Biological warfare agents

Biological warfare is distinct from nuclear warfare, chemical warfare and radiological warfare, which together with biological warfare make up CBRN , the military acronym for chemical, biological, radiological, and nuclear, warfare using weapons of mass destruction (WMDs). None of these are considered conventional weapons.

Biological Warfare (BW), also known as germ warfare, is the use of biological toxins or infectious agents such as bacteria, viruses and fungii with intent to kill or incapacitate humans, animals or plants as an act of war. Biological weapons (often termed bio-weapons, biological agents or bio-agents) are living organisms or replicating entities (viruses are not universally considered "alive", neither are prions), that reproduce or replicate within their host victims, or toxins derived from living organisms. Entomological (insect) warfare is also considered a type of biological weapon, however insects are far more likely to be used as vectors of biological agents, than as weapons themselves, they might also be used to attack crops. 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.

A country or a terrorist group that can pose a credible threat of mass casualties 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. The effects of such a weapon are now more evident, perhaps than any time previously, because of the 2020 COVID-19 pandemic. Whole nations had their manufacturing capacity reduced to virtually nothing for many weeks, international travel virtually came to a halt, and the financial impact is still unknown but, in the case of the USA alone estimates range from runs into 10 to 22 trillion US dollars.

As a tactical weapon for military use, a significant problem with a BW attack is that it would take days, weeks or even months to be effective, and therefore might not immediately stop an opposing force. Some biological agents have the capability of person-to-person transmission via aerosolised 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.

It has been suggested that rational state actors would never use biological weapons. The argument is that biological weapons cannot be controlled, meaning that the weapon could harm the offensive forces. An agent like smallpox or other airborne viruses would almost certainly spread worldwide and ultimately infect the user's home country.

It has also been suggested that the development of BW agents requires a degree of sophisticated science and technology. However, this argument does not necessarily apply to bacteria. For example, an anthrax agent can easily be produced and controlled in a high school laboratory at a very small cost. Also, using standard microbiological methods, bacteria can be suitably modified to be effective in only a narrow environmental range, and be rendered antibiotic resistant.

A biological weapon may be further used to bog down an advancing army making them more vulnerable to counterattack by the defending force. Note that these concerns generally do not apply to biologically derived toxins which while classified as biological weapons, the organism that produces them is not used on the battlefield, so they present concerns similar to chemical weapons.

History

As early as 400 BC, Scythian archers infected their arrows by dipping them in decomposing bodies or in blood mixed with manure. Greek, Persian and Roman authors from 300 BC quote examples of the use of animal bodies to contaminate wells and other sources of water.

In the 12th century AD, during the Siege of Tortona, Barbarossa used the bodies of dead soldiers to poison wells. They also used primitive chemical warfare agents including sulfur dioxide. In the 14th century AD, during the Siege of Caffa (1346), the attacking Tarter force hurled the bodies of plague victims into the city to attempt to inflict a plague epidemic upon the enemy.

During the French and Indian War (1754-1763) the British gave blankets from smallpox patients to the Native Americans to transmit the disease to the native tribes who would have had no immunological defence as the disease was unknown in North America.

During the American Civil War, a Confederate surgeon was arrested and charged with attempting to import yellow fever-infected clothes into the northern partsGruinard Island sign, 1986 of the United States, again as a crude attempt at biological warfare.

During World War I, the Germans developed anthrax, glanders, cholera, and the wheat fungus Claviceps spp. for use as biological weapons. They used Burkholderia mallei (the cause of glanders in horses) to infect horses being shipped from neutral countries to the UK and to France.  They allegedly spread plague in St. Petersburg, Russia,

