For as long as humans can remember, poisons have been used for assassinations. When humans first brought war upon each other, more soldiers were debilitated from diseases than from being captured by their human enemies. This observation might have led to the early exploitation and use of poisoning substances during war. The use of these disease agents or toxins in warfare during the last century resulted to the death of several tens of thousands of people.

Even before 300 BC, Persian, Greek, and Roman literature quote examples of the use of animal cadavers to contaminate wells and other sources of water. And as early as the sixth century BC, poisons were administered to enemy water supplies. Animal cadavers were used as substitute for poisons during the Greek and Roman eras, using human corpses. The Assyrians in 500 BC were also famous in poisoning enemy wells with rye ergot fungus causing hallucinations to target opponents. While Greeks poison water supply of Kirrha during the first Sacred War as long as 590 BCE which slaughtered the population and lead to the fall of Kirrha.

As far back as the well-known Trojan War in 400 BC were the Legend of Scythian archers employing poisoned-tipped arrows. Scythian archers dipped their arrows in decomposing bodies or in blood mixed with manure to infect their enemies. The Scythians archers of the Black Sea were described by Herodotus, a Greek historian of the fifth century B.C.E. as having 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 decomposed. This poison would certainly contain the bacteria Clostridium perfringins and Clostridium tetani causing gangrene and tetanus, this venom would attack red blood cells, nervous system and could even induce respiratory paralysis. A Scythian archer could launch about twenty arrows per minute and had a range of over 1,600 feet.

During the "Plague of Athens” in the Peloponnesian War and siege of the city-state of Athens by the Spartans, a devastating epidemic broke out which killed thousands of Athenians. It was suspected that Sparta poisoned the wells as recorded by the famous historian Thucydides, writing between 431 B.C. and 404 B.C. This may be the first reason that biological warfare agents have not been employed except in isolation and then by rogue states. It was suggested that the "plague of Athens" during the Peloponnesian War was Ebola and that Athenian reinforcements from Africa carried the virus to the city-state as according to a New York Times article of August 18, 1996. The reinforcements may have brought a regimental pet, an African Green Monkey, which was then the reservoir for the Marlburg virus, a close relative of the Ebola virus. Until this day, I was never known what the causative organism of the epidemic was.

In the Battle of Eurymedon, Hannibal won a great naval battle over Eumenes II of Pergomon using bio-warfare.  Hannibal was renowned as the great leader of the Cathagian Army and is famous of his leadership, logistics and strategic generalship, one of these is his employment of war elephants that crossed the Alps to attack Rome. However in 190 B.C., Hannibal demonstrated both naval leadership and effective bio-warfare by having suggested a more active approach when advising the Bithynians to catapult jars filled with venomous snakes towards enemy ships. When the enemy ships came within range, the earthen jars packed with the snakes were hurled at the opponent vessels where they broke discharging their terrifying occupants among the enemy sailors. Sea battle was won since the resulting chaos was effective. The Bithynians’ victory was likely due to the panic created by the surprise attack, rather than poisonous bites, revealing human psychology as a second important dimension during biological attacks.

In 1155 AD, Emperor Barbarossa broadened the scope of biological warfare by using the dead and decomposing bodies of soldiers as well as animals to poison wells during the battle of Tortona, Italy.

Later, the infamous Black Death of the 14th Century swept through Europe, the Near East, and North Africa and was probably the most devastating public health disaster in recorded history and one of the most dramatic examples ever of emerging or reemerging disease. The Tartar army (Mongols) besieging the city of Caffa, present day Feodosia in the Ukraine, used a combination of psychological warfare and bio-warfare. In 1346, the Tartars experienced an epidemic of bubonic plague; they however, converted their misfortune into an opportunity. In an attempt to initiate an epidemic, the Tartars hurled plague-infected corpses into the besieged Crimean city of Caffa, thus transmitting the disease to the residents; and that fleeing infected survivors of the siege spread plague from Caffa to the Mediterranean Basin. If this report is accurate, Caffa should be recognized as the site of the most spectacular incident of biological warfare ever, with the Black Death as its ruinous consequence. With this pestilence, Europe lost an estimated one quarter to one third of its population, and the mortality in North Africa and the Near East was comparable. Countries such as China, India, and the rest of the Far East are commonly believed to have also been severely affected. The disease that caused this grievous pandemic has generally considered to have been a bubonic plague, a zoonotic disease caused by the gram-negative bacterium Yersinia pestis, the principal reservoir for which is wild rats. This plague is primarily a disease of rats and other rodents and only when they become very plentiful in close contact with humans does the plague occur in man. The bites of the fleas called the Oriental rat flea as in this case is Xenopsylla cheopsis, which transmit the disease to humans. Perhaps, the fleas on the rats hunting in the Tartar camp probably traveled on their hosts into the city of Caffa before the first Tartar died of the plague. Nonetheless, the ultimate origin of the Black Death is uncertain—China, Mongolia, India, central Asia, and southern Russia have all been suggested. The attack at the siege of Caffa by the Tartar forces using plague-infected corpses was repeated in 1710, when the Russians besieging Swedish forces at Reval in Estonia catapulted bodies of people who had died from plague.

