Thomas J. Johnson
Associate Professor of Respiratory Care and Health Sciences
Division Director, Respiratory Care, School of Health Professions
In Sophocles' play Philoctetes (404 B.C.E.), he describes the main character Philoctetes as wounded by a poisoned arrow on his way to the Trojan War. This is the stuff of legend and myth but maybe legend has its origins in reality. We get our English word for poison or toxin form the Greek word toxikon, which in turn is derived from the Greek word for arrow, toxon. Herodotus, a Greek historian of the fifth century B.C.E. describes the Scythians archers of the Black Sea as employing poison-tipped arrows. According to Herodotus, Scythians used the decomposed bodies of several venomous adders indigenous to their region, mixed human blood and dung into sealed vessels and buried this mixture until it was sufficiently putrefied. This poison would certainly contain the bacteria of gangrene and tetanus (Clostridium perfringins and Clostridium tetani) while the venom would attack red blood cells, nervous system and could even induce respiratory paralysis. A Scythian archer had a range of over 1,600 feet and could launch about twenty arrows per minute.1
What is biological or bio-warfare? It is the use of biological pathogens (bacteria, viruses, fungi, and toxins derived from living organisms to kill or incapacitate one's enemies. So, from poisoned arrows (Scythians, and later the Viet Cong guerrillas) to poisoned wells (Sparta, Persia, Rome and others) to bombs with deadly bacteria (Japan, United States, Soviet Union and Iraq), the intentional use of biowarfare has been around for centuries.
During the siege of the city-state of Athens by the Spartans in the Peloponnesian War a devastating epidemic broke out which killed thousands of Athenians. The famous historian Thucydides, writing between 431 B.C. and 404 B.C. reported, "it was supposed that Sparta poisoned the wells."2 Even though Sparta won the Peloponnesian War, its reputation was destroyed. This may be the first reason that biowarfare agents have not been employed except in isolation and then by rogue states. Excellent propaganda then and now casts a shadow of guilt that can obscure the science. Interest in the Peloponnesian War persists until this day. A New York Times article (Sunday, August 18, 1996) suggested that the "plague of Athens" during the Peloponnesian War was Ebola.3 The article suggests that Athenian reinforcements from Africa carried the virus to the city-state. Even this is unlikely given the slow transportation from Africa and the incubation period of the Ebola virus. Of course the reinforcements may have brought a regimental pet, an African Green Monkey. The Green Monkey is the reservoir for the Marlburg virus, a close relative of the Ebola virus. It may never be known what the causative organism of the epidemic was.
Most people remember Hannibal as the great leader of the Cathagian Army. His employment of war elephants that crossed the Alps to attack Rome is an example of leadership, logistics and strategic generalship. Very few even know that he fought naval engagements. However in 190 B.C., he demonstrated both naval leadership and effective bio-warfare. In that year he won a great naval battle over Eumenes II of Pergomon using bio-warfare. Hannibal had earthen jars filled with venomous snakes, covered and taken on board his ships. When the enemy ships came within range, the earthen jars with the snakes were hurled at the enemy vessels where they broke discharging their terrifying occupants among the enemy sailors. The resulting chaos was effective and Hannibal won easily.4
One may debate whether or not even Hannibal's use of war elephants constituted bio-warfare. The Romans had horses that may have been made skittish by the size, smell and trumpeting noise of Hannibal's elephants. Hannibal may have heard how the Persian king Cyrus defeated the cavalry of King Croesus in 548 B.C. by placing a rank of camels in front of his infantry. Croesus's cavalry horses were panicked by the smell and sight of the unfamiliar animal.5
Later, in the 14th Century, the Tartar army besieging the city of Kaffa (present day Feodosia in the Ukraine) used a combination of psychological warfare and bio-warfare.6 The ubiquitous rat and an outbreak of the bubonic plague among their own troops worked for the Tartar army besieging Kaffa in 1346. Tartars catapulted bodies of plague victims over the walls of Kaffa in an attempt to initiate an epidemic upon the residents.5 The bubonic plague is primarily a disease of rats and other rodents. Only when they become very numerous in close contact with humans does the plague arise in man. The bites of the fleas (in this case the Oriental rat flea, Xenopsylla cheopsis) transmit the disease to humans. Most probably, the fleas on the rats scavenging in the Tartar camp probably traveled on their hosts into the city Kaffa before the first Tartar died of the plague.
