The Tale of the Dueling Neurosurgeons

by Sam Kean

  Ever obsessive, Vesalius agonized over every detail of Fabrica, including what paper and font to use, and he crossed the Alps from Italy to Switzerland to oversee its printing. For the first bound copy, he found another artist to hand-paint the drawings and, after cladding the book in purple silk velvet, carried it farther north and presented it to the Holy Roman Emperor, Charles V. It was June 1543, and in a remarkable coincidence, Nicolaus Copernicus had published On the Revolutions of the Heavenly Spheres a week before. But whereas On the Revolutions, written by a seventy-year-old astronomer, demoted human beings from the center of the cosmos, Fabrica, written by a twenty-eight-year-old anatomist, elevated us, celebrating us as architectural marvels. This near-pagan glorification of the body didn’t please everyone, not even some anatomists, who vilified Vesalius and demanded that he retract every criticism of Galen. (Vesalius’s former mentor smeared him as Vesanus, Latin for “madman,” with a pithy anatomical pun attached to its posterior.) Being ignorant of medical matters, Charles V adored Fabrica and promoted Vesalius to court physician.

  By 1559, though, Charles had died, and Vesalius found himself serving in the court of Charles’s son, the cold and remote Philip. He spent most days treating nobles for gout and VD and bowel obstructions, with little time for original work. So when word of Henri’s disastrous joust arrived, Vesalius jumped, dashing down to Paris on a relay of mail carriages, covering two hundred miles in forty-eight hours.

  He soon met Paré, and modern neuroscientists sometimes bite their knuckles at the thought of this encounter—two titans, meeting at last! They’d actually almost met before, in 1544, near Saint-Dizier, when the army Vesalius was serving with laid siege to Paré’s army. This time around, any “combat” would be mano a mano, and these two proud and ambitious men likely circled each other, sizing the other up. But they had little time to waste in posturing.

  If contemporary sketches are accurate, the king’s bedchamber had deteriorated into a zoo. Dogs ran about, apothecaries chopped up herbs and mummy bits at the foot of the bed, and courtiers circled like vultures, interrupting Henri’s rest. Henri lay on a four-poster bed with sumptuous blankets and a nude bust perched above the headboard. Case notes report that his face had swelled grotesquely, and his neck had stiffened like old French bread. His left eye could still see, but the lance had blinded the right and exposed the bone around the socket; the pus-stained bandage there surely clashed with the silk pillows. Given modern knowledge of brain trauma, we can surmise that Henri had a metallic taste in his mouth. Worst of all he could no doubt feel some dim black thundercloud, a massive headache, throbbing in the back of his skull. In his lucid moments, Henri gamely conducted state business, dispatching letters, arranging for his sister’s marriage to proceed, even condemning some Lutheran scum. But as his brain swelled and the headache spread, he grew confused, and his vision came and went. He slept fitfully, and asked repeatedly for soothing music, which was never denied him, and for Diane, who was.

  Miraculously, Paré and Vesalius found no fractures on Henri’s skull, not even a hairline crack. (Since ancient times, doctors had a few ways of searching for cracks. They might dab ink on the top of the head and watch whether it seeped through, or they might thwack the skull with a stick and listen, since cracked and intact skulls sound different, much like cracked and intact bells do.) Many court physicians rejoiced at this news and proclaimed that Henri would therefore live: like most doctors then, they believed that the brain could not suffer any serious damage in the absence of a skull fracture, much like an egg yolk can’t be damaged without the shell being cracked. (Some jurisdictions didn’t even recognize a blow to the head as murder unless it broke the skull.) And admittedly, skull fractures did look bloody awful, much more sickening than nonfractures, so the reasoning made some sense.

  Vesalius and Paré reasoned differently. Upon meeting the king, Vesalius produced a white cloth and asked Henri to bite down on it. Rather irreverently, he then ripped it from the royal mandible. Henri’s body convulsed, his hands shot to his head, he howled in pain. You can imagine the sound of a dozen swords being unsheathed at this affront, but the stunt convinced Vesalius that Henri would die. The author of Fabrica knew better than anyone how delicate the brain is—you can scoop it with a spoon, like ripe avocado—and long experience told him that people with pain so intense usually didn’t survive.

