Princeton University - Council of Science & Technology

POPE PRIZE

Essay 1
Disease of a Thousand Names
Laura Joy Grasso Fitzpatrick

Essay 2
Miracle Cell
Laura Joy Grasso Fitzpatrick

Essay 3
The Outsider with a Reputation
Howard G. Yu

Honorable Mention
Viola Huang

Disease of a Thousand Names

People in my family have a condition called Charcot-Marie Tooth (CMT) disease. Around age forty, my father started developing numbness in his extremities and lost feeling and muscle IN AN OPERATING ROOM AT NEW YORK University Medical Center in March 2008, with a tiny digital recorder tucked into the breast pocket of my indigo scrubs and a camera dangling from my wrist, I watched a man pull a blade through a hole in another man’s skull—faster than you might think—until a piece of the discolored gray matter that had been causing seizures flopped out into the surgeon’s gloved hand. I didn’t want to make any sudden moves or even breathe too heavily for fear that I would somehow harm the delicate organ laid open to the air. There was something beautiful about the brain, something that made my jaw slacken behind my surgical mask, and I had the sense that I was seeing something intimate, even though I’d never met the man on the operating table. I’d begun researching epilepsy in my junior year of college, after reading Oliver Twist made me wonder what it was about the disease that had captured Dickens’ imagination and prompted him to endow his villain, Monks, with seizures. To my knowledge, I had never known anyone with epilepsy, and at first, I had thought—as many readers might—that the disorder was of interest only to those who had it, and that whatever hold epilepsy had exerted on Dickens was a fluke. When I began reading statistics about the disease, though, that impression began to change. Epilepsy afflicts more Americans than Parkinson’s disease, multiple sclerosis, cerebral palsy and Lou Gehrig’s disease combined, I learned, yet it has historically received only a fraction of the federal funding for any one of those diseases. In the United States, 2.7 million people have epilepsy already, and more than five hundred new cases are diagnosed every day. Twenty-five thousand to fifty thousand Americans will die of seizures and related causes this year —potentially more than will die from AIDS, car accidents, or breast cancer. The annual public health cost of epilepsy, including medical procedures and lost earnings, totals close to $15.5 billion in the United States. Yet as a country we seem to know remarkably little about it; when Supreme Court Chief Justice John Roberts had his second seizure in July 2007, countless news articles explained the basis for an epilepsy diagnosis, then questioned whether the disorder would affect his ability to do his job. Summing up his surprise at the ignorance about a disease with such broad public health implications, Senator Barack Obama has compared the apathy around the mysterious and devastating disease to the nation’s lack of awareness, years ago, of polio. Soon I came to find that scores of other authors through the years have been just as intrigued by epilepsy as Dickens was—Tennyson, Poe, Carroll, Dostoevsky, and George Eliot, to name just a few. The disease, I learned, has also inspired artists and religious thinkers to philosophical meditations; epilepsy has historically been a lightning rod in the medical humanities. By writing about seizures these thinkers were tugging on threads of fear and wonderment, drawing on the associations with demons and saints that the illness has historically inspired, evoking in readers a visceral reaction. My growing awareness of the disorder’s rich cultural history was what drove me to seek out people living with epilepsy today, an experience that has prompted me to question the larger interplay among brain, body, and mind. A DOOR SLAMMING; THE WHISPER of a melody; rivulets of sunlight trickling through leafy trees—any one of these can be a trigger. In the recesses of the brain, a neuron takes aim. The shot misfires. A seizure begins. Some people experience a warning, actually a small seizure in itself—called a simple partial seizure—while the rest of the brain stands by and watches. Because information is spatially organized in the brain, with different groups of neurons controlling specific body parts, the effect of the seizure on the epileptic’s body depends on where it happens neurologically. If he is like the majority of those with partial epilepsy—let’s say he, because men are slightly more likely than women to develop the disorder —then his seizure will begin in one of his temporal lobes, located behind the ears. Home to auditory processing and semantics for speech and vision, the temporal lobe also contains the hippocampus, involved in memory formation. This seizure will therefore include none of the