I glanced over at Stephen’s room. The door stood open. I was glad he was out.
Katherine urged Jamie to make an informal call to the FDA and talk over his plans. But Jamie did not want to do it. “My bullshit capability’s not quite up to calling the FDA and saying, ‘I want to do this,’ ” Jamie said.
Next they turned to the toxicity study. They were testing each version of their viral capsule on mice and rats. A woman from Toxikon, a huge animal lab that does a lot of studies, had volunteered to consult on that.
“Awful name,” Jamie said. “Almost as bad as StressGen.” Jamie shepherded them onward through their list of to-dos. “Develop action plan,” he read aloud. That was on Jamie’s list. “I thought about it,” he reported. General laughter. “Actually, we got nearer than that.”
Jamie said he was working on their medical advisory board and he was trying to land one more celebrated biologist. “The hook is set,” Jamie said. “I want to let the fish swim around a little longer before we yank ’m.” He asked Lizzie to try to set up their next meeting. “I’d much rather do the sale in person.”
Although he was focused on the gene therapy, he was also eager to back the ALS vaccine. “We gotta get on the ball on this,” he said. “As soon as the vaccine comes out, I want it splashed across the world that we—I want to own it.”
Katherine asked where Matt During’s neurovaccine paper was. Jamie explained that Matt was getting critical reviews. “He’s got to do more experiments.”
“What are they objecting to?”
“It’s completely new. His last reviewers said, ‘This contradicts everything we think we know about the immune system.’ ”
I saw Katherine’s face register that.
Jamie went through the long and still-growing list of treatments that he and Matt had invented so far. The two cowboys’ capacity for monumental dreams had made a nightmare of their to-do list. The gene therapy alone was getting very complicated. “We’ve got Uptake,” Jamie began, meaning the glutamate uptake project, his EAAT2 gene therapy. “Two different possible technologies, three different promoters, and a couple of switches. So twelve different molecules we can use. Matt and I are talking about how we can narrow them down.”
“Good,” said Katherine.
“The safest molecule we can’t make,” Jamie said. “It’s too big.”
Stephen chose just that moment to walk back into the house. He stalked through the dining room silently with a glower and closed his door.
After a pause Jamie continued. The talk about the construct got technical. They hoped Dave Poulsen at Matt During’s lab was on schedule for October delivery. “Thing is, the technology keeps breaking,” Jamie complained. With gene therapy, most of the trick is getting a useful gene to insert itself in the right place and turn on. But gene therapists also want to be able to switch it off, if they have to. Genetic switches are finicky.
“We need to know the neural consequences,” Jamie went on. “We’re trying to decide, do we do the brain and spine or just spine? And we need to decide which of these twelve molecules we’re going to use. We could run a monkey trial—two monkeys with spine, two monkeys with brain.”
Lizzie sucked on a lollipop and scribbled minutes.
Rob tried to sum up the state of the construct. “So the point is, for me, we have many versions of the gunk. How do we boil it down to decide which gunk to use?”
He meant they had too many options, too many ways to put the construct together: too many different kinds of switches, enhancers, promoters. It was as if they had too many pieces in their LEGO set.
“Well, what’s really annoying is, I would rather inject the switched form into Stephen,” Jamie said again, “because then we could switch it off!”
“Maybe we have too much to choose from,” Katherine said.
I knew all this technology from the fly biologists I had hung around with for my last book. The fly guys had also spent their time designing experiments in which they inserted genes into their subjects and switched them on and off. I scrawled in my notebook, “What a difference a day makes.” In his fly lab at Cold Spring Harbor, Tim Tully had once said to me, “Thank God I just work on flies.” In another fly lab I had seen an old cartoon on the wall: a group of masked and gowned surgeons and nurses around the operating table, preparing for the first incision in a patient with six legs. The caption said, “He’s a very sick fly.”
I wondered what this meeting was like for Stephen to overhear or tune out. In his place I might have played computer games, too.