Despite the fact that the Geneva Protocol of 1925 forbad the use of biological warfare agents;  the Germans, Japanese, UK, USSR and USA all experimented with a variety of germ warfare agents during WWII. Anthrax and botulinum toxin initially were investigated by the USA for use as weapons, and sufficient quantities of botulinum toxin and anthrax cattle cakes were stockpiled by June 1944 to allow limited retaliation if the Germans first used biological agents. The USSR developed Francisella tularensis as a weapon and used it in 1942 against German troops during the Battle for Stalingrad, there were over 100,000 victims, significantly extremely large numbers of Soviet troops were also infected. Unit 731 operated Japan's secret germ warfare program. Rumours of the unit's activities in northern China had been circulating in Russia and the West since the late 1930s, but the details finally emerged through captured documents and the testimony of Japanese prisoners of war, when the unit was captured by the Soviets in 1945. The unit, commanded by Lieutenant General Shiro Ishii, experimented with anthrax, dysentery, cholera, and plague on as many as 3,000 U.S., British, and Commonwealth POWs. The Japanese had used crude BW weapons against the Chinese when they invaded Manchuria, causing some 6,00 deaths. They also attempted to attack the US mainland using balloons carrying fleas infected Yersinia pestis. It was not until 1988 that the Japanese acknowledged what had happened.

The British certainly experimented with Bacillus anthracis the cause of anthrax, most famously with anthrax spore bombs on Gruinard Island off the coast of Scotland in 1942. They exploded bombs containing B. anthracis on the island near restrained sheep, the sheep started to die after three days. This demonstrated the effectiveness of the weapon, unfortunately the island was then heavily contaminated with anthrax spores and couldn't be used for nearly 50 years, in fact it took several years to decontaminate the soil using formaldehyde (formalin diluted in seawater to give a 4% formaldehyde) solution.

At the same time the Ministry of Agriculture were making large volumes of anthrax vaccine at the Central Veterinary Laboratory at Weybridge in Surrey (in C-Block, framed in red, this is a recent picture and most of the buildings shown did not exist at that time, the webmaster actually worked in this building in the 1960s, but on animal health issues, not BW.

The UK also experimented with several other agents during WWII, including glanders. The work on glanders had been ongoing since the 1st World War, and was primarily concerned with the development of diagnostic tests and vaccines, and was conducted mainly at the Central Veterinary Laboratory under the leadership of Norman H. Hole, in the Pathology Department.

Cold War

The development of BW agents continued into the Cold War in the UK, USSR, USA, and certainly other countries. The UK unilaterally stopped biological weapon development in 1956, but continued work of a defensive nature at the Microbiological Research Establishment, Porton Down.

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. Signatories to this agreement are required to submit information annually to the United Nations concerning facilities where biological defense research is being conducted, scientific conferences that are held at specified facilities, exchanges of scientists or information, and disease outbreaks. The United States terminated its offensive biological weapons program in 1969 for microorganisms and in 1970 for toxins. American stockpiles of biological weapons were destroyed completely by 1973. However, the Soviet Union continued research and production of offensive biological weapons in a program called Biopreparat, despite having signed the convention. Currently some 165 countries have signed the treaty and none are proven, though ten are still suspected, to possess offensive BW programs. The Soviet Union continued to develop biological weapons from 1950-1980. In the 1970s, the USSR and its allies were suspected of having used "yellow rain" (trichothecene mycotoxins) during campaigns in Loas, Cambodia, and Afghanistan. During the Vietnam War, the Vietcong used punji stakes dipped in faeces to increase the morbidity from wounding by these stakes.

In 1985, Iraq began an offensive biological weapons program producing anthrax, botulinum toxin, and aflatoxin. During Operation Desert Shield, the coalition of allied forces faced the threat of chemical and biological agents. Following the Persian Gulf War, Iraq disclosed that it had bombs, Scud missiles, 122-mm rockets, and artillery shells armed with botulinum toxin, anthrax, and aflatoxin. They also had spray tanks fitted to aircraft that could distribute 2000 Litres over a target.

Currently some ten or so countries are suspected of having an offensive biological warfare program.

Bio-terrorism

Since the 1980s a number of terrorist organisations have used biological agents. The most frequent bioterrorism episodes have involved contamination of food and water. In September and October of 1984, 751 persons were infected with Salmonella typhimurium after an intentional contamination of restaurant salad bars in Oregon by followers of the Bhagwan Shree Rajneesh.

In 1994, members the Japanese Aum Shinrikyo cult attempted an aerosolized release of anthrax from the tops of buildings in Tokyo. In 1995, two members of a Minnesota militia group were convicted of possession of ricin, which they had produced themselves for use in retaliation against local government officials. In 1996, an Ohio man was able to obtain Yersinia pestis, the cause of plague, cultures through the mail.

