the United States’, Jerome Hauer, former Director of the Office of Emergency Management for New York City, declared that: "Most of the agents are not readily available. Most of the agents are not easy to make, and most of the agents are not easy to disperse."[9]  It should be noted that Aum Shinrikyo, the one non-state grouping that had anything like the resources to develop a biological weapons program, failed at all stages of their endeavours to grow a bomb (see the case study in section 5.3).

3.3 Delivery systems
Effective dissemination is challenging because the biological agent is a living organism that has to survive until it reaches the target. If bombs or rockets are employed to deliver the agent, explosives will be used to disperse the agent into the atmosphere. The detonation of the explosive produces heat and shock, which can kill the living micro-organisms. Dispersion by a spray system is less damaging to the agent than an explosive delivery system, although both are technically challenging if the necessary particle sizes are to be achieved. Once it has been dispersed into the atmosphere, the agent is exposed to the natural environment (e.g. ambient temperature and sunlight), which can in time, perhaps rapidly, cause the micro-organism to die.[10]  Weaponising an agent therefore requires knowledge in aero-biology – the science of the behaviour of biological organisms in the air.

It has been argued that for terrorist purposes, a sophisticated delivery system may not be required. As long as the required particle size has been achieved, biological agents can, at least in theory, be disseminated by crosswinds with few, if any, indications of hostile intent.

The United States carried out open-air tests in the 1950s and 1960s with biological simulants to evaluate US vulnerability to a biological weapon attack. Bacillus globigii was frequently used because of its similarities to Bacillus anthracis, the agent that causes anthrax. These tests showed that the wind would carry the agent some distance downwind before it lost its toxic potential.

Commercially available equipment, such as agricultural sprayers, may in theory be used to attack broad area targets. A single aircraft, for example, flying across the wind could disseminate a line of source agent approximately 200 kilometres long to infect an area of some 200 square kilometres downwind. Or a vehicle driven across the wind could be used to disperse the agent in a similar manner over a proportionately smaller area. However, when the Aum Shinrikyo cult tried such vehicle dispersal they failed. They equipped a van with a fan and specialized vents and drove it on the streets of Tokyo, attempting to release botulinum toxin. No one was harmed as a result of this test drive.[11] 

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Section 4:  The effects and military significance of biological weapons and the development of asymmetric warfare

One of the questions most frequently asked about any military capability is: to what extent does it constitute a militarily significant threat? When it comes to biological agents, there is no simple answer to that question. Once a pathogen infects its target population, all biological agents (except toxins) multiply inside the host. Small amounts – just a few micro-organisms of a biological agent – may therefore suffice to devastate a crop, a herd of animals or a city’s inhabitants, if the right quantity of agent is delivered precisely to the target population. In practice, however, the quantity of agent needed to create the intended effect is vastly larger than the effective dose to an individual because only a small fraction of the agent disseminated is inhaled or ingested by the target population. [12] 

The militarily significant quantity of agent depends on the concept of operations envisaged for the use of biological weapons – single overt attack, single covert attack or multiple simultaneous attacks of either type. Biological weapons are seen as strategic in nature, because their impact extends beyond the battlefield. They are considered weapons of mass destruction because under optimal conditions if all the significant problems over production and delivery can be overcome they could, in theory, cause massive casualties. However, to execute an attack on a significant military target, such as a port or an air base, using a missile or an aircraft with a dissemination system, it has been asserted that at least 100 kilograms of agent would be needed.[13] In a theoretical scenario, with a single aircraft leaving a trail of 100 kilograms of anthrax along a line upwind of Washington, D.C., it is claimed that 1 to 3 million deaths could result. In comparison, a one megaton hydrogen bomb dropped over the US capital would ‘only’ cause some 0.5 to 1.9 million deaths.[14] 

Doubt has, however, been cast upon predictions of infection, morbidity and fatality that may arise from such biological attacks. A scenario published in the SIPRI Yearbook 2000, based upon sophisticated computer modelling describes the effects of a cult disseminating anthrax over a busy shopping centre in central Tokyo. The agent is of a type and quantity similar to the anthrax that was accidentally released from a military microbiology facility in Sverdlovsk in 1979.[15] Given realistic conditions, about 20-30,000 people could be exposed to the cloud of spores. However, only around 300 people concentrated in a relatively narrow area would be infected. Fatalities would depend on how soon the agent was identified and treatment begun. This contrasts with the predictions that such an attack would result in mass casualties over large areas. Such an incident would nevertheless place a heavy burden on the authorities in terms of medical response and decontamination.