  For his part Paré drew on battlefield experience. Not infrequently a soldier beaned by a shell or cannonball would betray no external symptoms—he might not even bleed. But his mind would wax and wane, and his brain would soon shut down. To probe this mystery, Paré would perform a quick autopsy. Autopsies were rare and usually illegal back then, but such laws were relaxed on the battlefield. And when Paré did his furtive autopsies, he often found swollen and bruised and sometimes even dead tissue inside these brains—signs of a controversial new diagnosis called a concussion. Paré had also seen cases where the head took a blow on one side but the brain damage was concentrated on the opposite side—a so-called contrecoup injury. These were in fact often the deadliest injuries. So in a prediction to outdo even Nostradamus, Paré suggested that Henri’s brain had suffered a mortal contrecoup concussion, with damage localized in the back. Each man drew on different expertise in judging the king a goner, but they both disregarded the ancient imperative about gory head injuries necessarily being the worst. Instead of focusing on fractures and blood loss, they focused on the brain alone.

  As for actual treatments, they discussed trepanning the king’s skull to remove any excess fluids and “corrupted” blood, but the risks outweighed the benefits, and they gave the idea up. In the meantime they examined the heads of the decapitated criminals. History doesn’t record the exact methodology here—whether someone fixed each head inside a vise to provide a stable target, or perhaps strung the noggins up like piñatas to swing at—but Montgomery’s lance stump got quite a workout battering their mugs. It was a macabre mix of medieval brutality and modern experimental savvy, and Paré and Vesalius eagerly examined the targets for clues. Alas, the heads offered little inspiration for treatment.

  The two men could have learned a lot more by simply observing the king, whose suffering foreshadowed many great discoveries over the next four centuries of neuroscience. Henri continued to drift in and out of coherence, limning the borders of the unconscious. He suffered from seizures and temporary paralysis, two then-mysterious afflictions. Strangely, the paralysis or seizures would derange only half of his body at any one time, a clear hint (in retrospect) that the brain controls the body’s halves independently. Henri’s vision also went in and out, a clue that the back of the brain (where Paré expected to find the contrecoup damage) controls our sense of sight. Worst of all, Henri’s headache kept widening, which told Paré that his brain was swelling and that blood vessels inside the skull had ruptured. As we know today, inflammation and fluid pressure can crush brain cells, destroying the switches and circuits that run the body and mind. This explains why brain injuries can be lethal even if the skull suffers no fracture. Skull fractures can in fact save people’s lives, by giving the swollen brain or pools of blood room to expand into. The history of neuroscience has proved the brain amazingly resilient, but one thing it cannot stand is pressure, and the secondary effects of trauma, like swelling, often prove more deadly than the initial blow.

  King Henri II of France finally succumbed to an intracranial hemorrhage at 1 p.m. on July 10. Queen Catherine ordered every church to say six requiem masses daily and ordered all church bells—which had been bleating for the king—silenced. Amidst this sudden, sinister quiet, Vesalius and Paré began their famous autopsy.

  To cut open a king—to even suggest such a thing—was bold. In that era, anatomists might open someone up for one of two reasons, a public lecture or an autopsy. Both activities had a stink of the disreputable about them. By the mid-1500s a few cities, especially in Italy, had relaxed the old prohibition on dissections for teaching purposes, but only barel
y: authorities might allow one per year (usually in winter, to prevent spoilage), and then only of criminals, since an official sentence of “death and dissection” would wring a little more posthumous punishment out of the rogue. Most kingdoms limited autopsies to suspected cases of poisoning, infanticide, or other heinous acts. And in some cases an “autopsy” did not require actually cutting open the body. Why Catherine gave in to Paré and Vesalius and permitted a full, invasive autopsy of Henri isn’t clear, since everyone knew who had killed him and how, but history remains grateful she did.

