On and on, around and around he went. With the gene therapy, the foundation supported the work. There, both legally and ethically he could not profit, and yet he was sorely tempted to take it to Genzyme and sell it for millions and make it happen fast. In that case, my God, why was he not entitled to make money?
Why not, I thought, if he saved Stephen? Jeff Rothstein had told me what the end is like in ALS. He said most people, even most physicians, have no idea what it is like. It is even worse than the deaths of the fishermen in A Perfect Storm. “It’s like drowning, only prolonged. People just can’t suck in enough air. For some patients it lasts for weeks, for most it’s months. Slow lack of air, a constant air hunger. Oh, yeah, it’s horrible, it really is. And there’s nothing they can be given to be made more comfortable. We give people an external ventilator, but it can’t compensate in the long run for the lack of diaphragmatic breathing. There’s just not enough strength to bring enough air through your mouth and into your lungs. You’re suffocating, your breathing capacity keeps diminishing, your blood chemistry changes, and finally you have a heart attack.”
That afternoon Jamie delivered an eloquent lecture in the Socratic style, question and answer, question and answer, and by the end of it I was convinced that he should save Stephen for profit as fast as he possibly could and get rich.
We came into view of Manhattan. It was a beautifully clear, almost hazeless day in early September, one of those days when from many miles around you could see all the way to the towers of the World Trade Center. Did I notice them that day? In my memory, they seem to stand on the horizon like the twin towers of Jamie’s dream. I studied Jamie’s face in profile at the wheel, the way I had when we passed Genzyme on the way to his house, the biotech that had built itself on a single orphan disease. I thought that I had never seen anyone so young, gifted, ambitious, and deserving of a fortune. I would make his legend. I wanted to say, Jamie, if your cure works, and you form a company, I will quit my job and come work for you myself.
He finished his speech just as we pulled off onto the West Side Highway. The traffic slowed in every lane and he could no longer speed. After a monologue of five hours he seemed just as wired as ever. He kept worrying and gnawing his dilemma.
“A woman comes up to me in church today, and she says, ‘I was cleaning out an old purse,’ ” Jamie told me. “She holds up a twenty-dollar bill. ‘Do you take cash?’ ”
From the backseat Stephen broke a long silence.
“Who?”
It was the first word he had spoken for hours. His voice sounded thin, high, reedy, and small. I wondered if that strange reediness after his long silence was one of the first signs that the ALS had begun to touch his ability to talk.
“What?” Jamie asked sharply.
“Who was it?” Stephen asked again.
“Mrs. Smith.”
“How’s Mr. Smith?”
“Emphysema. A nasty disease. Don’t get that.”
Suddenly I felt for the hundredth time that Jamie was acting a part, even when he was agonizing. For one horrible moment I even wondered if any of this story was real at all.
Maybe Jamie was sincere in all this manic agonizing; or maybe he was only manipulating me into giving him my blessing. Maybe this was all just a game of bait and switch: The prize was The New Yorker, and the fortune that seemed almost in reach.
“Jamie,” I blurted out, “are you shitting me?”
“No, I’m not,” he said. “Am I, Stephen?”
“No,” said that awful voice from the backseat. “He’s not.”
We met up with Melinda and Wendy at Melinda’s father’s apartment in Chelsea. Phil Marsh’s apartment was large and sprawling, by New York standards, and the wiring work that Jamie had done was still neat, tidy, and rational. Everyone settled down on the sofas in the living room to watch The Simpsons. During the first commercial, Stephen said he had forgotten to pack a belt. He asked Jamie to lend him his. He claimed that Jamie had once stolen one of his. Jamie denied that. Phil lent Stephen a belt.
It was time for me to go check into a hotel and get some sleep. I was desperate to be alone again. But Jamie was still wired and he rode the elevator down with me to put in a few more words while I hailed a cab. Out in the street, the sun had set. The cars and trucks were turning on their lights. They were almost bumper to bumper, but they sped almost as fast as they had on Route 95. Jamie stepped down off the curb and raised both his hands. Why was I letting him flag me a cab? I had cast him as a hero, and now he would not stop acting like a hero, even when I wanted to get away. The traffic made Jamie launch full-tilt into a lecture on a new topic: global warming.
