His Brother's Keeper

by Jonathan Weiner

  “And so, that’s moving to me,” Stephen said. He seemed to be forcing himself to go on, even though he hated schmaltz. “It’s just like asking someone to hold up a rock for ten days. And you say, ‘Well, sure, I could do that for ten minutes—anybody could do it for ten minutes. But for ten days, it’s impossible!’ ”

  “And yet there he is.”

  “Yeah. And if you said, ‘Hold it up for ten days, or your brother dies—!’ ”

  With that, Stephen’s face suddenly contorted. “I mean, you know, he’s doing it, though.” His mouth worked. He choked up. “Oy vey!” he said.

  We sat in the cab of the truck. Stephen shot a sidelong glance at me.

  “I shouldn’t say oy vey,” he said.

  “Why not?”

  “I’m not allowed to, necessarily. I’m not even sure what it means.”

  He was not Jewish, but he had gotten the cry in the words just right. I said, “It means, Oy vey!”

  It was up to me to follow that with those reporters’ scene-of-the-disaster questions: How does it feel to know you are dying? It was my job that day to ask them, but I just could not do it. I think we were both happy to go back to talking about houses. We felt even more at ease when we got back to Jamie’s Victorian, a few minutes’ drive from their parents’ house on Mill Street. Jamie joined us, and he and Stephen showed me the Victorian and the carriage house. The carriage house was set back from the main house about fifty feet in a patch of woods. It looked to me like nothing more than a half-ruined garage. There were outcrops of stone around the carriage house, gray conglomerate boulders with big cobbles, like storm clouds full of hailstones. Jamie pointed them out to me as proudly as a realtor. Roxbury puddingstone, the State Rock of Massachusetts. A stone with a place in American history. Children around Boston have been climbing on Roxbury puddingstone since before the Revolution. Local churches are built of it. A thirty-ton monument of Roxbury puddingstone was sent down by train to the battlefield in Gettysburg to commemorate the 20th Massachusetts Regiment.

  “I’ll let Stephen tell you,” Jamie said, and went right on talking as we circled the carriage house. They would work with the Roxbury puddingstone in redesigning the house. “I love this idea that constraints make architecture interesting.”

  “Jamie’s stealing all my quotes,” said Stephen.

  “These are all Stephen’s quotes.”

  “We just want to achieve a separate feel,” Stephen added mildly, nibbling on a twig.

  “I love how this building sits inside this pocket of rock!” Jamie said.

  “And it’ll do that more when we’re done, actually, Jamie.”

  Stephen and Jamie trudged around the carriage house talking possibilities. They saw dormers on three sides. They would raise the ceilings and put in skylights. Stephen said he wanted to make the first two floors wheelchair-accessible. But he wanted to design the ramps in a way that would be aesthetically pleasing, he said, “noninvasive.”

  Jamie laughed. “And all the while we have to figure out how not to lose money,” he told me. “ALS has economic consequences. The expense starts at $10,000 a year. Ends up $170,000 a year, with intubation and round-the-clock care.” Intubation means a plastic breathing tube in the windpipe, and an artificial respirator.

  “Assuming you want that,” Stephen said. He leaned against a tree behind the ruin, near a big storm cloud of Roxbury puddingstone. “My feeling is, you get to that point and you don’t want to keep going. Shit-piles of family around by then.” Absentmindedly, as he spoke, he removed a bug from Jamie’s collar. Jamie endured this unconscious brotherly gesture and endured the drift of Stephen’s thoughts with a kind of tender blank-faced look. Suddenly we were having one of the conversations that Stephen and I had avoided in the truck. My father and I were talking about this now, too—to intubate or not to intubate. I thought my mother’s living will made her wishes clear. My father did not. Now Stephen was telling Jamie what he wanted.

  Stephen slouched against the tree, looking off toward a few crows that hopped on the grass at the edge of the woods.

  “How do you know that now?” Jamie said. “Intubation could cost you a night’s worth of medical intrusive care, and buy you a year and a half of high-quality life.”

