History of Chemical and Biological Warfare Agents
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Biological warfare (BW), also known as germ warfare, is the use of pathogens such as viruses, bacteria, other disease-causing biological agents, or the toxins produced by them as biological weapons (or bioweapons).
There is a clear overlap between biological warfare and chemical warfare, as the use of toxins produced by living organisms is considered under the provisions of both the Biological and Toxin Weapons Convention and the Chemical Weapons Convention. Toxins, which are of organic origin, are often called "midspectrum agents".
A biological weapon may be intended to kill, incapacitate, or seriously impair a person, group of people, or even an entire population. It may also be defined as the material or defense against such employment.
Biological warfare is a military technique that can be used by nation-states or non-national groups. In the latter case, or if a nation-state uses it clandestinely, it may also be considered bioterrorism.
Biological warfare has been practiced repeatedly throughout history. Before the 20th century, the use of biological agents took three major forms:
- Deliberate poisoning of food and water with infectious material
- Use of microorganisms, toxins or animals, living or dead, in a weapon system
- Use of biologically inoculated fabrics
The ancient world:
The earliest documented incident of the intention to use biological weapons is recorded in Hittite texts of 1500-1200 B.C, in which victims of plague were driven into enemy lands. Although the Assyrians knew of ergot, a parasitic fungus of rye which produces ergotism when ingested, there is no evidence that they poisoned enemy wells with the fungus, as has been claimed.
According to Homer's epic poems about the legendary Trojan War, the Iliad and the Odyssey, spears and arrows were tipped with poison. During the First Sacred War in Greece, in about 590 BC, Athens and the Amphictionic League poisoned the water supply of the besieged town of Kirrha (near Delphi) with the toxic plant hellebore. The Roman commander Manius Aquillus poisoned the wells of besieged enemy cities in about 130 BC.
During the 4th century BC Scythian archers tipped their arrow tips with snake venom, human blood, and animal feces to cause wounds to become infected. There are numerous other instances of the use of plant toxins, venoms, and other poisonous substances to create biological weapons in antiquity.
In 184 B.C, Hannibal of Carthage had clay pots filled with venomous snakes and instructed his soldiers to throw the pots onto the decks of Pergamene ships. In about AD 198, the city of Hatra (near Mosul, Iraq) repulsed the Roman army led by Septimius Severus by hurling clay pots filled with live scorpions at them.
Medieval biological warfare:
When the Mongol Empire established commercial and political connections between the Eastern and Western areas of the world, its Mongol armies and merchant caravans probably inadvertently brought bubonic plague from central Asia to the Middle East and Europe. The Black Death swept through Eurasia, killing approximately one third to one half of the population and changing the course of Asian and European history.
During the Middle Ages, victims of the bubonic plague were used for biological attacks, often by flinging corpses and excrement over castle walls using catapults. 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 (now Theodosia). It has been speculated that this operation may have been responsible for the advent of the Black Death in Europe.
At the siege of Thun l'Eveque in 1340, during the Hundred Years' War, the attackers catapulted decomposing animals into the besieged area.
The 18th Century:
The Native American population was decimated after contact with the Old World due to the introduction of many different fatal diseases. There are two documented cases of alleged and attempted germ warfare. The first, during a parley at Fort Pitt on June 24, 1763, Ecuyer gave representatives of the besieging Delawares two blankets and a handkerchief that had been exposed to smallpox, hoping to spread the disease to the Natives in order to end the siege. William Trent, the militia commander, left records that clearly indicated that the purpose of giving the blankets was "to Convey the Smallpox to the Indians."
British commander Lord Jeffrey Amherst and Swiss-British officer Colonel Henry Bouquet, whose correspondence referenced the idea of giving smallpox-infected blankets to Indians in the course of Pontiac's Rebellion. Historian Francis Parkman verifies four letters from June 29, July 13, 16 and 26th, 1763. Excerpts: Commander Lord Jeffrey Amherst writes July 16, 1763, "P.S. You will Do well to try to Inocculate the Indians by means of Blankets, as well as to try Every other method that can serve to Extirpate this Execrable Race. I should be very glad your Scheme for Hunting them Down by Dogs could take Effect,..." Colonel Henry Bouquet replies July 26, 1763, "I received yesterday your Excellency's letters of 16th with their Inclosures. The signal for Indian Messengers, and all your directions will be observed."
While the intent for biological warfare is clear, there is a debate among historians as to whether this actually took place despite Bouquet's affirmative reply to Amherst and each having written to the other about it twice. Smallpox transmitted to Native American tribes could have been due to the transfer of the disease to blankets during transportation. Historians have been unable to establish whether or not this plan was implemented, particularly in light of the fact that smallpox was already present in the region, and that scientific knowledge of disease at that time had yet to discover bacteria or develop an understanding of plague vectors.