stereotypical thrashing and foaming we so often associate with epilepsy. Instead, the senses and the mind stir. The feeling takes the mystical name of “aura” from the Greek word for “breeze.” In The Idiot, Fyodor Dostoevsky described an aura like the ones he may have had, “a moment or two when his whole heart, and mind, and body seemed to wake up with vigor and light.” Most people are not so lucky; the vast majority experience a wide range of unsettling sensations: déjà vu (when a novel situation seems to have happened before), jamais vu (when a familiar situation seems alien), peculiar smells, noises no one else can hear, distorted sounds, strange tastes, blurry vision, racing thoughts, tingling skin, panic, euphoria, dizziness, headache, nausea, or numbness. These can last for one to three minutes, with the person fully conscious all the while. To other epileptics, the seizure comes as an utter surprise. Almost anything can prompt it: reading, writing, speaking, being startled, listening to music. For some people, thinking too hard—about a chess move, a vote for President, a tip calculation—can bring on a seizure. Particularly in certain parts of India, some people with epilepsy report that seizures begin if they pour hot water over their heads —whether due to genetic reasons or bathing habits, scientists cannot say for sure. Doctors in Hong Kong found that some patients’ seizures began when they played the pattern-making game Mah-jongg. Many women experience more seizures around the time of their menstrual period. If a patient can identify his triggers, he can try to avoid them. But some patients see no pattern at all. On an Internet epilepsy support group, one woman wrote a poem about her trigger, lamenting that even a thing of beauty can be a threat: “I am afraid of rainbows /and wish I could look into an oily puddle /and not shudder.” The seizure takes hold when an unusually large number of nerve cells are stimulated at once in the patient’s cerebral cortex. This is the neuron-rich ribbon where consciousness lives, where language, thinking, and memory have their roots: a grooved mound of gray matter the consistency of pudding, tucked close under the surface of the skull. Here, a morass of nerve cell bodies act as flesh telegraph operators, wiring messages to the limbs and the trunk and the organs by way of the white matter, a glistening, milky substance made of connective fibers called axons that stretch up to a meter long. Our normal function depends on the inhibition of these impulses; if they’re all jabbering at once, the body doesn’t know what to listen to and the telegraph receivers get overloaded. Another way to think about it: allowing too many neurons to excite in the brain is equivalent to plugging in too many appliances at once in your home. Essentially, a fuse blows. The neurons fire uncontrollably. Sometimes, the abnormal electrical activity will spread to another part of the cerebral cortex, becoming a complex partial seizure that causes the person to lose awareness. If the seizure travels to the frontal lobe, which controls movement, he will perform automatisms: he might pick at his clothes, smack his lips, or wander. He might bicycle his legs or thrust his pelvis. He repeats words that sound nonsensical. He may express inappropriate emotions, such as rage, fear, or sudden joy. Sometimes the seizure will continue to grow, so that the storm takes over the entire brain at once, plunging the cortex, the subcortical structures, and the brainstem into a generalized, or grand mal, seizure. If the epileptic has been standing, his body goes rigid, and he collapses to the ground—the reason epilepsy has been known through history as “the falling sickness.” For ten to twenty seconds—the tonic phase—he flexes his trunk and wrenches his elbows up and away. His back, his neck, his arms and his legs all stretch in opposite directions as if trying to flee his ravaged body. He may let out a cry, the sound of air being propelled out through his rapidly contracting vocal cords. He may stop breathing altogether. His pulse quickens and his blood pressure climbs; sweat pours down his body. The pressure in his bladder rises, but the muscles all over his body are clenching so hard that he cannot urinate. Now the seizing man’s brain begins to fight back, trying to calm itself. The thalamus—the structure at the top of the brainstem, which connects to the spinal cord, transmitting sensory signals from the cerebral cortex to the rest of the body —gives off an inhibitory impulse. Again and again it tries to calm the hyperexcited neurons, causing the electrical storm in the brain to flicker on and off. This struggle, called the clonic phase, lasts up to two minutes. The neurological power contest plays out in the body, too: the patient’s rigidity gives way to convulsions, his muscles relaxing