His Brother's Keeper

by Jonathan Weiner

  That year, the Human Genome Project was racing ahead and it gave hope to almost everyone in biology, from the most conservative to the most radical, that the new age of molecular medicine might be coming soon. When the project was done, humans would know the location and the code of every single human gene. The more we know about our genes and what they make, the more we understand where the making and remaking goes wrong. As the Human Genome Project matured, Matt predicted, more and more drug targets would appear. Then the immune system, which is so good at recognizing foreign invaders, could be trained to recognize hundreds or thousands of the malformed proteins the body itself has made. The Human Genome Project would teach us more and more about our own molecular engineering, and Matt and others would teach the immune system more and more tricks. Some mismade proteins it would clear away like a scalpel. Others it would neutralize. Still others it would modulate so that the proteins and their cellular neighbors could work correctly again.

  Matt was considering heart surgery for a first trial of his neurovaccine. Like a small stroke, heart surgery can damage the brain: Whenever there is an interruption in circulation, the brain loses some neurons. With the right neurovaccine, he could immunize people prophylactically and protect them against the damage.

  Teaching the immune system to heal what it could not heal without our help—Jamie found the idea visionary and thrilling. He knew just enough to talk gamely about it after his year at the Neurosciences Institute, since Edelman had won his Nobel Prize for his work on the immune system. Jamie urged Matt to consider a patient with ALS for his first test of the neurovaccine, since protection against glutamate damage there could mean everything.

  The lunch went so well that Jamie and Matt had dinner, too. Soon they were spending weekends sailing together, both talking at high velocity. Matt During’s apartment in Philadelphia is just a block or two from his laboratory, and Jamie began staying there often on his drives back and forth from Newton to Baltimore and Philadelphia while they planned the genetic engineering of Stephen. Paola Leone liked the project, too; from her first meeting with Jamie, she was deeply moved by the Heywoods’ crisis. Paola was as emotional and empathetic as Matt was pragmatic. Her office was decorated with photographs she had taken of Canavan toddlers, and half a dozen stuffed animals and scrawled drawings, presents from doomed little children. She shared her three-story Philadelphia row house with a cat, a rabbit, and two German shepherds, Gnocci and Bambi.

  Jamie told Stephen’s doctor, Bob Brown, about his project with Matt During. In Baltimore, he told Jeff Rothstein, the discoverer of the EAAT2 problem. Rothstein happily agreed to run the tests on ALS mice to see if an EAAT2 therapy did extend their lives. In Philadelphia, Jamie, Matt, and Paola planned to design and build a DNA package containing the EAAT2 gene. Gene therapists call this “the construct.”

  Once they had built the construct, they would inject it into the mice. If the DNA injections helped the mice, they would test the injections on monkeys to see if they did any harm. If the injections passed those tests, then Matt and Paola and their team at Jefferson would inject the DNA into Stephen.

  Jamie had now heard through the grapevine that Margaret Sutherland, the young researcher at Vanderbilt in Tennessee, had crossed some of her mice, which made too much EAAT2, with some ALS mice. He was very curious to know what had happened there. But injecting the DNA into the spines of the ALS mice would be the most direct test of his idea that they could try.

  Jamie, Matt, Paola, and some of the young scientists in their laboratory celebrated the plan at Paola’s row house in Philadelphia, and they all got drunk. Jamie and Matt played game after game of pool down in Paola’s basement. Jamie began trouncing Matt, and he could see that Matt was not taking it well. They are both competitive at everything they do, and Matt did not want to lose. Jamie liked seeing that. He needed a partner in this project who did not want to lose.

  Matt won the next round of pool.

  Jamie flew Matt up to Newton to meet his family. John and Peggy held a big dinner party, and all of the Heywoods feted Matt During.

  Twenty

  Moral Capital

  Now that Jamie had put his dream team together, he had to raise money. The whole family pitched in again to plan what Jamie billed as the First Annual Belly Dance Extravaganza. (That “First” was typical Jamie.)

  I once watched Melinda belly dance at Karoun, a Middle Eastern restaurant in Newtonville, the place where she earned her way as an undergraduate at Wellesley. Melinda danced out, clinking finger cymbals, wearing a costume of strings of coins and a pleased smile. The smile was not exactly a come-on smile. It was the smile of the dance.

  I was sitting at a table with John, Peggy, and Jamie. “Do you know which one she’s doing tonight, Peggy?” asked John, in his proper British accent, looking absolutely comfortable and at home.

  “Candles, I think.”

  Melinda laid a tray of burning candles on the floor. Then with a flourish she set it on her head and began to gyrate and undulate to the music. She looked very beautiful.

  “Well,” said John, “she started out as a young child, dancing with her mother. And danced pretty steadily since. Well, you know, trumpeters earn their way through college playing trumpet, and belly dancers earn their way through college belly dancing.”

  Melinda left the dance floor and came around the tables for tips. She gave Jamie a few knocks with her hip as she went by, explaining to the next table, “I know him.”

  “Melinda’s very good at this,” said John. “She keeps it very lighthearted and funny.”

  Jamie seeded her sequined girdle with a twenty. John inserted a ten. “We don’t get it back,” Peggy explained.

