Jamie also called me at night from his desk in the Victorian. He surfed the Web for ALS news while he talked. With the Web, biomedical insiders and even outsiders could now monitor global research instantaneously, which even the greatest medical specialists could not do a decade before. So Jamie would scan PubMed while he talked to me, and sometimes I would hear his rapid-fire voice begin to slow down. “Oh, look at this…Holy shit…I’ve got to e-mail this to Matt.”
“What is it?”
“Well, this study, which came out…in Poland…two days ago…”
As Ben said, it was the ALS channel: all ALS, all the time. Jamie’s personal life was getting squeezed out to the edges. Melinda was pregnant now, and even that good news was cast was cast in the strange, harsh light of ALS. That night, just before he hung up, Jamie said, “Oh, we went to our sonogram today. We saw the baby. The nurse was looking for the facial shot, right? And then we kept getting this great shot of this curved spine and the skull.” Jamie laughed. That was the part of the human anatomy he had been studying compulsively for the past half year. That was the model that sat on the desks of almost all the ALS experts he had visited. He had been learning his way around images like the one in the sonogram ever since the night that Stephen had called him after his appointment at Massachusetts General.
“You know,” Jamie said, “that was the baby picture I wanted, and it was the only one I didn’t get, because the nurse didn’t think that anyone would want to look at a curved spine and a skull. But that was the photograph I understood.”
The baby was due on April 20, 2000. If he stayed on schedule, by that time he should have genetically reengineered the nerves in Stephen’s spine.
The more Jamie learned about gene therapy, the more he wondered if the nonprofit route was the way to go. Jamie was beginning to think if his gene therapy project should be for profit after all. He began talking of upping the ante again.
Not everything in the gene therapy world was nonprofit. Most of the work was for profit. According to a study by the NIH, more than half of the gene therapy trials registered with the RAC in 1999 and 2000 were paid for by private money. That was true of James Wilson, across town from Matt During at the University of Pennsylvania. Like Matt During, Wilson was a rising star in the field of molecular medicine. He had been thirty-seven when he joined Penn as the John Herr Musser Chair in Research Medicine; and director of Penn’s new Institute for Human Gene Therapy; and professor at the Wistar Institute nearby in West Philadelphia. His institute was housed in a new sixty-million-dollar facility at Penn’s medical school.
Wilson had founded a biotech company, Genovo, based in Sharon Hill, Pennsylvania, four years before. He owned nonvoting stock in the company and the company paid Wilson’s lab within the institute almost five million dollars a year.
Among many other projects, Wilson was working that year on a gene therapy for ornithine transcarbamylase (OTC) deficiency, a rare metabolic disorder. Babies born with it—mostly boys—cannot break down ammonia efficiently, and most of them die soon after they are born. Normally the liver breaks down ammonia so the body can get rid of it in the urine. As the ammonia builds up, the baby goes into a coma and dies.
Volunteers in most gene therapy trials are, like the parents of Canavan babies or like the family of Stephen Heywood, looking at a situation so desperate that they are willing to take almost any risks. But Wilson’s OTC trial was unusual for the field because he and his team included people who had milder forms of the disease. All volunteers, healthy or dying, know that they may lose their lives, and that the benefit may only be for people with their disease years afterward. But most healthy volunteers have many years to lose.
That spring while Jamie and Matt raced to prepare a gene therapy for Stephen, a young man named Jesse Gelsinger had enrolled in Wilson’s trial. He had a treatable form of OTC and could survive with the help of pills—he took about fifty a day—and a strict nonprotein diet. The gene therapy was not designed for people with a treatable case of OTC. It was meant for newborn babies who would die without it. Wilson and his group thought the gene therapy they were testing was safe enough to include Gelsinger even under those circumstances.
The boy’s father, Paul Gelsinger, a handyman in Tucson, Arizona, had raised him; Jesse’s mother was more or less out of the picture. Paul read the eleven-page patient consent form and cautioned his son. He made what he felt was a reasonable guess and said, There’s risks here. There’s a one in five thousand chance of complications.
The boy looked at his father. I can beat that, Dad.
His father took a snapshot of him on his eighteenth birthday, which he chose to spend enrolling in the trial. Later that picture appeared around the world: the young man posing in front of the famous statue in Philadelphia of Rocky, the underdog prizefighter, Jesse Gelsinger flexing his biceps with his fists raised to the sky. It was the first big thing he had done in his life.
Matt During and Jamie Heywood decided to form a biotech company together, though they were still not sure if their EAAT2 gene therapy should be profit or nonprofit. Meanwhile, in the welter of projects that Matt was running or proposing to run, Jamie kept working with all his charm, energy, and cunning to keep the gene therapy moving fast. He was in a delicate position. He was the project manager and he was also an outsider at all of these labs. And both Matt and Jamie were continually flying into new projects. Now that they were thinking of starting a company together, there was, besides the urgency of saving Stephen, the urgency of getting ahead of the competition. With their jockeying with each other, and their jockeying for their projects, and their jockeying against the clock and the competition, meetings between Matt and Jamie began to get complicated. Jamie still had one goal: to save Stephen. But Matt wanted to advance the molecular revolution all along the edge of medicine. At every meeting Jamie would try to focus Matt’s attention on the gene therapy while Matt would pitch Jamie six new dreams of revolutionary therapies, which he thought they should add to their new company’s growing list of hypothetical projects. They were two cowboys galloping together.
