Biological warfare

Biological warfare (BW)—also known as germ warfare—is the use of biological toxins or infectious agents such as bacteria, viruses, and fungi with intent to kill or incapacitate humans, animals or plants as an act of war. Biological weapons (often termed "bio-weapons", "biological threat agents", or "bio-agents") are living organisms or replicating entities (viruses, which are not universally considered "alive") that reproduce or replicate within their host victims. Entomological (insect) warfare is also considered a type of biological weapon.

Biological weapons may be employed in various ways to gain a strategic or tactical advantage over an adversary, either by threats or by actual deployments. Like some of the chemical weapons, biological weapons may also be useful as area denial weapons. These agents may be lethal or non-lethal, and may be targeted against a single individual, a group of people, or even an entire population. They may be developed, acquired, stockpiled or deployed by nation states or by non-national groups. In the latter case, or if a nation-state uses it clandestinely, it may also be considered bioterrorism.

There is an overlap between BW and chemical warfare, as the use of toxins produced by living organisms is considered under the provisions of both the Biological Weapons Convention and the Chemical Weapons Convention. Toxins and Psychochemical weapons are often referred to as midspectrum agents. Unlike bioweapons, these midspectrum agents do not reproduce in their host and are typically characterized by shorter incubation periods.

Overview
Offensive biological warfare, including mass production, stockpiling and use of biological weapons, was outlawed by the 1972 Biological Weapons Convention (BWC). The rationale behind this treaty, which has been ratified or acceded to by 165 countries as of 2011, is to prevent a biological attack which could conceivably result in large numbers of civilian fatalities and cause severe disruption to economic and societal infrastructure. Many countries, including signatories of the BWC, currently pursue research into the defense or protection against BW, which is not prohibited by the BWC.

A nation or group that can pose a credible threat of mass casualty has the ability to alter the terms on which other nations or groups interact with it. Biological weapons allow for the potential to create a level of destruction and loss of life far in excess of nuclear, chemical or conventional weapons, relative to their mass and cost of development and storage. Therefore, biological agents may be useful as strategic deterrents in addition to their utility as offensive weapons on the battlefield.

As a tactical weapon for military use, a significant problem with a BW attack is that it would take days to be effective, and therefore might not immediately stop an opposing force. Some biological agents (smallpox, pneumonic plague) have the capability of person-to-person transmission via aerosolized respiratory droplets. This feature can be undesirable, as the agent(s) may be transmitted by this mechanism to unintended populations, including neutral or even friendly forces. While containment of BW is less of a concern for certain criminal or terrorist organizations, it remains a significant concern for the military and civilian populations of virtually all nations.

History
Rudimentary forms of biological warfare have been practiced since antiquity. During the 6th century BC, the Assyrians poisoned enemy wells with a fungus that would render the enemy delirious. In 1346, the bodies of Mongol warriors of the Golden Horde who had died of plague were thrown over the walls of the besieged Crimean city of Kaffa. It has been speculated that this operation may have been responsible for the advent of the Black Death in Europe. The British army used smallpox in New South Wales in 1789 having attempted to use it as a weapon earlier when they gave contaminated blankets to the Lenape during Pontiac's War (1763–66).

The advent of the germ theory and advances in bacteriology brought a new level of sophistication to the theoretical use of bio-agents in war. Biological sabotage—in the form of anthrax and glanders—was undertaken on behalf of the Imperial German government during World War I (1914–1918), with indifferent results. The Geneva Protocol of 1925 prohibited the use of chemical weapons and biological weapons.

Interwar period and WWII
With the onset of WWII, the Ministry of Supply in the United Kingdom established a BW programme at Porton Down, headed by the microbiologist Paul Fildes. The research was championed by Winston Churchill and soon tularemia, anthrax, brucellosis, and botulism toxins had been effectively weaponized. In particular, Gruinard Island in Scotland, during a series of extensive tests was contaminated with anthrax for the next 48 years. Although the UK never offensively used the biological weapons it developed, its program was the first to successfully weaponize a variety of deadly pathogens and bring them into industrial production.

