Medical investigators in Virginia and Maryland are engaged in an unusual public tussle over the death of a celebrity patient whose presumed death-by-poisoning has come under growing scrutiny.
It's not often that doctors and medical researchers argue in public over a possible misdiagnosis. But when the patient has been dead for 2,327 years -- and when that patient just happened to have conquered the entire known world by the time he was 25 -- well, the usual courtesies of patient confidentiality can hardly be expected to apply.
So it is that ancient descriptions of Alexander the Great's final days are being scrutinized anew for clues to the Macedonian king's death. Amid a growing consensus that an infectious disease, not poison, was the likely killer, experts have narrowed their focus to typhoid or a brain inflammation caused by West Nile virus -- two competing diagnoses proposed by medical sleuths in Baltimore and Richmond, respectively.
It's a duel of opinions unlikely to be fully resolved. Although historical documents indicate that Ptolemy, the Egyptian general, had Alexander's body preserved in honey and his sarcophagus displayed for many years, the corpse was eventually lost to history. So scientists have no tissues to test for microbial DNA or other clues.
But getting a final answer is not really the point, said John Marr, state epidemiologist for Virginia's Department of Health.
"It's intellectual candy," Marr said of his post-postmortem. "And it's a reminder of how to look at signs and symptoms, which is something that's being lost as the art of medicine is being usurped by electronic messiahs" such as laboratory tests, echocardiograms, scans of various kinds and other modern tools of diagnosis.
The debate began in earnest six years ago when David Oldach and colleagues at the University of Maryland School of Medicine published a report concluding that Alexander had died of typhoid.
The university has a proud history of diagnosing illnesses of the long-dead. A special program there devoted to the practice takes on a new celebrity each year -- concluding in recent years that Beethoven died of cirrhosis and syphilis, and Edgar Allen Poe of rabies.
Oldach's team relied largely on remarkably detailed descriptions of Alexander's death recorded by Plutarch a few centuries after the event. Alexander's medical chart, Oldach determined, would have read something like this: A 32-year-old soldier, widely traveled, with many wives and one son and a history of excessive alcohol consumption, experienced escalating fever, great thirst, profuse sweating and acute abdominal pain soon after returning to Babylon. For two weeks the patient suffered from delirium, loss of voice and increased weakness, gradually progressing to paralysis and death.
In the December 1998 issue of Emerging Infectious Diseases, a journal of the federal Centers for Disease Control and Prevention, Oldach and his colleagues concluded that Alexander's symptoms pointed to typhoid, a life-threatening bacterial disease, transmitted by contaminated food and water, that causes sustained high fevers, can be accompanied by stomach pains and sometimes affects nerves -- possibly accounting for Alexander's paralysis.
Then, in 2002, a group preparing a documentary about Alexander asked Marr to reconsider the evidence for typhoid. Marr read Oldach's paper and was at first inclined to agree with it. "But then I said, 'What the heck. Let's re-look at this thing from a larger scale,' " he recalled.
That meant going beyond the descriptions of Alexander's symptoms to include questions of what was going on at the time around Babylon (near today's Baghdad), including the kinds of plants and animals there and what the landscape and climate were like.
While Marr was doing so, he got a call from a colleague studying West Nile encephalitis, an unusual complication of West Nile virus infection that can cause a polio-like syndrome called flaccid paralysis.
"That made a light flicker in my head," Marr said. "I remembered that Alexander was awake but had to be carried."
Then Marr and fellow epidemiologist Charles Calisher of Colorado State University found a passage in Plutarch's writing that other diagnosticians had not noted.
As a still-healthy Alexander had approached the Western gates of Babylon, something strange happened: A flock of ravens flew erratically overhead, and several fell dead at Alexander's feet.
Marr and Calisher knew that corvid birds, a family that includes ravens and crows, are exquisitely susceptible to West Nile. In fact, finding dead crows in the Bronx in 1999 first alerted scientists that the Old World disease had reached the United States.
They also knew that West Nile was first identified, and probably originated, near Egypt. And they learned that the Western approach to Babylon would have taken Alexander along a swamp -- one probably inhabited by mosquitoes, which transmit West Nile from birds to humans.
No one knows whether the disease existed 2,000 years ago. But when Marr and Calisher loaded all of Alexander's symptoms -- along with the word "ravens" -- into a computer program that diagnoses infectious diseases, the software backed up their intuition: West Nile encephalitis.
Case closed? Hardly.
This month's issue of Emerging Infectious Diseases includes several letters to the editor responding to Marr and Calisher, whose report appeared in the December 2003 issue. Oldach and his colleagues were among the letter writers.
Because Plutarch wrote about events already past, the Marylanders wrote, he had ample opportunity to inject "predictive" signs, including some linked to the then-popular practice of avian augury -- predicting events from bird-related clues. In Plutarch's other writings, they noted, "wild birds perched on the forum" before Caesar's assassination; a flock of crows "pecked the ends of the ropes" as Cicero fled in a ship after Marc Antony's death sentence; and Remus "saw six vultures" shortly before his death.
"Marr and Calisher, perhaps unaware of the magnitude of Plutarch's obsession with avian auguries, have been led down the feathered path," they quipped.
The Virginians took the critique as intended: lightly. Truth is, they had briefly mentioned in their December report the possibility that Plutarch had resorted to a bit of reverse fortunetelling.
If additional research offers convincing evidence that typhoid was, in fact, the cause of Alexander's death, Marr and Calisher wrote in a response to Oldach, the two "are willing to eat Corvus brachyrhynchos" -- the scientific name for American crow.