Jamie would groan. “I’m getting burned.”
“I’ve got a few more ideas.”
“If you give me any more ideas I’m going to pass out.”
“Let’s see, we’ve got the botulinum toxin vaccine, which may or may not be a good idea….”
“You’re reaching on that one, Matt.”
Because Jamie wanted Matt to move as fast as possible with the gene therapy, he wished Matt had not assigned the first phase of the work, the development of the DNA package, to Dave Poulsen. Poulsen was the postdoc who had shown me the gene gun and the little golden spots the size of dimes. It was his job to engineer the virus that would carry the DNA into the spines of the hundred test mice and then into Stephen’s spine. Poulsen was working at this task very slowly and methodically, at a pace that drove Jamie crazy. He wondered if Matt would have given his gene therapy project to Poulsen if Matt had believed it might save Stephen.
Early one morning in September, Jamie dropped by Matt During’s office as if he lived around the block, and had not driven down that morning before dawn from Newton. “Just stopped by for guidance,” Jamie said. “Without taking more than two minutes of your time.”
Matt did not seem to hear him. He was reading a paper about stem cells on his computer screen, with his usual absolute absorption. After a moment, he looked up and offered to print out a copy for Jamie.
Jamie nodded.
“The press release or the paper?” Matt asked, poker-faced. That was a dig. Press releases are issued by journals for science writers and other outsiders who may not be able to follow their articles. “I’m sorry,” Matt said. “I’m being insulting, I know.”
Of course, Jamie really was out of his depth most of the time, and by now Matt knew it. On the other hand, Matt himself, in his fever to start revolutions all along the edge of medicine, could get out of his depth, too; and Jamie knew it.
“I’m sorry,” Jamie replied in the same brotherly tone. “Are you an expert on stem cells?”
“I’ve been to—” Matt rattled off a list of lectures and international seminars. “I know a little bit about stem cells.”
Like Dolly, stem cells were a bolt from the future, and in the fall of 1999 the future was still looking like an Eden re-made. Dolly herself had given birth to a lamb, and her Scottish vets called her Bonnie: “a bonnie wee lamb.” With stem cells, biologists could now hope to build and rebuild living bodies the way architects built and rebuilt cathedrals. They could dream of taking any cell from the body and coaxing it to become the cornerstone of a new cathedral. They could govern the growth of life and they could shape the repair.
Matt turned at last from the screen and faced Jamie. He had just gone to an informal talk at Jefferson about stem cells, he said, and now he had an idea for a stem cell project that might help Stephen. The results he had heard at the talk were not even published yet. But if Matt put them together with this paper on his monitor, they suggested that one might inject stem cells that normally make blood, hematopoetic stem cells, into a brain, and the cells might make new neurons instead of blood.
Matt handed Jamie a copy of the new paper in Science about turning brain into blood. “Which is the opposite of what we want to do. But the same principle applies.”
“Unless it doesn’t,” said Jamie. Matt’s idea sounded wild to him. In any case, Jamie had decided to let other people in the ALS community work on stem cells. He wanted to stay focused on his gene therapy. A visit with Matt During was like a visit to the alchemist, the wizard, the wonderful wizard who keeps dancing off into a dozen fairy-tale projects and possibilities.
Jamie did not want to go near this with his ALS Therapy Development Foundation. But he could consider it for their new start-up, a little biotech company they called CNScience—Central Nervous System Science. And if he and Matt kept it entirely separate from the foundation, then there would be no ethical conflict with his making money from the stem cell project.
Matt pitched. Jamie sat in his chair in the position of the Thinker, leaning toward Matt. “Do you have people to do this experiment? What’s the name of the guy at Jeff?”
But Matt did not answer. He was staring at the monitor again.
“What’s the name of the guy at Jeff?” Jamie asked again.
“Yeah, it’s pretty interesting, actually,” Matt said, as if he had not heard. “People who work on blood don’t think about the brain. You need to remember that. They think about cancer.” He had thought of this idea only because he knew a little about stem cells and he knew a lot about nerve-death diseases.
“Will anybody else look at this and make the connection?”
“Yeah. People like Mulligan. So we’ve got to move quickly. It’s a big breakthrough.”
“If it works. OK, we’re off-mission here, though. I’m monopolizing your time.”
