What made them sick (book excerpt: Solving History's Great Medical Mysteries)

The cause of Alexander's death remains a mystery even today, after over two millennia of scrutiny and speculation. Inconsistencies in the historical record have been, in no small part, responsible for the difficulty in diagnosing his illness. Contemporary accounts of the disorder are long lost, and those secondary accounts that remain were written centuries after the fact. The two most important, by Plutarch and Arrian (lst-2nd century C.E.), are based on the Royal Ephemerides, the so-called "Royal Journals" (journals allegedly written by Macedonian historians during Alexander's lifetime and covering the last ten years of his reign), and on the long lost texts of contemporary historians, Ptolemy and Arisrobolus. These accounts describe a fatal illness lasting eleven days and characterized by fever, progressive weakness, loss of the power of speech (aphonia) and death. According to Plutarch and Arrian, the illness began suddenly with high fever shortly after heavy drinking at a feast given by Medius, and following another held earlier that same evening in honor of Nearchus, Alexander's naval commander. Plutarch maintained that Alexander did not have pain, as others had written, positing instead that this symptom had been added to the clinical record to render Alexander's death as tragic and as moving as possible.

Diodorus Siculus (lst century B.C.E.) and Justin (3rd century C.E.), the two other principal sources of Alexander's clinical history, maintain that pain was a prominent initial symptom, although they do not mention its location. According to their accounts, it was severe and penetrating in character and began immediately after Alexander had consumed a massive draft of wine, suggesting, at least to Justin, that the wine had been poisoned.

Based on these accounts, it can be concluded with reasonable certainty that Alexander died of an acute illness marked by high fever and progressive weakness with terminal immobility and loss of speech. He might also have had abdominal pain. He had been drinking heavily at the time and most likely for a considerable period before. Although of remarkably strong constitution, he had sustained numerous, severe battle injuries in his lifetime, not the least of which was a hemopneumothorax (blood and air in the chest cavity resulting from a punctured lung) three years prior to his terminal illness. During the same campaign in which he received these wounds, he was exposed to, and more than likely contracted, an argosy of communicable diseases including both malaria and dysentery. A little less than a year before his own death, Alexander's friend and lover, Hephaestion, died of an acute febrile illness, having at least some of the features of typhoid fever. If Curtius (1st century C.E.) is to be believed, when Egyptian and Chaldean embalmers were summoned several days after Alexander died, they were afraid to approach, so life-like was the body, even though it had languished in the sultry Mesopotamian air for nearly a week.

What could have caused such an illness? In the centuries since Alexander's death, many theories have surfaced. None has been universally accepted, because no diagnosis offered to date has explained all the disparate features of Alexander's illness.

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This next excerpt looks at illnesses that kept Florence Nightingale bedridden for 30 years. She died at 90 of old age complicated by Alzheimer's disease.

The patient was advised to return to England to complete her convalescence, but would not. She was determined to remain with the army until the last soldier left the East for home. She did, however, accept Lord Stafford's offer to recuperate at his summer residence at Therapia, a few miles west of Constantinople. Those who saw her when she arrived described her as emaciated, weak and pale, and looking much older than her 35 years. Her physicians suspected that the extreme exhaustion that lingered long after the fever had subsided "was more from the previous overstrain on mind and body than from the fever [itself]."

By the end of July, she was able to resume her letter writing and to take evening walks on the shore of the Sea of Marmara. Gradually her strength returned, and in August she was able to resume the full rush of her work. Her doctors and friends urged continued rest, but she would not listen. So long as there remained sick and wounded in the Levant to be cared for, she was resolved to continue her work.

At the beginning of October, the patient developed sciatica, followed in late November by earaches, chronic laryngitis, dysentery, rheumatism and insomnia. She began to experience intermittent feelings of despair compounded by the loss of several of her nurses to the fever that had nearly taken her own life. She took their loss hard, knowing they had remained with the army primarily out of devotion to her. And yet, at no time did she harbor even a passing thought of deserting her post. She remained until the end of the war, until the last transport had sailed, working indefatigably at great cost to her own comfort and health, resolved to show that a woman, too, had the strength to suffer and to endure.

To her physical disabilities and crushing workload were added the accusations of an English press growing increasingly critical of the medical and military handling of the war. The army was plagued by organizational chaos and logistical blunders obvious to even the most casual investigative reporter. The army's administrative shortcomings compounded her own problems of supervising a diverse contingent of nurses of varying social status, religion, political loyalty and level of training. Self-doubt and obsession with failure began to intrude increasingly into the patient's thoughts.

When the war finally ended in 1856 and the patient returned to England, her family noted distressing changes in her appearance, personality and behavior. At 36, she had become hardened and aged by illness and exhaustion. She slept no more than two hours a night and complained of persistent fever and lack of appetite. She never left her room and for a month was scarcely off her sofa, feeling then much as she did when recovering from her fever at Balaclava. In spite of these symptoms, her doctors could find no physical evidence of disease and concluded that extreme exhaustion from overwork had taxed every organ to the limit. They believed that rest alone would restore her. That year and the next the patient suffered from insomnia, nausea at the sight of food, irritability, nervousness and varying levels of depression. In August of 1857, when she was 37, she experienced her first attack of severe palpitations and tachycardia.

In September of 1857, following an episode of fever similar to the one she experienced in the Crimea, the patient declared herself an invalid and began limiting her visitors. Within a year, shortness of breath, weakness, syncope, indigestion and flushing of the face and hands were added to her growing list of complaints. In 1861 she developed "nervous tremors" and "spinal pain" so severe she was unable to walk and had to be carried from bed to sofa. For the next six years she was confined to bed.

The patient was seen in consultation by Dr. Charles Edouard Brown-Sequard, the leading specialist in spinal disease of the day, who diagnosed "congestion of the spine" caused by constant worry. He advised rest and a moratorium on the patient's incessant letter writing since her return from the front. However, she was then deeply involved in efforts to reform the army (later nursing), and would not abandon her crusade even at the cost of risking the paralysis Brown-Sequard warned might develop if her spinal congestion were not arrested.

In March of 1862, unrelenting pain caused the patient to long for death, even though she was only 42. She wrote her mother:

Sometimes I wonder that I should be so impatient for death. Had I only to stand & wait, I think it would be nothing -- tho' the pain is so great that I wonder how anybody can dread an operation. If Paget could amputate my left fore quarter, I am sure I would have sent for him in half an hour.

Reprinted by arrangement with ACP Press, American College of Physicians, from Post Mortem: Solving History's Great Medical Mysteries by Philip A. Mackowiak, MD. Copyright 2007 by American College of Physicians. $29.95.