His Brother's Keeper

by Jonathan Weiner

  The doctor sent Stephen to a hand surgeon, who sent him to a group of neurologists. The problem was simple, the atrophy of a muscle, but a thousand things can cause that. Sometimes, in rare cases, the cause is psychological, emotional, spiritual. The young Sigmund Freud wrote a paper on organic versus “hysterical” paralysis at the suggestion of Jean Martin Charcot, the great French neuropathologist who first described amyotrophic lateral sclerosis, ALS.

  Cases of hysterical paralysis are curiosities in the medical literature, although the neurologist and writer Oliver Sacks once experienced the phenomenon himself. Sacks was hiking alone up a steep mountain in Norway when he rounded a boulder and came face-to-face with a bull in the path. Sacks panicked, ran back down the slope, fell, and hurt his leg badly, paralyzing it. A surgeon repaired the damaged muscle but after the operation Sacks discovered that his leg was not only still paralyzed, it no longer felt like his own, as if it were not even attached to him. “The muscle was toneless,” Sacks writes in his memoir about the experience, A Leg to Stand On, “as if the flow of impulses in and out, such as normally and automatically maintain muscle tone, had been completely suspended. The neural traffic had stopped, so to speak, and the streets of the city were deserted and silent. Life—neural life—was suspended for the moment, if ‘suspended’ was not itself too optimistic a word.” Sacks had to wait a long time before the signals got through again and he had two legs to stand on.

  Stephen’s doctors did nerve-conduction tests. They ruled out a pinched nerve, carpal tunnel syndrome, and many other possibilities, including psychological paralysis. They thought Stephen might have benign focal amyotrophy, also known as Hirayama syndrome, which is an inexplicable weakening of a single limb. The doctor who led the group told Stephen that his nerve damage would probably never heal. If he did have Hirayama syndrome, the weakness would not progress. His condition would have to be watched. If it did progress, that might mean that Stephen had the beginnings of ALS. The neurologist mentioned that possibility very casually, and Stephen played it down when he got home. He had Hirayama syndrome, and it was just a nuisance.

  Oh, it’s this weird thing that was discovered in Japan, and there you go. And it’s no big deal, your arm gets weaker for a year and a half, and then it stops.

  He was fine about it. He could learn to build houses with his left hand.

  Of course, you always want two hands. But you don’t need two strong hands, you need one strong hand. It’s only when you have two weak hands that you’re screwed.

  While Stephen sold the house and talked with neurologists, in the spring of 1998, Jamie and Melinda moved to La Jolla, and Jamie started his new job at the Neurosciences Institute. Their apartment on Pearl Street had a sliver of Pacific view. They could sit in the evenings and watch the sun set through the waving fronds of palm trees. They could hear the waves all night.

  Up on the mesa at the institute, Jamie was pleased to see that his new office had a beautiful redwood desk with green, architect-designed file drawers underneath it. The desktop computer was top of the line, the latest, fastest machine, with a big nineteen-inch monitor. Because Edelman envisioned the place as a scientific monastery, his architects had designed the scientists’ offices to look like monks’ cells. But they were stylish cells with poured concrete walls, and each cell had its own small mystic figure impressed in the concrete. Jamie had seen that kind of design element in his architecture magazines. The design in his own office wall was a series of dots, a sort of mystic ellipsis, significance to be determined.

  Rather than hide Jamie away in a business office or in administration, Edelman had put him in the middle of the theory group. “He just dropped me right in like I was one of the scientists,” Jamie says. “I think no one knew what to make of me—including myself, a little, at the beginning.” He had never been a scientist, and he did not look like one. The neuroscientists’ uniform at the institute was a polo shirt and a pair of khakis—they looked as if they had all crawled out of The Gap. Jamie wore expensive jackets and ties that made the scientists smile among themselves. He dresses better than our director—and Edelman wears a suit every day.