  Vesalius had laid out the proper steps for opening the skull in Fabrica. This usually involved lopping the head off to make examining the brain easier, but out of deference to the king, he merely elevated the chin in this case, by placing a wooden block beneath the royal nape. Someone grabbed a fistful of the king’s graying hair to steady the skull, while someone else (presumably Vesalius, the expert dissector) began sawing an inch above the eyebrows. After circling the head and removing the skull vault, he encountered the thin membranes (the meninges) surrounding the brain. In Fabrica Vesalius suggested that students nick the meninges with their thumbnails and unwrap them. He then encouraged students to plunge their fingers in and squeeze and fondle every fold: dissection was as much a tactile as a visual pleasure for him. But with Henri, Vesalius restrained himself once again—probably in part because Henri’s brain didn’t look all that appetizing. The front and sides looked normal, but in the rear—antipodal to the blow*—Vesalius and Paré found pools of blackened fluids beneath the meninges, like blisters about to burst. The brain itself had also yellowed and putrefied back there, a puslike mass that measured one thumb’s width across by two thumbs’ widths high. Equally important, they found that the wooden shards from Montgomery’s lance had never penetrated the brain.

  It’s not always clear what Vesalius and Paré understood, in modern terms, of how brain damage kills. In their reports they often lapsed into talk of imbalanced humors and “animal spirits” escaping Henri’s body. They knew nothing of neurons or localization. And the shards from Montgomery’s lance probably led to an infection that weakened Henri and hastened his death—a complication they couldn’t have grasped. But the duo understood well enough that the “commotion” and “corruption” in the back of Henri’s brain, along with the resultant pooling of blood, had ultimately killed him. Trauma to the brain alone, they determined, could be deadly, even without a skull fracture. And in proving this, they vastly outdid the mutterings of that old phony, Nostradamus. Nostradamus had bloviated about lions and cages of gold. Vesalius and Paré had predicted what sort of damage they’d find inside Henri’s brain and exactly where they’d find it—and find it they did. They proved science the superior clairvoyant.

  The fallout from Henri’s death poisoned most everything he loved. After him, French kings were forbidden from jousting, for their own protection. Diane de Poitiers had to surrender the jewels and estates and place at court she’d earned as Henri’s mistress. The new French king, the frail François II, died just seventeen months later, after contracting an earache while hunting. The next king in line, Charles IX, was ten years old, so Catherine assumed power as regent—putting an Italian, a Medici, in charge of France.

  Henri’s death had actually crushed Catherine: despite his shabby treatment of her, she loved him. (She even swapped her original royal symbol, a rainbow, for a broken lance.) But her policies over the next few years betrayed his hopes for peace and precipitated decades of civil war between Catholic Royalists and Protestants. These wars reached their nadir with the St. Bartholomew’s Day Massacre in August 1572, which Catherine likely engineered. Although intended as a surgical strike against key Protestant leaders, the killing fed on itself, and mobs spread across the countryside, butchering thousands; historians call it less a day of massacre than a season. One Protestant targeted was none other than Gabriel Montgomery, who, while in exile after manslaughtering Henri, had renounced Catholicism. After the St. Bart’s massacre Montgomery fled to England, but he returned the next year to battle the royalists, capturing Normandy and threatening to conquer all of northern France. A lengthy pursuit ended with royalist troops capturing him in 1574, and Catherine had the pleasure of seeing the man she still blamed for her husband’s death quartered and then beheaded.

  As for the scientists, Paré had treated François II on his deathbed in 1560. The boy’s earache had led to a buildup of fluid on the brain, but once again Paré declined to trepan a king of France. No one quite knows why he refused, and nasty rumors have always circulated that Paré (à la Hamlet) slipped poison into the young king’s ear, probably at Catherine’s request, so she could reign as regent. But there’s another reason Paré did not perform emergency neurosurgery. The risks involved with trepanning were high, and he knew he would likely incur the blame for any mishap. That was doubly true since Paré had converted to Protestantism by this time, and therefore—far from being someone that Catherine would entrust with a murder—actually held a precarious position in Her Majesty’s government. Indeed, Paré barely survived the St. Bartholomew’s Day Massacre a dozen years later.

