His Brother's Keeper

by Jonathan Weiner

  “You’re screwed.”

  “There is a huge gap between what they say and what they will do. Maybe you should take this overseas.”

  But Jamie did not want to do that. If the gene therapy or the vaccine looked to be effective, he had to try them soon and in such a way that he could offer them to the many people who needed them. Otherwise everyone alive who had ALS would be dead. “I don’t want to do this on the sly. I want to do this right. I don’t want to bend the rules. Because it’s important.”

  “Why don’t we just look at this from a very simple perspective?” Paola said. “You don’t want to do harm. So why don’t you focus on toxicity? Just make sure that what you want to do is not going to harm patients.”

  As they talked, Paola doodled in her own legal pad, drawing simple brackets and parentheses. Her page was even more spare and abstract than Jamie’s, with no words at all. She was such a passionate scientist that she saw the work almost as impatiently as Jamie. When they gossiped about a new arrival in another lab, Paola told him, “He’s a scientist, you won’t like him.” And they both snorted.

  Now Jamie brought up the tricky subject of the postdoc Dave Poulsen. He explained to Paola that Matt During had given Poulsen the key job of making the construct for the gene therapy test in the mice, and Poulsen was holding things up. In Baltimore, Jeff Rothstein was ready to go—he had the mice and he was ready to inject them with the DNA. Poulsen had had the stuff for fifteen days now and he just sat on it.

  Paola closed the door, and confided that she was not fond of Dave Poulsen. She had problems with his work. He was their slowest postdoc, she said. He never worked on weekends, never stayed at the lab past two or three in the afternoon. “Which is great. We should all live that way.”

  “The mice are ready to go at Johns Hopkins,” Jamie said again. “They’re ready to go. It’s an expensive trial. We need to get them treated. We’ve got seven mouse trials waiting at Hopkins! Well, I can get Dave excited. I’m good at this. I’ll fly him up to Boston to meet my brother. I’ll give him a consulting fee, $5,000.”

  “That’ll help. Money talks.”

  Jamie treated Matt and Paola to lunch, an expensive lunch, and more than once he steered the conversation to Dave Poulsen. Matt listened like a politician; Paola looked upset. The more she listened, the madder she looked. She told Matt that they had to try to light a fire under Poulsen or fire him.

  Matt listened with a slight smile. He told me later that he thought Poulsen was working well. Jamie and Paola were being too hard on one poor postdoc.

  “He’s killed other projects!” Paola cried. “We’ve given him millions of other chances!”

  “Hey!” Jamie waved his hands. “End of topic! End of topic! OK? Here’s what we need to do.” He laid out a strategy for the lab meeting that afternoon. “I mean, no mistakes. We don’t have time to make mistakes.”

  After lunch, Paola Leone, Matt During, Jamie Heywood, and half a dozen of the lab’s postdocs pulled up chairs in Matt’s office. The calendar on the wall was from the Louvre. The photograph from September was a pair of marble hands sculpted by Rodin to form something like the spire of a cathedral. A white lab coat hung on Matt During’s door. A candle flickered on the windowsill in the hot city air of Indian Summer.

  The postdocs draped themselves comfortably around Matt’s office. Like him, most of them chatted in broad New Zealand accents. As usual they had the air of cool, droll partners on a climbing rope, and so did Matt. There was always some of that feeling in Matt’s office: the planning of a difficult ascent. But Dave Poulsen sat against the far wall from Matt, looking stolid. Paola leaned against the door-jamb and glowered at him.

  Long afterward, I asked Poulsen about that day. I tracked him down at a lab in Missoula, Montana. “There were a lot of experiments needed to be done,” he told me over the phone, “and to get them done in time I had to live in that lab twenty-four/seven. That’s partly why I left and came back here. I had a family with three kids. I’d leave home it was dark, I’d come home it was dark. Weeks would go by when I didn’t see my lawn, let alone my kids. These experiments aren’t things that happen overnight. Science takes time. Jamie wanted us to give him something he could put into his brother tomorrow. And he felt like anything short of that was just—being lazy, or that we just simply didn’t understand. And I think it was just the other way around. Jamie just didn’t understand how science worked.”