The defenders subsequently contracted the bubonic plague and abandoned the city to the Tartars. Merchants from Genoa had been trading in the Crimean port when the Tartars attacked. The surviving Genoese returned to Italy via their ships and most likely brought the plague to Europe. In October of 1347, the merchant ships docked in Genoa.7 The Genoese ships must have had stowaways -- rats. The rats with their fleas disembarked and proceeded to change the face of Europe forever.8
Chroniclers of the period report that the plague had spread from Italy to Spain and northward to France. By 1350, the plague was in Scandinavia. In more densely populated areas or cities such as Paris, Oxford and London almost 66% of the population was killed. Other, more isolated regions such as Bohemia were virtually unscathed since traders rarely ventured into them.
Medieval Europe responded with many reactions. A few people decided that since life was short, indulging in pleasures while you could was the order of the day. Others saw the plague as the Christian God's punishment for sin. The power of the Catholic Church increased in the face of imminent death. Some Christians believed that self-desecration would make up for past sins. One movement, the Flagellants believed that whipping themselves and others would atone for sins. Besides self-abuse, they scapegoat others, specifically the Jews. This led to mass persecutions. Of course, none of these actions altered the course of the epidemics of the plague.
The result of the introduction of the bubonic plague into Europe was devastating. There were too few people to work the land, estates lost financial power that, in turn, provided an opportunity for kings to centralize power. Teachers and tutors in universities died and, with them, learning. Hence the term Dark Ages.
Without an idea of what caused the disease or how it spread, people were helpless. The University of Paris Faculty of Medicine reported in March of 1345 that the alignment of planets caused the plague. Others proposed that the night air, swamps, or the burning of bodies during war poisoned the air. As a result, the plague would wreak havoc on Europe for the next four hundred years.9
After an incubation period of 2 to 10 days, there is an abrupt onset of symptoms. These range from high fevers, headaches, muscle pain to nausea and vomiting. The bubo develops in the groin as the legs are the most commonly flea bitten part of the body. Dark skin eruptions often encircle the neck. The plague victim develops shock or low blood pressure with an ashen pallor. As the disease progresses limbs become black from gangrene. The plague is not transmissible from person-to-person unless the microorganism invades the victim's lungs in late stages of the disease where it becomes the pulmonic form of the disease. Untreated, the plague has a mortality rate of approximately 60%. The pulmonic plague has a mortality rate of nearly 100%.10
In both story and song the bubonic plague is present in Western literature. Robert Browning's The Pied Piper of Hamlien is one better-known story.11 Consider too this familiar children's rhyme:
Ring around the rosy
(The feverous face encircled with pustules)
A pocket full of posies
(Flowers placed on the foul smelling victim)
(Septic shock that precedes death, wearing of mourning ashes, or burning of the corpses of the plague victims?)
All fall down
(The victim dies)
This seemingly innocuous childhood rhyme comes to us from the children of 17th century London England. It is a folk memory of the plague.12
This was not the last time that the bodies of plague victims were used in warfare. Again in 1710, the Russian Army besieging the Swedes holding Reval in Estonia tried the catapulting of corpses of those who died of the plague. Again the success of the tactic was due in no small way to the panic and hysteria that the plague induced in people.13
The first recoded "weaponized" biological agent in North America occurred during the French and Indian Wars (1754 to 1767). The agent was smallpox. The method of delivery was blankets not bombs. Sir Jeffrey Amherst who was the commander of British forces in North America formulated a plan to "reduce," as he so clinically expressed it, the size of the Native American tribes that were hostile to the crown.
