|Year : 2014 | Volume
| Issue : 4 | Page : 204-209
Historical and preventive aspect of biological warfare
Shrikant Mishra1, Bhavesh Trikamji2
1 Department of Neurology, Keck School of Medicine USC; Department of Neurology, David Geffen School of Medicine UCLA; Department of Neurology, Olive View-UCLA Medical Center, Sylmar; Department of Neurology, VA Greater Los Angeles HSC, Los Angeles, California, USA
2 Department of Neurology, Olive View-UCLA Medical Center, Sylmar; Department of Neurology, VA Greater Los Angeles HSC, Los Angeles, California, USA
|Date of Web Publication||11-Nov-2014|
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History has witnessed several civilizations and nations fall prey to bioterrorism. With the rise of new technology, more sophisticated weaponry is being instituted by nations worldwide. Countries spend significant revenue in research and development of their defense infrastructure. We take a look at the evolution of bioterrorism to its current state today. The data were collected from literature review of various online sources such as PubMed, EMBASE, Google scholar, UCLA, and USC libraries over a 2 years period in 2013 and 2014 at Los Angeles, California, USA. We discuss the historical aspects and preventive strategies of biological warfare. We characterize the various kinds of biological weapons and their role in spreading terrorism. In emergency situations where every second count, being equipped with management strategies for biological warfare will help in preventing further damage. This review aims at preparing the physicians for disaster management and disease control.
Keywords: Biological warfare, biological weapons, bioterrorism, chemical toxins, history of biological weapons
|How to cite this article:|
Mishra S, Trikamji B. Historical and preventive aspect of biological warfare. Int J Health Syst Disaster Manage 2014;2:204-9
| Introduction|| |
Biological weapons (BWs) and chemical toxins have been used in wars since time immemorial. The cave men who started using arrows poisoned with juices and wine find their place in the earliest of this history. As proportions grew bigger, weapons were designed. What was once conceived as a mode of protection against enemies is now one of the largest billion dollar industries in the world. Today the world spends some $1000 billion annually on the military. With the advent of technology BW that once required sophisticated research and development can now easily be manufactured in one's own backyard. With new BWs challenging humanity every other day, it becomes quintessential to be aware of these threats and develop means to avoid them. Our review aims at looking into various aspects of BW.
| Prehistoric Era|| |
Attempts to use BW date back to antiquity. Various references in the Hindu epic "Ramayana" and "Mahabharata" point to use of toxic arrows even before 400 BC. The oldest documented evidence of BW is recorded in Hittite texts of 1500-1200 BC, in which victims of tularemia were driven into enemy lands, causing an epidemic. Two other reported cases occurred in the 6 th century BC, with the Assyrians poisoning enemy wells with rye ergot and Greek general Solon's use of the purgative herb Hellebore during the siege of Krissa.  Scythian archers infected their arrows by dipping them in decomposing bodies, snake venom, in blood mixed with animal feces as far back as 400 BC. Persian, Greek, and Roman literature from 300 BC quote examples of dead animals used to contaminate wells and other sources of water. In the battle of Eurymedon in 184 BC, Hannibal of Carthage won a naval battle against King Eumenes II of Pergamon by firing earthen vessels filled with venomous snakes at the enemy ships. During the battle of Tortona in 12 th century AD, Barbarossa used bodies of dead and decomposing soldiers to poison the wells of enemies.  In the year 1346, plague broke out in the Tartar army during its siege of Kaffa (present day Feodossia, Ukraine). The attackers hurled the corpses of plague victims over the city walls. The plague epidemic that followed forced the opponents to surrender. Some people infected from that plague who emigrated from Kaffa may have started the Black Death pandemic, which later spread throughout Europe and resulted in the deaths of nearly 25 million people (one-third of its population). This was repeated in 1710, when the Russians besieging Swedish forces at Reval in Estonia catapulted bodies of people who had died from the plague. 