During 1998 and 1999, multiple hoaxes occurred in the USA, involving the threatened release of B. anthracis. Nearly 6,000 persons across the United States have been affected by these threats.

From September to November 2001, a total of 23 confirmed or suspected cases of bioterrorism-related anthrax (10 inhalation, 13 cutaneous) occurred in the United States. Most cases involved postal workers in New Jersey and Washington DC, and the rest occurred at media companies in New York and Florida, where letters contaminated with anthrax were handled or opened. As a result of these cases, approximately 32,000 persons with potential exposures initiated antibiotic prophylaxis to prevent anthrax infections.

According to a study by the Centers for Disease Control and Prevention (CDC), an intentional release of anthrax by a bioterrorist in a major US city would result in an economic impact of $477.8 million to $26.2 billion per 100,000 persons exposed.

Categories of agents

The US Centers for Disease Control and Prevention (CDC) classify biological agents based on the ease of transmission, severity of morbidity, mortality, and likelihood of use, into 3 categories.

Category A  includes the highest priority agents that pose a risk to national security because of the following features:

• They can be easily disseminated or transmitted person-to-person causing secondary and tertiary cases.
• They cause high mortality with potential for major public health impact including the impact on health care facilities.
• They may cause public panic and social disruption.
• They require special action for public health preparedness.

Category B Agents contains the second highest priority agents because they:

• They are moderately easy to disseminate
• They cause moderate morbidity and low mortality
• They require specific enhancement of CDC's diagnostic capacity and enhanced disease surveillance

Category C Agents contains agents with the third highest priority include emerging pathogens that could be engineered for mass dissemination. The characteristics that render them amenable to bioterrorism are:

• Availability
• Ease of production and dissemination
• Potential for high morbidity and mortality and major health impact.
• Possible BW Agents

N.B. The classification and naming of organisms (taxonomy) changes over time, perhaps more frequently in microbiology than many other areas of the biological sciences. As an example the cause of glanders in man and animals has been known as: Glanders bacillus, Corynebacterium mallei, Mycobacterium mallei, Bacillus mallei, Actinobacillus mallei, Pfiefferella mallei, Malleomyces mallei, Loefflerella mallei, Acinetobacter mallei, Pseudomonas mallei and is now known, at the time of writing, as Burkholderia mallei.

The letters in (brackets) represent the NATO military codename(s). The letters in [square brackets] represent the  National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) classification of organisms., as described above. Several groups of organisms could be used in biologic warfare:

• Bacteria
• Protozoa
• Viruses
• Fungi
• Toxins

Bacteria

Bacteria (singular: bacterium) are microscopic, single-celled organisms that thrive in diverse environments. They can live in soil, the ocean, thermal springs and inside and  on the human body. Human  relations  with bacteria are complex. Sometimes bacteria, are helpful such as by turning milk into yogurt or cheese. In other cases, bacteria are destructive, causing diseases like pneumonia and tuberculosis.

Bacteria are classified as prokaryotes, which are single-celled organisms with a simple internal structure they lack a nucleus, and contain DNA that either floats freely in a twisted, thread-like mass called the nucleoid, or in separate, circular pieces called plasmids. Ribosomes are  spherical units in the bacterial cell where proteins are assembled from individual amino acids using the information encoded in ribosomal RNA.

Bacterial cells are generally surrounded by two protective coverings: an outer cell wall and an inner cell membrane. Certain bacteria, like the mycoplasma, do not have a cell wall at all. Some bacteria may even have a third, outermost protective layer called the capsule. Whip-like extensions often cover the surfaces of bacteria - long ones called flagella or short ones called pili - that help bacteria to move around and attach to a host.

Protozoa

Protozoa are eukaryotic unicellular organisms, which together with single-cell algae and slime molds belong to the Protista kingdom. The protozoans contain a membrane-surrounded nucleus and cellular organs. Most protozoa have, at least in some stage of their life, structures such as flagella or cilia that enable them to move and, for some species, to obtain nutrients. Most protozoa are microscopical. They live in moist conditions and only a few are parasites. Protozoans usually multiply asexually by binary or multiple fission. Some are capable of sexual reproduction. Intestinal protozoans infect faeco-orally and cause gastrointestinal signs to dogs. Some vector-borne protozoans may cause generalized clinical signs that involve many organs.Infections caused by protozoa can be spread through ingestion of cysts (the dormant life stage), sexual transmission, or through insect vectors.