If disease detection and bio-defence/emergency services were prepared to treat the approximately 30,000 exposed people with antibiotics within a few days after the incident, the consequences would be limited. Without any medical treatment most of the 300 people would die. Different environmental conditions or choice of a highly contagious agent would place different pressures on the response services.[16]  A highly contagious agent such as smallpox would present a far more serious medical problem, perhaps even a catastrophe.

Despite the disagreement of likely effectiveness, the quantity-to-effect ratio, in theory, elevates biological agents to the class of strategic weapons, whether the pathogens are used against humans, crops or livestock. Consequently, military and civilian leaders the world over regard biological weapons with a great deal of apprehension. "The one that scares me to death, perhaps even more so than tactical nuclear weapons, and the one we have less capability against is biological weapons," said Gen. Colin Powell, then Chairman of the Joint Chiefs of Staff.[17] 

It is important here to underline that, in terms of mass casualties, the principal threat of biological weapon development and use comes not from the terrorist brewing bio-weapons in the bathtub. The real and present danger lies with the proliferation of bio-weapons programmes among states (as discussed in section 5.2).

Given their relative affordability and effectiveness, some small or less developed countries may regard biological weapons as an ‘equalizer’ capable of compensating for inadequacies in their conventional forces and offsetting the otherwise superior military strength of an opponent. Many commentators see them as the ‘poor man’s atom bomb’, a weapon to be used in today’s new asymmetric warfare.[18]  In January 2001, then US Secretary of Defence William Cohen phrased the new paradigm thus:

At the dawn of the 21st Century, the United States now faces what could be called the Superpower Paradox. Our unrivalled supremacy in the conventional military is prompting adversaries to seek unconventional asymmetric means to strike what they perceive as our Achilles heel.[19] 

This danger had been recognised by the US military in 1997 in the US Quadrennial Defence Review which stated: "In particular, the threat or use of chemical or biological weapons (CBW) is a likely condition of future warfare, including the early stages of war to disrupt U.S. operations and logistics…. Indeed, US dominance in the conventional military arena may encourage adversaries to use such asymmetric means to attack our forces and interests overseas and Americans at home". [20]  The latest Quadrennial Defence Review, released on 1 October 2001, chillingly adds: "On September 11, 2001, enemies of the US demonstrated the capability to carry out large scale, non-conventional attacks against the US homeland; asymmetric attack against the sovereignty of the US became a reality".[21] 

4.1 Advances in biotechnology and the development of tomorrows’ biological weapons [22] 
On 5 August 1970, Nobel Laureate Joshua Lederberg told an informal meeting of the UN Conference of the Committee on Disarmament a stark truth, that: "the potential undoubtedly exists for the design and development of infective agents against which no credible defence is possible, through the genetic and chemical manipulation of these agents".[23]  The techniques that would allow the genetic manipulation of biological agents began to be developed in earnest in the 1970s and have become known as recombinant DNA technology or genetic engineering. They involve the transferring of genetic material between organisms and species, allowing dramatic changes to be made in the characteristics of the recipient.

Genetic engineering has since been expanded by the development of rapid DNA sequencing technology that has led to the field of genomics – the extraction of information from the DNA sequences of organisms, and the analysis and cataloguing of that information.

A second aspect of this revolution has been the increasingly precise understanding of the physical chemistry of protein folding and of the diversity and mutual interactions of the many thousands of different proteins in the living cell, a field generally known as proteomics. Thus, immensely powerful experimental and modelling techniques have become available in the last few decades that allow an unprecedented capability to modify living organisms and their products in precise and predictable ways, and to design small molecules to interact with proteins in living organisms and alter their functioning in predictable ways. The relevance of these technologies to biological weapons development is obvious. Indeed, it has been alleged that the Soviet biological weapon programme already employed genetic engineering to create novel agents.[24] 

It is almost certain, as was demonstrated in Iraq’s offensive biological weapons programme, that a proliferator nowadays will attempt initially to weaponize the agents which have been previously used in major offensive research programmes, or other unmodified organisms. Thus the ‘classical’ agents developed in the middle of the 20th Century by the United Kingdom, United States and former Soviet Union – anthrax, botulinum toxin, tularemia, etc. – would likely be the first agents of choice. However, after the development of a functional biological weapons programme along classical lines, it is possible that proliferators may turn to agents developed through genetic engineering techniques.

