It was almost as if nature had invented a biological sleeping agent to combat the wishes of ambitious men.

From The Illustrious Dead by Stephan Talty. Page 33.  An early appearance of typhus in warfare.

In 1527 the forces of King Francis (bolstered by a contingent from Henry VIII) met Charles’s mercenary army at the Italian port city of Naples, the French army with 30,000 men, the Imperial army of Charles with 12,000. If Francis could destroy the army inside the walls, Spain’s power, so dominant for so long, would be broken at least for the near future and perhaps for centuries.

But then a pathogen appeared in the ranks and began to kill wantonly. “There originates a slight internal fever in the person’s body,” wrote one ambassador, who later died of the illness, “which at first does not seem to be very serious. But soon it reappears with a great fervor that immediately kills.” It was the same inscrutable microbe that had emerged at the Spanish siege of Granada.

Bodies began to pile up. The Italian sun beat down on men who had fallen into stupors or raving fevers. Each day brought more cases, and soon the sick began to die in terrible numbers. “The dangers of war are the least we have to think about,” wrote one commander. The French lieutenants, convinced the air in the plain had turned bad, urged their commander to retreat to the hills, where the atmosphere was cooler and fresher. But he refused and the epidemic “literally exploded.” Desertions increased; men faked illness to get out of the death zone. Out of a force of 30,000, only 7,000 were fit for duty. Soon two out of every three of the soldiers had died, most of them from the nameless pathogen.

At the end of August, the French forces broke from their camps and fled in panic, leaving their artillery and their sick comrades behind. The siege was broken. Charles’s forces ran them down on the road from Naples to Rome, stripping, robbing, and killing the remnants. “Without a doubt,” one observer wrote, “one would not find in all of ancient and modern history so devastating a ruin of such a flourishing army.” Francis’s men were skeletal, sick, some of them clothed only in tree leaves. The disease claimed more on the way and bodies could be seen heaped on the side of the road. Of the 5,000 who started the retreat, perhaps 200 arrived safely in the holy city; from there, some French troops were forced to walk all the way back to their native land.

The effects unspooled for years. Spain dominated the Continent, King Francis was humiliated and France radically weakened. Pope Clement VII rejected Henry VIII’s petition for divorce as a direct result of the defeat. Infuriated, the king broke with Rome and led his country into the Church of England.

Even today, a believer kneeling to pray in a High Anglican Church worships, at least partly, in a structure built by an invisible microbe.

The conflict revealed crucial aspects of the epidemic disease: It seemed to need large groups of people to thrive. It left dark spots on the torsos of many of its victims, sparing the hands and face (making it harder to detect in men who wore full uniforms). It had a terrifying mortality rate, up to 95 percent, among the highest of any epidemic disease known to humankind. And it had a decided predilection for war. It was almost as if nature had invented a biological sleeping agent to combat the wishes of ambitious men.

Nearly three hundred years after the siege of Naples, Napoleon reclaimed Francis’s sword after conquering Spain and brought it back to Paris in glory. He’d revenged the monarch’s humiliation. And now Napoleon imagined he was about to embark on a war that would share in the same codes of war.