did poison from the styx kill alexander the great?

THE DEADLY STYX RIVER OF GREEK MYTH
DID POISON FROM THE STYX KILL ALEXANDER THE GREAT?
Adrienne Mayor Research Scholar, Classics & History of Science, Stanford, [email protected]
Antoinette Hayes Toxicologist, Pfizer Research, [email protected]
Myth: The Styx, River of Hades
At the gloomy River Styx, portal to the Underworld, the gods swore sacred oaths. If they lied, Zeus
forced them to drink the water, which “struck them down with an evil coma. They were unable to
move, breathe, or speak for one year.” (Hesiod, ca 750 BC)
Charon crossing the Styx, oil on wood, Joachim Patinir
Water from the Styx (identified as the Mavroneri River in Greece, see below) was said to be deadly to
mortals. “Its lethal power was first recognized after goats tasted the water and died,” wrote Pausanias
(ca AD 170). “It dissolves crystal and pottery and corrupts bronze, lead, tin and silver vessels. The only
thing able to resist corrosion is the hoof of a mule or horse. I have no actual knowledge that this was
the poison that killed Alexander, but I have certainly heard it said.”
Alexander’s Mysterious Death in Babylon, 323 BC
At one of many all-night drinking parties in Babylon (in modern Iraq), Alexander’s companions heard him
cry out from a “sudden, sword-stabbing agony in the liver.” The conqueror of the known world took to bed
with abdominal pain and very high fever. He never recovered. Over the next 12 days, he worsened, moving
only eyes and hands, unable to speak; paralysis followed by deathlike coma. Alexander was pronounced
dead on June 11, just before his 33rd birthday. Various theories for cause of death have been proposed:
heavy drinking, septicemia, pancreatitis, malaria, West Nile fever, typhoid—and accidental or deliberate
poisoning (hellebore, arsenic, aconite, strychnine).
Legendary Styx Poison Suspected
Death of Alexander the Great, Karl Theodor von Piloty
Alexander’s closest friends believed that his enemies (many had motives) murdered him with poison.
Some suspected “the icy cold exudation or dew, gathered from the mossy rocks at the high Styx waterfall,”
carried to Babylon sealed in a mule’s hoof. Some of Alexander’s symptoms seem to match ancient Greek
myths about the Styx—he even lost his voice, like the gods. (Arrian, Plutarch, Diodorus, Justin)
Naturally Occurring Deadly Toxin?
The Styx (now called Mavroneri, “Black Water”) originates in the high limestone mountains of Achaia,
Peloponnese. “Plunging over jagged mountains, the cold water of the Styx cascades” over a limestone
crag to form the highest waterfall in Greece (200 meters, 650 feet). In modern times, locals avoid
drinking the water and say it corrupts vessels.,
Achaia
Consistent ancient literary evidence suggests that something in the Styx/Mavroneri gave rise to its
poisonous reputation. The stream probably contains corrosive or caustic minerals that eat metal and
other materials. These conspicuous effects, observed in antiquity, made the water undrinkable.
Styx/Mavroneri Falls, Mt Helmos, Achaia, photo by R. Pone
But the Styx may have hosted soil-derived killer bacteria as well. We suggest that the “mythic” poison
from the Styx was a powerful bacterium new to modern science: calicheamicin. A secondary metabolite of an extremely toxic, gram-positive soil bacterium (Micromonospora echinospora), calicheamicin
was discovered in the 1980s in caliche, crusty deposits of calcium carbonate that form on limestone.
Naturally occurring calicheamicin is extraordinarily potent—one of the most
cytotoxic substances known (cellular lethality greater than that of ricin or cyano morpholinyl anthracycline, Lode et al. 1998). A small amount causes irreparable double-strand breaks in DNA and apoptosis (genetically programmed
cell death), and could lead to massive organ failure (liver, heart, kidney, bladder, lung, nervous system), and death. Cytotoxic agents attack rapidly dividing cells (bone marrow, intestinal epithelium,
hair follicles, epithelial cells of trachea and esophagus); symptoms include severe pain, weakness, fatigue, swelling of mouth and throat. Death would likely be imminent as there is no antidote once a lethal dose is ingested.
Caliche
Conclusion
Although scientists have not yet looked for calicheamicin in Greece, caliche is common in Greece’s arid, limestone-dominated
landscape, sometimes encrusting moss/lichen. (Higgins and Higgins 1996; Clendenon 2009) We propose 3 hypotheses:
•Calicheamicin was present in the Styx region in antiquity
•Its poisonous effects were observed in antiquity
•Alexander’s death appeared to some to be caused by this poison
We may never know the real cause of Alexander’s death. If he was poisoned, the agent may have been an easily available
plant such as aconite, rather than calicheamicin scraped from Stygian limestone in Greece and transported to Babylon. Yet,
just as Alexander’s friends believed his symptoms fit those of fabled Styx poisoning, it’s interesting to compare Alexander’s symptoms to the deleterious
effects of calicheamicin, which is 1,000 to 10,000 times more toxic to normal cells than any known substance.
The rumor that an “icy cold poison gathered from the rocks of the Styx waterfall” killed Alexander may have had a basis in scientific fact.
For details and references, see our working paper: http://www.princeton.edu/~pswpc/papers/authorMZ/mayor/mayor.html