Jamie and Robert both wore neatly pressed long-sleeved shirts and khakis, and they looked very young to me. Robert’s brown hair was longer than Jamie’s and windswept. He wore stylish wire-frame glasses, a small silver earring, and sandals. The waitresses in the café kept looking at both of them.
“We held a foundation meeting in Dad’s lab a few days ago,” Jamie told me. It was a scientific seminar about ALS. He called it ALS 101. Not the usual project that got talked about at the Sloan Automotive Laboratory, Jamie said with a laugh. “It’s a ’50s, engineering, mechanical kind of building. And we took it over for two days.” The leader of the seminar was Jamie’s mentor and old office mate, the Walking Library of the Neurosciences Institute. For a few days Joe Gally was living his dream: He was teaching molecular biology at MIT, and his students were listening as if what he had to say meant life or death.
Jamie and Robert told me they were trying to rate all of their options in terms of risk and reward. They talked about Jamie’s gene therapy project and Matt During’s idea for a neurovaccine, his trick of getting the immune system to heal the brain. During’s idea was so novel that he had still not gotten it published. Reviewers of the paper kept insisting that he do more experiments to prove that his technique really did what he claimed it could do. Jamie explained that unlike gene therapy, where each treatment has to be meticulously fitted to each disease, a neurovaccine could be adapted quickly to different neurodegenerative diseases. He had persuaded him to try out a vaccine to treat ALS. “The way I think about it, it’s a whole new kind of medicine,” he said. “Like gene therapy or stem cells. A whole new way of manipulating the body. Very exciting and potentially very powerful. This is why Matt is such a genius.”
The gene therapy was moving along fast now, Jamie told me. “The experiment started today,” he said, glancing at his watch. Jeff Rothstein, the ALS expert at Johns Hopkins, had started injecting ALS mice with some genetically engineered viruses from During’s lab. “This is exciting,” Jamie said. “The work would have gotten to ALS eventually, but it wouldn’t have happened for a long time.”
If Matt During could make a vaccine against ALS, I wondered if he could also make a vaccine against Lewy body dementia. But I kept that thought to myself. In those days I did not talk much about my mother, even with Jamie.
“I don’t know if the neurovaccine will work,” Jamie went on. “It’s very clear that the gene therapy project is still the best we’ve got going. The vaccine’s ambiguous. I’m excited, but I’m worried it might be toxic. I’ve also got seven to ten other ideas.”
And he did—but as Robert confessed to me later, those were all so much window dressing.
I told Jamie and Robert that I was amazed how much they had accomplished.
“At this point, we’re three folks in a living room,” Robert said wryly.
“Better than a basement, though,” said Jamie.
I looked at them, out on the sunny deck of Paganini, drinking bottled water. The image of the Internet start-up seemed about right. They were young, they were excited, they were frankly selling their youth and excitement, and it really was hard to judge how much else they had. They were a brand-new start-up, and they entertained me with the kind of hyper sales patter that was circulating in 1999 in Cambridge, Boston, San Francisco, and Seattle, the rhythm of the charming sell. Every few minutes, Jamie checked his cell phone.
“Why don’t I hear it ring?” I asked, feeling like a rube. Jamie was an early adopter and I was a late adopter.
“It’s set on vibrate,” Robert explained. We both watched Jamie listen to his messages. “When Jamie doesn’t know what else to say, he says, ‘The only thing we don’t have is time. The only thing we don’t have is time.’ And it’s true,” said Robert.
Jamie slipped his phone back in his pants pocket. “Another slogan,” he said: “ ‘Our responsibility is to spend money irresponsibly.’ ”
“This is war,” said Robert. “The enemy is disease. To win you need all different kinds of missions and platoons. We’re like psycho commandos doing really wild stuff. We could fail. But if we hit, we’re going to hit big. The doctors are more conservative.”
“And they should be,” said Jamie. “They’re playing for the long haul.”
“We’re trying to make it happen fast.”
“Make it happen fast for Stephen.”
“We’re a venture capital firm,” said Robert. “The model is exactly the same. But instead of raising money to give away to scientists, we’re raising money to try to cure ALS ourselves. It’s so simple.”
I doubted that “it’s so simple” but let it go. Jamie was giving me his sell-you-the-moon stare. He had a salesman’s way of holding eye contact with a level gaze and beaming pure energy. “I come from an environment where you figure out how to make someone do what you want them to do,” he said. “It’s not that I’m a biologist, or a doctor, or a rich man. But I’m enough of all those elements now that we can make something happen. Never underestimate the power of hubris. I’m too stupid to know not to try. There’s a certain power to that. Just get in there and start swingin’. No reason why we can’t have therapy fast. Just got to move mountains. So what? Mountains can be moved. They’ve been moved before. Hopefully I can blow you away again in two more months.”
“Jamie says, Keep setting impossible goals, and keep meeting them. We said, Let’s raise two hundred thousand, and we got two hundred thousand,” said Robert.
“Helps to have moderately wealthy friends—and a lot of them,” said Jamie.
“We made a plan and we did it,” said Robert. “And by the way, I don’t have any moderately wealthy friends. OK? Don’t include me in that.”
Jamie ordered us three more bottles of fizzy water.
“Working up quite a bill in fizzy water lately,” said Robert.
If emotional intelligence is the ability to feel many sides of a question at the same time, as Daniel Goleman says, then by the time the shadows lengthened in the street outside the café, I must have had a very low IQ. I forgot my reporter’s objectivity. Jamie and Robert had charmed me so completely that I forgot myself, and the sick, and the life-and-death questions that lay ahead for all of us. All I knew was that they were offering me a wonderful story on a charmed summer day, and I was ready to join their adventure.