Jamie taped up a new master plan on the wall: “UPTAKE: GETTING TO THE GUNK!” The gunk was the stuff they would inject into Stephen’s spine. Jamie was so excited to be approaching his goal that he seemed to forget that gene therapy had never worked. “This is totally cool!” he cried.
“Now, ‘Uptake—Manufacturing,’ ” Robert announced.
“Could you not think in shorthand?” Jamie asked.
“I can. It’s just not your shorthand. I’m not in your head, you know.”
“You guys have been together too long,” said Katherine.
“We have. I think we need marriage counseling,” said Robert.
Now they talked about biotechs in Germany, scientists in Switzerland, regulations and their rationale, transporting the gunk across state lines. Katherine Evans kept coming back to the rules of the game. “It’s not something that’s tweeze-apartable by logic,” Katherine explained, when Jamie protested. “It’s not about common sense. It’s what the regulations are.”
They would try out the procedure on monkeys first. They would get the monkeys from medical supply houses. Unlike the rats and mice, the monkeys would not have ALS. But monkeys have much more humanlike spines, brains, and immune systems. “I’ll tell you, I used to have moderately mixed feelings about animal tests,” Jamie said. “But when you’re trying to decide what to do for your brother, your perspective changes quickly.” He thought the injections would probably go into the spine, not the brain. “You don’t die if you lose your spine.”
“What does it do in the brain?” asked Katherine.
“You can lose a lot. So I’d rather do the spine. If you dump into the brain, you’ve changed a major neurotransmitter.” He meant glutamate. “I don’t feel good about that. You’ve changed how you think. I guess we’re going to go spinal.”
“Isn’t this about as much as we can do today?” Katherine asked.
Jamie looked at his watch. “It’s still twenty minutes to five,” he said, in a tone of mock reproach.
“Each one of these is a lot of work,” Katherine said, pointing at the long list of to-do items on the chart. “When you get down to the nitty-gritty and the nitty-gritty beyond that, it’s a lot of work. Which translates to time.” She asked Jamie how much time he thought it would all take.
“I think this is two people in Matt’s lab for eight weeks, based on Matt’s infrastructure.”
“If this was a real clinical trial for Merck,” Katherine said, “it would be thirty people or so.” Although Jamie talked in wilder moments as if he had a hundred, in reality he was relying on the people in that room, the reluctant postdoc Dave Poulsen at Matt During’s lab, and a few other postdocs in Baltimore and Auckland.
Jamie told her he thought they might know what the gunk should be by November 1, a little over a month.
“You know, there is a thing about haste, in drug development,” Katherine said. “There is economy here,” she said, pointing at the neat flowchart she had drawn on her yellow legal pad, when she laid out the standard path a drug takes from invention to delivery. “Economy in doing one step at a time. As opposed to doing everything in parallel.” She had a solid, level, truth-talking tone. She was asking sharp questions, again and again. A middle-aged product manager has met many cowboys and self-made matadors, and knows how most of them end up.
“Put down November 15, we start safety,” Jamie said. “That’s pretty aggressive,” he acknowledged to
Katherine.
“Yeah,” Katherine said, as if he had just stated something too obvious to mention.
“I can do it.”
“No problem for you, Jamie.”
They both looked at the list they had just made. I could see what Katherine meant. The list looked impossible.
It was 4:55. “We need to do assignments now,” Katherine told Jamie.
“In the last five minutes,” Jamie noted.
“Jamie’s going to do it all!” Katherine announced. Everyone laughed and the meeting broke up. While Robert gathered up the loose papers, Katherine and I talked quietly at the far end of the dining-room table. “They’re not full of self-pity,” Katherine said. “If they had that element of self-pity, you could almost not stand it. I like them. I feel maternal. I like their spirit. I think Jamie will always find people to help him.
“But it’s a lot of work, it’s a lot of politics, a lot of sensitivities, and we don’t know what the results will be. I think Jamie is in a unique situation. Because he’s not a scientist, not an ALS researcher, you could quibble whether he’s picked the right project. Well, I think that’s almost beside the point, if you know what I mean. Why would a layman be able to pick something to do that the researchers in the field didn’t pick?”