intermittently and then stiffening again. Half a dozen tremors wrack his body every second. As the periods between the contractions grow longer, urine finally bursts from his bladder. All this activity stops only when the synapses have used up their neurotransmitters—they’ve spent their ammunition. The seizure is over. The whole ordeal has taken only a few minutes. The person may remain unconscious for a time, while his brain partially or completely shuts down and his body quiets. He begins to breathe again. Gradually, he awakens, most likely confused. Pain washes through his muscles. He may feel weak or be paralyzed on one side of his body or all over. A blank fills his memory where the seizure should be. This welcome rest may not last long: some people’s neurons are quick to rearm. These patients have multiple seizures in quick succession. Like waves crashing overhead while the patient struggles to surface, this phenomenon—called status epilepticus, or “status”—can eventually drag him under. In adults, status can bring on a stroke, render breathing impossible, cause infection or even, in a quarter of all adults and as many as half of those aged eighty or older, death. Fifty long minutes in status killed Vladimir Lenin at age fifty-three. Why certain seizures peter out and others are relentless is a mystery, making status a rare but threatening possibility. Even if the epileptic suffers only one seizure today, he may endure after-effects for hours or days to come. He may be irritable; Dostoevsky used to remember the period after his seizures this way: “Especially at night, by candlelight, an indefinite hypochondriac melancholy, and as if a red, bloody shade (not color) upon everything.” If this was the patient’s first unprovoked seizure, some studies suggest his odds of having another one in the next six months are fifty-fifty. After a second seizure, his odds of having a third may be close to 80 percent. Having epilepsy also makes a person statistically more likely to develop other conditions, though the relationship may not be causal: one study, for instance, found that more than three quarters of patients with temporal lobe epilepsy reported memory problems; and a quarter to a half of people with epilepsy suffer from depression. Epileptics who are otherwise in good health are also about twenty-four times more likely than those without it to die suddenly and with no explanation—and scientists have no idea why. The riddle of a seizure itself, in other words, is only the beginning. EPILEPSY IS A MOST VOCAL DISEASE, announcing itself with sudden force. But it leaves mystery in its wake. It is a chameleon illness, a shape-shifter; “epilepsy” is not a single disorder, but a collection of disorders that all cause seizures, leading some physicians to use the term “the epilepsies” instead. This ambiguity is reflected in the many words we use to describe it. Known as the “disease of 1,000 names,” throughout history epilepsy has inspired evocative and often fearful descriptions. Each name, like a tale woven by Scheherazade on one of her 1,001 nights, is a story in itself. Some of the names have roots in physical description. The Latin “apoplexia parva,” meaning “little stroke,” reflects the fact that a seizure can sometimes look like a stroke and even leave half of the body temporarily paralyzed. In “Sonko nanay,” a fifteenth-century Inca term for “heart sickness,” resounds the ancient belief that seizures originated in the heart—the seat of the mind, they believed—and not the brain. In ancient China, different seizure types were named after animals, including the goat, horse, pig, cow, chicken, or dog, depending on the sound the patient made during the seizure. Other names reflect superstition or fear. “Morbus scelestus,” for instance, is Latin for “criminal disease”; the link that name suggests between epilepsy and crookedness persisted for centuries and was the subject of studies in well-respected scientific journals as late as the 1970s. Some names acknowledged the same mysterious power that provoked the fear, but suggested ambivalence instead of revulsion. Many cultures have names that translate to “Hercules sickness,” because the ancient Greek demigod was believed to have had epilepsy. Inca variations included “Aya huayra,” meaning “wind of the dead,” or, more poignantly, “llaqui oncuy,” for “disease of sadness.” One of the largest groups of names reflects the idea that epilepsy, long known as the “sacred disease,” comes from the heavens. The ancient Egyptian name “nesejet” contains two silent hieroglyphics: one, a man with a stick, translates to “danger”; the other, a cobra, means “coming from God.” Christians years ago knew the disorder as “daemonic suffering,” brought about by evil spirits; some, inspired by the passage in the Gospel of Luke in which Jesus expels a malignant