I looked at Jamie as he stood there at the curb, young, tall, handsome, elated, as incandescent with power, light, and hubris as he had been that morning by the Honeywell Club. He told me about his father’s latest work at the Sloan Automotive Laboratory to reduce greenhouse gas emissions, to help treat the planetary fever. Suddenly I felt tired and mean.
“That’s even more heroic,” I said.
“He’s not trying to cure the problem,” said Jamie, and hailed my cab.
Thirty-Two
The Sharks I Am Afraid Of
The next morning, we piled into Jamie’s car again and got back onto 95, heading for Matt During’s laboratory in Philadelphia. Jamie and I sat in the front, Stephen and Wendy in the back. Melinda was staying in New York to spend the day with her father.
As we sped down toward Philadelphia, Jamie talked with the same manic intensity as he had the day before, while Stephen and Wendy murmured to each other in the backseat. Jamie lectured me about the future of artificial intelligence. He talked about computer networks and neural networks at the Neurosciences Institute. He explained his plans for start-ups, his old hopes for turning the institute’s ideas into gold.
I told him about a friend I had known back in my student days who had hacked into the Ma Bell telephone system as a freshman at MIT. My friend had built some kind of electronic noisemaker that emitted a series of R2D2 whistles into the mouthpiece of a pay phone and gave him free calls anywhere in the world for as long as he liked.
“And now he’s a billionaire,” Jamie said.
“Actually, he became a geologist.”
“Big mistake.”
“No, it wasn’t a mistake, Jamie,” I said. I was angry again. “He did what he wanted to do, because he loved doing it.”
“Ah,” Jamie said. “I can hear the wheels turning.”
I thought, This guy is way ahead of me. He was also driving eighty-five miles an hour. He changed lanes suddenly.
“Slow down!” Stephen said in his reedy voice.
“You didn’t used to be this fucking paranoid before you got sick,” Jamie said. He swerved into a new lane.
Stephen protested again.
I craned around to look at him in the backseat.
“I’m glad you’re looking out for us.”
Stephen had his arm around Wendy. He gave me a look. “It’s us I’m looking out for,” he said. He said it in a sort of flat black voice, absolutely without intonation. He left it to me to figure out that the word to italicize was us. Remember us? Do not lose sight of us.
Long afterward, Jamie and I talked about that trip and the strangeness in Stephen’s voice. He had heard it, too. “It was emotion,” Jamie said. “I think there was a fair amount of emotion—partly about the visit to Matt’s lab, and partly about you. He was feeling like a subject. He felt that I was not taking him along because he was my cool brother but because I wanted him to be a poster child for my project. He didn’t relish that role—it was like he was on display. None of us in our family is good at playing that role. I think Stephen was wondering, ‘Why am I doing this? What am I adding here? I’m just a symbol.’ And Wendy being there. There was a lot going on.
“I never did that again. I didn’t put him on display again. Paola, I love her, and Matt is just a joy for me to be around, but they were my friends. I don’t
think Stephen really cared about seeing the lab. What I was doing was bringing up the emotional level for my team. You use the tools you have. Stephen wouldn’t say anything, but you heard the emotion in his voice.”
In Matt During’s office, there was the same picture on the calendar for September of 1999, the sculpture by Rodin. I wondered if it was a present from Jamie from the Louvre, a subtle reminder to Matt, like the ALS pillow that Jamie kept promising to Dave. One of the pictures in the calendar was Rodin’s L’Adieu, a marble head with white gracile fingers raised to the lips.
Jamie made brisk introductions and got down to business.
“So I have some interesting news, Matt.”
He told Matt the story all over again. The mouse was almost ten months old. “Jeff was jumping up and down! He was pumped!”
Matt listened at his desk with his eyebrows crooked upward, tight creases around his mouth and eyes, and scribbled notes. The beautiful screen saver on Matt’s computer monitor was a false-color scan of the human hippocampus.