Even within the constraints of existing biotechnology, scientists believe that it is already possible to carry out the following:

• Adaptation of an existing pathogen to increase its virulence or durability in the environment;
  
  

• Genetic alteration of benign micro-organisms so that they are able to produce a toxin, venom or bio-regulator. If this is coupled with use of large fermenters, production could be on an industrial scale. A number of pharmaceutical products such as growth hormone or insulin are already produced in this way;
  
  

• Alteration of deadly micro-organisms so that they are able to defeat standard identification, detection and diagnostic methods; and
  
  

• Development of micro-organisms which are resistant to antibiotics, standard vaccine and therapies. According to Alistair Hay, a CBW expert from Leeds University in the United Kingdom, manipulations of this type may have already occurred in Russia.

Hay helped debrief defectors from Biopreparat that had worked on biological warfare until 1992. The scientists claimed to have developed a form of Yersinia pestis, the causal agent of plague, that was resistant to 16 different antibiotics.[25]

4.2 Future trends in biotechnology and genetic engineering
Below we examine how further developments in biotechnology and genetic engineering might be used to develop tomorrow’s bio-weapons.

(i) Targeting the immune system
As understanding of the human immune system develops along with the ability to redesign proteins it could be possible to develop highly specific weapons which attack the immune system in various ways. For instance, rather than deliberately infecting a target population with a single disease, a biological aggressor could instead use a toxin to cripple the immune system of the target, and nature would insure that opportunistic infections of many different kinds ensued. Or a novel toxin agent could derange the immune system so that it becomes directly pathogenic itself, causing debility or death through its malfunctioning. Such attacks already occur outside the laboratory. For example, the naturally occurring staphylococcal enterotoxin B (SEB) exerts its incapacitating effects in part via specific effects on the immune system. Physiological systems other than the immune system could also be targets for such attack.

(ii) ‘Designer’ biological weapons
Novel weapons could use normal proteins involved in immune system modulation, discovered through genomic studies, that become toxic when they are in unnaturally high concentration or present in tissues from which they are normally absent. Similarly, proteins normally expressed in a specific developmental stage could be weaponised by delivering them to cells that are in a different stage of development.

Development of novel protein toxins is not the only application of bio-informatics to bio-weapon development. The ability to recognize the genes for different classes of protein (e.g. surface receptors) in genomic sequences, and to predict their three-dimensional shape and infer their function from comparative genomics and proteomics, will shortly lead to an important increase in our understanding of the ways that the physiology of cells is modulated by external signals. This will, in turn, allow the design of small molecules that bind to such surface receptors and alter their function in predictable ways. Such ‘designer’ weapons could be immensely potent, easy to manufacture and stable.

(iii) Genetic targeting
Two concerns arise from the possible development of genetically targeted weapons: those that may be used to target the genetic characteristics of different ethnic groups; and those that may be used to target crops and animals.

(a) Human Genome Project and the ethnic bomb
The Human Genome Project (HGP) is an international collaboration, centred in the United States and sponsored by the National Human Genome Research Institute. Its goal is to sequence and identify all the genes on the human genome. The work is nearly complete and has been extended to discover the functions of these genes.

The work of the HGP is important given concern over the possible development of weapons targeted at the specific genetic characteristics of different ethnic groups. It has been argued that "if investigations provide sufficient data on ethnic genetic differences between population groups, it may be possible to use such data to target suitable micro-organisms to attack known receptor sites for which differences exist at cell membrane level or even to target DNA sequences inside cells by viral vectors."[26]  These kinds of novel bio-weapons, developed from the application of genomics and proteomics, would only affect individuals with the particular target protein or structure against which they were designed. In many cases the target would be nearly universal within the human species. However, in other cases there might be alternative structures, and only individuals with a particular form of the structure would be vulnerable to the toxic effects of the new weapon. This possibility has led to speculation about ‘ethnic weapons’ that would affect one ethnic or racial group while leaving others untouched.

Thankfully, among humans the amount of intra-group genetic variation is generally greater than the inter-group variation, making it highly unlikely that such weapons would affect only one ethnic group or ‘race’. Indeed, many analysts share the view of the Royal Society: "…these developments are some years away and in some cases are likely to be more fictional than real".[27]  However, it appears that research into such an ethnic weapon has already been attempted (see box 1 on Project Coast).