But Matt ignored him again. Just the day before, Paola Leone had gotten a shipment of human stem cells for their Canavan work. Now Matt saw an opportunity not only for treating Stephen but also for their new biotech venture. Matt leaned toward Jamie and explained what he had in mind in a high-velocity, slightly conspiratorial voice like Jamie’s own. “The key, from the intellectual property point of view, is just to do it,” Matt concluded. “I don’t think anyone else is going to move as quickly.”
“The ALS community has pretty much accepted that stem cells are nonharmful,” Jamie allowed.
“This is something really worth doing quickly. You could blow people away. You could just blow people away.”
“OK. I’ll write this up, too,” Jamie said, in an executive voice. He made a few notes, looking concentrated and decisive. He would add stem cells to their list of candidate projects at CNScience. I think the chance of getting out ahead of everyone else tempted him almost as much as it tempted Matt.
“Nothing’s been published yet,” Matt said again.
“The only people who know about this were at the meeting,” Jamie conceded. “Small group.”
“But there were high-powered people in that group. High-powered. So we need to move quickly.”
Next, Jamie dropped in on Paola Leone in her office down the hall from Matt’s. With Paola he knew he could focus on gene therapy. Paola played the same role in the Canavan gene therapy project as Jamie played in his gene therapy project. She was the manager; she was there to usher the project along. On the walls of her office, she had hung some of the photographs she had made of toddlers with Canavan. One was a beautiful picture of babies and toddlers propped on a couch, helter-skelter, like dolls. They were resting on the couch, and somehow because none of them could move very much, they looked as if they were floating in space in zero gravity. All of them were tiny, with heads too big for their bodies, and they were lying just as they had been set down. Some Canavan babies were able to function longer than others. Propped on a shelf, Paola had a framed drawing of a frog, scribbled in green crayon, and inscribed by a parent, “To Doctor Paola, Love Max.”
The calendar on the wall was international. It said “September Septembre Septiembre September.” Her windows looked out across a narrow courtyard at the yellow brick walls of the medical building.
“I have to download you,” Jamie said briskly. He wanted to know all about her experience with Canavan, getting experimental gene therapy approved by the FDA.
Paola described the details of the approval process in the United States and in New Zealand.
“That’s kind of all off, now, isn’t it?” Jamie said. “Running trials in New Zealand is harder.”
“Yes, because of this,” Paola said tersely, nodding toward the photographs of all the babies they had worked with in their Canavan trial. They would not be able to do that again in New Zealand anytime soon. Now it was up to the FDA whether Jamie’s gene therapy and the Canavan project would go ahead. And Paola pointed out that there was one consideration in Jamie’s study that they had not had to worry about with the toddlers. “Because your ALS patients are sexually active, they’ll worry about the germ line.” The FDA would want to see animal safety studies, including primates, to make sure the DNA injection did not find its way somehow into eggs and sperm.
Paola’s phone rang. It was Matt, asking for stamps.
“Stamps?” Jamie cried, after she hung up. “Doesn’t his secretary handle that?”
“I’m going to teach you about dynamic incompetence,” Paola said cryptically, and laughed. “This is the way I make him dependent.”
Jamie ran through his list of projects with Paola and explained why he was most interested in the gene therapy. “I have patients begging me for help right now,” Jamie said. There were risks with gene therapy but they did not worry him as much as some of the other projects on his list. “The neurovaccine scares me,” Jamie said. “That could rip out every nerve in your body.”
Paola explained the ins and outs of FDA approval for gene therapy while Jamie made a few spare notes in his white legal pad—half a dozen bottom lines, always bottom lines. His conversation, too, was always bottom line now: He spoke not impatiently but briskly, the model of a project manager. He flipped through Paola’s draft of her Canavan proposal to the FDA. When she handed him the paperwork that she was preparing for their next Canavan trial, Jamie skimmed through it, stared, and gave a small smile. Paola had just handed him exactly what he needed. The Canavan project was so much like his own that he could imagine modeling his on hers; it might save him months. Suddenly he blushed, bowed his head as if he did not want Paola to see his face, and ran a hand through his hair.
“It’s the same as mine,” he said. “Just a different gene.”
“Exactly.”
Jamie told Paola that he would be testing the gene therapy on one hundred mice.
“One hundred mice, that’s huge.”
“I know.”
“If something goes wrong with just one, a stroke or something, there
may be more questions—did that experiment cause that problem?”
“I ask the question, what is going to make me confident enough to treat Stephen.”
“Hmm.”
With the brain vaccine, Jamie thought he wanted one or two people to try it before Stephen. “The question is, what are the rules on what you can do? Does that have to go to the FDA? If you want to try it on late-stage patients, I can get patients that are months from death, guaranteed. There are people who are contemplating suicide at the same time as they are contemplating something radical.”
“I think it can be done if you have a very clear consent form,” said Paola. “But do you really want to do that?” In the Canavan trials, she had had parents begging her for two years to inject DNA into their babies’ brains. She had never forgotten how some of those parents reacted when their baby had a seizure. “They are looking at me like—”
His Brother's Keeper Page 20