  We listened to the faint suss of traffic and the breeze in the trees. A dog barked. Jamie broke the mood and turned back into a Realtor.

  “This is a great dog neighborhood!”

  The carriage house had been abandoned a long time. There was an old rotten canoe propped on its side against it. The door was white, weathered, peeling paint, with gray wood showing through. “We’ll save the big front door,” said Stephen. “And maybe put it on a motorized slide. Computerized.”

  “Computerized?” Jamie said.

  “Computerized. Oh, sure. I’m going to computerize the house. And I’ll just shout out, ‘Door,’ and it’ll slide right open.”

  Remembering the scene now, I realize that the Heywoods could not have talked much about the future. Stephen at least had thought very little about it. If he had, he would have remembered that he was going to lose his voice.

  Today Jamie often talks to ALS patients who are near the start of their road, where Stephen was then, people who are still busy just enjoying life—and why not? “Denial is a fine place,” Jamie likes to say. “It’s in Egypt.”

  Inside, the carriage house was a wreck. A lawn mower was parked just inside the doorway. Beyond that, the floors and walls were dark and in ruin, with cobwebs draped and drooping everywhere. Jamie and I went up the steps first and waited on the second floor while Stephen followed very slowly after us. He kept half-stumbling and apologizing to us for the scares. His right leg was trembling with what neurologists call fasciculations. Rock climbers call it “sewing-machine leg.” Stephen’s fasciculations made the steps an adventure for all three of us. They were steep, and the old treads had been worn narrower from overuse.

  “The stairs will have to be a little more code next time,” Stephen said, and looked around. “This is rat shit, Jamie.”

  “There’s tons of rat shit,” Jamie agreed.

  “That’s really unpleasant,” said Stephen happily. “Look at the paneling in that wall. That could make some great paneling on the outside wall. Then this could be the living room, kitchen, dining room.”

  “But all open.”

  “But all open. Upstairs, bedrooms. And downstairs, a playroom for kids. This could be a door right here.” He gestured at a bare window darkly shaded with cobwebs.

  I saw nothing but ruins and junk.

  “Nice roof,” I offered.

  “Nice roof,” Jamie agreed, emphatically. “Yeah, this is a really nice project.”

  Up a ladder, in the middle of the hayloft, a desk that once belonged to a lawyer was still covered with his papers. We picked up correspondence from 1938. Someone must have decided to close up the place without touching the desk. The papers themselves were covered over with dust and cobwebs. I stooped and picked up a book from the floor. It was an ancient Funk and Wagnalls New Standard Dictionary. Much later on, when I was looking at the carriage house with Melinda, I said, “Some old lawyer left his last case open.”

  “He wasn’t an old lawyer,” she said. “He died young.” His widow had stayed on in the house for sixty years after he died. She lived alone all that time.

  But Jamie did not mention that. He was selling me the house, and his plan, and his brother, and their amazing story, all at once. The floorboards were rotten and they shook as we walked. “Look!” Jamie said. “This is the coolest music stand on earth. Cast iron. Weighs about eight tons. Maybe it’s an artist’s easel. This was all really nice furniture before it was destroyed. This will be a great space. There’s the original hayloft door. Stephen will make it glass—you could open it up for a breeze in the room. I always wanted to do one of those Pennsylvania barns. Stephen is an amazing craftsman. He doesn’t like architects. He thinks they draw something and walk away.”
<
br />   “My quotes.”

  Slowly we made our way back down the steep and narrow stairs.

  “Needs a very large Dumpster,” Stephen said, looking up at the place from outside. “But the fun part will be pulling out the wood and salvaging everything.” He pointed out details he liked, as he had been doing throughout the villages of Newton all afternoon. “Wonderful diamonds over the windows. Crosses. All real-dimension lumber, not like the crap they make today.”

  We strolled back to the main house. “This place is major TLC, too,” Stephen said with satisfaction, scanning the eaves. “Long-term. It took me how many years to do my first house?

  “Hooh! I’m tired,” he said.

  The carpenter and the engineer leaned back against Stephen’s truck with their arms identically crossed on their chests, wearing identical grins, looking up at the Victorian.