spirit from a young boy having convulsions, called it the “scourge of Christ.” Even today, the debate over terminology for the disease is fraught. In recent decades, many doctors have moved to abandon the term “epilepsy,” which comes from the Greek word for “to seize” or “to attack.” They refer instead to a “convulsive disorder” or “seizure disorder” in an effort to allay fear and stigma historically associated with the name. WHATEVER WE CALL IT, ONE IN THREE adults knows someone with epilepsy, yet only a fraction of those could provide a definition of the disorder. To some extent, no one can fault lay people for ignorance; after all, even the best minds in brain study can’t pin down a definition. At the annual meeting of the American Epilepsy Society I attended in December 2007, for instance, hundreds of epileptologists, neurologists, neurosurgeons and other medical professionals from around the world thronged a room where five of their most distinguished colleagues were giving a lecture. The topic: “What is a seizure?” The moderator was quick to point out the irony. “If you need to go to that talk,” he joked, “aren’t you at the wrong meeting?” The remark met with knowing laughter. Of the five doctors giving presentations, only one took a stab at explicitly defining epilepsy. Borrowing from Supreme Court Justice Potter Stewart’s famous definition of pornography, he said: “I know it when I see it.” We have learned remarkably little since a British pioneer of neurology identified epilepsy as a “disorderly discharge of nerve tissue” in 1863. We still don’t know why 65 percent of seizures begin, and our medicines are useless for one in three people with epilepsy. We don’t always know how to identify a seizure: some people in the throes look like starry-eyed daydreamers; others are violent and angry; still others show no outward signs at all. Even when we observe the lines on a brain scan zigging and zagging abnormally, we can’t be sure we’re seeing a seizure. If you have unusual brain activity for ten seconds, the conventional wisdom says, then you are having a seizure. But what about when it lasts for nine? If some of the persistent questions about epilepsy seem arbitrary, others are profound. First among those is the historical link between epilepsy and brilliance. The association began with Aristotle, whose catalogue of “great epileptics” included Socrates, Hercules, Ajax, and Plato; scholars expanded the list through the Renaissance to include, among others, the Holy Roman Emperor Charles V and the Italian poet Torquato Tasso. Nearly all the diagnoses of historical figures have doubters, and such controversies can never be resolved posthumously; still the length and breadth of the suggested list is astonishing. The list of creative people who some scholars believe had epilepsy is especially remarkable. Composers include George Frideric Handel, Tchaikovsky, and Beethoven. Leonardo da Vinci and Pythagoras, too, may have had the disease. In addition to Dostoevsky, writers who could have had epilepsy—many of whom created characters who suffer from the disease—include Dante, Moliere, Sir Walter Scott, Jonathan Swift, Edgar Allan Poe, Lord Byron, Charles Dickens, Leo Tolstoy, and Gustave Flaubert. Michelangelo may have had epilepsy, and Vincent Van Gogh almost certainly did; “the storm within,” as he called the disease, is reflected in the turbulent brush strokes he is known for, and he created some of his greatest masterpieces, including Road With Cypress and Star (1890), Wheat Field with Crows (1890), and, most famously, The Starry Night (1889), during the time near the end of his life when he had his worst seizures. We may never know whether the possible relationship between epilepsy and creativity is causative or merely correlative. Some neurologists argue that because epilepsy is common, it is likely to afflict some uncommon people. Others say that because seizures damage one part of the brain, another area may have a chance to overdevelop. Some psychiatrists suggest a third option: the deeply felt experience of a seizure may instill in the epileptic a desire to seek out creative enlightenment, making the correlation a result of inclination and not innate ability. Nonetheless, an observation that the Irish critic and poet Edward Dowden made in his 1877 essay, “The Scientific Movement and Literature,” is as true today as it was then. “The time has not yet come when it may be possible to perceive in complete outline the import of science for the imagination and the emotions of men,” he wrote, “but that the significance is large and deep we cannot doubt.” Epilepsy’s significance is large and deep for more than just the “great epileptics.” For every person with the disease, seizures are not merely physical incidents, but powerful, symbolic events that affect brain, body, and mind.