Regardless of whether this plan was carried out, trade and combat provided ample opportunity for transmission of the disease. See also: Small pox during Pontiac's Rebellion.
The 19th Century:
In 1834 Cambridge Diarist Richard Henry Dana visited San Francisco on a merchant ship. His ship traded many items including blankets with Mexicans and Russians who had established outposts on the northern side of the San Francisco Bay.
Local histories document that the California smallpox epidemic began at the Russian fort soon after they left. Blankets were a popular trading item, and the cheapest source of them was second-hand blankets which were often contaminated.
During the American Civil War, General Sherman reported that Confederate forces shot farm animals in ponds upon which the Union depended for drinking water. This would have made the water unpleasant to drink, although the actual health risks from dead bodies of humans and animals which did not die of disease are minimal.
Jack London in his story '"Yah! Yah! Yah!"' describes a punitive European expedition to a Pacific island deliberately exposing the Polynesian population to Measles, of which many of them died s:South Sea Tales/"Yah! Yah! Yah!". While much of the material for London's South Sea Tales is derived from his personal experience in the region, it is not certain that this particular incident is historical.
The 20th Century:
During the First World War, Germany pursued an ambitious biological warfare program. Using diplomatic pouches and couriers, the German General Staff supplied small teams of saboteurs in the Russian Duchy of Finland, and in the then-neutral countries of Romania, the US and Argentina.
In Finland, Scandinavian freedom fighters mounted on reindeer placed ampules of anthrax in stables of Russian horses in 1916. Anthrax was also supplied to the German military attache in Bucharest, as was Glanders, which was employed against livestock destined for Allied service.
German intelligence officer and US citizen Dr. Anton Casimir Dilger established a secret lab in the basement of his sister's home in Chevy Chase, Maryland, that produced Glanders which was used to infect livestock in ports and inland collection points including, at least, Newport News, Norfolk, Baltimore, and New York, and probably St. Louis and Covington, Kentucky. In Argentina, German agents also employed Glanders in the port of Buenos Aires and also tried to ruin wheat harvests with a destructive fungus.
During the 1948 Israel War of Independence, Red Cross reports raised suspicion that the Jewish Haganah militia had released Salmonella typhi bacteria into the water supply for the city of Acre, causing an outbreak of typhoid among the inhabitants. Egyptian troops later captured disguised Haganah soldiers near wells in Gaza, whom they executed for allegedly attempting another attack. Israel denies these allegations.
During the Cold War, US conscientious objectors were used as consenting test subjects for biological agents in a program known as Operation Whitecoat. There were also many unpublicized tests carried out on the public during the Cold War.
E120 biological bomblet, developed before the U.S. signed the Biological and Toxic Weapons Convention
Considerable research on the topic was performed by the United States (see US Biological Weapon Testing), the Soviet Union, and probably other major nations throughout the Cold War era, though it is generally believed that biological weapons were never used after World War II. This view was challenged by China and North Korea, who accused the United States of large-scale field testing of biological weapons, including the use of disease-carrying insects against them during the Korean War (1950-1953).
Biological warfare is the deliberate use of disease and natural poisons to incapacitate humans. It employs pathogens as weapons. Pathogens are the micro-organism, whether bacterial, viral or protozoic, that cause disease. There are four kinds of biological warfare agents: bacteria, viruses, rickettsiae and fungi. Biological weapons are distinguished by being living organisms, that reproduce within their host victims, who then become contagious with a deadly, if weakening, multiplier effect. Toxins in contrast do not reproduce in the victim and need only the briefest of incubation periods; they kill within a few hours.
Biological Weapons Characteristics:
Ideal characteristics of biological weapons targeting humans are high infectivity, high potency, non-availability of vaccines, and delivery as an aerosol.
Diseases most likely to be considered for use as biological weapons are contenders because of their lethality (if delivered efficiently), and robustness (making aerosol delivery feasible).
The biological agents used in biological weapons can often be manufactured quickly and easily. The primary difficulty is not the production of the biological agent but delivery in an effective form to a vulnerable target.
For example, anthrax is considered an effective agent for several reasons. First, it forms hardy spores, perfect for dispersal aerosols. Second, pneumonic (lung) infections of anthrax usually do not cause secondary infections in other people. Thus, the effect of the agent is usually confined to the target. A pneumonic anthrax infection starts with ordinary "cold" symptoms and quickly becomes lethal, with a fatality rate that is 90% or higher. Finally, friendly personnel can be protected with suitable antibiotics.
A mass attack using anthrax would require the creation of aerosol particles of 1.5 to 5 micrometres. Too large and the aerosol would be filtered out by the respiratory system. Too small and the aerosol would be inhaled and exhaled. Also, at this size, nonconductive powders tend to clump and cling because of electrostatic charges. This hinders dispersion. So the material must be treated to insulate and discharge the charges. The aerosol must be delivered so that rain and sun does not rot it, and yet the human lung can be infected. There are other technological difficulties as well.