  I inserted three ones.

  “Excellent technique,” said Melinda.

  She and her sister Piper had been dancing for drachmas and dollars since the age of seven. They said they would be happy to shimmy for the Heywood family cause with their trays of burning candles, their jugglers’ torches and impossibly balanced swords.

  “Beauty, brains, and a back,” said Melinda.

  Down in the basement, where they planned the extravaganza, Jamie paced between the door-desk and the workbench and delivered speeches about the mission of the new foundation, and what they were about to make possible. Usually his audience consisted of Melinda, Peggy, and Robert. Stephen and his carpenter’s assistant kept passing through, tromping up and down the stairs.

  Stephen was still working on his parents’ master bathroom. He had expanded the project to include a home office for Peggy at the landing at the top of the stairs, with skylights at clever angles to let in maximum light. Like Jamie, he always had a way of drawing high-powered people into his projects. His carpenter’s helper this time was a two-star marine general with Purple Hearts from Vietnam, a retired man of about sixty with a bit of a limp. Since retiring from the army, John Brickley had served as director of the American Lung Association in Massachusetts. Stephen hired him in the middle of all this action on their home front. Brickley said he wanted to learn carpentry from a pro. Stephen paid him the standard wages of a carpenter’s apprentice. He and the general were a match in manly taciturnity and neither ever talked about the other’s limp. Whenever any of the Heywoods told Brickley how much they appreciated his help, he would shrug. There’s only so much golf you can play.

  Jamie’s speeches in the basement were also typical Jamie—raising the ante. He barely had his ducks in a row, and he and Melinda were agonized that they were paying Robert’s salary, and buying a two-thousand-dollar printer, and living in the house on Mill Street, all on his parents’ money—while slowly running out of money themselves. But Jamie foresaw an organization that would work like a machine to cure one incurable disease after another. They could do it. He could see the whole thing in his head. Again and again he explained that ALS is an orphan disease, too small and too baffling to be worth even a minor investment by a pharmaceutical house. Merck or Pfizer would not gamble the time or
money on basic research in ALS: too long a shot for too small a pot. But if, with a small investment, Jamie and his team could show that his EAAT2 gene therapy idea or Matt During’s neurovaccine was promising, then a biotech like Genzyme would be interested. Then they might spend a few million dollars to develop it.

  “Contrast ALS with heart disease,” Jamie would say. “This stroke stuff of Matt’s—when that paper of his comes out, people are going to be clamoring at the door to get it. The neurovaccine is going to be worth billions, so an investment now of a few million is totally worth it.”

  Jamie was dreaming there, pumping himself up and pumping his troops. He did that often. Of course, it was impossible for any of them to know what might be about to happen and what would never happen. So much more had already happened than any of them had expected when Jamie came home from California. When you listened to Jamie, it was easy to forget that gene therapy had not yet saved a soul.

  He was thrilled by the idea of combining a nonprofit foundation with a corporate spirit. As a desperate entrepreneur, not a scientist, he was sure that he could make science race ahead. “Research is slow,” Jamie would say. “Development is fast.” They would yank EAAT2 out of the doldrums of academia. “You get it out of the hands of PhDs and into the hands of technicians, who actually work for a living.”

  That was pure Jamie. It was also typical of the tension between activists and scientists. Activists want action. Scientists want knowledge—for its own sake, and for the infinite and unpredictable ways that knowledge can help lead to action. Not long ago a famous biologist told the actor and activist Christopher Reeve, “You can never do enough basic science.” The Christopher Reeve Paralysis Foundation no longer supports that biologist.

  “I’m just saying all these things for the first time out loud,” Jamie would say, for the tenth time, pacing up and down in the basement, and building castles in the air with the money they hoped they were about to raise. He foresaw a staff of roving scientists who would read everything new in the literature, like Joe Gally, and go out to talk to people in every field on the borders of ALS, hunting for clues. “These are the kind of things that science is both good at and bad at. Epilepsy researchers don’t talk to ALS researchers. It just doesn’t happen. They don’t go to the same conferences.”

  He harped on epilepsy because he was thinking of the young researcher Margaret Sutherland in Tennessee. By now the litter of mice she had gotten by breeding ALS mice and the mouse she had engineered, a mouse that made extra EAAT2, must be growing up. But she was not talking about them. She was a young scientist, and it was the kind of side project that could go on for years, without a publication in the scientific literature and without ALS people ever even hearing about it.

  Jamie saw himself as the impresario of a band of scientific operators. He would be a sort of Robin Hood of WIIF’M, convincing the rich to give to the poor, winning by brains, charm, cunning, moral capital, and super salesmanship. “There is all this amazing stuff going on out there in science,” Jamie said. “We’re acting here as a moral venture firm. We are a venture firm operating in the interest of our shareholders—which is the survival of the patients who have ALS now. Moral capitalism! That is one of our greatest resources, our degree of moral capital! How much do we have in the bank? We have a lot in the bank! Basically we have unlimited funds in terms of moral capital.”