When the USA entered the war, mounting British pressure for the creation of a similar research program for an Allied pooling of resources, led to the creation of a large industrial complex at Fort Detrick, Maryland in 1942 under the direction of George W. Merck. The biological and chemical weapons developed during that period were tested at the Dugway Proving Grounds in Utah. Soon there were facilities for the mass production of anthrax spores, brucellosis, and botulism toxins, although the war was over before these weapons could be of much operational use. The most notorious program of the period was run by the secret Imperial Japanese Army Unit 731 during the war, based at Pingfan in Manchuria and commanded by Lieutenant General Shirō Ishii. This unit did research on BW, conducted often fatal human experiments on prisoners, and produced biological weapons for combat use. Although the Japanese effort lacked the technological sophistication of the American or British programs, it far outstripped them in its widespread application and indiscriminate brutality. Biological weapons were used against both Chinese soldiers and civilians in several military campaigns. In 1940, the Imperial Japanese Army Air Force bombed Ningbo with ceramic bombs full of fleas carrying the bubonic plague. Many of these operations were ineffective due to inefficient delivery systems, although up to 400,000 people may have died.

Postwar period
Considerable research into BW was undertaken throughout the Cold War era by the US, UK and USSR, and probably other major nations as well, although it is generally believed that such weapons were never used. In Britain, the 1950s saw the weaponization of plague, brucellosis, tularemia and later equine encephalomyelitis and vaccinia viruses, but the programme was unilaterally cancelled in 1956. The United States Army Chemical Corps weaponized BWs as the M143 bursting spherical bomblet and US conscientious objectors were used as consenting test subjects for tularemia in a program known as Operation Whitecoat.

Biological and Toxin Weapons Convention
In 1969, the UK and the Warsaw Pact, separately, introduced proposals to the UN to ban biological weapons, and US President Richard Nixon terminated production of biological weapons, allowing only scientific research for defensive measures. The Biological and Toxin Weapons Convention was signed by the US, UK, USSR and other nations, as a ban on "development, production and stockpiling of microbes or their poisonous products except in amounts necessary for protective and peaceful research" in 1972. However, the Soviet Union continued research and production of offensive biological weapons in a program called Biopreparat, despite having signed the convention. By 2011, 165 countries had signed the treaty and none are proven—though nine are still suspected —to possess offensive BW programs.

Offensive
It has been argued that rational people would never use biological weapons offensively. The argument is that biological weapons cannot be controlled: the weapon could backfire and harm the army on the offensive, perhaps having even worse effects than on the target. An agent like smallpox or other airborne viruses would almost certainly spread worldwide and ultimately infect the user's home country. However, this argument does not necessarily apply to bacteria. For example, anthrax can easily be controlled and even created in a garden shed. Also, using microbial methods, bacteria can be suitably modified to be effective in only a narrow environmental range, the range of the target that distinctly differs from the army on the offensive. Thus only the target might be affected adversely. The weapon may be further used to bog down an advancing army making them more vulnerable to counterattack by the defending force.

Anti-personnel


Ideal characteristics of a biological agent to be used as a weapon against humans are high infectivity, high virulence, non-availability of vaccines, and availability of an effective and efficient delivery system. Stability of the weaponized agent (ability of the agent to retain its infectivity and virulence after a prolonged period of storage) may also be desirable, particularly for military applications, and the ease of creating one is often considered. Control of the spread of the agent may be another desired characteristic.

The primary difficulty is not the production of the biological agent, as many biological agents used in weapons can often be manufactured relatively quickly, cheaply and easily. Rather, it is the weaponization, storage and delivery in an effective vehicle to a vulnerable target that pose significant problems.

For example, Bacillus anthracis is considered an effective agent for several reasons. First, it forms hardy spores, perfect for dispersal aerosols. Second, this organism is not considered transmissible from person to person, and thus rarely if ever causes secondary infections. A pulmonary anthrax infection starts with ordinary influenza-like symptoms and progresses to a lethal hemorrhagic mediastinitis within 3–7 days, with a fatality rate that is 90% or higher in untreated patients. Finally, friendly personnel can be protected with suitable antibiotics.

A large-scale attack using anthrax would require the creation of aerosol particles of 1.5 to 5 µm: larger particles would not reach the lower respiratory tract, while smaller particles would be exhaled back out into the atmosphere. At this size, conductive powders tend to aggregate because of electrostatic charges, hindering dispersion. So the material must be treated to insulate and neutralize the charges. The weaponized agent must be resistant to degradation by rain and ultraviolet radiation from sunlight, while retaining the ability to efficiently infect the human lung. There are other technological difficulties as well, chiefly relating to storage of the weaponized agent.

Agents considered for weaponization, or known to be weaponized, include bacteria such as Bacillus anthracis, Brucella spp., Burkholderia mallei, Burkholderia pseudomallei, Chlamydophila psittaci, Coxiella burnetii, Francisella tularensis, some of the Rickettsiaceae (especially Rickettsia prowazekii and Rickettsia rickettsii), Shigella spp., Vibrio cholerae, and Yersinia pestis. Many viral agents have been studied and/or weaponized, including some of the Bunyaviridae (especially Rift Valley fever virus), Ebolavirus, many of the Flaviviridae (especially Japanese encephalitis virus), Machupo virus, Marburg virus, Variola virus, and Yellow fever virus. Fungal agents that have been studied include Coccidioides spp..

