His Brother's Keeper

by Jonathan Weiner

  I remember how I felt not long afterward when Stephen Salloway, my mother’s neurologist in Providence, finally made a diagnosis of her condition. Salloway said it might be Lewy body dementia, which is one of his special research interests. LBD is another rare, progressive neurodegenerative disease, also fatal and incurable. It usually kills after about seven years. My mother had been sick for at least a year by then—maybe even for nine, if you counted the way her mood had darkened after she fell in Vermont. Now a doctor was telling us that he could do nothing to save her. Having a diagnosis to give out to my mother’s sisters and to the rest of the family did help a little, but as Donne observed on his sickbed, “It is a faint comfort to know the worst, when the worst is remedilesse.”

  My mother’s death sentence should have been easier for me to take than Stephen’s was for Jamie. The day that Stephen called Jamie, December 16, 1998, happens to be my mother’s birthday. She was seventy-four that year. No one considers a natural death at that age a tragedy. But she was my mother. To her and to everyone in our family her suffering had already been a tragedy. News like that is hard to take in. Most doctors do not try to treat their own families, and maybe science writers should not expect too much from themselves, either. At first, I did not want to learn about Lewy body dementia. I did not even want to know what Lewy bodies are.

  In La Jolla, as the Neurosciences Institute emptied out for the evening, Jamie sat in his office searching the Web. He scanned the abstracts of another dozen medical papers from universities as close by as San Diego and as far away as Tokyo, Tel Aviv, and Barcelona. The prognosis was roughly the same everywhere he looked.

  To keep himself from panicking, he tried to focus on the positive. In all of this bad news, it’s as good as it gets, he told himself again and again. There is no better group than Steve’s. All of these were only averages: Individual prognoses were completely unpredictable. The cosmologist Stephen Hawking had been diagnosed with ALS when he was twenty-one. Now he was almost sixty. And at least there was riluzole, which did slow the disease at least a little. Why did it help? That might be a clue. The whole force of biomedicine was coming together everywhere. A cure might be just over the horizon of the new millennium. Maybe he could bring it closer.

  Jamie found these thoughts hopeful, although a few months later, the Associated Press would run a story about ALS patients that began: “The hard part about having a fatal disease in 1999 is that the promises of miracle cures, genetic antidotes and bio-cocktails twinkle all around like lights of distant rescue ships—too far off to be of any assistance.”

  When Jamie looked up from his desk, four hours after Stephen’s call, the sun was getting low in the sky. From the window he could see a piece of the parking lot and the playground of the institute’s day-care center, empty and beginning to fill with shadows. He phoned Melinda and asked her to pick him up. When he stood to collect the papers that lay in his printer tray, he felt dizzy. He noticed, as if from a great distance, that he was shivering violently. He pulled on the warmest layer he had in the office, a wool-lined suede coat that he had bought ten years before at a secondhand shop on Newbury Street in Boston’s Back Bay. Then he found his way with difficulty through the corridors of the institute and drifted outside. He felt physically injured, as if he had just staggered out of a car wreck or a collapsed building, as if he were trailing blood and going into shock. It was a mild evening but the coat did not stop the shivering. Melinda met him in the parking lot and drove him home.

  They watched the sun set together from a cliff over the Pacific, chanting “Let Stephen be healed! Let Stephen be healed!” Melinda told him the sun would take their prayers around the world and deliver them to Stephen in Boston. That evening she wrote in her diary, “It is too early to be fatalistic. We don’t know what is going on. We don’t know…. Jamie is drowning his emotions in front of Quake and the TV. He played Steve tonight at Quake and talked to him on the phone at the same time. Steve, he said, sounded like he pretty much believes he’s got this thing and that he’s a goner…. Jamie said, ‘Miracles do happen in our family. There is a lot of power and healing in this family.’ I don’t know if I can cry anymore tonight or if it’s the right thing to do. It’s too early, MUCH too early. Ridiculous to go too far when we don’t know anything.”