Diseases considered for weaponization, or known to be weaponized include anthrax , ebola, Marburg virus, plague , cholera , tularemia, brucellosis, Q fever, Bolivian hemorrhagic fever, Coccidioides mycosis , Glanders, Melioidosis, Shigella, Rocky Mountain spotted fever, typhus , Psittacosis, yellow fever , Japanese B encephalitis , Rift Valley fever, and smallpox . Naturally-occurring toxins that can be used as weapons include ricin, SEB, botulism toxin, saxitoxin, and many mycotoxins. The organisms causing these diseases are known 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.
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 counter insurgency. Though herbicides are chemicals, they are often grouped with biological warfare as bioregulators in a similar manner as biotoxins. Scorched earth tactics or destroying livestock and farmland were carried out in the Vietnam war and Eelam War in Sri Lanka.
The United States developed an anti-crop capability during the Cold War that used plant diseases (bioherbicides, or mycoherbicides) for destroying enemy agriculture. 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 water sheds 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.
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"
Role of public health departments and disease surveillance:
It is important to note that all of the 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.
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.
A sampling of Bacillus anthracis-Anthrax
A biological agent is a bacterium, virus, prion, fungus, or biological toxin that can be used in bioterrorism or biological warfare. More than 1200 different kinds of biological agents have been described and studied to date. Applying a slightly broader definition, some eukaryotes (for example parasites) and their associated toxins can be considered as biological agents.
Biological agents have the ability to adversely affect human health in a variety of ways, ranging from relatively mild allergic reactions to serious medical conditions, even death. These organisms are ubiquitous in the natural environment; they are found in water, soil, plants, and animals. Because many biological agents reproduce rapidly and require minimal resources for preservation, they are a potential danger in a wide variety of occupational settings.
Antibiotic resistance is a specific type of drug resistance when a microorganism has the ability of withstanding the effects of antibiotics. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population. Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion (between individuals) by conjugation, transduction, or transformation. Many antibiotic resistance genes reside on plasmids, facilitating their transfer. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug. The term antimicrobial resistance is sometimes used to explicitly encompass organisms other than bacteria.
Antibiotic resistance can also be introduced artificially into a microorganism through laboratory protocols, sometimes used as a selectable marker to examine the mechanisms of gene transfer or to identify individuals that absorbed a piece of DNA that included the resistance gene and another gene of interest.
The widespread use of antibiotics both inside and outside of medicine is playing a significant role in the emergence of resistant bacteria. They are often used in animals but also in other industries which at least in the case of agricultural use lead to the spread of resistant strains to human populations. In some countries antibiotics are sold over the counter without a prescription which compounds the problem. In human medicine the major problem of the emergence of resistant bacteria is due to misuse and overuse of antibiotics by doctors as well as patients. Other practices contributing towards resistance include the addition of antibiotics to the feed of livestock. Household use of antibacterials in soaps and other products, although not clearly contributing to resistance, is also discouraged (as not being effective at infection control). Also unsound practices in the pharmaceutical manufacturing industry can contribute towards the likelihood of creating antibiotic resistant strains.
Certain antibiotic classes are highly associated with colonisation with superbugs compared to other antibiotic classes. The risk for colonisation increases if there is a lack of sensitivity (resistance) of the superbugs to the antibiotic used and high tissue penetration as well as broad spectrum activity against "good bacteria". In the case of MRSA, increased rates of MRSA infections are seen with glycopeptides, cephalosporins and especially quinolones. In the case of colonisation with C difficile the high risk antibiotics include cephalosporins and in particular quinolones and clindamycin.
Antibiotic resistance can be a result of horizontal gene transfer, and also of unlinked point mutations in the pathogen genome and a rate of about 1 in 108 per chromosomal replication. The antibiotic action against the pathogen can be seen as an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce. They will then pass this trait to their offspring, which will result in a fully resistant colony.
The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are:
Drug inactivation or modification: e.g. enzymatic deactivation of Penicillin G in some penicillin-resistant bacteria through the production of Î²-lactamases.
Alteration of target site: e.g. alteration of PBP-the binding target site of penicillins-in MRSA and other penicillin-resistant bacteria.
Alteration of metabolic pathway: e.g. some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid.
Reduced drug accumulation: by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell surface.
Specific consensus recommendations are made regarding the diagnosis of anthrax, indications for vaccination, therapy for those exposed, postexposure prophylaxis, decontamination of the environment, and additional research needs.
Of the numerous biological agents that may be used as weapons, the Working Group on Civilian Biodefense has identified a limited number of organisms that could cause disease and deaths in sufficient numbers to cripple a city or region. Anthrax is one of the most serious of these diseases.
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