In late Spring 1763 there was an outbreak of smallpox in the garrison of Fort Pitt. This produced a bacterial delivery system that the medical world would now refer to as a "fomite," an inanimate object capable of naturally containing or transporting an infectious agent. Blankets and a handkerchief laden with the pus or dried scabs from the smallpox sores of the infected British troops were collected in Fort Pitt's infirmary. These blankets and handkerchiefs were usually burned. This time they were collected and saved.14
On June 24, 1763, one of Amherst's subordinates a Captain Ecuyer ceremoniously gave the blankets and one handkerchief to the Indians invited to confer at the Fort. History does repeat itself. This is uncannily similar to the Trojan Horse, the "infection" which brought down Troy. Captain Ecuyer recorded rather chillingly in his diary, "I hope it will have the desired effect."15 This "gift" may have had its intended effect. Native American tribes in the Ohio Valley suffered a smallpox epidemic. It must be noted that the immunologically naive people are most vulnerable to diseases not indigenous to their region. Native American tribes across America experienced serious losses due to their contact with Europeans and their African slaves. Additionally, the use of fomites to transmit smallpox is inefficient compared to respirable aerosolized particles. Imagine how effective Amherst and Ecuyer would have been if they could have sprayed the Native American villages.
When we consider the dearth of knowledge regarding diseases and disease transmission, the biowarfare (BW) of Amherst and Ecuyer is ahead of its time. In one of those remarkable ironies of history, it was an English physician, Edward Jenner who discovered the smallpox vaccine in 1796. What is also remarkable is the fact that science did not discover the germ theory and how diseases are transmitted until the late 1870's. With the work of Louis Pasteur (1822-1895) and Robert Koch (1843-1910) and the subsequent development of microbiology in the late 19th century, it was finally possible to isolate, produce and weaponized biological agents.16
Germany may be credited with opening of the modern biological warfare program during World War I. Covert operations in Romania infected sheep destined for export to Russia with anthrax. The German Legation in Romania had laboratory vessels containing cultures confiscated. Subsequently, the Bucharest institute of Bacteriology and Pathology identified Bacillus anthracis (anthrax) and Bacillus mallei (Glanders, a respiratory tract infection of horses and mules). Meanwhile, German saboteurs in France infected horses and mules. Even before the American entry in to the war, covert German bacteria warfare was attempted in the United States with the contamination of animal feed and infection of horses intended for export.17
In the period between the World Wars, there was an attempt to regulate warfare. This well-intentioned but ineffectual effort resulted in the Geneva Protocol. Thus the first attempt to limit the use of biologicals in warfare was the 1925 Geneva Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and Bacteriological Methods of Warfare.18 While prohibiting the use of bio-weapons, the treaty did not seek to prevent the research, production, or possession. There was no provision for inspection. Many countries that ratified the protocol stipulated the right for retaliation. An interesting footnote to history, the United States did not ratify the Geneva Protocol until 1975.19
Little known and yet remarkable in its scope is Japan's biological warfare program during World War II. Probably, the most extensive and most horrorific biological weapons research and deployment occurred in Manchuria from 1932 until the end of the war.20 This program, innocuously entitled as Unit 731 was located in Pingfan Manchuria. Under the direction of Dr. Shiro Ishii from 1932 to 1942 and then Kitano Misaji from 1942 until 1945, Unit 731 employed a staff of over 3,000 scientists and technicians. Unit 731, sprawled over 150 building and five satellite camps. Additional sub-units were located in Mukden, Changchun and Nanking.
Experimentation on prisoners using Shigella (bacterial dysentery*), Vibrio cholerae (cholera) and Yersinia pestis (the bubonic plague) was part of the Unit 731 program. At least 10, 000 prisoners died. Most from "experimental infection" and the remaining were executed after experiments for autopsy. 21
Under interrogation, scientists and technicians admitted to 12 "field trials" of weaponized biologicals. Eleven Chinese cities were attacked with biological agents. These attacks ranged from water supply contamination to food contamination with cholera, anthrax, Salmonella and the plague. Cultures of these agents were sprayed from aircraft.