  Scientists at the institute share their offices. That is another Edelman touch, meant to encourage conversation and cross-fertilization. Jamie’s office mate was a molecular biologist named Joe Gally, who had been Edelman’s first graduate student back at Rockefeller. Joe Gally helped do some of the early work on the immune system that led to Edelman’s Nobel Prize. Then Joe went off to travel the world. When he returned, he got a job teaching biochemistry and cell biology at a medical school in Tennessee. At a certain point Joe lost his job in a departmental shuffle, and he called Gerald Edelman. If I can’t teach, at least I want to learn, he said. Now he was deeply involved in the life and science of the institute. He was absentminded about time, space, clothes, almost everything but molecular biology. But he still missed teaching, and he was a mentor to many of the institute’s younger scientists.

  Joe was one of the legends of the institute. Directors of other research laboratories told stories about him. In the folklore, Joe was said to have the powers of memory of an idiot savant. Edelman was rumored to have hired him to read every page of every issue of virtually every biological journal as it was published online. Although that was not really true, Joe Gally did serve the institute’s neuroscientists as a living encyclopedia. They called him the Walking Library.

  The office that Jamie shared with Joe was right across from the espresso machine—the caffeinated nerve center of the institute, the best spot in the building for meeting neuroscientists. Jamie could meet the institute’s scientists over coffee and then explore the institute by jumping from office to office and lab to lab. That was perfect for Jamie. He also went to the lectures of visiting scientists and the weekly meetings of the journal club, where neuroscientists at the institute took turns telling each other about new and exciting research papers.

  Because Jamie had never taken a biology course, wandering into those talks was a little like walking into the courtyard of the Neurosciences Institute. He got his first confused, dazzled impressions of the spectacular invisible architecture that most people will never see. The human body is home to each one of us and it is also one of the most exotic places on the planet.

  Jamie knew, of course, that living bodies are made of cells. Cells are to the human body what bricks or beams are to a building: the basic units of living architecture. Excluding viruses, single cells like an amoeba or a bacterium are the smallest living things on earth, and a human body is made of about 300 trillion cells living and working together. Ten thousand cells in a row would stretch several inches, about the length of the lifeline in a man’s palm. They are called cells because one of the first scientists to see them through a microscope, Robert Hooke, in the seventeenth century, was fascinated by architecture. Hooke studied a thin slice of cork and saw innumerable tiny chambers, and he was reminded of monks’ cells in a monastery.

  Most of the lectures at the Neurosciences Institute were about the action one level down, inside cells, in the complicated Tinkertoy structures that we call molecules, of which the double helix is the most famous example. If cells are the building blocks of living bodies, then molecules are the building blocks of cells. Ten thousand sugar molecules in a row would stretch from one end of a cell to the other. And each molecule is made of atoms—tens, hundreds, thousands, sometimes tens of thousands of atoms.

  Jamie was intrigued by the molecular gadgetry in the human body. In exploded, false-color views, floating in black space, these molecular machines look beautiful and strange. From an engineer’s perspective, life looks like nothing but molecular gear. Some molecules inside a cell work like pumps, some like valves, some like filters, some like pliers and screwdrivers, some like clocks. Where anatomists a few hundred years ago argued about the mechanisms of our body’s organs, now they argue mostly about the workings of our molecules. In muscle, for instance, there are molecular motors that drive
the action, and these motors can be dissected and examined. Biologists argue about whether one motor pulls at a muscle fiber by hauling it hand over hand like a sailor; or whether the molecule pulls at the fiber by bowing down, pulling, stretching up, and then bowing down and pulling again, like an inchworm.

  Jamie thought about Stephen. Somewhere in there, probably at the very smallest scale of the architecture, something had gone wrong. In the beginning maybe just one molecule had gone missing, and now Stephen was losing the use of his right hand.

  In the evenings, Jamie browsed through one of his new boss’s books, Bright Air, Brilliant Fire: On the Matter of the Mind. It was a new sacred book, not to be read in the bathtub. Jamie tried to visualize the gear inside a human brain at the level of cells and then at the level of molecules and atoms. For breaks, he played his favorite computer game, Quake, one of those combat games in which an action hero runs across the faces of burning planets, killing enemies and fighting to save the galaxy. Jamie, Stephen, and Ben were talking two or three times a day, as always. Sometimes they played Quake on the Web while they talked, arm wrestling across space, dueling a few hundred miles apart.