(b) Targeting crops and animals [31] 
The possibility of a state or non-state actor acquiring or developing a species-targeted bio-weapon designed to attack the staple crops and domestic animals on which a particular nation depends for food should also be considered. The development and use of anti-crop and anti-animal biological weapons is not new. Although not of direct battlefield utility, anti-animal and anti-crop biological weapons have been developed by several states (as detailed in box 2 below). The rationale for such weapons is to strategically weaken the food generation potential and infrastructure of the targeted country.

Previous anti-crop and anti-animal bio-weapons programmes have utilised naturally occurring pathogens, but the possibility of genetically modified organisms being weaponised should be re-examined in light of the rapid advances in genome studies, particularly in relation to crop plants. Gene manipulation has led to crops with increased resistance to insects and salt, and drought tolerant plants and modified strains of rice with increased levels of vitamins and iron. The expertise gained from such benign plant genome studies could be turned to bio-weaponry.

Increasingly in the developing world, but more so in the developed world, agriculture relies on the monoculture of genetically identical plants, or the intensive husbandry of highly inbred animals. This makes crop plants and domestic food animals ideal targets for such genotype-specific weapons. This vulnerability is further enhanced by the high density and huge numbers of individual plants and animals often involved. These are ideal conditions for rapid and effective contagion.

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Section 5:  The proliferation of biological weapons

5.1 Proliferation during World War II and the Cold War
In 1925 the Geneva Protocol was signed. Although this treaty prohibited the use of biological weapons in war, it did not ban research and development of such weapons. Subsequently a number of European countries developed bio-weapons during the 1930s and 1940s.[34]  However, the only fully documented case of biological weapons being used by one state to attack another involved Japanese hostilities against China during the Second World War. These attacks caused substantial numbers of fatalities.[35]  In the immediate post-war period at least three countries – the former Soviet Union, the United Kingdom and the United States – are known to have had ambitious biological weapons development programmes, building on earlier wartime work.

During the Second World War, most UK testing was conducted on an island off the northwest coast of Scotland called Gruinard. Government scientists concentrated their development and testing efforts on the lethal effects of anthrax, using sheep to evaluate the effectiveness of the disease. As a result of the large amount of anthrax agent dispersed on the island, the hardiness of the anthrax spores and the number of sheep infected, it was only in 1990, after a concerted decontamination programme that the UK government declared the island safe.[36]

The UK government soon combined its biological weapons development efforts with those of the Canadian and US governments. However, the UK’s offensive bio-weapon programme, which was centred at Porton Down, was subsequently closed in the early 1960s.[37]  Some bio-defence work continues at Porton Down today.

In the United States, during World War II and in the years immediately following, much work centred on research, development and production of biological weapons containing anthrax. These efforts continued in the 1950s under Project St. Jo, a programme to develop and test anthrax bombs and delivery methods for possible wartime use against Soviet cities. In order to determine quantitative munitions requirements, 173 releases of non-infectious aerosols were secretly conducted in Minneapolis, St. Louis and Winnipeg – cities chosen because they had the approximate range of conditions, including climate, urban and industrial development and topography, that would be encountered in the major potential target cities of the former Soviet Union. The proposed delivery weapon was a cluster bomb holding 536 biological bomblets, each containing 35 millilitres of anthrax spore slurry and a small explosive charge fused to detonate upon impact with the ground, thereby producing an infectious aerosol to be inhaled by people downwind.

During the US programme, ten different bio-agents were developed including anthrax, tularemia, brucellosis, Q-fever, and Venezuelan equine encephalitis, as well as fungi for the destruction of rice and wheat crops. These were introduced into the US biological weapons stockpile, along with biological bomblets for high-altitude delivery by strategic bombers and spray tanks for dissemination of biological agents by low-flying aircraft. According to published accounts, these developments culminated in a major series of biological weapons field tests using various animals as targets, conducted at sea in the South Pacific in 1968.[38] 

On 25 November 1969, President Nixon announced the unilateral and unconditional renunciation of biological weapons by the United States, stating that: "Mankind already carries in its own hands too many of the seeds of its own destruction".[39] Following an executive order the US programme was summarily terminated, and the Department of Defence was instructed to destroy all its bio-weapons. The US administration subsequently announced that it had destroyed all its existing stockpiles by the end of May 1972. President Nixon pledged that the US biological programme would be restricted to "defensive purposes, strictly defined".[40]  He also declared that, after nearly 50 years of US recalcitrance, he would seek Senate agreement for ratification of the 1925 Geneva Protocol.