Unit 731 weaponized the plague in an interesting way. Plague infected rats were fed upon by laboratory bred fleas. The Japanese then collected the now infected fleas, containerized them and released them over Chinese cities from low flying aircraft. It was reported that up to 15 million fleas were released in each attack. Although the Chinese National Health Administration attributes wartime plague epidemics on these attacks by the Japanese of Unit 731 conditions in China during the war precluded rigorous epidemiological and bacteriological data collection.
Bio-warfare is a two-edged sword. Unit 731 was so secret and the Japanese troops in China were so under-trained and unequipped to deal with biological weapons that Japanese casualties resulted from these attacks. In 1941, the attack on Changteh ostensibly resulted in nearly 10,000 cholera cases and 1,700 deaths among the Japanese troops. This may be the second disadvantage of BW: the difficulty in protecting one's own troops. Kitano Misaji terminated these "field trials" in 1942. Both the United States and the Soviet Union's Biological Warfare program owe their germination to the work of Unit 731. The Soviets captured Unit 731. US forces captured Shiro Ishii and Kitano Misaji and granted them immunity from war crimes if they divulged their BW secrets. US had no research in either offensive or defensive BW early in World War II. Only when the intelligence agents of the Office for Strategic Services (OSS) discovered the activities of Unit 731 did the US initiate its own offensive germ warfare program at Camp Detrick, Maryland in late 1942.22
The British secretly developed their own biological warfare program focused on anthrax. To test the effectiveness of weaponized anthrax delivered by a conventional bomb the British chose Gruinard Island off the coast of Scotland. The island was bombed in experiments to determine the best dispersal. Then in 1943, there was an outbreak of anthrax in sheep and cattle on the coast of Scotland that faced Gruinard Island. Attempts at decontamination by starting brushfires failed as spores of anthrax had been embedded in the island's soil thus making total decontamination impossible to this day. This creates the third disadvantage of BW use by a nation; the difficulty in decontamination may preclude the use of acquired territory.23,24
It is interesting to note that the Nazi offensive BW program limited itself to inhuman experiments not unlike Japan's Unit 731. Prisoners in Nazi concentration camps were forcibly infected with a wide variety of bacteria, protozoa and even a virus, Hepatitis A. These horrors were ostensibly experiments done to study pathogenesis and to develop vaccines and sulfa drugs rather than to develop weaponized versions of these pathogens. There is a positive note to this inhumanity; it was used against the Germans in an area of occupied Poland. Polish physicians in the region used a vaccine (formalin-killed Proteus OX-19) to produce a false-positive test for typhus. German troops were not dispatched to the area to round up its residents for deportation to concentration camps, thus saving an unknown number of people.25
Meanwhile the US offensive biological warfare program was begun in 1942, under the Direction of the War Reserve Service, a civilian agency. It had research and development facilities at Camp Detrick, MD with production in Terre Haute, IN and testing in Mississippi and Utah. The Terre Haute production facility had inadequate engineering safety measures. This precluded large-scale biological weapons production. However the Camp Detrick "pilot plant" produced 5000 bombs of anthrax.26
During the Korean War (1950 - 1953) new production facility at Pine Bluff, AR was constructed incorporating adequate biosafety measures. These safety systems are to protect the staff and the people and livestock in the vicinity. Additionally, a program to protect troops in the field with vaccines, anti-sera and therapeutic agents was initiated in 1953. Weaponization of microorganisms was begun in 1954.
The Cold War between the US and the USSR intensified with propaganda and an arms race unlike any the world has seen. At the United Nations General Assembly, the Soviet Union accused the United States of using germ warfare in Korea. It was this accusation that changed the focus of the US program. It also resulted in secret and controversial experiments.