  Melinda called her sister, Piper, and cried, then her father and cried. “Questions to ask ourselves,” she wrote in her journal. “What do we want to be? What do we want to do? What are our options/ potentials? It feels like the answer is lit for us in neon: YOU SHOULD GO TO BOSTON.”

  Another entry, a day later: “Peggy is whacked out and so are we. Whacked out people should unite in support of one another. What a time this is. Sometimes I am just staring with my stomach in knots…. I am in a state of shock, I think. But not denial. Jamie is surfing the Net looking up ALS information, determined to come up with a cure. I am working on the miracle side of things, and almost unbelievingly telling people a little bit about what’s going on.”

  On December 18, two days after Stephen’s call, Jamie met with the institute’s research director and gave notice. He said he had not found much in his year there that he could bring to the marketplace: I don’t see anything worthy of your investment or mine. Given his family news, he had to move back home. He would be leaving the institute when his year’s contract was up on February 15.

  That gave Jamie a little less than two months. In that time he planned to draw on every resource he could tap in the institute. He would search all the new sciences of life. He would find some way to pull Stephen back from the dead.

  Part Two

  The Plan

  For nothing in the whole world can be brought To equal the agility of thought.

  LUCRETIUS

  Nine

  The Repair Man

  I once asked my father what he thought of Jamie Heywood’s leap from engineering into genetic engineering.

  “If you understand a system well, whether it is a pulley, or a circuit, or an engine, then you can deal with it,” he said. “Once you understand it, then you say, OK, it’s a system, and I can deal with it.” An engineer could not think about life that way before the rise of molecular biology. “But today you can talk about genes, DNA, and protein. You can say, OK, I deal with systems, and as long as there is nothing in this system outside of physics and engineering, I can do it.” If what has broken is nothing but a system made of molecules, an engineer can try to fix it.

  My father himself had always worked on a plane much more abstract than John Heywood, author of Internal Combustion Engine Fundamentals. The book my father wrote while my brother and I were growing up is titled Statistical Mechanics of Elasticity. It gets highly mathematical by the bottom of page 2. The only part we could read was the dedication: “To Ponnie.” While taking care of my mother, Dad was working on a reprint edition of Statistical Mechanics of Elasticity for Dover Press. The book describes the kinds of long-chain molecules you find in rubber bands, and analyzes the way they strain when you stretch one. Trying to help Dad toward the bestseller list, my brother suggested a subtitle: Statistical Mechanics of Elasticity: And What It Can Do for You.

  Many of my father’s former students were going into the new biology, where their skills with math, computers, and systems helped them study life’s molecular machinery. Some of the mathematical tools my father experimented with in the 1970s and 1980s were now used routinely by big international teams of biologists and engineers. There are long-chain molecules in living flesh, too. DNA is one of them.

  “That’s the concept of an engineering education,” he said. “You learn basic science so clear that you can then apply it to whatever you’re faced with. I would say, an engineer with sufficient self-confidence would feel that way about moving into genetic engineering. Not every engineer. Many get to know a small area and never step out. But a good engineer would decide: OK, it’s a system. I have to learn a lot but I can grapple with it.

  “Again, this is not an
ordinary fellow who would do that.”

  Melinda called Jamie the Repair Man. The first time they visited her mother in Athens, Jamie walked into her apartment and decided to fix the toilet. Her mother had turned off the water to the toilet tank because of a leak a few decades before. “To flush,” Melinda explains in one of her many unpublished essays about life with Jamie, “you had to fill up a plastic bucket we kept in the tub, heave it over to the toilet bowl, and splash the water down in a great wave. This is how we had been dealing with elimination since I was a kid….”

  “Forget the Parthenon,” says Melinda. Jamie spent his first day in the ancient city touring Praktiker, the Home Depot of Greece. He fixed the leak, replaced the broken seat cover, and assembled a new plastic table in the garden. Before nightfall, the American in Athens had ascended his porcelain throne, and found it good.