“Good, good,” said Matt. “Do you know what promoter she used?”
Now their conversation became technical. It had to do with the additions that go along with a gene to make it work, to make it express itself properly.
Jamie explained to Matt that mice with too many EAAT2 pumps seemed to be perfectly healthy. “Only thing is, they don’t learn,” he said.
“What do you mean, they don’t learn?”
Jamie told him about the maze tests the mice had failed.
“That makes sense,” said Matt.
“Yes. If they don’t have enough glutamate in the cells, that’s a problem.”
To Jamie the best part of the news was that it implied he was right: He was interfering with the right molecule in the neural cascade.
Matt listened in his “Thinker” pose, under the Rodin on the calendar. “Makes sense,” he said again.
“How far have you gotten to searching down the rights to the stuff?” Jamie asked.
Meanwhile Stephen and Wendy had picked up some reprints of Matt’s scientific papers from his coffee table.
Matt’s colleague Paola Leone came in to join the meeting.
“I was just reading your paper, or trying to,” Stephen told her politely.
Jamie went on talking to Matt, talking strategy now. “Not to get political about this stuff, but to get political…”
Wendy wore her big platinum engagement ring. She leafed through a journal, skimming a story with the headline “When Smoke Gets in Your Genes.” She and Stephen both looked tense.
I told Wendy softly that Matt and Jamie looked like brothers.
“Only Matt looks more rugged,” said Stephen.
“I’ve lived a harder life,” Matt said from his desk as he sketched various DNA cocktails for Jamie on Post-it notes. The sketches looked like little rows of boxcars: promoters up front linked to genes linked to more attachments ending at the caboose of the stop codon. Matt scrawled acronyms above some of the boxcars.
What he was diagramming was a little length of artificial DNA, the piece of DNA they would inject into Stephen’s spine. They had figured out what they were going to inject into Stephen now. The hollowed-out viruses they would use would carry very little DNA of their own: All but a few percent would be deleted. So each virus capsule would be essentially an empty syringe. And into each one they would pack that single linear strand of DNA composed of a promoter to make the gene work, and then the gene itself, and then a little more genetic apparatus, including a piece of DNA called woodchuck hepatitis virus postregulatory element.
The woodchuck element was an innovation that Matt had picked up from another genetic engineer, Tom Hope of the Salk Institute. In some tests a fragment of woodchuck element boosted the productivity of the gene he injected by more than fortyfold. Matt had been the first to use the woodchuck element in adeno-associated virus. In one test, he injected the virus loaded with the woodchuck promoter and also a luciferase gene from a firefly into a rat’s brain. He could see that the gene got where he aimed it, and that it switched on, because the nerve cells around the tip of the needle lit up and glowed green.
They also had figured out how to get this artificial piece of DNA to the cells that needed it in Stephen’s spine. They could concentrate the virus particles at more than 10,000,000,000,000 per microliter in a vial. Injecting three microliters in one spot would be enough to reach nerve cells extending several millimeters all around the tip of the needle. And the surgeon Fred Simeone, chairman of the neurology department at Jefferson, had decided how he would get the needle into the cervical spinal cord. He would go in from the front, through the throat.
Though the treatment they were planning was highly experimental, there were so many desperate ALS patients that Jamie and Matt did not expect any trouble finding twenty-five volunteers between the ages of eighteen and eighty who would be willing and able to give informed consent. They would not even have to advertise; they could recruit them all from Jeff Rothstein’s clinic at Johns Hopkins. Rothstein was glad to cooperate, partly because the gene therapy focused on replacing the EAAT2 gene that he had shown is defective in patients with ALS. And of course Stephen would be among the twenty-five volunteers.
Stephen and Wendy sat waiting like patients in any doctor’s office. But instead of National Geographic, Wendy was now reading a scientific paper from the coffee table with the title “Environmental Enrichment Inhibits Spontaneous Apoptosis, Prevents Seizures and Is Neuroprotective.” And one of the patient’s doctors and one of his brothers were murmuring with their heads together over a notepad, trying to design a dangerous new therapy for the patient on the spot. Otherwise, it was an ordinary scene.