The American program elected to use so-called "Surrogate Biological Agents" that were ostensibly non- pathologic to humans. These surrogates were used to simulate the employment of more deadly organisms. In a highly classified program bacterium such as Serratia macescens and Bacillus subtilis (the classic college microbiology lab bacteria) were sprayed in US cities. The program was shut down in 1969.
In the San Francisco experiment with Serratia marcescens 5,000 particles per minute were sprayed from the coast inward. One man died and ten others were hospitalized by an infection that was never followed up. Declassified information indicates that during the test there was five to ten times the normal infection rate in San Francisco areas that were sprayed.
More alarming were the tests to determine the vulnerability of the New York City subway system to biowarfare. In 1966, Bacillus subtilis was released into the subways. The results of this experiment showed that the release of an organism in just one station would infect the entire underground subway system due to winds and vacuum created by the passing subway trains.27 The declassified information was published in Leonard Cole's 1988 book, Clouds of Secrecy. One wonders if it was read by the cult Aum Shinrikyo for its planning of a nerve gas (sarin) attack on the Tokyo subway in March of 1995. The cult was weaponizing anthrax, botulinum and had even attempted to obtain the Ebola virus for a weapon.28
Meanwhile in Southeast Asia, the spread of war created one clear use of biological warfare and several accusations. In Vietnam, the Communist Viet Cong guerrillas dug pits and implanted spikes of bamboo and other woods that were contaminated with human feces. These were called punji pits.29 The unwitting combatant or non-combatant who stepped into the pit was impaled upon the spikes and were inoculated with material that would produce a rapid and virulent infection.20 The Soviet Union was accused of using mycotoxins as "yellow rain" in support of communists armies in Cambodia and Laos. However there was no confirming evidence.
President Nixon signed National Security Decisions 35 and 44 in November of 1969 and February of 1970 terminating the United States offensive BW weapons program. This mandated the cessation of offensive BW research and the destruction of the BW arsenal. The only permitted research was defensive, such as diagnostic tests, vaccines and chemotherapies. As a direct result of the termination of the offensive BW program, the US Army Medical Research Institute for Infectious Disease (USAMRIID) was established at Ft. Detrick, MD.30 None of USAMRIID's research is classified. Nearly simultaneously in 1969 Great Britain submitted a proposal to the United Nations Committee on Disarmament. It includes a prohibition on the development, production and stockpiling of biological weapons. By 1972, the United Nations Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological and Toxin Weapons and Their Destruction (BWC)31 was ratified by member nations. There were some notable violations.
The Soviet Union continued offensive biological warfare program after signing the 1972 BWC under the title of Biopreparat. Under the Ministry of Defense, Biopreparat ran a minimum of 6 research laboratories with 5 weapons production facilities. At least 55,000 scientists and technicians worked for Biopreparat. Even with these resources there was a terrible failure of Biopreparat's biosafety systems.
Western intelligence agencies long suspected that the military facilities in the Soviet city of Sverdlovsk, now Ekaterinburg, Russia was a biological warfare research facility. In April 2, 1979, an outbreak of a disease that affected 94 people and killed at least 64 occurred in the city of Sverdlovsk located nearly 850 miles east of Moscow. The first victims died after 4 days and the last died 6 weeks later. People and animals in a narrow zone down wind of the facility were infected. Livestock as far away as 50 km from the facility died. The Soviet government reported that the deaths were caused by tainted meat, intestinal anthrax.32 Then 13 years later, President Boris Yeltsin admitted that the anthrax outbreak was the result of an unintentional release of anthrax.33
The dispersal of the anthrax spores with the prevailing wind and the meteorological conditions was a classic plume. Considering that this was an accidental release and the effects were felt for 50 km, one must consider the range and causalities that would have resulted if this were a deliberate attack. Russia permitted a Western team of scientists that included Prof. Matt Meselson to visit Sverdlovsk in June 1992 and again in August 1993.34 Despite KGB confiscation of medical documents, the scientists were able to document that the victims were clustered in a straight line downwind of the facility. Of course they were not able to determine what exactly caused the release or what specific activities were being conducted at the Sverdlovsk military facility. This incident demonstrates the effectiveness of the first route of infection, inhalation.