  That afternoon, Matt and his group attacked the chief engineering problem ahead of them: designing a DNA package small enough to fit inside the virus case. Jamie was right in there with them. They were trying to figure out how to leave out 640 base pairs.

  Now and then Jamie ran his hand through his hair and leaned back in his chair: “Ahh, you’re right, you’re right!

  “It’s packageable but it’s big,” he said at last.

  “It’s a little optimistic but I think we can do it,” said Matt. “Dave?”

  “Well, we’ve got a couch out in the hall now,” Dave said gloomily, in the voice of Eeyore, “so I’ll have a place to sleep.”

  “I’m behind the eight ball with Jeff Rothstein,” Jamie said, speaking not to Dave Poulsen but to Matt During. “He had expected to start in August and here it is September.” He was asking Dave Poulsen to move—but he was asking delicately.

  Outside, there was a murmur of thunder.

  Jamie shifted topics and talked about places to inject the stuff into Stephen’s spine. They all joined in that conversation, and as they did they pointed to their own backs. “Cervical is…?” Jamie asked, and pointed. “Yeah,” said Matt, and pointed at a spot on the back of his own neck. As he did there was more thunder.

  This was one of the problems that scared Jeff Rothstein in Baltimore. Matt and Jamie hoped the DNA injection would not only improve strength in Stephen’s arms but might reach the bulbar region, which would improve breathing and speaking. “I don’t think so,” Rothstein said, when I asked him about that. “I know that’s what they hope. I don’t think so. The bulbar musculature is controlled by a part of your brain called the brain stem. And that’s within the cavity of your cranium, which is actually above the top of the spinal cord. So I doubt it. I guess it’s theoretically conceivable that their injection of fluid would actually diffuse far enough. I doubt it.

  “And the flip side is, if it migrated that far, it could also be toxic. And that’s part of the brain you do not want to poison. It’s that part of your brain that regulates all of your core breathing functions. That’s where people shoot themselves in the head and kill themselves.”

  There is a legend that Cain did not know how to kill Abel. Out in the field, he worked his way up Abel’s body until he found the throat. Jamie was his brother’s keeper, but Jamie did not know how to save Stephen, and now here he was working his way up to the back of Stephen’s neck.

  At just that moment, while Jamie and Matt were arguing about where in Stephen’s neck to insert the needle, Dave Poulsen interrupted the meeting. “I’ve got to get home early today,” he said. “Is there anything else we need to discuss?”

  Lightning and thunder. “Thought it was my ears ringing but it’s not,” said Matt, distractedly.

  Dave Poulsen stood up. He gave them all a big, grizzled, mournful grin. He missed Montana, he said. “Montana was therapeutic. This is the opposite of therapeutic.” At the door he paused and said again, “So I guess I’ll be sleeping in the lab.”

  Jamie stood up, too, and shook Poulsen’s hand. He gave him one of his small Superman half-smiles. “I’ll buy you a pillow. An ALS pillow. You can call me in the middle of the night. I’m always up.”

  Part Four

  The Sign

  To do science, you must never lose a child’s hope.

  GÜNTER BLOBEL

  Twenty-Five

  Jamie’s Old Room

  In late September I booked a flight to Boston. On my way to the airport I stopped in Princeton to teach a seminar, “Science and Li
terature: Parallel Lines.” It was the second year I had taught the course. The year before, I had focused on the young writers around the conference table, and the course had gone well. But this class was not beginning well. I could not stop talking about the Heywoods.

  Jamie had offered to put me up for a few days at his parents’ house on Mill Street. He and Melinda were not ready to put people up in the Victorian, he said. They were just squatting there and most of the rooms were still empty, bare and raw. I would be more comfortable at his parents’. Or, if I needed my own space, I could stay at the Newton Hilton.

  Normally it is better for the mental health of writers and subjects if they spend some time apart during long days of interviewing. Otherwise profilers and their profilees get jumbled together in each other’s heads like cubist portraits. But I wanted to see the Heywoods at home, so I told Jamie that I would accept his parents’ offer and stay with them. I felt awkward and a little ashamed at the thought of staying with them in the middle of their crisis, even though the Heywoods wanted the publicity.