Smallpox virus has long been used as a lethal weapon in a biological warfare. The decimation of the American Indian population in 1763 is attributed to the widespread distribution of blankets previously used and thus infected by smallpox patients as gifts by the invading forces.  Native Americans defending Fort Carillon sustained epidemic casualties that directly contributed to the loss of the fort to the English. During the French and Indian War of 1754-1767, British forces under the leadership of Sir Jeffrey Amherst provided Indians, who were loyal to the French, with blankets used by smallpox victims in a plan to spread the disease.  Allegations were made during the American Civil War by both forces, especially against the Confederate Army, for the attempted use of smallpox to cause disease among enemy forces.
World war I
It was not until World War I (WWI) that this kind of warfare gained as much magnitude as to kill thousands with one strike. Anthrax was a BW agent that was employed by German forces during the WWI. The Geneva Protocol of 1925 prohibited the use of chemical weapons and BWs, but said nothing about experimentation, production, storage, or transfer. The interwar period was a period of development of BW by many nations, most notably the Empire of Japan. WWII was no different as far as the use of nerve gases and other gases is concerned, yet there exists a key distinction due to the nuclear arsenal that dominated toward the end. Cold war era saw a huge accumulation of biological agents in the Soviet Union. Recent resurgence in biological and chemical warfare has been a sad and regretful contribution by terrorists who threaten to destroy entire cities with the use of this unconventional weaponry.
The evolution of chemical and BWs is broadly categorized into four phases. In the first phase, gaseous chemicals like chlorine and phosgene were used in Ypres, Belgium in WWI. The second phase ushered an era of use of nerve agents such as tabun, a cholinesterase inhibitor, and also the beginning of the anthrax and plague bombs of WWII. The third phase was constituted by the use of lethal chemical agents such as Agent Orange, a mix of herbicides stimulating hormonal function resulting in defoliation and crop destruction. This phase also included the use of a new group of Novichok and mid-spectrum agents that possess the characteristics of chemical and physiologically active compounds. The fourth phase coincides with the era of the biotechnological revolution and the use of genetic engineering. 
Chemical warfare during world war I
The first use of chlorine on the Western Front came on April 22, 1915 at around 5 pm when German troops at Ypres discharged 180,000 kg. 180 tons of chlorine gas from 5730 cylinders on the line between Steenstraat on the Yser Canal, through Bixschoote and Langemark to Poelcappelle. The gas cloud that blew with the wind either killed or caused the French and Algerian troops in the opposing trenches to flee thus opening an 8-9 km gap in the Allied line. Later, on May 31, 1915 chlorine was employed on the Eastern Front, by the Germans at Bolimow, near Skierniewice, 50 km southeast of Warsaw. This time, the attack employed 12,000 cylinders, releasing 264 tons of chlorine along a 12 km line. There were nearly 200 chemical attacks during WWI using gas released from cylinders; the largest of these occurred in October 1915 when the Germans released 550 tons of chlorine from 25,000 cylinders at Rhiems. As the war continued, many toxic compounds in addition to chlorine were tested for utility as chemical warfare agents. Phosgene was used for the 1 st time by the German army on December 19, 1915 when 88 tons was released from 4000 cylinders against British troops at Nieltje in Flanders. Bischloroethyl sulfide (mustard gas) was first used in an artillery attack on July 12, 1917 by the Germans. Notably, this agent caused more casualties than any other chemical agent used during WWI. A few other significant chemical agents that were used during this period were trichloromethyl chloroformate (diphosgene), hydrogen cyanide and arsine-based "Clarks." 