  Nevertheless, during the intervals of peace in Paris, Paré thrived. He wrote a handbook for military surgeons and an anatomy textbook that plagiarized Vesalius. (Paré didn’t see this as a big deal, calling his appropriation “as harmless as the lighting of one candle from the flame of another.”) He also campaigned against mummies and unicorn horns and other bogus cures. Most important, Henri’s autopsy inspired Paré to write a book about head wounds. It called attention to the danger of contrecoup injuries and pooling fluids, and it continued the vital work of pairing specific brain injuries with specific symptoms—the modus operandi of neuroscience for the next four centuries. The world’s finest surgeon spent his twilight in Paris, having served four kings, and he died in his bed in one of his five houses.

  Vesalius met a nastier end. Within a month of Henri’s autopsy, King Philip quit cold Brussels for sunny Spain. Vesalius followed, and soon wished he hadn’t. There are two competing stories about what finally drove Vesalius from Spain. The less likely story says that Vesalius got a little too anxious to start the autopsy of a noblewoman one night—and found her heart still beating when he cut her open. Her family supposedly called in the Inquisition, and Vesalius saved his neck only by agreeing to make a pilgrimage to Jerusalem.

  The second story, while probably more truthful, is even stranger. The Spanish heir apparent, Don Carlos, called the Infante, was a weak and febrile boy. No one had much sympathy for him, however, since he was also a psychopath. Born with teeth, he delighted in gnashing his nursemaids’ nipples until they bled and became infected, and he spent much of his childhood roasting animals alive. By his teenage years he’d moved on to deflowering young girls. One night in 1562 the Infante tore down the stairs to snatch a maiden he’d spied, but karma tripped him. He somersaulted and smashed his noggin at the bottom of the staircase, lying there bleeding for some time. Spanish doctors failed to cure the prince, so Philip sent Vesalius. Vesalius found a tiny but deep red wound at the base of the prince’s skull, and he suggested trepanation to alleviate pressure. The Spanish doctors, spiteful at a foreigner’s interference, refused. Instead, they allowed the local townsfolk to dig up the desiccated, century-old corpse of Friar Diego, a cook at a local monastery and a reputed miracle-worker. The townsfolk then entered the Infante’s bedchamber to slip Diego beneath the boy’s sheets—and the boy, who was more or less out of his wits by then, snuggled up to and began dreaming of visits from the friar. A few days later he’d improved little, and Vesalius finally prevailed upon the other doctors to puncture the skull near the eye socket and drain some pus. The Infante recovered within a week after this, but the doctors and townsfolk universally credited Diego, who was later canonized for Vesalius’s miracle.

  The whole farce disgusted Vesalius and convinced him to quit Spain. So he arranged a holy pilgrimage to escape. He first visited Padua, where he�
��d produced Fabrica, and arranged to get his old job as professor back. Nevertheless, perhaps feeling guilty about using a pilgrimage as a ruse, Vesalius continued to the Holy Land, landing at Jaffa in the summer of 1564. He visited Jerusalem and the plains of Jericho, and sailed back satisfied, but he never reached Padua. He’d booked passage on a cut-rate tourist ship with inadequate supplies, and when storms ravaged the vessel on the return voyage, passengers began expiring from a lack of victuals and fresh water. Like something out of Géricault’s The Raft of the Medusa, corpses were being heaved overboard, and for once in his life the sight of dead bodies spooked Andreas Vesalius. He went half mad, and scrambled ashore as soon as the ship staggered to Zakynthos, an island in what’s now western Greece. According to different accounts, he either died at the gates of Zante, a port city, or crawled to a filthy inn where the locals, wary of the plague, let him die alone. Either way, it was an anticlimactic death. There was no autopsy to determine what had killed him.

  In the end, about the only person, place, or thing to gain from Henri’s death was the incipient field of neuroscience. On a basic level, Henri’s autopsy confirmed beyond a doubt that contrecoup injuries existed, and that the brain could suffer trauma even if the skull remained undamaged. It’s a lesson, sadly, we’re still relearning today. Rope-a-dope boxers and quarterbacks and hockey enforcers continue to shake off concussions on the theory of no blood, no harm. But each concussion effectively softens up the brain and ups the chances of more concussions. After multiple blows, neurons start to die and spongy holes open up; people’s personalities then disintegrate, leaving them depressed, diminished, suicidal. Four centuries have passed, but macho modern athletes* might as well trade pads for armor and go joust with Henri.