The Cold War is responsible for the first documented modern assassination using a biological agent. In an operation out of the pages of an Ian Fleming's James Bond spy novel, the KGB and the Bulgarian secret police executed a flawless and as yet unsolved murder. Yuri Andropov, the chairman of the Soviet KGB reportedly authorized technical assistance and training for the operation.35
On September 7, 1978 Georgi Markov a Bulgarian writer and journalist who worked for the BBC and for Radio Free Europe left home for work at the BBC. It was his habit to take the Waterloo Bridge bus to the BBC headquarters. As Markov neared the queue of people waiting for the bus, he suddenly felt a stinging pain in the back of his right thigh. He turned and saw a heavyset man in his 40's stooping over to pick up a dropped umbrella. The man hailed a taxi and disappeared.
Unconcerned, Markov continued to work where he told his colleagues what happened. He showed one BBC friend a red pimple-like swelling on his thigh. That evening Markov developed a high fever and he was taken to a London hospital and treated for a non-specific type of blood poisoning. Three days later he was dead.36
On autopsy a tiny pellet was found in the wound in Markov's thigh. This pellet had an empty X-shaped cavity with two 0.34 mm holes. Toxicology results determined that Markov had been murdered by a poison, ricin. The ricin was encapsulated in a waxy base designed to melt at body temperature thus releasing into the tissues the ricin toxin. Ricin is a toxin that is derived from a plant source, a biological agent.
Ricin, the untreatable toxin of the Markov umbrella murder can be weaponized as an aerosol. With an average lethal dose of 1/5,000th of a gram it remains a potent BW agent. Under the 1972 Convention, it is defined as a "schedule one" controlled substance. Unfortunately, the worldwide processing of over 100,000,000 metric tons of castor beans results in a 5% waste mash. This waste mash is ricin toxin.37
While there were numerous claims that the Soviet Union employed mycotoxins, a.k.a. "yellow rain" in Cambodia, Laos and Afghanistan, there was no conclusive proof. Meteorological conditions, background fungal infections, and even bee pollen were confounding the findings of investigators. Then in September 1984 in Wasco county east of Portland, Oregon a cult called the Rashneeshee successfully contaminated the salad bars of 10 restaurants in the county. This second route of infection by a BW agent, the oral intake of contaminated food or water, resulted in 751 cases of salmonella poisoning. This was the first known bio-terrorist attack.38
It may not have been the last by a long shot. The Aum Shinrikyo cult that was responsible for the Tokyo subway gas attack had sent members to Africa to collect samples of the virus Ebola and had even experimented unsuccessfully with aerosolizing anthrax.39 Fortunately for Japan their efforts were unsuccessful.
The Iran-Iraq War (1980-1988) was marked by numerous documented use of chemical weapons by Iraq. The UN Secretary General dispatched a team of specialists that conclusively verified allegations of Iraqi use of chemical agents to induce over 2,200 casualties. Despite numerous allegations of BW use by Iraq, the United Nations could not verify the reports.40
As we have seen Biowarfare in its many forms is not new. From poisoning well water to poisoning salad bars in restaurants, from poisoned arrows of 300 BC to poisoned punji stakes of 1960's, from catapulting plague victims to dissemination of the plague by aircraft, warfare has included biological agents. The weaponization of these agents despite prohibitions will continue. The defense will run a parallel course. Will they be used again? It is only a question of when.
* A Japanese physician, Shiga during the 1898 epidemic in Japan, discovered the bacterium that causes dysentery, Shigella dysenteriae. Other species of the bacilli have been discovered in the Philippines, the US and Europe. There are four main groups of bacilli but for purposes of treatment this is unnecessary. This pathogen differs from the protozoan or amebic form of the disease.