  In retrospect, I can see that the story already was jumbled in my head. The closer we came to the moment of truth, the more confusing the picture looked. I could no longer tell how much of our hope was real; and sometimes, when he was at his most electric and charismatic, I still wondered how much of Jamie was real. That past spring, in the Caribbean, Jacques Cohen’s babies had looked like a Solomonic problem. Now that we were in the thick of Jamie’s race, it looked monstrously complicated, too. The stakes felt higher every day. I bounced around among them like a pinball.

  At the time I felt ashamed of my own confusion. But confusion was inherent in the project. None of us could see far enough ahead to know what was right to do. Our hope and fear seemed to grow, the closer we came to the crisis. We were all agitated and we were all looking for signs.

  Jamie met me at Logan Airport. As we drove along Memorial Drive, on the Cambridge side of the Charles River, I glanced across to the Boston side and saw an amazing building gleaming in the dark above the water. It looked like a morph between a grand New England Victorian and a millennial palace, lit dramatically to give an impression of dark brick wings and much glass. It was a beautiful sight, ghostly and brown, Boston transfigured into a dream of the future, floating by itself above the dark river.

  “Genzyme,” Jamie said. He told me that it was a biotech company dedicated to orphan diseases. “They built the whole company on one disease they’ve cured,” he said. “Maybe one of the Hassidic disorders. A protein therapy. They make about 130 million a year off it.”

  I looked this up later. Genzyme’s first drug, Ceredase, was a treatment for Gaucher’s disease, a rare genetic disorder that can cause an enlarged spleen and liver, and neurological problems. When the company won government approval to market Ceredase in 1991, people at Genzyme thought only about one thousand people would use it. But the incidence of the disease had risen. That year there were nearly 3,000 people using Ceredase around the world. Under the Orphan Drug Act, a company that gets FDA approval for a drug first is granted seven years’ exclusive rights to sell it in the United States. Genzyme charged patients or their insurance companies as much as $170,000 a year for Ceredase, so the drug was a bonanza for the company. That year Genzyme was expecting sales of almost half a billion dollars.

  “ALS could represent a fifty-million-dollar market,” Jamie said as we drove on along the river. “People will fight for that.” Jamie was wrestling daily now with his choice of nonprofit or profit. He admitted that he still had the start-up itch. He was sure his gene therapy would be huge if it worked—and getting big-money investors would be a much faster way to get a lot more money for the project. Which way could he develop his therapy fastest? Should he partner with a company like Genzyme—fold himself into someone else’s company and lose control? Or should he retain control and build a start-up of his own? Running a nonprofit might be three or four times cheaper, by his reckoning, because people trust nonprofits. When no one stands to get rich, the surgeon volunteers. Hospital costs stay low. The FDA plays by different rules. If you do not have anything to gain, people believe in your data and intentions. Of course, if you sell your idea to Genzyme, you have a powerful company to make and market your drug. But the Heywoods’ friends and family and the congregants at Grace Church were not giving Jamie money so that he could get rich, and that is what would happen if he sold his gene therapy to Genzyme. “This is a really difficult topic,” Jamie said. “At some level, some little old lady’s dollars are going to make somebody money.”

  In the dark of the car, I looked at him. Occasionally I remembered that Jamie’s chances of success were still very small. More often, I felt as if he might be just a turn of the road from building something even grander than Genzyme. A new palace on the Charles River did not seem impossible.

  Well, I thought, if Jamie makes his fortune this way, trying to save his brother’s life, what is wrong with that? But I worried about the palace across the river. It was hard enough to think clearly about any of this without visions of gold rising in the dark. Matt and Jamie had incorporated their start-up a few days before, CNScience. They had other start-up names floating around, too, which they sometimes mentioned in passing: Uptake Pharmaceuticals, Neurologix. On my last call to Jamie to plan my trip to Newton, a new voice had answered the phone: Lizzie McEnany, another honorary Heywood, the daughter of one of Peggy’s oldest friends. Lizzie sounded very professional and about sixteen years old.

  “CNScience!” she said.

  “What?”