Toxins that can be used as weapons include ricin, staphylococcal enterotoxin B, botulinum toxin, saxitoxin, and many mycotoxins. These toxins and the organisms that produce them are sometimes referred to as select agents. In the United States, their possession, use, and transfer are regulated by the Centers for Disease Control and Prevention's Select Agent Program.

The former US biological warfare program categorized its weaponized anti-personnel bio-agents as either Lethal Agents (Bacillus anthracis, Francisella tularensis, Botulinum toxin) or Incapacitating Agents (Brucella suis, Coxiella burnetii, Venezuelan equine encephalitis virus, Staphylococcal enterotoxin B).

Anti-agriculture
Anti-crop/anti-vegetation/anti-fisheries: The United States developed an anti-crop capability during the Cold War that used plant diseases (bioherbicides, or mycoherbicides) for destroying enemy agriculture. Biological weapons also target fisheries as well as water-based vegetation. It was believed that destruction of enemy agriculture on a strategic scale could thwart Sino-Soviet aggression in a general war. Diseases such as wheat blast and rice blast were weaponized in aerial spray tanks and cluster bombs for delivery to enemy watersheds in agricultural regions to initiate epiphytotics (epidemics among plants). When the United States renounced its offensive biological warfare program in 1969 and 1970, the vast majority of its biological arsenal was composed of these plant diseases. Enterotoxins and Mycotoxins were not affected by Nixon's order.

Though herbicides are chemicals, they are often grouped with biological warfare and chemical warfare because they may work in a similar manner as biotoxins or bioregulators. The Army Biological Laboratory tested each agent and the Army's Technical Escort Unit was responsible for transport of all chemical, biological, radiological (nuclear) materials. Scorched earth tactics or destroying livestock and farmland were carried out in the Vietnam war (cf. Agent Orange) and Eelam War in Sri Lanka.

Biological warfare can also specifically target plants to destroy crops or defoliate vegetation. The United States and Britain discovered plant growth regulators (i.e., herbicides) during the Second World War, and initiated an herbicidal warfare program that was eventually used in Malaya and Vietnam in counterinsurgency operations.

Anti-livestock: In 1980s Soviet Ministry of Agriculture had successfully developed variants of foot-and-mouth disease, and rinderpest against cows, African swine fever for pigs, and psittacosis to kill chicken. These agents were prepared to spray them down from tanks attached to airplanes over hundreds of miles. The secret program was code-named "Ecology".

Attacking animals is another area of biological warfare intended to eliminate animal resources for transportation and food. In the First World War, German agents were arrested attempting to inoculate draft animals with anthrax, and they were believed to be responsible for outbreaks of glanders in horses and mules. The British tainted small feed cakes with anthrax in the Second World War as a potential means of attacking German cattle for food denial, but never employed the weapon. In the 1950s, the United States had a field trial with hog cholera. During the Mau Mau Uprising in 1952, the poisonous latex of the African milk bush was used to kill cattle.

Unconnected with inter-human wars, humans have deliberately introduced the rabbit disease Myxomatosis, originating in South America, to Australia and Europe, with the intention of reducing the rabbit population – which had devastating but temporary results, with wild rabbit populations reduced to a fraction of their former size but survivors developing immunity and increasing again.

Entomological warfare
Entomological warfare (EW) is a type of biological warfare that uses insects to attack the enemy. The concept has existed for centuries and research and development have continued into the modern era. EW has been used in battle by Japan and several other nations have developed and been accused of using an entomological warfare program. EW may employ insects in a direct attack or as vectors to deliver a biological agent, such as plague. Essentially, EW exists in three varieties. One type of EW involves infecting insects with a pathogen and then dispersing the insects over target areas. The insects then act as a vector, infecting any person or animal they might bite. Another type of EW is a direct insect attack against crops; the insect may not be infected with any pathogen but instead represents a threat to agriculture. The final method uses uninfected insects, such as bees, wasps, etc., to directly attack the enemy.

Research and development into medical counter-measures
In 2010 at The Meeting of the States Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and Their Destruction in Geneva the sanitary epidemiological reconnaissance was suggested as well-tested means for enhancing the monitoring of infections and parasitic agents, for practical implementation of the International Health Regulations (2005). The aim was to prevent and minimize the consequences of natural outbreaks of dangerous infectious diseases as well as the threat of alleged use of biological weapons against BTWC States Parties.