  The spring of 1999 was the perfect time for a millennial venture. Technology start-ups were raising ridiculous amounts of money. The tide that had raised real estate values in Palo Alto and made Stephen’s cottage sell for almost a million dollars was now lifting all boats. On the stock market, eBay was trading for almost 4,000 times earnings. The ratios at Amazon.com and Priceline.com were even better. Their ratios were infinitely better, as one market cynic pointed out a little later, since their stocks were skyrocketing and they had no earnings at all. In Silicon Valley, the founder of Netscape was now dreaming of swallowing up the whole health-care industry in a sort of giant Pharma.com he called Healtheon.

  Investors with stakes in the Valley were looking at biotech. Wall Street put six billion dollars into biotech that year. That was six times more than the Street had invested the year before. It was sixty times more than investors had thought the industry was worth ten years before. The investment frenzy fed on itself. Leaders of biotechs could turn around and use investors’ mania to raise more money and draw new recruits. William Haseltine, the director of Human Genome Sciences, an apostle of regenerative medicine, gave a talk to grad students at Johns Hopkins that spring titled “A Coming of Age.” “Accompanying the exploding interest in genomics,” he said, “our stock price has nearly tripled in the past six and a half months.”

  Melinda still danced at Karoun one night a week, and the owners treated the Heywoods like family. They turned their place over for the First Annual Belly Dance Extravaganza at cost.

  “My parents were a little nervous about asking for money from their friends and stuff like that, but they did,” Stephen told me a little later. “I know that’s been quite hard. Also, my dad asking his colleagues I think was quite difficult.” But John and Peggy each wrote letters to friends and family, and Jamie and Melinda and Robert called everyone they could think of. At the same time they encouraged Stephen and Wendy to live their lives. They did not want them to lose their time alone together. The two of them were now deeply absorbed in each other and trying to forget how short a time they might have. On the night of June 1, 1999, Wendy wrote in her journal:

  One-half hour of the first day of June left. Nine months with Stephen, nine wonderful months. I knew I had love in my future, but I never dreamed I could be this happy.

  I stop sometimes, my foot drags just so in the middle of a quick step, my stomach drops and silently I plead, No. I’ve made so many deals with God of late I am up to my eyeballs in religious debt. It is impossible for me to believe I would be without this most wonderful, giving, sweet man. How lucky I am to have this incredible man in my life.

  Sometimes I want to rush things, marry him, have children. Do it now. But I want him to be happy with his time-frame for his plans. I know he has our future mapped out in his head and it’s a route I’d never doubt. I trust him. And, the rushing feeling always follows some discussion about ALS. Although part of me wishes I had a ring to wear for my visit home. Christ, I feel like such a girl for writing that!

  On the night of June 3, 1999, every seat in Karoun was taken by scientists, Heywoods, honorary Heywoods, neighbors, well-wishers, congregants from Grace Church. Jamie made a speech praising the extraordinary scientists in the room. He explained that he was concentrating on gene therapy because that was the fastest way he could get a treatment into Stephen. He spoke with honorable realism of his chances—more realism than he normally allowed himself. But he was candid about his need for optimism in the face of his chances. “I’ve struggled with this. A few months ago—well, I say that, but actually it was only a few weeks ago—I made the decision to believe that we can do this. We can beat this disease.

  “Time is the only thing that matters,” Jamie said. “I cannot make this clear enough. Time is the only thing I cannot go out and get more of.

  “Now I’d like to hand this over to my brother, who promises to lighten it up.”

  Stephen stepped up to the microphone. He was two weeks away from his thirtieth birthday. He still looked very fit, taller and sturdier than Jamie. He told the crowd that he thought Jamie’s enterprise was like an Internet stock. He meant that it was young, innovative, glamorous, and they would all enjoy spectacular returns on their investments.

  He and Ben had always been movie freaks, Stephen said. “We don’t necessarily like good movies. We like Hollywood movies. And one thing Hollywood is great at is a tearjerker. The scene that always gets me in a Hollywood movie is when someone dies to save someone else’s life.” Lately, Stephen went on, he found himself imagining a situation like that more and more often. In his daydreams he died a heroi
c death, rescuing a family of five from a fire. “Except I’ll be in a wheelchair, so it will have to be a very slow fire, in a house with ramps.” Sometimes he wondered why he was daydreaming like that. When he tried to explain it to himself, he said, other clichés came into his mind, like the old line, “You have to live your life like every day is your last. Which I think is ridiculous,” Stephen added, “because you’d be hung-over every morning, and no one would ever take out the garbage.” Still, Stephen guessed that he was giving himself that Hollywood ending because he wanted his life to have meaning. “Another cliché.”

  Jamie had given him a great gift, Stephen said. “It’s the ability to live my life, with my friends and family, as I see fit, while knowing that my life will have meaning. I know that my illness will save other people’s lives. So, Jamie, thank you.

  “You all know my family,” Stephen said. “Many of you know me. I personally guarantee that out of this will come a breakthrough, a treatment, or a cure.”

  Stephen made his way back to his table, and Robert Bonazoli took the microphone. “There’s an old saying, ‘If I can’t dance, I don’t want to be a part of your revolution,’ ” Robert said. “Well, if there’s one thing we have in our revolution, it’s people who can dance.”