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In 1392, the King of France rode out of a forest near Le Mans, killed four of his own knights, and had to be wrestled to the ground by his uncle. He was twenty-three. He had been on the throne for twelve years. He would remain on it for another thirty.

Charles VI of France, called the Beloved by his people and the Mad by history, suffered the first documented episode of what would become a lifelong illness in that forest. There would be more than forty further attacks over the next three decades. He would, at various points, fail to recognize his own wife, refuse to bathe for months, and run through the corridors of his palace howling like a wolf. He would also, famously, become convinced for a period that he was made of glass — and have iron rods sewn into his clothing to prevent himself from shattering.

The court physicians of medieval France could do nothing for him. 

Six hundred years of subsequent diagnosis has only recently done much better.

In June of 323 BCE, Alexander the Great died in Babylon. He was thirty-two.

He had taken the known world from the Adriatic to the Indus in a decade. He had crossed two continents at the head of an army. He had survived a near-drowning in an icy river, a stone to the head, and an arrow through the lung. And then, over the course of eleven or twelve days, a fever did what no army had managed. The most powerful man on earth was dead before his next campaign began.

We have several accounts of those final days, written by historians who were not there. We have a strange chain of rumors about poisoning, a court full of plausible suspects, and a body that — according to one source — did not begin to decompose for six days.

The suspects are ancient. The arguments are not. 

In the summer of 430 BCE, something horrific tore through Athens.

The city was at war with Sparta, packed beyond capacity with refugees from the countryside, and entirely unprepared for what came through its gates next. Within four years, perhaps a quarter of the population was dead, including the man who had led Athens into the war. We have an eyewitness account of the disease from Thucydides, who caught it himself, and survived to write it down. 

We have, in the last twenty years, fragments of DNA recovered from a mass grave of its victims.

However, we still cannot agree on who, exactly, was the killer.

This episode walks through the candidates: typhus, typhoid, measles, and a few stranger guesses — and asks what the evidence will and will not let us conclude. One of them has been the leading suspect for almost a century. One of them has direct molecular evidence behind it. They are not the same suspect, and that is where the trouble begins.