  Six

  Ponyenka

  In February of 1998, while Stephen Heywood sold his house and went to see his first neurologist, and Jamie Heywood joined the Neurosciences Institute, my mother had her first appointment with a neurologist in Providence, Rhode Island. She was worried about her memory. The neurologist, Stephen Salloway, gave her a standard set of tests for cognition and memory problems. Like doctors she had seen before, Salloway could not make a diagnosis.

  One week after that appointment, my mother had some trouble walking. She told my father that her legs hurt. Then she began to stumble and fall.

  One fine Sunday morning that spring, I drove to New York City with my two boys to spend the day with my parents. My father and mother had driven down from Providence to spend the weekend in a hotel in the city. My wife, Deborah Heiligman, stayed home that day. She writes children’s books, and she had a deadline.

  I met my parents at the Metropolitan Museum of Art. We showed the boys the halls of medieval armor. It was one of the first brilliant days of that spring, and the sun hit our eyes when we came out and started down the long flight of stone steps toward Fifth Avenue. My mother’s sister Doris and her husband Mort had met us at the museum, and they were walking down the steps on my father’s side. I was on my mother’s side, and Aaron and Benjamin were just in front of us, with Benjamin, who was nine, reaching backward a little awkwardly to hold his grandmother’s hand. We had gotten most of the way down toward the sidewalk when Benjamin hesitated and half-turned to look back up at her.

  My mother was seventy-four, but she looked much younger. She kept fit playing tennis and bowling, and she was wearing sneakers. Benjamin had not pulled at her hand, and she should have been fine. Still, she faltered. I took her arm just above the elbow with enough force to steady her. But something was wrong: She was collapsing toward the steps like a rag doll, or like a marionette whose strings have snapped. I managed to keep her from toppling forward, but as she sank down onto the steps I fell forward myself, thrown by the unexpected weight of her free fall. It was a good thing we were already most of the way down the steps. I somersaulted, head over heels, and hit the sidewalk spread-eagled on my back. The camera that was slung around my neck thwacked down an instant later, right next to my ear.

  The crowd made a circle around me, but I jumped back to my feet. I was all right. Up on the steps, my mother and the rest of the family looked all right, too. My father was focused on my mother’s fall. I could tell that neither of them had seen me go down. My mother was gently laughing off what had happened, to show my father that she was fine.

  Even my old camera seemed fine. The barrel of the lens was dented, but the shutter still clicked.

  Back in Providence, Salloway, the neurologist, did more tests, but he was not sure what was wrong with her. Many neurological diseases have distinct names, but they are really constellations of problems that shade into each other. That makes them hard to tell apart. It also suggests that if neurologists could understand what starts just one of the nerve-death diseases, they might understand many of them. Some neurologists hope or dream that there will turn out to be just one problem at the start, and when they find it, they can zap it.

  One sign that many of these diseases are linked is the strange case of the Chomorros, the Polynesians on the South Pacific island of Guam. In most years in the second half of the twentieth century, one out of three on Guam died of nerve-death disease. Sometimes the disease looked like ALS, sometimes like Parkinson’s, in other cases like Alzheimer’s or a rarer condition, progressive supranuclear palsy, PSP, also known as Steele-Richardson-Olszewski syndrome, after the three doctors who first identified it in 1964. The youngest of those three doctors, John Steele, moved to Guam early in his career and has spent decades there, convinced that the Chomorros were the missing key to them all.

  Steele knew that whatever caused that epidemic, which was known locally as lytico-bodig, it was almost over. The only Chomorros who died of it had been born on the island before or during World War II. Baby boomers and their children and grandchildren did not get lytico-bodig. So if he hoped to solve the mystery, time was running out on Guam.

