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Alexander entered Sardis unopposed a few days after his victory on the Granicus, and appointed various satraps to rule Anatolia, under the control of independent boards in charge of taxation.
Some cities were allowed to maintain democratic systems, much like Athens, in exchange for submission to Macedon and monetary support; but the Persian commander Memnon remained on the loose, holed up at Halicarnassus, not far from Rhodes, with the remainder of his army and the Persian fleet on the Aegean. It took a daring assault, in which Alexander was again in risk of losing either the battle or his life, to take the city and give notice that now Darius III had a serious problem in his hands.
Memnon escaped Halicarnassus with the Persian fleet, that he used to cause havoc in the Aegean; he took Chios, and secured an alliance with Sparta as well as an understanding with Athens’ Demosthenes, always up for betrayal, to trigger an anti-Macedonian uprising in the largest Greek city.
However, Memnon died in 333 BC during the siege of Mytilene, and his plans petered out. By that time, Alexander was already marching through Cappadocia, where he was met by the imperial army led by Darius III himself, at a place called Issus by the Mediterranean Sea, near the modern border between Syria and Turkey.
Darius III, who took the time to levy soldiers from every corner of the empire, is unlikely to have gathered fewer than 100,000 soldiers1. This wasn’t as large an army as those raised by his forebears in the Fifth Century BC, since many in the empire were already hedging their bets against a possible Achaemenid defeat.
Still, this was an army that couldn’t be fed for a long period, so the Persians couldn’t simply look for the more favorable terrain for their cavalry. Instead, they chased the enemy, positioned themselves along the route northwest back towards Anatolia, and lined up for battle at a relatively narrow defile. They had the sea on their right, rugged terrain on the left, and the Pinarus River in between the two forces.
This was all the advantage that Alexander, with an army perhaps half the size, needed. Leaving his general Parmenion in command of the center and a small left-wing detachment, he massed his best troops and the Macedonian cavalry on the rugged terrain, under his own command.
The Persians crossed the river and attacked the center and the Macedonian left, leading to an even clash between Greek mercenary hoplites fighting for the Persians and those in the Greek army, while Alexander cut down the Persian left. When he saw an opening, he mounted his horse, Bucephalus, and led a daring cavalry charge towards the exposed position where Darius III himself was leading the battle, from a chariot.
In what may be one of the most striking moments of military history, the Macedonian king, surrounded by his companions, sliced through Persian infantry and cavalry, heading for a singular combat against the Persian emperor. Darius III, who wasn’t cut out for that, jumped off the chariot, threw his royal diadem away, and fled the battlefield on horseback.
A unique chance at high drama had been lost, but a great victory had been won. As the Persian army routed, Alexander took Darius’ wife, two of his daughters and his mother-in-law as prisoners.
News of the defeat, technically the first by a Persian army personally led by the emperor – since Xerxes I didn’t lead the fleet at Salamis himself – shocked the empire. Darius offered a peace treaty that would have made Alexander fabulously wealthy, and king of the lands he had already conquered; Alexander disdainfully responded that he was already king of Asia, and he would be the one making border adjustments.
In a sign of strategic shrewdness, Alexander didn’t immediately press his advantage by aiming straight for Susa. From Issus, it was a relatively short march down the Mediterranean coast to Phoenicia, a key to Persian power that had been weakened by a major rising against Artaxerxes III a few years before2. Alexander’s army soon put Tyre, the largest city in the region, under siege.
This was a smart move because Alexander knew that things back home weren’t all that stable. Both Athens and Sparta remained nests of anti-Macedonian sentiment, and tribes in Thrace also rebelled after the Battle of Issus. Persian fleets sailing from Phoenician ports in support of any anti-Alexander uprising had to be removed from the equation.
Aristotle, meanwhile, enjoyed the most productive years in career in Athens. The story that Alexander's troops took time off from conquering the known world to send rare and fabulous specimens back to Alexander's old teacher, first told by Pliny, appears to have no foundation in fact, like many of Pliny's tales. But Aristotle's experiments and observations, while only a small part of the prehistory of science3, help to explain why Aristotle has such an exalted position in the modern pantheon of philosophers.
Additionally, his experience with Alexander and the Macedonians informed Aristotle’s theory of causality, which proposes four causes for any given fact. This is a helpful tool for studying political events and is superior to simpler, later notions that economic interests (“material cause” in Aristotelian jargon) can explain everything – a fact that Aristotle, who spent much time among the economically backward but bellicose and consistently successful Macedonians, understood from a very early age.
The Macedonian regent in Greece, Antipater, was left to handle a revolt of Agis III, king of Sparta, who saw in Alexander’s Asian campaign the long-awaited chance to take back control over the Peloponnese after the disastrous defeats at Leuctra and later at Mantinea.
With Persian gold that funded an army 20,000 strong, Agis secured many allies but no help from Athens, which remained under Antipater's control. Greece was not stirred.
Quintus Curtius Rufus (in the 1st century AD) provides a colorful breakdown of the Persian forces in his History of Alexander (3.2.1-10 and 4.11.6-13): “The Medes had 10,000 horsemen and 50,000 foot-soldiers. Among the Barkanians there were 200 horsemen armed with double-edged axes and small shields closely resembling the cetra [i.e. Spanish shields]. They were followed by 10,000 foot-soldiers armed in the same manner as the horsemen. The Armenians had sent 40,000 foot-soldiers, besides 7,000 horsemen. The Hyrkanians had mustered 6,000 as excellent horsemen as those descent groups (gentes) could furnish, as well as 1,000 Tapurian horsemen. The Derbikians had armed 40,000 foot-soldiers, most of whom carried spears tipped with bronze or iron, but some had hardened the wooden shaft by fire. These were also accompanied by 2,000 horsemen from the same descent group. An army of 8,000 foot-soldiers and 200 horsemen had come from the Caspian sea. With these were other less known descent groups that had mustered 2,000 foot and twice that number of horsemen. Another 30,000 Greek mercenaries who were excellent young soldiers were added to these forces. However, Darius’ hurried approach prevented him from calling in the Bactrians, the Sogdians, the Indians, and others living near the Red sea [including what we now call the Indian Ocean], whose names were unknown even to Darius himself. The one thing that Darius did not lack was soldiers.”
That supposedly led to the self-immolation of up to 40,000 people in Sidon during its siege by the Persians.
Here, it's worth remembering that the idea of natural selection began as a just-so story, more than two millennia before Darwin, partly thanks to Aristotle. Darwin belatedly learned this when, a few years after the publication of “On the Origin of Species,” in 1859, a town clerk in Surrey sent him some lines of Aristotle, reporting an apparently crazy tale from Empedocles. According to Empedocles, most of the parts of animals had originally been thrown together at random: “Here sprang up many faces without necks, arms wandered without shoulders . . . and eyes strayed alone, in need of foreheads.” Yet whenever a set of parts turned out to be useful the creatures that were lucky enough to have them “survived, being organized spontaneously in a fitting way, whereas those which grew otherwise perished.” In later editions of “Origin,” Darwin added a footnote about the tale, remarking, “We here see the principle of natural selection shadowed forth.”