By Philip A. Mackowiak, MDIn the January issue of the journal Clinical Toxicology, investigators at the University of Otago in Dunedin, New Zealand and the University of Birmingham, United Kingdom offer yet another theory as to the cause of the untimely death of Alexander the Great just prior to his 33rd birthday. Their article has generated considerable chatter over the internet. In it, they propose that Alexander was poisoned by wine laced with an extract of Veratrum album (white hellebore). They base their theory on the fact that of all of the poisons proposed to date as Alexander’s killer, none is as likely as white hellebore to produce the symptoms Alexander is purported to have manifested during his 11-day terminal illness –“sudden epigastric and substernal pain accompanied by nausea and vomiting, followed by bradycardia and hypotension with severe muscular weakness.”
Poisoning, in fact, was one of the earliest explanations for Alexander’s sudden demise. Of the possible assassins, Antipater had, perhaps, the most to gain from the king’s murder and thus, was an early suspect. He had consolidated a position as regent of Macedonia during Alexander’s absence in the East and likely feared for his own safety given the scores of officials who had lost their posts and their heads on Alexander’s return from India. According to the poison theory, Antipater was assisted in the murder by Aristotle, who feared for his own life after his nephew, Calisthenes, had been implicated in an earlier assassination plot. The poison was reputed to have been so toxic that it had to be transported to Babylon in the hoof of an ass. Antipater’s son, Cassander, was said to have conveyed it to the king’s court, where it was administered to Alexander by his taster, Iolaus, at a banquet hosted by Medius.
Although both Arrian and Plutarch were skeptical of the poison theory, it deserves consideration, if for no other reason than many, like Antipater, would have welcomed Alexander’s death in 323 B.C. Alexander had offended many of his fellow Macedonians by adopting the dress and customs of the vanquished Persians. His plans for yet another campaign around the horn of Arabia and along the coast of North Africa must have been greeted with alarm by his exhausted army. By the time of his death, he had become neurotically suspicious of independent achievement. Moreover, his claim to be the son of Zeus-Amon was abhorrent to the Macedonians, not just because of the absurdity of his pretension of divine status, but also because it was an insult to the memory of Philip, their former king. And perhaps most important, Alexander was surrounded by an extremely able and ambitious staff, each eager for his own share of the empire. Thus, the possibility that Alexander was murdered, poisoned in fact, cannot be dismissed easily.
Unfortunately, the historical record contains varying descriptions of Alexander’s signs and symptoms during his terminal illness. Plutarch, for example, maintained that Alexander had no abdominal pain, as others had written, positing instead that the symptom had been added to the clinical record for the purpose of rendering the king’s death as tragic and as moving as possible. In those accounts in which abdominal pain is mentioned, its precise location is not given. Therefore, we cannot be certain that Alexander had the “epigastric and substernal pain” that is characteristic of poisoning with white hellebore. Likewise, neither nausea nor vomiting is mentioned in any of the accounts, and, of course, although Alexander’s physicians likely monitored his pulse, their records contained no observations that might enable us to recognize “bradycardia and hypotension” as a feature of the king’s final illness. In fact, fever is the only feature of the illness that is consistent throughout the historical record. Fever was one of Alexander’s earliest complaints. The first day of the illness it was severe enough that Alexander retreated to his bath house for relief and spent the night there. The next day, the fever seemed to subside only to return that evening and then increased steadily throughout the illness.
Fever is not a cardinal feature of arsenic poisoning, hellebore poisoning or any of the other poisons that Alexander’s associates might have used to kill him. Although there is no way to know for certain what killed Alexander, his clinical picture was much more consistent with an infection, one dominated by fever, a fever so debilitating that it rendered a man of legendary stamina and strength too weak to raise his head as his troops filed by his bed in silent review – typhoid fever, for example.
Philip A. Mackowiak is Professor and Vice Chairman, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. He is author of Diagnosing Giants: Solving the Medical Mysteries of Thirteen Patients Who Changed the World.
Images: (1) Alexander the Great, Ny Carlsberg Glyptotek, Copanhagan, Denmark, by Michiel2005. CC BY-NC 2.0 via Flickr. (2) The Death of Alexander the Great after the painting by Karl von Piloty. Public Domain via Wikimedia Commons.