Alexander the Great's Mysterious Death: Poisoned wine or Intestinal Bug?

A history resource article by Mary Harrsch © 2015

Head of Alexander the Great photographed at
The Capitoline Museum in Rome, Italy by
Mary Harrsch  © 2005.

I noticed that a program entitled "Alexander the Great's Mysterious Death" on the Discovery Channel put forward the hypothesis that Alexander died from an accidental overdose of hellebore, a poisonous plant used to induced vomiting in ancient times.

[Alexander the Great, Photographed at the Capitoline Museum, Rome, Italy by Mary Harrsch © 2005 ]

Back in 1998, however, a group of doctors gathered for a clinical pathology conference at the University of Maryland Medical Center expressed their belief that Alexander was killed by an intestinal bug:

Alexander the Great, who ruled much of the ancient world until his death in 323 B.C., was conquered at age 32 not by an enemy, but possibly by a tiny intestinal bug. In an analysis based on available historical records, physicians at the University of Maryland Medical Center believe that Alexander was the victim of typhoid fever.

Their analysis, titled, "A Mysterious Death," is published in the June 11 issue of the New England Journal of Medicine. The most popular theories among historians previously have been that Alexander was poisoned or had died of malaria.

In the week before he died, historical accounts say Alexander the Great had chills, sweats, exhaustion and high fever, all of which are typical symptoms of certain infectious diseases, including typhoid fever.

"He was also described as having severe abdominal pain, causing him to cry out in agony," says David W. Oldach, an infectious disease expert at the University of Maryland Medical Center and lead author of the article.

"That was an important clue, because untreated typhoid fever can lead to perforation of the bowel and may have been the reason for his abdominal pain," according to Dr. Oldach, who is also an assistant professor of medicine at the University of Maryland School of Medicine.

"My discussions with Dr. Oldach and his colleagues caused me to change my mind about what caused the death of Alexander the Great," says Eugene N. Borza. Ph.D., professor emeritus of ancient history who taught for 31 years at Penn State University. Dr. Borza, who is also an author of the New England Journal article, previously thought that malaria caused Alexander's demise.

A curious symptom described in ancient accounts is that Alexander's body did not begin to decay for at least several days after his death. Dr. Oldach says while that defies reason, those around him may have gotten that impression because of another complication of typhoid fever, called ascending paralysis. It is a neurological problem that starts with the feet and moves up the body, paralyzing muscles and slowing down breathing. It can make a person look dead, even if he is not. Alexander may have been in that state for a few days before he died.

The death of Alexander the Great.  Courtesy of History.com.

 Accounts of the death were not consistent with poisoning, although Dr. Borza says that has been a popular belief. "It was an ancient conspiracy theory. People have often suspected a conspiracy when a famous young person dies unexpectedly." Dr. Borza says ancient Greeks who didn't succumb to disease as a child or a battlefield wound often lived into their 70's, because of a healthy diet and constant physical activity.

The New England Journal of Medicine article is believed to be the first collaboration between medical scientists and an historian to answer an ancient question about what caused a famous historical figure to die. Dr. Borza says the earliest surviving accounts about Alexander's death available today were written three centuries after he died, so there was not a lot of information to go on.

"Even so, we found out that much of the scant information we do have is credible, because it makes sense to the medical community. It is important for us to be able to validate the evidence and set the record straight. As historians, that's what we try to do," says Dr. Borza.

For his analysis, Dr. Oldach also had to rely on historical medical accounts of what happens when typhoid fever goes untreated with antibiotics, which did not become available until the 1950's. U.S. physicians today rarely witness untreated patients in the late stages of typhoid fever.

Typhoid fever comes from salmonella typhi, an organism that lives only in humans and can be spread by contaminated water or because of poor hygiene.

Update: 2/18/2015:  

In January 2014 an article was published in the Journal of Clinical Toxicology.  Co-authored by the University of Otago 's Dr. Leo J. Schep, from the National Poisons Centre in New Zealand, the researchers theorized that Alexander was killed by a toxic wine created using a fermented form of Veratrum album (also known as white hellebore) sometimes used to induce vomiting.  The study's authors detailed the potential deadliness of the plant in the study abstract:

"Veratrum album flower" by Alpsdake.
Courtesy of  Wikimedia Commons.

Veratrum poisoning is heralded by the sudden onset of epigastric and substernal pain, which may also be accompanied by nausea and vomiting, followed by bradycardia and hypotension with severe muscular weakness.

"Exposure to extracts from this plant causes clinical effects similar to [Alexander's] reported signs and symptoms," Schep observes, "Of note was the duration of symptoms, which could continue for more than 12 days if intoxicated patients are not treated."

Personally, I think the analysis by the pathologists in Maryland appears more credible (to me) since they evaluated the overall reported symptoms as detailed in fragments of the ancient sources rather than focus on the relatively immediate reactions Alexander experienced at a banquet with his generals that has long been viewed historically as suspect.  If Alexander's digestive tract was  already severely compromised (by a pathogen like typhoid), his consumption of normal wine at the banquet  could have triggered an acute episode of abdominal distress. Without his remains, however, I guess we will never know!

Mary Queen of Scots Miscarriage Points to Collusion in Death of Lord Darnley

Mary Queen of Scots at Madame Tussaud's Wax Museum in
London.  Photographed by Mary Harrsch © 2006

A history resource article by Mary Harrsch © 2015

Interesting article in the Times Online about research by modern gynecologists:

"Mary Stuart, Queen of Scots, was an “adulteress and liar” who plotted to kill her husband in order to marry her lover, a study by modern gynecologists has suggested.