  Twenty-Seven

  The Jamie Factor

  At the foundation one afternoon, Jamie and Melinda and Jamie’s staff of two met with a consultant he had hired, Katherine Evans. She was his new project manager and she also saw herself as a tough-love mentor, he told me. Jamie had warned me that the meeting would be a review of everything they did not know. “So it’s going to be a brutal and depressing meeting.”

  It was a Friday afternoon, two o’clock, a time when most offices are slouching toward the weekend, when the meeting began. Jamie and Melinda were setting the table for lunch in the dining room of the Victorian, within sight of their desks and computers. The dining room was unfinished but Melinda had added quirky touches to decorate it. Black cats cut out of tin perched or prowled or draped themselves on each white lintel. Sun shone through wide-parted, many-splendored drapes in the bay window, an Indian print with a gold border. Against one wall, a table made of an old Singer sewing machine held green plants growing in baskets. Displayed on the Singer was a lighthearted coffee-table picture book, Master Breasts, paintings of breasts by the Old Masters. Under the chandelier, Melinda had spread the table with an old hippie floral tablecloth that she had found in Provence. The whole house was Victorian with touches of her child-of-gypsies style.

  Katherine Evans was middle-aged, Chinese American. She had been project manager in the development of a genetically engineered version of erythropoietin, a human protein that boosts red blood cell production (it is used for patients on kidney dialysis). Katherine had worked on erythropoietin at a biotech called Genetics Institute, racing against a rival biotech, Amgen. There had been a highly publicized patent battle. Amgen had won, and erythropoietin was now famous in the overlapping worlds of medicine, biotech, venture capital, and Wall Street as biotech’s biggest success story: Worldwide it was the best-selling product in biotech history. That year, according a press release on Amgen’s Web site, the company expected its sales of erythropoietin to reach almost half a billion dollars.

  Katherine was now coming off another drug development failure. She was consulting while she looked for her next job. The loss was still raw for her. As a consultant, she had a faint aura of grief and bereavement, of enforced singleness.

  An old friend of hers in the industry had called and asked if she would give Jamie some advice. “When I first got the phone call, I thought—what has Bruce gotten me into?” she told me softly, and I nodded. I felt the same way about my friend Ralph.

  At that afternoon’s meeting, Katherine was supposed to give Jamie an overview of the drug development process. She would help him put together a master plan—how to get approval from the FDA for human clinical trials. Before we started, I asked her to give me a quick introduction to drug development.

  “You know Stephen is in the next room,” she warned me quietly and urgently. He was playing a computer game called Starcraft. He had no energy that afternoon, he complained to us through the open door. The game was not going well.

  Katherine explained to me how different Jamie’s project was from standard drug development. Usually, the story of a new drug starts with a drug company. It could be a biotech or Big Pharma. The company makes the product. Once they have their product, they need assays to define what the product is. They need to test its purity and stability. Then the substance is usually tested in vitro for activity. And then in vivo in small animals, a few mice or rats, for toxicity. Not hundreds of animals yet. Then in more mice, and rats. Then in dogs, rabbits, pigs, monkeys. “Don’t write dogs!” she cried. With animal tests, they look at safety and efficacy. They test different formulas of a drug, and when and how it is delivered. They test that the agent is safe and the route of administration is safe.

  Next, there is a Phase 1 study with volunteers. Usually the test involves a dozen people or so, to see if the drug is well tolerated. In Phase 2, the drug testers find out about dose and regimen. They find out what dose works best. They find the half-life of the product. They do a number of Phase 2s, with different patients. They may do four Phase 2s. This can take years.

  Then they design Phase 3. Here they want to hit a home run. The Phase 3 trials are double-blind, placebo-controlled. “You design absolutely the best, tightest study you can. So that at the end of the day you can apply for product license approval from the FDA. Or new drug approval.”

  Normally, Katherine explained, all this would be done within a company by specialists who were used to working together as a team. But of course no one else was working on Jamie’s idea—or, as Katherine put it in the jargon of biomedicine, “on this particular indication.” And normally the total cost of the project would be tens of millions of dollars. To bring out a new drug, a giant pharmaceutical house may spend almost a billion dollars and ten years.