  Unfortunately, Melinda writes, “the most appreciative audience to these bathroom heroics turned out to be the Repair Man himself.” Her mother was sure the toilet would break again as soon as Jamie was gone. She went right on flushing with buckets of water.

  The first time Jamie visited Melinda’s father in Manhattan, he found a different problem to fix. Phil Marsh is a folk-rock musician. In his apartment in Chelsea, according to Melinda, he had created a vast network of extension cords and phone wires, and they snaked through the long hallway from room to room. Again Jamie set off for a hardware store “to forage among wire clips and linking thingies and whatnot.” He made the apartment’s wiring so neat and rational that it seemed to disappear. And all Phil could do was worry about the day he might have to take it apart.

  “You can see the clash of cultures for yourself,” Melinda concludes. “My clan is Content With The Way Things Are, his clan Fixes Things That Are Broken.”

  Now Melinda was in awe of the Repair Man, and also jealous, because Jamie’s search for a cure took his mind off what was torturing hers. He had vanished into his office.

  “While Jamie was at work,” Melinda wrote later, “I ran around La Jolla in a daze, stared cowlike at the sea.” She and Jamie had lived with his parents on Mill Street when they were just starting out. Back then, Melinda had fit in beautifully in “that coven of Heywoodness,” as one of her friends once told me. But now Melinda confided to her journal that moving back scared her. “A plan is needed. The couple cannot be subsumed back into the parental household, or I will lose my center and so will the couple.”

  On the phone, Stephen sounded calmer than anyone else in the family, and he tried to cheer her up. The day after his test at Massachusetts General, he told her, he had developed a horrendous case of hemorrhoids. He had never had hemorrhoids before, and he told her all about it.

  And as I understand it, many millions of Americans…

  Every word he said made her laugh hysterically.

  Stephen told me about the hemorrhoids later on, without the comedy routines. “I know it was stress,” he said. “And after that I started having problems in my feet. I would have numbness in my legs. It must have been a pinched nerve, because my whole region from my knees to my upper back was locked tight. I was taking piles of ibuprofen. I was just so tense. I mean, it hurt to move, I couldn’t bend over.”

  He went back to the neurologists at Mass General and they put him through another MRI. Nothing was wrong—or nothing new. His right hand was still weak, and his right foot felt a little weak now.

  Slowly Stephen calmed down, and his body relaxed. As his body stopped panicking, he wondered how he should spend the last few years of his life. He was in love with Wendy. On the night he learned he was dying, he had called her and blurted, If it is ALS, will you have my baby? But could he really ask Wendy to do that? Would it be fair to ask her to marry him? Sometimes he thought he should buy a new Harley and take off. Out in California, one of Melinda’s circus friends told her that she would love to “get Stephen pregnant.” Melinda passed the word to Stephen, to make him smile.

  Stephen laughed about that. Wendy was not amused. Uh, hello, she said. Girlfriend standing here.

  But poor Wendy pointed out to Stephen, as calmly as she could, that she would feel less valued if he decided to do that.

  For Jamie a clock had started ticking the instant he heard Stephen’s voice in his call from Storrow Drive. Now the clock hung over him and followed him like the face of the moon wherever he went, day and night. Suddenly he felt miraculously lucky to be at the Neurosciences Institute. He had started there the very same week that Stephen went to see a doctor about his right hand. He could not be better placed to figure out how to save Stephen.

  Jamie felt shy about telling his news at the institute. The year before, at his job interview, he had told Edelman about Stephen’s first symptom, the weakness of the right thumb and forefinger. Now, when Jamie told him the diagnosis, Edelman winced, nodded, and shot him a sharp bright glance of sympathy. Jamie saw that Edelman had suspected the worst from the start.

  With his office mate Joe Gally, Jamie was not sure he could trust his voice. It was one thing to sit alone at his computer and search PubMed. When Jamie typed the keywords “ALS” and “prognosis,” he had known that PubMed would be smart enough to search the vast scientific literature under not just “ALS” but also “amyotrophic lateral sclerosis” and “Lou Gehrig’s disease.” But now he had to ask Joe, the Walking Library, for the kind of research assistance that only a human being can provide.