  “Doesn’t that sound good?” She laughed.

  Jamie owned the EAAT2 idea. He had made the first important description of the concept, and he would soon be filing for a patent on it. If anyone wanted to sell the idea to patients, they would need a series of patents, and one of them would now have to be Jamie’s. Unfortunately, there was already one patent on the EAAT2 gene. The scientists who found the gene had patented it. That was a problem, Jamie said. “In a market that’s worth only fifty million, you need to own the whole market or you’re crushed. You’ll never recover your costs. In pharma, it’s all of the marbles or none of the marbles. And that makes it nasty. That’s why drugs are so expensive.” To make the package he was developing attractive to Big Pharma, or profitable to CNScience, Jamie had to try to put a big package together.

  What if he went for the money? Or what if he did not, and then someone else did? He told me about his favorite Internet idea back at the Neurosciences Institute, his concept for getting commercials onto computer screens. He had walked away from that one when he went home to Newtonville. Now it was well funded. Someone else had gotten rich overnight with his idea. He had opened the Wall Street Journal one morning and there was his baby. “I’m pissed off about it!” he cried, and his kid’s voice broke with indignation.

  But Jamie was afraid that he would lose credibility with almost everyone—including me—if he did turn this into a race for profit, and he could not afford to lose credibility. The task of putting together something like this quickly was enormous. With his gene therapy, the paperwork alone would be monstrous, even though he now had Paola’s Canavan proposal to use as a template. Not long before, he told me, a company filing for approval from the FDA for a new drug had to send over four semitrailers full of data.

  As we entered Newtonville, I asked Jamie how his parents were doing. He gave me a techie’s answer. It was also a strikingly self-centered answer. “My mother is extremely sensitive to my state of mind,” he said. “She seems to have an amplified pickup to my state of excitement or depression. My dad is totally pumped.”

  Jamie turned onto Mill Street and swung into the driveway of his parents’ house. We cut across the backyard under a few tall trees. That September was warm in New England, and high above us I could see by the shadows against the sky that the trees’ crowns were still full. Jamie picked up a sledgehammer from where it leaned against one tree and propped it against the side of the po
rch. The back door was open, and John and Peggy Heywood met us in their kitchen. Peggy was in her robe. They each welcomed me as warmly as if I were an old friend. Peggy told me that Stephen and Wendy were sleeping in the Cave. Peggy had prepared one of their guest rooms upstairs: Jamie’s old room.

  I could not fall asleep that night. Sitting up in the bed, I flipped the pages of a travel book that I found on a shelf, The Happy Isles of Oceania, by Paul Theroux, who had toured the islands of the South Pacific alone in a folding kayak. The book reminded me of my own adventures in the Galápagos—which I remembered now as simpler than this one. Once in a tent at a beach camp with no other human beings for fifty miles around, I had scribbled in my notebook, “To be awakened by the dawn and Darwin’s finches.”

  When I told my mother about that adventure, back in her old kitchen in Providence, she shook her head. “What a romantic.”

  Sometimes now I wished I had never gotten into the subject of millennial medicine. I daydreamed about the Galápagos as if the islands were paradise. I wanted to go back to that tent.

  When I let myself hope for Jamie and Stephen, I knew that I got carried away. It was a little strange for me to feel hopeful when almost no one else was. Even Matt During was more excited about his own brainchildren. Whenever Matt told him that the neurovaccine made the rats smarter, Jamie would protest: “You don’t know much it scares me when you say that!” He did not want the treatment to do anything more to Stephen than what it had to do, he said: Save those dying nerves. If the neurovaccine changed the behavior of Matt’s rats, who knew what it might do to human beings? “Memory is a side effect!” Jamie would yell, again with his kid’s voice climbing and cracking on the high notes. “Memory is toxic!”

  Money can be toxic, too. How distracting would it be for both Matt and Jamie if they were trying to weigh their options for saving Stephen and at the same time they stood to get rich quick? And what role did I play in this, their exclusive shadow and storyteller? Just by having signed on, by bringing the promise of the gold seal of The New Yorker to their project, I might help them save a life, and make their fortunes. Or, if things went wrong, I might help hurry a death.