Role of public health and disease surveillance
It is important to note that all classical and modern biological weapons organisms are animal diseases, the only exception being smallpox. Thus, in any use of biological weapons, it is highly likely that animals will become ill either simultaneously with, or perhaps earlier than humans.

Indeed, in the largest biological weapons accident known– the anthrax outbreak in Sverdlovsk (now Yekaterinburg) in the Soviet Union in 1979, sheep became ill with anthrax as far as 200 kilometers from the release point of the organism from a military facility in the southeastern portion of the city (known as Compound 19 and still off limits to visitors today, see Sverdlovsk Anthrax leak).

Thus, a robust surveillance system involving human clinicians and veterinarians may identify a bioweapons attack early in the course of an epidemic, permitting the prophylaxis of disease in the vast majority of people (and/or animals) exposed but not yet ill.

For example in the case of anthrax, it is likely that by 24–36 hours after an attack, some small percentage of individuals (those with compromised immune system or who had received a large dose of the organism due to proximity to the release point) will become ill with classical symptoms and signs (including a virtually unique chest X-ray finding, often recognized by public health officials if they receive timely reports). By making these data available to local public health officials in real time, most models of anthrax epidemics indicate that more than 80% of an exposed population can receive antibiotic treatment before becoming symptomatic, and thus avoid the moderately high mortality of the disease.

Common epidemiologic clues that may signal biological attack

 * Large numbers of ill persons with a similar disease or syndrome.
 * Unusual illness in a population.
 * Higher morbidity and mortality in association with a common disease or syndrome or failure of such patients to respond to usual therapy.
 * Single case of disease caused by an uncommon agent (i.e. small pox, viral hemorrhagic fever, pulmonary anthrax).
 * Several unusual or unexplained diseases coexisting in the same patient without any other explanation.
 * Disease with an unusual geographic or seasonal distribution (i.e. influenza in the summer).
 * Illness that is unusual (or atypical) for a given population or age group such as an outbreak of measles-like rash in adults.
 * Unusual disease presentation such as pulmonary instead of cutaneous anthrax.
 * Similar genetic type among agents isolated from distinct sources at different times or locations.
 * Unusual, atypical, genetically engineered, or antiquated strain of an agent or antibiotic resistance pattern.
 * Stable endemic disease with an unexplained increase in incidence (i.e. plague).
 * Simultaneous clusters of similar illness in non-contiguous areas, domestic or foreign.
 * Atypical disease transmission through aerosols, food, or water, which suggests deliberate sabotage.
 * Ill persons who seek treatment at about the same time.
 * No illness in persons who are not exposed to common ventilation systems when illness is seen in persons in close proximity who have a common ventilation system.
 * Unusual pattern of death or illness among animals, that precedes or accompanies illness or death in humans.

Identification of bioweapons
The goal of biodefense is to integrate the sustained efforts of the national and homeland security, medical, public health, intelligence, diplomatic, and law enforcement communities. Health care providers and public health officers are among the first lines of defense. In some countries private, local, and provincial (state) capabilities are being augmented by and coordinated with federal assets, to provide layered defenses against biological weapons attacks. During the first Gulf War the United Nations activated a biological and chemical response team, Task Force Scorpio, to respond to any potential use of weapons of mass destruction on civilians.

The traditional approach toward protecting agriculture, food, and water: focusing on the natural or unintentional introduction of a disease is being strengthened by focused efforts to address current and anticipated future biological weapons threats that may be deliberate, multiple, and repetitive.

The growing threat of biowarfare agents and bioterrorism has led to the development of specific field tools that perform on-the-spot analysis and identification of encountered suspect materials. One such technology, being developed by researchers from the Lawrence Livermore National Laboratory (LLNL), employs a "sandwich immunoassay", in which fluorescent dye-labeled antibodies aimed at specific pathogens are attached to silver and gold nanowires.

In the Netherlands, the company TNO has designed Bioaerosol Single Particle Recognition eQuipment (BiosparQ). This system would be implemented into the national response plan for bioweapons attacks in the Netherlands.

Researchers at Ben Gurion University in Israel are developing a different device called the BioPen, essentially a "Lab-in-a-Pen", which can detect known biological agents in under 20 minutes using an adaptation of the ELISA, a similar widely employed immunological technique, that in this case incorporates fiber optics.