  Joe looked moved when he heard about Stephen, and he promised to teach Jamie about ALS. He warned him that the literature on the disease is confusing. ALS is a complex disease with many tributaries. In December of 1998, there were at least a dozen plausible theories about its cause. But Gally told Jamie that a remarkable paper had been published in the field that past March.

  The date struck Jamie as another coincidence. It was the same month that Stephen had first gone to see the doctor.

  Joe Gally had found this paper so interesting that as soon as it came out, he had introduced it at one of the weekly meetings of the institute’s journal club. Joe was a very useful member of the journal club. When he brought in a paper, he could not only explain why it was exciting, he had also read all the references the authors cited at the bottom of their paper; and he knew a good deal about them, and about their references, too. Each piece of new science is like a brick in a city that rests on seven cities buried underneath.

  The paper that interested Joe had appeared in the journal Neuron. The chief author was Jeffrey Rothstein, a neuroscientist at Johns Hopkins University in Baltimore who specializes in the study and treatment of ALS. Rothstein and his colleagues at Hopkins had found a defect in the machinery that nerves use to communicate. The defect was extremely subtle, and it was a kind of problem that biologists did not understand very well.

  Gally had tried to explain the significance of this paper to everyone at the journal club. He told Jamie to start there.

  Jamie began reading Rothstein’s paper at the office. He took it home that night, along with a few more papers to help him understand it, and a few more in reference to those. Next to him in bed, Melinda was reading Tuesdays with Morrie. It is not a comforting book for the families of ALS sufferers—at least, not at the very start of the adventure. Melinda found it brutal to have the future brought before her face. She tortured herself with images of Stephen in a wheelchair like Morrie; Stephen with a breathing tube taped to his neck; Stephen frightened like Morrie, the old professor, terrified of choking to death, of being drowned by his own saliva. When Melinda closed the book her cheeks were wet. She had decided that she and Jamie would have to have a baby and name him Stephen, and he would play with his uncle Stephen.

  Jamie heard her close the book and he glanced at her face. “I’m not reading that book,” he said. He rolled over in bed with a groan.

  “I’m going to find a cure.”

  Ten

  An Imperial Message

  Kafka wrote a short short story that might almost be about ALS. It is cal
led “An Imperial Message.”

  The emperor, so a parable runs, has sent a message to you, the humble subject, the insignificant shadow cowering in the remotest distance before the imperial sun; the emperor from his deathbed has sent a message to you alone…. The messenger immediately sets out on his journey; a powerful, an indefatigable man; now pushing with his right arm, now with his left, he cleaves a way for himself through the throng; if he encounters resistance he points to his breast, where the symbol of the sun glitters; the way is made easier for him than it would be for any other man…. But how vainly does he wear out his strength; still he is only making his way through the chambers of the innermost palace; never will he get to the end of them; and if he succeeded in that nothing would be gained; he must next fight his way down the stair; and if he succeeded in that nothing would be gained; the courts would still have to be crossed; and after the courts the second outer palace; and once more stairs and courts;…and if at last he should burst through the outermost gate—but never, never can that happen—the imperial capital would lie before him, the center of the world, crammed to bursting with its own sediment. Nobody could fight his way through here even with a message from a dead man. But you sit at your window when evening falls and dream it to yourself.

  Stephen’s brain was sending messages continually to the muscles of his body. If he had been as healthy as he still looked and felt, those messages would have traveled in a flash from his brain all the way down to his toes, or to the thenar eminence of his right hand. But the brain’s messages travel in stages. To reach the limbs they have to travel out through nerves that run through the gates of the skull and down through the spine. Those are the motor neurons. They are bundled together like cables, and each individual nerve is a long, thin, delicate strand. These motor nerves carry all the messages that command the muscles in the limbs to work: to run, walk, hammer, saw, turn a key in a lock.