An extraordinarily toxic bacterium harbored by the "infernal" Styx River might have been the fabled poison rumored to have killed Alexander the Great (356 to 323 B.C.) more than 2,000 years ago, according to a scientific-meets-mythic detective study.
The research, which will be presented next week at the XII International Congress of Toxicology annual meetings in Barcelona, Spain, reviews ancient literary evidence on the Styx poison in light of modern geology and toxicology.
According to the study, calicheamicin, a secondary metabolite of Micromonospora echinospora, is what gave the river its toxic reputation.
The Styx was the portal to the underworld, according to myth. Here the gods swore sacred oaths.
"If they lied, Zeus forced them to drink the water, which struck them down. The 8th-century B.C. Greek poet Hesiod wrote that the gods were unable to move, breathe or speak for one year," co-author Adrienne Mayor, a research scholar at Stanford University's Departments of Classics and History of Science, told Discovery News.
Another account by the Greek geographer Pausanias (110 to 180) reported that the river could ruin crystal, pottery and bronze. "(The) only thing able to resist corrosion is the hoof of a mule or horse," he wrote.
"Indeed, no ancient writer ever casts doubt on the existence of a deadly poison from the Styx River," Mayor, author of the Mithradates biography, "The Poison King," said.
The researchers believe this mythic poison must be calicheamicin. "This is an extremely toxic, gram-positive soil bacterium and has only recently come to the attention of modern science. It was discovered in the 1980s in caliche, crusty deposits of calcium carbonate that form on limestone and is common in Greece," author Antoinette Hayes, toxicologist at Pfizer Research, told Discovery News.
Now called Mavroneri, "Black Water," the Styx originates in the high mountains of Achaia, Greece. Its cold waters cascade over a limestone crag to form the second highest waterfall in Greece.
"Unfortunately, the geochemistry of the river has not yet been studied by modern scientists; therefore, there is no scientific data to support the plausible and interesting calicheamicin theory," Walter DAlessandro, hydro-geochemist at the Italian National Institute of Geophysics and Volcanology in Palermo, told Discovery News.
Whether Alexander really died from poisoning, as some of his closest friends believed, is pure speculation, Mayor and Hayes concede.
"We are not claiming that this was the poison that killed Alexander, nor we are arguing for or against a poison plot," Mayor said.
"However, such a sacred poison, used by the gods, would be appropriate for Alexander, who was already being thought of as semi-divine," she added.
Alexander fell ill at one of many all-night drinking parties in Babylon, in modern Iraq, crying out from a "sudden, sword-stabbing agony in the liver." The overlord of an empire stretching from Greece to India, was taken to bed with abdominal pain and a very high fever.
Over the next 12 days, he worsened. Alexander could only move his eyes and hands and was unable to speak. He later fell into a coma.
Alexander was pronounced dead on June 11, 323 B.C. — just before his 33rd birthday.
Retrodiagnoses for his mysterious death have included poisoning, heavy drinking, septicemia, pancreatitis, malaria, West Nile fever, typhoid, and accidental or deliberate poisoning (hellebore, arsenic, aconite, strychnine).
"Notably, some of Alexander's symptoms and course of illness seem to match ancient Greek myths associated with the Styx. He even lost his voice, like the gods who fell into a coma-like state after drinking from the river," Mayor said.
The poisoning diagnoses were rejected by many experts because few poisons induce fever. Furthermore, even fewer such poisons were available in Alexander's time.
However, naturally occurring calicheamicin, which is extremely cytotoxic, could still be the culprit.
"Cytotoxins cause cell death and induce high fever, chills, and severe muscle and neurological pain. Therefore, this toxin could have caused the fever and pain that Alexander suffered," Hayes said.
According to Richard Stoneman, the foremost expert on the myths of Alexander, the theory offers a good explanation for the Styx's ancient reputation.
"I personally think that Alexander probably died of natural causes — either typhoid or an overdose of the hellebore used to treat his illness — but other views are possible," Stoneman, author of "A Life in Legend: Alexander the Great," told Discovery News.