Melinda overheard that. She was walking through the dining room with her wet hair done up in a towel, rubbing her belly and nibbling another rice cake. Melinda was belly dancing at Karoun that night, in spite of her sick stomach.
“The answer is that it’s Jamie!” she said. “That’s always the answer! Really!” She stretched tall, shooting both arms up in a V in the open doorway, and shouted, in mock-cheerleader style, “It’s the Jamie Factor!”
Katherine Evans disappeared from the scene soon after that. She was out of the picture—or at least, she was out of the picture that Jamie was trying to paint for me. I never heard him mention her name again.
Twenty-Eight
Generation X
On Saturday night, Peggy served a minor feast in the solarium. After dinner, Jamie and Stephen put their long legs up on the ledge of the wainscoting and faced each other like bookends from opposite ends of the table. They talked with John and Peggy about tools, houses, real estate, and the stock market. Stephen found it hard to imagine that the market could ever go down.
“It can happen, children,” said Peggy.
“I don’t doubt that the economy can do other than expand,” Stephen said, “but until it happens I won’t believe it.” He had just read an editorial in the Boston Globe that made him happy. It was a defense of Generation X. People laugh at us, Stephen said, people make jokes. “And yet we’re the ones driving the economy!”
“Oh, yeah,” said Jamie, sarcastically.
“Well, it’s true!” Stephen said, his voice climbing an octave just the way Jamie’s did when he got excited or indignant. By then the giddiness of the stock market rise was beginning to seem like the new state of the universe. Here and there, money people were talking about a bubble, but software engineers in the Valley were holding on to their stocks. “Nobody wants cash: it’s too final,” one Silicon Valley investment analyst had written that summer in the Wall Street Journal. Why trade stocks for dollars? Behind the dollars stood Uncle Sam—just old Uncle Sam. “Internet paper, on the other hand, is backed by smart entrepreneurs who work like dogs through the night to change the world.” The engineers were bringing us the future in the fall of ’99.
During Stephen’s speech, Jamie stared at him from the other end of the table. Stephen caught his look and flushed. Between the two of them, it was Jamie who represented the smart entrepreneurs who worked like dogs through the night. Stephen was on the whatever side of Generation X. He was the grasshopper among the ants. He had built his first house with credit card debt, two mortgages, loans from his brothers and his parents. He confessed that he had even bought his Harley when he was in debt. Then one month before he finished his house, the Harley was stolen.
This was Peggy’s cue to cry, ritually and ruefully, “It was a miracle!”
I told them how much I enjoyed these meals with them in their wonderful solarium. Stephen said he once had plans to renovate an old farmhouse in Vermont. He made blueprints for a silo, a greenhouse, and even a solarium like the one we were sitting in. With innovations in heating and cooling, a glassed-in porch could work even in Vermont. His solarium design would stay warm in the worst New England winters. “This is not that crazy,” Stephen said.
“This is not crazy?” said Jamie.
“It was brilliant,” said his mother.
“Shit, when’s your birthday?” Stephen asked Jamie suddenly, looking stricken. “November 4? October 4?” His voice climbed an octave again. “Shit! What do you want?”
“A router-planer.” Jamie went back on the attack. “What the hell are you doing renting a fourth-floor walk-up?”
“He’s an optimist, and so am I,” said Peggy, warmly. “Besides, he needs the exercise. Don’t you, Stephen?”
The four of them talked late while I listened, admiring the gallant way they all held up under the weight. There was the weight of hope and there was the weight of knowledge—the weight of the way things are. The odds against Jamie’s plan were so long that hope hurt: Hope almost felt like the heavier weight. When the dinner-table talk finally broke up that night, Stephen apologized to me for the intensity of the story that they had lured me into.
“I’m just passing through,” I said. “If you can handle it, I can handle it.”
“We’ve adapted,” Stephen said. “You’re going to come out of this with the bends.”