  There it was again: the voice of the way things are. Whenever I talked with people besides Jamie, I had to try to sober up, and I wanted to less and less. When I talked that month with Jeff Rothstein in Baltimore, I told him that I hoped to end my New Yorker profile of the Heywood brothers with the excitement of the trial.

  “In reality—” Rothstein began, and backed up. “I don’t know how much you know about trials. But the first time you stick something new into a human being, the only thing you really care about is, is it safe. I’ve had to admonish Jamie greatly about this. ‘You have hopes that are different from what we have as responsible physicians.’ That is, the first time you try something new, you gotta know, can I do this without harming someone? And that’s all this first trial is. The reality is, we’re trying something that hasn’t been done. I mean, in the very crudest sense, we’re going to stick a needle in your spinal cord, inject something, and hope that it helps you. The first thing we want to do is make sure that it doesn’t hurt you. And that’s what a Phase 1 trial’s about. Can you do whatever you want to do safely? And if you can do it safely, the next step is to say, ‘Gee, what happens when you do it?’

  “There’s a long series of hurdles to make a drug. This is the first one. Can we put in the DNA and not hurt someone, sticking a needle in the spinal cord?” Rothstein was afraid that the operation itself would be hard for a surgeon to bring off. It would be much trickier than sticking a needle into the brain to cut out a tumor. “In your brain, you have a lot of leeway. But your spinal cord is the thickness of the tip of your index finger. Not big. Not big. And a mistake there is catastrophic. Especially at the level of the cervical spinal cord. That’s sort of the equivalent of Christopher Reeve’s injury. The last thing I want to do is have anyone undergo this procedure and come out paralyzed from the neck down.”

  Katherine and I both knew what an extraordinary maze she had just diagrammed on her yellow pad with her mechanical pencil; and we were both old enough to feel parental and protective as we watched Jamie and Melinda lay out cartons of take out Thai food. They made a fine sight, Jamie with his thousand-watt energy, his Boy from Tomorrow look, Melinda rubbing her pregnant stomach and nibbling on a rice cake. She was not showing yet.

  “You’re smiling,” I told Katherine.

  “I smile a lot,” Katherine said.

  Jamie c
ut in. “At the Heywood table the etiquette is, fight. Fight for what you want.”

  Everyone at the table dug in but Melinda, who had no appetite—her morning sickness lasted most of the day. While we ate, Stephen opened the door of his computer room and passed through the dining room. “I won,” he said gloomily. He was not hungry, either. He went out to get his pickup truck and buy some more wood. He was going to walk a mile or two to his truck, which was back at the house on Mill Street. He refused Robert and Jamie’s offers of a ride. After he had gone out the door, a silence weighted the air. What was in that silence? I wondered. It contained everything that everyone in the room was choosing not to say.

  After lunch, Jamie began the afternoon meeting. Robert Bonazoli stood at a flip chart with a list of duties, which he had spelled out all the way down to who ordered the bottled water.

  First he talked about their temperamental printer. It gave them error messages, it talked back: “Too hot or humid to print.” They had to buy an air conditioner for the printer. “I love our printer,” Jamie said. “ ‘I don’t feel like it right now.’ ” Robert said Melinda was working on taking care of the printer. “And the pregnancy thing she’s working on full-time,” Robert added.

  Robert had spent a lot of time on the next fund raiser. In December they were planning a joint fund raiser with the Massachusetts chapter of the ALS Association, ALSA: a Christmas concert at Jordan Hall of the New England Conservatory. The orchestra, the Longwood Symphony Orchestra, was made up entirely of doctors, nurses, and other medical people. They would play Beethoven’s Fifth. Jamie and his foundation had now built their mailing list up to 9,700. They were calling it “A Concert in the Key of Hope.”

  Next, Lizzie reported that she had found some great sites on the Web, including a new journal of gene therapy. She had subscribed. Now they could just double-click on results and get them. There was a team in Switzerland just then that was injecting genes into the human spine.