World war II and after
During WWII, British and American scientists considered the smallpox as a potential BW. Later, due to the development of a vaccine, it lost its potentially toxic lustre. In 1954, Brucella More Details suis became the first agent weaponized by the US at Pine Bluff Arsenal in Arkansas, when its offensive BW program was still active. Brucella weapons, along with the remainder of the US biological arsenal, were destroyed in 1969, when the offensive program was disbanded. In November 1969, President Nixon officially halted the US offensive BWs program, bowing to pressure from the American people who had been abhorred by the use of chemical weapons during the Vietnam War. WWII saw the use of nerve agents (Tabun, a cholinesterase inhibitor) and the beginning of anthrax and plague bombs. It was the launch of an era that would be sustained by nerve agents. There were huge accumulations of anthrax in USSR mainly during the post-WWII and cold war era. In April 1979, an incident occurred in Sverdlovsk (now Yekaterinburg) in the former Soviet Union, manifested in the accidental aerosol release of Bacillus anthracis spores from a Soviet Military microbiology facility: Compound 19. The Soviet Ministry of Health blamed the deaths on the consumption of contaminated meat and for years controversy raged in the press over the actual cause of the outbreak. All of the evidence available to the US government indicated a massive militarized release of aerosolized B. anthracis spores. In the summer of 1992, US intelligence officials were proven correct when the new Russian President, Boris Yeltsin, acknowledged that the Sverdlovsk incident was in fact related to military developments at the microbiology facility. In 1985, Iraq began an offensive BWs program producing anthrax, botulinum toxin, and aflatoxin. During Operation Desert Storm, 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 developed spray tanks fitted to aircraft that could distribute agents over a specific target. In 1995, two members of a Minnesota military group were convicted of possession of ricin, which they had cultivated themselves for use in retaliation against local government officials. In 1996, an Ohio man attempted to obtain bubonic plague cultures through the mail. 
Napalm; a sticky, gasoline-like substance that can melt the skin off its victims was developed in 1943 by Harvard chemist Louis Fieser et al. Though it became infamous during the Vietnam War, napalm that was used as a weed killer had a devastating impact during WWII, when a single US firebomb raid in Tokyo killed an estimated 100,000 people. A stranger napalm application never came to fruition: the napalm bat-bomb. Project X-ray, as it was called, was a US plan to release explosive bats: flying mammals strapped to napalm-laced time bombs in Japanese cities, in hopes that the animals would find wooden houses to roost in and blow up. Despite several successful trial runs, the bat-bomb project was ultimately cancelled when the officer in charge realized the arsenal wouldn't be ready for deployment until 1945. 
Developed in the 1940s yet not tested, the chemical weapon Agent Orange was meant to target plants, not people. Therefore, subsequent harmful physiological effects on humans were never realized. During the Vietnam War, the US Army sprayed local landscapes with this herbicide to destroy the opposition's food and cover not realizing the health dangers it would pose to Vietnamese civilians and US soldiers alike. Dioxin, the toxic ingredient in Agent Orange, can remain in the human body for over a decade, causing cancer, diabetes, and Parkinson's disease in US veterans, as well as certain birth defects in children of veterans. Nerve agents are the most lethal and quickest-acting category of chemical weapons. A single drop of sarin or the deadlier VX can kill a person in minutes. Iraq became the first country to employ nerve agents on the battlefield when it released them as airborne chemicals, along with mustard gas, during the Iran-Iraq War. Though a party to the Geneva Protocol, Iraq began employing chemical weapons against Iran as early as 1983. By 1988, reports had surfaced of nerve agents being used against Kurdish Iraqis in the north; one detailed the Iraqi government killing up to 5000 Kurds in a single chemical attack at Halabja, possibly including deadly sarin and VX. 
In August 1991, the United Nations carried out its first inspection of Iraq's biological warfare capabilities in the aftermath of the Gulf War. On August 2, 1991, representatives of the Iraqi government announced to the leaders of United Nations Special Commission Team that they had conducted research into the offensive use of B. anthracis, botulinum toxins, and Clostridium perfringens (presumably one of its toxins).  This open admission of BWs research verified many of the concerns of the US intelligence community. Iraq had extensive and redundant research facilities at Salman Pak and other sites, many of which were destroyed during the war. In 1995, further information on Iraq's offensive program was made available to United Nations inspectors. Field trials were conducted with Bacillus subtilis (a simulant for anthrax), botulinum toxin, and aflatoxin. Biological agents were tested in various delivery systems, including rockets, aerial bombs, and spray tanks. In December 1990, the Iraqis filled 100 R400 bombs with botulinum toxin, 50 with anthrax, and 16 with aflatoxin. In addition, 13 Al Hussein (Scud) warheads were filled with botulinum toxin, 10 with anthrax, and 2 with aflatoxin. In all, Iraq produced 19,000 L of concentrated botulinum toxin (nearly 10,000 L filled into munitions), 8500 L of concentrated anthrax (6500 L filled into munitions) and 2200 L of aflatoxin (1580 L filled into munitions).