  Early in the 1990s, Oliver Sacks visited Steele on Guam and joined him on his rounds, seeing patient after patient who had what looked to Sacks like ALS or PSP. Even for the professional these are not easy encounters. Sacks writes: “I felt drained by seeing these patients with lytico and bodig in their final, terrible stages, and I wanted desperately to get away, to lie down and collapse on my bed, or swim again in a pristine reef. I am not sure why I was so overwhelmed; much of my practice in New York involves working amid the incurable and disabled, but ALS is rare—I may see only one case every two or three years.” Steele, who kept up a jovial booming manner with his patients, wept in private because after thirty years he still could not do anything to help.

  Guam is not the only case like that. There is another on an island off the coast of Japan; and in the French West Indies in the late ’90s another epidemic of nerve-death disease was discovered on the island of Guadeloupe. There the disease began the way it did on Guam, with clumsiness, unsteadiness, postural instability with early falls. The syndrome was ten times more prevalent on Guadeloupe than in Europe or North America, and it was confusingly variable. In one study, a team of neurologists looked at a random sample of 220 consecutive patients who had been seen by the neurology service at Guadeloupe University Hospital in Pointe-à-Pitre and diagnosed with what was being called atypical Parkinson syndrome. Of those 220 patients, more than 90 had some kind of parkinsonism, 58 seemed likely to have PSP, 50 had well-defined Parkinson’s disease, 15 had ALS with parkinsonism, and one had probable multiple system atrophy.

  So a large number of nerve-death diseases may be linked, and no one knows how many others are also linked but still unidentified. John Donne wrote on his sickbed: “O miserable abundance, O beggarly riches! how much doe we lacke of having remedies for everie disease, when as yet we have not names for them?” Because many neurological diseases shade into each other, many of the names we do have are probably spurious; and the first beginnings of neurodegeneration are usually impossible to trace, as James Parkinson observed in London in 1817 in his classic “Essay on the Shaking Palsy”: “So slight and nearly imperceptible are the first inroads of this malady, and so extremely slow is its progress, that it rarely happens, that the patient can form any recollection of the precise period of its commencement.”

  My mother did think she knew how it started. She and Dad spent summers in a mountain cabin near Marlboro, Vermont, for the music festival. On a hike up there in the late ’80s, she had a bad fall. She slipped on wet leaves and pine needles and went sliding down the path fast in a sitting position until she hit a tree. Her legs flew around it to either side and her forehead whacked into the trunk. When she f
elt her memory begin to fail a few years later, and her thoughts began to get dark and painful to her, my mother blamed that fall. People with neurodegenerative diseases often report that they had had an accident or a period of great stress about two years before symptoms appeared. So maybe that fall did the damage, but no one really knows. Maybe it was the onset of the disease that made her fall.

  She got moody, absentminded, a bit paranoid. She thought she had Alzheimer’s. Once when I was visiting my parents in Providence, and my mother and I were alone in the kitchen, she pointed at the kettle on the stove. It was steaming. “Did you put that kettle on?” she asked. She was looking at me sidelong, strangely, as if the answer to her question would be cosmic and she almost could not bear to hear it.

  No, but so what, Ma? You’re fine.

  When she was young, her nickname was Ponnie, or Ponyenka, which is a Polish endearment that means Little Miss. Her father was a tailor who had a shop on Manhattan’s Lower East Side. His greatest success was the Shirley Temple dress, which appeared on the cover of Life magazine in the middle of the Depression. So my mother and her sisters dressed in style in Bensonhurst. Their family name was Mensch, which means, roughly, a good person, a human being in the best sense, a deep, broad character, as in the Yiddish proverb, “Ten lands are more easily known than one mensch.” My mother’s given name was Florence, after the loveliest city in the world. So, a lovely human being. But there was also something a little fragile and nervous about her, even when she was young, and everyone who loved her felt protective of their Ponyenka.

  She married a graduate student at Columbia: an engineer, Jerome Harris Weiner, my father. He became a professor there, and taught engineering and applied mathematics. He did well in the boom after the war, when Vannevar Bush called science the Endless Frontier. It was almost as good a time to be an engineer then as it was at the end of the century. My father took our family on sabbatical years abroad in Italy and Israel, with weeklong Atlantic crossings on the Queen Elizabeth and the Independence.