Synthetic BW
Theoretically, novel approaches in biotechnology, such as synthetic biology could be used in the future to design novel types of biological warfare agents. Special attention has to be laid on future experiments (of concern) that:


 * 1) Would demonstrate how to render a vaccine ineffective;
 * 2) Would confer resistance to therapeutically useful antibiotics or antiviral agents;
 * 3) Would enhance the virulence of a pathogen or render a nonpathogen virulent;
 * 4) Would increase transmissibility of a pathogen;
 * 5) Would alter the host range of a pathogen;
 * 6) Would enable the evasion of diagnostic/detection tools;
 * 7) Would enable the weaponization of a biological agent or toxin

Most of the biosecurity concerns in synthetic biology, however, focused on the role of DNA synthesis and the risk of producing genetic material of lethal viruses (e.g. 1918 Spanish flu, polio) in the lab.

United States

 * Fort Detrick, Maryland[[Image:B-w-scientists.jpg|thumb|250px|right|Researchers working in [[Biosafety level|Class III cabinet]]s at the U.S. Army Biological Warfare Laboratories, Camp Detrick, Maryland (1940s).]]
 * U.S. Army Biological Warfare Laboratories (1943–69)
 * Building 470
 * One-Million-Liter Test Sphere
 * Operation Whitecoat (1954–73)
 * U.S. biological defense program (1956–present)
 * United States Army Medical Unit (USAMU; 1956–69)
 * U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID; 1969–present)
 * National Biodefense Analysis and Countermeasures Center (NBACC)
 * U.S. entomological warfare program
 * Operation Big Itch
 * Operation Big Buzz
 * Operation Drop Kick
 * Operation May Day
 * Project Bacchus
 * Project Clear Vision
 * Project SHAD
 * Project 112
 * Horn Island Testing Station
 * Fort Terry
 * Granite Peak Installation

United Kingdom

 * Porton Down
 * Gruinard Island
 * Nancekuke
 * Operation Vegetarian
 * Operation Harness off Antigua, 1948–1949.
 * Operation Cauldron off Stornoway, 1952. The trawler Carella accidentally sailed through a cloud of pneumonic plague bacilli (Yersinia pestis) during this trial. It was kept under covert observation until the incubation period had elapsed but none of the crew fell ill.
 * Operation Hesperus off Stornoway, 1953.
 * Operation Ozone off Nassau, 1954.
 * Operation Negation off Nassau, 1954-5.

Soviet Union and Russia

 * Biopreparat (18 labs and production centers)
 * Stepnagorsk Scientific and Technical Institute for Microbiology, Stepnogorsk, northern Kazakhstan
 * Institute of Ultra Pure Biochemical Preparations, Leningrad, a weaponized plague center
 * Vector State Research Center of Virology and Biotechnology (VECTOR), a weaponized smallpox center
 * Institute of Applied Biochemistry, Omutninsk
 * Kirov bioweapons production facility, Kirov, Kirov Oblast
 * Zagorsk smallpox production facility, Zagorsk
 * Berdsk bioweapons production facility, Berdsk
 * Bioweapons research facility, Obolensk
 * Sverdlovsk bioweapons production facility (Military Compound 19), Sverdlovsk, a weaponized anthrax center


 * Institute of Virus Preparations
 * Poison laboratory of the Soviet secret services
 * Vozrozhdeniya
 * Project Bonfire
 * Project Factor

Japan

 * Unit 731
 * Zhongma Fortress

Iraq

 * Main articles: Iraqi biological weapons program and Iraq and weapons of mass destruction (passim)


 * Al Hakum
 * Salman Pak facility
 * Al Manal facility

South Africa

 * Project Coast
 * Delta G Scientific Company
 * Roodeplaat Research Laboratories
 * Protechnik

List of people associated with BW
Bioweaponeers:
 * Anton Dilger
 * Ira Baldwin
 * Paul Fildes
 * Rihab Rashid Taha
 * William C. Patrick III
 * Kanatjan Alibekov, known as Ken Alibek
 * Vladimir Pasechnik
 * Sergei Popov
 * Kurt Blome
 * Eugen von Haagen
 * Kurt Gutzeit
 * Erich Traub
 * Shiro Ishii
 * Arthur Galston (unwittingly)
 * Wouter Basson

Writers and activists:
 * Matthew Meselson
 * Jeanne Guillemin
 * Sheldon H. Harris
 * Joshua Lederberg
 * Richard Preston
 * Arthur Galston
 * David Willman
 * Leonard A. Cole
 * Nicholas D. Kristof
 * Ed Regis
 * Stephen Endicott
 * Edward Hagerman