The threat of biological warfare (BW) has increased in the last two decades, with a number of countries working on the offensive use of these agents. The extensive program of the former Soviet Union is now primarily under the control of Russia. Recent revelations from a senior BW program manager who defected from Russia in 1992 outlined a remarkably robust biological warfare program, which included active research into genetic engineering, binary biological and chimeras, and industrial capacity to produce agents. There is also growing concern that the smallpox virus, which is believed to be stored at only two laboratories; one at the Center for Disease Control and prevention in Atlanta and other at the Institute for Viral Precautions in Moscow, may be available in other countries around the globe.
Finally, there is an increasing amount of concern over the possibility of the terrorist use of biological agents to threaten either military or civilian populations. There have been cases of extremist groups trying to obtain microorganisms that could be used as BWs. The 1995 attack at the Tokyo subway system with Sarin, a nerve agent raised awareness that terrorist organizations could potentially acquire or develop weapons of mass destruction (WMD) for use against civilian populations. Subsequent investigations revealed that the organization had attempted to release botulinum toxins and anthrax on several occasions. The Department of Defense has been leading a federal effort to train the first responders in 120 American cities to be prepared to act in case of a domestic terrorist incident involving WMD. In addition, since the 1980s, several terrorist organizations have become users of biological agents. Usually, these cases amount only to hoaxes. However, the following exceptions have been noted. In 2001, anthrax was delivered by mail to US media and government offices killing 5 people and infecting 17 others. Dr. Bruce Ivins, a US biodefense researcher who later committed suicide was identified as the man behind these attacks. In December 2002, 6 terrorist suspects were arrested in Manchester, England, and it was found that their apartment was serving as a "ricin laboratory." Among them was a 27-year-old chemist who was producing the toxin. Later, on January 5, 2003, British police raided two residences around London and found traces of ricin, which led to an investigation of a possible Chechen separatist plan to attack the Russian embassy with the toxin. Several arrests were made in this regard. On February 3, 2004, 3 US Senate office buildings were closed after the toxin ricin was found in the mailroom that serves Senate Majority Leader Bill Frist's office. More recently, on May 29, 2013 two anonymous letters were sent to the New York City Mayor and to the offices of Mayors against Illegal Guns in Washington DC that contained traces of the deadly poison ricin. A letter containing ricin was also alleged to have been sent to US President Barack Obama at the same time. During the recent Syrian civil war, both the government of Bashar al Assad and anti-government forces accused each other of using chemical weapons such as sarin. Syria is currently believed to have one of the largest stockpiles of chemical and BWs in the world, including stores of deadly sarin, mustard, and VX gases.  Due to the extensive efforts of Organization for the Prohibition of Chemical Weapons, the elimination of chemical weapons from Syria has been possible. For taking up this mammoth task, this organization was awarded Nobel Prize in Peace last year.
| Discussion|| |
Biological warfare is the intentional use of microorganisms and toxins (microbial, plant or animal origin) to produce disease and/or death in humans, livestock and crops.  Biological WMD are, usually, clubbed with the nuclear, biological, and chemical weapons in the acronym NBC [Table 1] and [Table 2]. However, biological WMD is a lot different. While nuclear and chemical attacks can cause massive destruction within minutes, biological attacks spread over a considerable amount of time. The focus on biological WMD is attributed to the following features, one of which is low production costs - hence they are aptly referred to as the "Poor Man's Atomic Bomb"/"Poor Man's WMD."  For atomic bombs, conventional weapons and nerve-gas weapons, the cost per casualty would be approximately $2000, $800 and $600, respectively. However, for BWs the cost would be about $1 per casualty. Nondetection by routine security systems and easy access to a wide range of disease-producing biological agents are few other features. Biological toxins are among the most toxic agents known. For example, the quantity of botox in the dot of an "i," when delivered properly, is enough to kill about 10 people. Furthermore, BWs have the added advantage of destroying an enemy while leaving his infrastructure intact as booty for the winner. 