Protozoa are broken down into different classes:

• Sporozoa (characterized by being one-celled, non-motile, parasitic, and spore-forming)
  
• Flagellates (characterised by having tail-like structures that flap around to move them)
• Amoebae (which move using temporary cell body projections called pseudopods)
• Ciliata (which move by beating multiple hair-like structures called cilia)

Many common -and not so common - infections are caused by protozoa. Some of these infections cause illness in millions of people each year; other infections are rare and may be disappearing.

Viruses

Viruses are infectious agents that can only replicate within a host organism, in other words they are obligate parasites. They can infect a variety of living organisms, including bacteria, plants, and animals. They are extremely small, most being too small to  be seen under a light microscope, they have a very simple structure. When a virus particle is independent from its host, it consists of a viral genome, or genetic material, contained within a protein shell called a capsid. In some viruses, the protein shell is enclosed in a membrane called an envelope. Viral genomes are very diverse, since they can be DNA or RNA, single or double-stranded, linear or circular, and vary in length and in the number of DNA or RNA molecules.

The viral replication process begins when a virus infects its host by attaching to the host cell and penetrating the cell wall or membrane. The virus's genome is is released  from the protein and injected into the host cell. Then the viral genome hijacks the host cell's control mechanisms, forcing it to replicate the viral genome and produce viral proteins to make new capsids. Next, the viral particles are assembled into new viruses. The new viruses burst out of the host cell during a process called lysis, which kills the host cell. Some viruses take a portion of the host's membrane during the lysis process to form an envelope around the capsid.

Following viral replication, the new viruses may go on to infect new hosts. Many viruses cause diseases in humans, such as influenza, chicken pox, AIDS, the common cold, SARS, and rabies. The primary way to prevent viral infections is vaccination, which administers a vaccine made of inactive viral particles to an unaffected individual, in order to increase the individual's immunity to the disease.

Fungi

Fungi (singular fungus) are eukaryotes and are an extremely diverse group including yeasts, moulds and mushrooms. They, unlike most other organisms have chitin in their cell walls. Fungi are heterotrophs, absorbing their food by directly from their environment. Typically they secrete digestive enzymes into their surroundings. They are non-photosynthetic. Except for the flagellated spores of a few species, fungi are non-motile. Fungi are separate from structurally similar slime moulds. Most fungi are inconspicuous due to their small size and their lifestyles, many only become visible during the fruiting or reproductive phases. Fungi have long been used as a food source - mushrooms - or in the making of food and drink - as yeasts in the making of bread and alcoholic beverages.

There are an estimated 2.2 million species, most of which have yet to be studied.

Relatively few fungi are pathogenic to man, although some produce mycotoxins which can cause fatal consequences. Fungi do cause considerable  impact as agents of plant disease and spoilage of food products.

Toxins

Biological toxins are poisonous by-products of microorganisms, plants, and animals that produce adverse clinical effects in humans, animals, or plants. A toxin has been defined as "a poisonous substance that is a specific product of the metabolic activities of a living organism and is usually very unstable, notably toxic when introduced into the tissues, and typically capable of inducing antibody formation" (Merriam-Webster Dictionary). Biological toxins include metabolites of living organisms, degradation products of dead organisms, and materials rendered toxic by the metabolic activity of microorganisms. Some toxins can also be produced by bacterial or fungal fermentation, the use of recombinant DNA technology, or chemical synthesis of low-molecular-weight toxins. Because they exert their adverse health effects through intoxication, the toxic effect is analogous to chemical poisoning rather than to a traditional biological infection. Biological toxins are produced by certain bacteria, fungi, protozoa, plants, reptiles, amphibians, fish, echinoderma (spiny urchins and starfish), mollusks, and insects.