A long-term epidemic of tularemia, the ‘Hittite plague’ spread through the Eastern Mediterranean in the 14th century BC, which can be traced back to a focus for outbreaks in Canaan along the Arwad-Euphrates trading route. This epidemic contaminated an area stretching from Cyprus to Iraq and from Israel to Syria. It constitutes as one of the record of biological warfare in history when the wars spread the disease to central Anatolia, from where it was deliberately brought to Western Anatolia. The symptoms of the Hittite plague, its mode of infection, and geographical area, were identified with the causative agent as Francisella tularensis. 

In 1495, Spanish forces supplied and sold with wine contaminated with the blood of leprosy patients to their French enemies during battles in Southern Italy.

Polish troops in the seventeenth century attempted to fire saliva from rabid dogs towards their enemies.

In the 1675 Strasbourg Agreement, France and Germany made the first pledge against the use of poisoned weapons in warfare.

 During a war with Sweden in 1710, Russian troops might still have catapulted plague victims into the Baltic city of Reval.

The French and Indian Wars from 1754 to 1767 marked the first recoded "weaponized" biological agent in North America. The agent was a Variola virus causing smallpox. British forces under the direction of Sir Jeffrey Amherst as commander in North America formulated a plan to diminish the Native Indian population or to "reduce," as he so clinically expressed it, the size of the Native American tribes that were unsympathetic to the British crown. He suggested the deliberate plan of giving blankets that had been used by smallpox victims to the Native Americans in a plan to spread the disease.

An outbreak of smallpox in the garrison of Fort Pitt occurred in the late spring of 1763. Usually, blankets and a handkerchief contaminated with 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 eventually burned. However, they were collected and saved to effectuate the plan of annihilating the Native American tribes. One of Amherst's subordinates, Captain Ecuyer gave the blankets and one handkerchief to the Indians invited to confer at the Fort which led to the suffering of the Native American tribes in the Ohio Valley with smallpox epidemic. Nevertheless, the use of fomites to transmit smallpox is comparatively inefficient compared to respirable aerosolized particles. Imagine how effective Amherst and Ecuyer would have been if they could have sprayed the Native American villages. Considering the deficiency of knowledge regarding diseases and disease transmission, the biowarfare (BW) of Amherst and Ecuyer is somewhat ahead of its time. In one of those significant ironies of history, it was, Edward Jenner, an English physician, who discovered the smallpox vaccine in 1796. What is also remarkable is the fact that it was not until the late 1870's that science discovered the germ theory and how diseases are transmitted. The subsequent advancement of microbiology in the late 19th century with the work of Louis Pasteur and Robert Koch, it was finally possible to isolate, produce and weaponized biological agents.

During the Siege of Mantua in 1797, Napoleon attempted to use swamp fever to flood fields around Mantua to enhance the spread of the disease now known as the mosquito - transmitted malaria. Napoleon and the French forces looked on happily after twelve years, watching British troops dying from swamp fever in the marches of Holland, where they set up camp.

Some evidence proposed that during the civil war in the United States, smallpox may have been deliberately used as a biological weapon. The Confederate doctor Luke Blackburn attempted to infect federal troops using contaminated clothing carried by smallpox and yellow fever patients. Nonetheless, yellow fever was soon discovered to be solely transmitted by mosquitoes, leaving claims that soldiers died from such an attack rather unbelievable.

The description of these historical attempts of using diseases in biological warfare illustrates the difficulty of differentiating between a naturally occurring epidemic and an alleged or attempted biological warfare attack—a problem that has continued into present times.