Characteristics of an ideal biological weapons
Highly infectious, highly effective, efficiently dispersible, readily grown, produced in large quantities, stable on storage, resistant to environmental conditions, nonavailability of vaccines and resistant to treatment.
Definition of a biological weapon
Biological weapons are defined as microorganisms that infect and grow in the target host producing a clinical disease that kills or incapacitates the host [Table 1] and [Table 2]. Such microbes may be natural, wild-type or a result of genetically engineered organisms. These also include substances that interfere with normal behavior, such as hormones, neuropeptides and cytokines. There exists a possibility to create "designer" substances that would specifically target a particular cell-type in an enemy (e.g. people with blonde hair and blue eyes).
Genetically-modified biological weapons
Russia has developed a new form of anthrax that can elude the vaccine that American troops receive. This may become the first genetically modified microorganism to be officially listed as a BW. There might be a possibility to place multiple virulence/toxic capacities within a single organism or to fuse two toxic proteins together so that both would be functional as genetically modified BWs (e.g. botox and ricin). These kinds of BWs can be expected to appear on the scene sooner rather than later. 
There are no parasitic microbes (protozoans) listed above as BWs. But that does not mean they could not be employed for such a purpose. For example, a variety of protozoan species are candidates for BWs-Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia. Cash crops that have been targeted in anti-crop warfare are sweet potatoes, soyabeans, sugar beats, cotton, wheat, and rice. The agents used to cause economic losses with the latter two foreign-exchange earnings were Puccinia graminis tritici and Piricularia oryzae, respectively. The use of such warfare focuses on the destruction of national economies benefiting from export earnings of wheat-an important cereal crash crop in the Gulf region. 
Delivery of biological warfare
Transport can be as complex as using Scud missiles to deliver BWs within range of about 500 miles or as simple as using a motor vehicle or a car that could cruise the streets of a city, while emitting a fine spray of BW-aerosol through a fake tailpipe or other small vent. Even a hand-pumped sprayer like those used to spray insecticide on one's garden can be used. An individual carrying a large suitcase or backpack could disperse BW material while walking the streets. A book/letter can be contaminated with anthrax. , Umbrella weapons consist of a projectile weapon buried in the disguise of an umbrella. This weapon shoots as tiny pellet having a hole drilled through it, which is filled with toxins like ricin. The hole is covered with wax that melts when the projectile enters the body due to the body heat.  Robotic delivery offers another likely possibility. Such robots would be small enough to be camouflaged as pieces of wood or rock and could be programmed to bring themselves underground until actioned. They could even be solar-powered and hence they could function independently for long periods.
| Conclusion|| |
Mankind has come a long way with the aid of science and technology. The emphasis on BW has never been this large. With growing technology, several nations encounter never ending threats from biological and chemical warfare. It has become almost impossible to fathom the magnitude of BW these days. The governments worldwide are faced with the herculean task of updating their research and development strategies to combat various threats from BW. The best approach is to stay focused and act wisely in times of political unrest. The government has to take up efforts in creating centers for preparedness at local, state and national levels. Both military and civilian population should be educated on the threats and prevention from BW [Table 3].  Being equipped with the tools of management, physicians can play a vital role in the event of a BW. Ultimately, governments and various political organizations have to work in synergy to eliminate the threat of BW.
|Table 3: Emergency service duties to be performed at chemical/BWs release|
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[Table 1], [Table 2], [Table 3]