An intriguing medical analysis claims that Mary, the cousin of Elizabeth I, concocted a story of kidnap and alleged rape to justify her marriage to her third husband – potentially shedding light on a 400-year-old royal murder mystery.

Far from being the saintly and wronged Roman Catholic monarch portrayed in portraits and films, Mary was actually a “moral loose cannon”, whose striking beauty and sex appeal gave Elizabeth other reasons to imprison and execute her, the researchers suggest.

The study revolves around the report by Claude Nau, Mary’s adviser and secretary, that on July 24, 1567, at Loch Levan Castle, Kinross, Mary miscarried twins. Information about the miscarriage is scant, but in May 1567, just 12 weeks after the murder of Mary’s second husband, Lord Darnley, the Scottish Queen married James Hepburn, fourth Earl of Bothwell, who had abducted and “ravished” her at Dunbar Castle, in April, some sources say.

Henry Stuart (Lord Darnley) with his wife/cousin, Mary Queen of Scots circa 1565
by unknown artist.  Image courtesy of Wikimedia Commons.

Mary later claimed that her pregnancy began after her marriage but experts now say this is impossible.

In a study published in the Journal of Family Planning and Reproductive Healthcare, Lesley Smith, a medical historian, claims that it would have required modern microscopes and knowledge about fetal development to identify that the miscarriage was of twins after the seven weeks of pregnancy that Mary claimed.

It would also have been an “astonishing coincidence” if conception occurred at the time of the “rape”, and even then the twins would have been just 12 weeks old and hard to identify upon miscarriage.
Instead, it is more likely that “the widowed Mary had an affair with Bothwell, became pregnant and had used the abduction story as a cover for her condition and justification for marriage,” Ms Smith says.

Along with other historians, she believes both Mary and Bothwell to have been implicated in the death of Darnley, a drunken and controversial figure who was found strangled at Kirk O’Fields, Edinburgh, after being married to Mary for just 19 months.

Bothwell was a prime suspect but was acquitted at what is now regarded as a sham trial.

James Hepburn, the 4th Earl of Boswell c. 1535-1578.
Image courtesy of Wikimedia Commons.

“Mary had an undoubted passion for Bothwell, her supposed kidnapper, and did not try and escape from him despite ample opportunity. By contrast, she hated Darnley and was publicly separated from him by the time of his murder. The suspicion of an affair is not a new idea,” Ms Smith says, “but the medical evidence brings us very much closer to the likely truth.”

Tony Roberts, a consultant obstetrician at Queen’s Hospital, Burton on Trent, says that it would have required “a sensible and weathered eye” to identify a twin miscarriage at 12 weeks.

“If you want to prove pregnancy, a midwife in those days should have been able to do this, but standards were low, even for a queen,” he adds.

As such, Claude Nau’s report of the miscarriage implies that Mary became pregnant by Bothwell well before the abduction. The unlikely possibility that Darnley was the father would have left the Queen at least five months pregnant with the twins, a condition which would have been “hardly unnoticeable”, Ms Smith says.

The researcher, who is the curator of Tutbury Castle in Staffordshire, where Mary was held prisoner, says her theory further explains the animosity between Mary and Elizabeth I.

Remains of Tutbury Castle in Staffordshire, England where Mary Queen of Scots
was held prisoner.  Image courtesy of Wikimedia Commons.

“Mary Stuart was a remarkable specimen of humanity,” she writes. “She was 5 ft 11 in when the average woman was around 4 ft 11 in, so she was the equivalent of 6 ft  5 in by modern standards. [She] was also beautiful and very sexually attractive. “All in all, Mary Queen of Scots was a very dangerous creature to the unmarried Protestant Elizabeth, and her physical presence made her positively intoxicating to anyone who met her.”

She said: “All the available evidence creates a damning impression. Elizabeth probably considered Mary to be a moral loose cannon and fool for men. It is also interesting that, while Mary was prisoner in England there was no Catholic nation that made a serious attempt to release her: was there a more widely held view that she was better out of the way?”

Queen of plots

December 1542 Mary born to James V of Scotland. Her father dies when she is six days old and Mary becomes Queen of Scotland

1548 Henry VIII begins his “rough wooing” — a military campaign designed to impose marriage to his son on Mary. Instead she promises to marry the French Dauphin and flees to France

1559 Marries François II

1561 She returns to Scotland following François’s death

1565 Marries Henry Stuart, Lord Darnley, her first cousin, below. Their son, James I of England, is born the following year

February 1567 Darnley found dead. James Hepburn, 4th Earl of Bothwell, bottom, is prime suspect

April 24 1567 Mary visits her son for the last time at Stirling but is abducted by Bothwell and taken to Dunbar Castle, where she is allegedly raped

May 15 1567 She marries Bothwell, a Protestant, to preserve her honour, but is condemned by the Scottish nobility

July 24 1567 Imprisoned at Loch Levan Castle by her own people, she miscarries twins and is forced to abdicate the Scottish throne

May 1568 Mary escapes but is defeated at Battle of Langside and flees to England, where she is captured and spends the next 19 years as a prisoner

1578 Bothwell dies, insane and imprisoned in Denmark

1587 Mary is found guilty of treason and executed.