Biological weapons

Infectious agents or toxins are not of themselves biological weapons, they have to be weaponised. This means three things chiefly:

• they must be made available in a form that may be stored, in the  case of spore forming organisms this is relatively easy. Freeze-drying (lyophilisation) may well be an option using technology commonly used in vaccine production.
• they must be capable of being delivered to the target in such a way as to be effective.
• a delivery system has to be available, this could be simply an atomiser, or in the case of dry spores it could be an explosive device as was used in the UK's Gruinard Island experiments shown in the video above. Probably the simplest delivery system used in recent years was the post.

Biological warfare research/production sites:

United States

• Fort Detrick, Maryland (1943-69)
• Horn Island Testing Station (1943-46)
• Fort Terry (1952-69)
• Granite Peak Installation (1943-45)
• Vigo Ordnance Plant (1942-47)

United Kingdom

• Microbiological Research Establishment (MRE) at Porton Down (1940-)
• Gruinard Island

USSR

• Biopreparat (Russian: Биопрепарат) - 18 labs and production centers (1973-91)
• Stepnagorsk Scientific and Technical Institute for Microbiology, Stepnogorsk, northern Kazakhstan (1982-91)
• Institute of Ultra Pure Biochemical Preparations, Leningrad, a weaponized plague center (1974-91)
• Vector State Research Center of Virology and Biotechnology (VECTOR), a weaponized smallpox center (1974-2020)
• Institute of Applied Biochemistry, Omutninsk (1988-1991)
• 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
• Vozrozhdeniya

Japan

• Unit 731 (1937-45)
• Zhongma Fortress (1930-37)

Iraq

• Al Hakum (1989-1991)
• Al Hazen Ibn Al Haitham Institute (1974-78)
• Salman Pak facility (1979-1985)
• Ibn Sina Centre
• Al Manal facility (1993-??)
• Al Taji (1978-87)

South Africa

• Delta G Scientific Company (1982-93)
• Roodeplaat Research Laboratories (1983-93)

Canada

• Grosse Isle, Quebec (1939-45)
• Experimental Station Suffield, Suffield, Alberta (1950-68)

Cold War Trials

From 1950 until 1978 UK scientists, occasionally in collaboration with the USA, conducted numerous trials in the UK, where biological agent simulants were sprayed or otherwise disseminated over large areas of the UK. Such simulants included fluorescent powder and dead or living bacteria (Serratia marcescens, Bacillus globigii (now known as B. subtilis ) and Escherichia coli). Other experiments subjected animals to infection with biological warfare agents. Similar tests were conducted by the USSR using Serratia marcescens and Bacillus thuringiensis, including tests on the Moscow Metro with the latter organism.

In 1979, an accidental release of anthrax from a weapons facility in Sverdlovsk, USSR, killed at least 66 people this was denied until 1992.

Film of a secret Biological Warfare Trial in 1952. The tests were conducted jointly by the Microbiological Research Establishment (Porton Down) and the Royal Navy near the Isle of Lewis in the Outer Hebrides. Live bacteria of several species, including Yersinia pestis (plague) were sprayed into the air exposing guinea pigs and monkeys to infection. The reference to this experiment on Wikipedia refers to an airport in Venezuala as a source of some material, this is due to a confusion over the letters NRD (probably miss-heard MRD, Merida) which actually refer to the Naval Replenishment Depot. The pontoon was part of the "Mulberry" floating harbour scheme used in WWII. WARNING you may find some of this film disturbing.

The Lyme Bay Trials (1966)

Biological Warfare trials undertaken by the UK Government in 1966. The trials were performed by the Microbiological Research Establishment, Porton Down. They involved spraying viable bacteria into the air, and tracing their spread over Dorset and the surrounding areas.

Civil Defence Corps

The Civil Defence Corps continued BW protective training until 1968. This was quite basic as the rapid identification of organisms, or even the identification that an attack had taken place was not possible at that time. They worked on the assumption that if there had been an explosion of relatively low power, and no chemical agent had been identified, that a BW attack had taken place. Of course this ignores the fact that there are other methods of disseminating BW agents, e.g. spraying, or polluting water supplies. In any case the basic protection was the same, one wore a respirator which protected against inhalation of agents, and underwent the same decontamination procedures as for chemical agents. If there was a high risk an NBC suit would have been worn.

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