It was Saturday night, and Jamie and Stephen decided to make it another Boys’ Night Out. They drove back to the Victorian that John and Peggy had bought them. Every Boys’ Night Out they played Quake on the foundation’s computers with Robert Bonazoli.
Since I was not interested in computer games, I stayed at John and Peggy’s. We cleared the dishes. Peggy wondered why it was almost always boys who played those games. It was very mysterious. Her sons had been playing them forever. Stephen had taught Dungeons and Dragons at an arts camp in Newton. Jamie and Ben had run the group. That was in pre-computer days.
Maybe this was a story of genes and behavior, nature and nurture, Peggy said. The passion for these games certainly came from the boys themselves. “No one tells the boys they should play these games.”
“Actually,” I said, “everyone tells the boys they shouldn’t play these games.”
“You keep wondering what skills they’re learning that will be ‘useful in later life.’ ”
When we had cleaned up, John Heywood and I went into the Heywoods’ den. He was usually so quiet that I wanted to talk with him alone to get to know him a little better. In the Heywood family, Peggy talked and supported and understood. John did not talk as much, but he also supported, and his sons felt he also understood.
John belongs to a singing group called The Grace Notes. It was started by a former teacher of Jamie’s. The leader of the group seems to think of John as the very model of the Dignified Englishman, so he is always casting him against type—making him “Honey Bun” from South Pacific in a coconut bra. That month John was rehearsing “Well, Did You Evah” by Cole Porter whenever he was stuck at stoplights and airports.
What a swell party, a swelligent, elegant party this is!
John spoke with a deliberate distance, an effort to survey from a height, to speak with composure and long perspective. A British cool that was not frosty. He told me how much he valued the closeness of his sons and his family—I think that was what mattered to him, not the nature of Jamie’s project but that he was doing it, that Stephen had come home when he was sick and that Jamie had come home to try to save him. John had not grown up in such a family himself. “My family is small. Peggy’s one of five. And they all have kids. And they all get together. Very different from mine. And, any excuse. Well, not just any excuse, but they get together often. I’
ve learned a lot about extended family from her. And our kids have picked that up, too.”
When I asked John what he thought about Jamie’s chances with his gene therapy, I was surprised to hear how pessimistic he was. That was an even bigger surprise than when I had asked Matt During the same question. “You’re not going to hit a home run the first time,” John said. “In fact, it’s unwise to try.” He served on Jamie’s board of advisers and went to the weekly meetings. But he let me understand that he stayed out of it for the most part because this was Jamie’s project. His role in the family was to be the provider. “My job is to do my job so there’s a good income coming in.” They had to be saving for later, John said, staring down at his hands, his palms cupped upward. Stephen’s illness would soon be costing them almost $200,000 a year.
While we were talking, the phone began ringing and ringing in the kitchen, and we ignored it. Peggy had already gone to bed. The phone kept ringing. A few rings, then stop, then a few rings again. The answering machine was turned on, and I thought I could hear shouting from each message. Finally I told John that we should answer the phone. When he played back the tape in the kitchen, we heard Jamie’s voice. He was calling from the Victorian. He sounded elated, almost manic. “Pick up the phone! Dad, pick up the phone!”
When we phoned Jamie, he was still shouting. John put the call on speakerphone so we could both hear Jamie’s voice: “Jeff Rothstein just called me. He met with Marge Sutherland. The mouse is still alive! It is so far beyond any record that Jeff is jumping up and down. He’s off the charts.”
Stephen got on the line, too. He shouted, “The mouse that should be dead is still alive!”
Margaret Sutherland was the young epilepsy researcher at Vanderbilt. Rothstein had just bumped into her at a neurosciences meeting and asked her how her work was going. And she had told him. And then Jeff had called Jamie. They had both been waiting all year to hear about her experiment. Sutherland told Rothstein that she had crossed just one ALS mouse with one EAAT2 mouse. In that litter, only a single mouse had inherited both the ALS and EAAT2 genes. That mouse had gotten both the poison and what Jamie hoped was the antidote. All of the other mice in the litter had died as expected, at the age of five months, paralyzed and choking.
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