In addition, he announced US support for an international treaty proposed by the United Kingdom, banning the development, production and possession of biological weapons. This led to the Biological and Toxin Weapons Convention (BTWC) of 1972.[41] 

A number of factors lay behind the decision of the United States to get out of the offensive biological weapons business and promote an international norm banning their possession. The US government apparently feared that biological weapons could act as an ‘equaliser’ and erode its conventional and nuclear power. It also believed that by putting biological weapons ‘off limits’, the likelihood of their use would be reduced and that an important control principle would be established. The US administration, including its professional military establishment, also believed that biological weapons were too unpredictable for US military use. The US government recognised that verification was an intractable problem but in rejecting biological weapons, it also needed to push for an international norm against possession. The US initiative was a turning point for international control of biological weapons.

However, whilst the United States and United Kingdom closed down their offensive bio-weapons programmes, it eventually became evident that the former Soviet Union had not. Intelligence reports were reinforced by testimony from Soviet defectors at the beginning of the 1990s. The most famous of these is Dr Kenneth Alibek, former First Deputy Director of Biopreparat, who defected to the United States in 1992. Alibek, testifying in May 1998 before the Joint Economic Committee of the US Congress, stated that during the 1980s and 1990s the biological weapons programme of the former Soviet Union had become the most sophisticated in the world, operating in secret even after the Soviet Union signed the BTWC in 1972.

This testimony and further publications by Alibek cannot be fully substantiated due to the secret nature of the work but are generally accepted as valid. In them, Alibek describes the enormous size and scope of the Soviet biological weapons programme.[42]  In the late 1980s and early 1990s, for example, over 60,000 people were involved in the research, development and production of biological weapons. Hundreds of tons of anthrax weapon formulation – the prepared agent, ready to be placed into spray tanks, bomblets and missiles – were stockpiled, along with dozens of tons of plague. The total production capacity of all of the facilities involved was many hundreds of tons of various agents annually.

Alibek also alleged that the Soviet biological weapons programme had developed agents for which no prevention or cure exists, such as unique strains of plague, and that attempts were made to develop smallpox viral bio-weapons based on genetic analysis and engineering techniques. After the success of the World Health Organisation to eliminate smallpox worldwide, only the US Centers for Disease Control and Prevention (CDC), and Vector, the Russian State Research Centre of Virology and Biotechnology in Koltsovo, Novosibirisk are legitimate holders of the variola virus – the cause of smallpox. Alibek has claimed that Russian scientists not only weaponised the disease but also moved samples from the Koltsovo facility to other laboratories in Russia.[43]  Similar use of gene manipulation was alleged in a Russian press article which stated that the anthrax accidentally released in Sverdlovsk in 1979 had been genetically altered in order to have the greatest possible effect on adult men.[44] 

Official confirmation of this illegal programme came in 1992 when the then Russian President, Boris Yeltsin, admitted that the former Soviet Union had continued an offensive biological weapons programme in breach of the BTWC and announced that he was halting it.[45]  Although this programme officially ended in 1992, concerns about covert Russian programmes persist and are described in the case study in section 5.2 below.

5.2 Proliferation concerns today
Today intelligence analysts believe that several countries have or are developing covert offensive biological weapons programmes. In March 2000, the Director of the US Central Intelligence Agency (CIA) stated that:

About a dozen states, including several hostile to Western democracies – Iran, Iraq, Libya, North Korea and Syria – now either possess or are actively pursuing offensive biological and chemical capabilities for use against their perceived enemies, whether internal or external. Some countries are pursuing an asymmetric warfare capability and see biological and chemical weapons as a viable means to counter overwhelming US conventional military superiority. Other states are pursuing BW programs for counterinsurgency use and tactical applications in regional conflicts, increasing the probability that such conflicts will be deadly and destabilizing.[46] 

Because the technology required for biological weapons development can be relatively easily obtained and camouflaged by states, the true number of bio-weapon producers and possessors and the extent of biological weapons holdings is uncertain. Furthermore, it is hard for the public to assess the proliferation threat, since so much of the information publicly available comes directly or indirectly from just one source: the US government and its agencies. This, of course, raises questions of reliability and possible political motivation in the public threat assessments produced. Although there are certain variations in the list of alleged proliferators the following states are frequently reported as having or seeking an offensive biological weapons capability: China, Egypt, Iran, Iraq, Israel, Libya, North Korea, Russia and Syria.[47]  Concerns regarding the biological weapons capabilities of Pakistan, South Korea and Taiwan have also been raised by US government agencies.[48]  Most recently, concerns have been expressed about Afghanistan (see Box 3).