As usual, Jamie was pressing Matt to do a little more a little faster than he was prepared to do. “Jeff Rothstein doesn’t look at behavior that much,” said Jamie. “You have a very good behavior lab in New Zealand.” He suggested a test that Matt could try, to see if the injections really would make the mice stupid.
“I have a grant to submit in three days,” Matt replied in a compressed voice. “It’s a huge stress.” But Jamie made him promise the test.
As we were leaving the room for Wendy and Stephen’s tour of the lab, I stopped to look at the calendar over Matt’s desk. Jamie noticed me looking at it and he hung back while Stephen and Wendy got a few steps ahead on the tour with Matt and Paola.
“At the Louvre, I kept looking at Rodin’s hands,” Jamie said. “I was looking at this stuff and Stephen was tripping on the steps. And I was just gone. I was losing it.”
We caught up with the group. Wendy was frowning and following Paola’s explanations of the lab’s innovations as if her life depended on it. She leaned forward as she listened. “If you’re putting this into the brain,” she asked, “how are you targeting the brain?”
Paola explained. They injected genes directly into a specific part of the brain, like the hippocampus. She talked about their Canavan trial, and how the virus had been injected directly into the brain to bypass the blood-brain barrier. She was standing in an open doorway marked “Biohazard BL-2.” Wendy wore a fixed frown as she listened, which she seemed to erase almost by an act of will whenever she looked up at Stephen’s face.
In the prep room, where rows of lab coats hung on pegs, they stopped to look at a white rat in a cage. It was sniffing away at the room as it paced from one wall of its cage to another, its pink nostrils working. The rat was an albino, with red eyes and a pink nose that was sniffing toward them like crazy.
“We used to have a pet rat at Colgate,” Stephen said. “Thor.”
“What’s going on with this one?” Wendy asked Paola.
Paola showed them the laboratory bench where they would operate on the rat. As she began to explain the procedure, Stephen folded his arms across his chest. I remembered how I had felt when I first toured the lab, how charged it all looked with hopeful and horrible possibilities. But when he spoke, Stephen sounded cheerful. �
�Amazing that all this equipment exists, you know?” he said to Wendy. He was walking more easily, as if he felt more at home with each step, admiring the equipment. “These are great. These are beautiful. Look, on wheels.”
Paola showed them incubators where they grew big batches of cells. She opened one to show them the cells growing there by the billions in little petri dishes. The incubator was lined with copper.
“Why copper?” asked Stephen.
“Copper to kill off any stray yeast and bacteria,” said Paola.
“See, we could do it,” Stephen told Wendy. “Copper counters. I use a lot of copper in my building projects,” he told Paola. “It’s a beautiful material.”
His face kept lighting up at all the neat new Macs in their colorful translucent clamshells on the laboratory benches. Then he got interested in the layout of the new offices. He was concerned about all the doors between rooms and halls and the sections of labs. They made it harder for the doctors and scientists to get around.
Stephen was not afraid of much. But he had now seen Matt’s movie about super-smart sharks twice, at Matt’s suggestion, and he had developed a little phobia about sharks. In the seminar room, one of the magazines on the conference table was the November issue of Aqua. The cover showed a Polynesian woman standing next to an outrigger in blue, rippling shallow water, sharks swimming around her. The cover line read, “Shark Time in Polynesia: Rangiroa’s Toothy Attractions.”
“Well, honey,” Wendy said, teasing him. “It looks like we’re not going to Polynesia!”
“This is not the kind of shark I’m afraid of,” said Stephen, primly.
Jamie found Dave Poulsen, who was preparing the DNA cocktail they would inject into Stephen’s spine.
“By the way,” Jamie told him, “this is the guy we’re doing all this for. Dave, this is Stephen.”
“Hi,” Dave Poulsen said. He stared down at the floor and then glanced up again. He did not quite meet Stephen’s eyes.
His Brother's Keeper Page 27