It was easy to feel that way—and it was just as hard to force oneself to stay realistic. For Jamie and Stephen that had to be hardest of all. Jamie told me that Stephen and Wendy had decided to put the Cave behind them and get a place together. They had found a beautiful apartment on Beacon Street, in Boston’s Back Bay. Jamie could not understand it. The place they had picked was a fourth-floor walk-up.
By the end of dinner at the café, Jamie seemed to think he had sold me on his story almost too well. “Still,” he reminded me at last, “we’re painting a pretty picture here. There’s really hard stuff going on. My brother is probably going to die.”
I wanted to deny it.
“That’s reality,” Jamie said. “He’s someone I love dearly, someone I am very close to. That makes these things hard. Rob can tell you. It’s going to be murder to go through as it happens. So I don’t want to paint too pretty a picture. It’s very scary and hard. I don’t mean in a business sense. When I saw Stephen collapse! You just want to go put your fist through walls.”
When I got to know Jamie better, I realized that he very rarely mentioned the possibility of Stephen’s death. In fact, I do not think I ever heard him mention it again. Once, much later, I asked him if he had really believed what he said to me that day at the café. “What your rational mind knows and what your heart knows are different things,” Jamie told me. “I think I knew rationally exactly what the chances were, and every time I sat down and thought about it I went to that correct understanding. And I don’t think I ever deluded myself. The other side of that is, I haven’t had a problem I haven’t been able to fix yet. I’ve managed to fix everything I’ve tried to fix in
life, whether it be a house or a machine or a design. So I knew the chances were close to zero but I also haven’t missed yet.
“I think that’s a constant internal struggle. It takes hope to dream about opportunity. And yet you need to keep yourself in the real world all the time. I knew the odds were incredibly slim. Yet I was still hopeful. It’s that combination of realism and hope that makes you go like crazy for those small odds.”
“Look at the scientific process,” Jamie said at the café as we finished the last of our coffees. Somewhere in the course of his race he had made time to read my books and he knew how different this story was for me. The scientists I write about spend decades, lifetimes, on their projects. “And we’re saying we’re going to do it in months,” Jamie said, and shook his head. Pensively he stirred the ice in his cappuccino with a straw. “It’s invigorating and it’s kind of terrifying. Sometimes I get to Friday and I just melt. Just gone. What I do is try to keep fifty balls in the air. And one hundred scientists. It’s a mess, a total mess.”
One hundred scientists? I should have doubted Jamie again. But he knew how to sell even when he was fretting and being realistic, which is a useful skill for an entrepreneur and impresario like Jamie. Looking back, I wonder if as a superb salesman of the near-impossible, he was anticipating my skepticism. He thought he was talking to an entirely rational mind. He did not know he had sold me so well that I was not feeling skeptical at all.
“Some might say our project is hopeless,” Robert said, in the same tone as Jamie. “A skeptic would say that Jamie is tilting at windmills like Don Quixote. But the difference is, this could work. So you ignore the odds.”
I felt elated: drunk on hope, admiration, and fizzy water. Jamie and Robert had charmed our waitress, too. She was about twenty. She came back after we had paid the bill and stood at our table looking at Robert.
“Well,” she said. “Wherever you’re going tonight, whatever road you choose, and however that road may twist and turn along the way, I hope you have a wonderful ride.”
“Thank you,” Robert said.
But she did not leave. She kept on looking at Robert.
“Where are you going?” she asked.
Twenty-Three
Lead into Gold
The next morning, Stephen and Wendy flew from Boston to Paris. Ben and Melinda went with them. Jamie took care of a little more business; then he joined them, and they all had a good time. There was one bad moment when Stephen stumbled on a long flight of stone steps at the Louvre. It was like my mother’s fall on the steps of the Met. But her falls were sudden: the marionette with the snapped strings. Stephen had a way of falling in slow motion. Even when he was walking on a level he would keel very slowly off balance while struggling hard to right himself over a space of twenty-five feet. Sometimes Jamie thought Stephen was almost funny to watch—when he was not on a flight of stairs.
There was another bad moment in Paris when Stephen challenged Melinda to arm wrestle. She knew that he wanted her to try her hardest. Feeling crappy about it, she forced his right hand down to the table.
While they played in Paris, I took a train to Philadelphia to see the gene therapist Matt During at Jefferson Medical College. On the way down I thought about the chance that I might do something for my mother. I love my father dearly, and we are very close. But in the first few years of her illness he could be exasperating. First there was the battle to get him to take my mother to a psychologist when her personality darkened and she began to brood. To him that sounded like a shameful step. When I pushed him, he always gathered himself up into formality, and I went from Jon to Jonathan. “Well, Jonathan, it’s up and down, your mother goes up and down. This week she seems a little better.” How many times we had that conversation! “Well,” and that repressive pause, “Jonathan.” As if to push me back into the rows of chairs in a classroom—to make some room between the lecturer and his audience of one. He said the thing to do was wait.
And when she began her rag-doll falls, how long it took for him to agree to put in a railing on the front stairs and remove the throw rugs she kept tripping over. At least that was how it seemed to me. Everything was so slow, so slow. He was holding on—each step would acknowledge her decline and the change that had come to them, and he was holding on to the way things were. Just to roll up a rug would be to begin dismantling the beautiful house she had created when they first moved in. He did not want my advice, and he did not want anyone else to know what was happening to her. In summer even on the hottest days I could not persuade him to open the curtains, the shades, and the windows.
(My father saw it all differently, of course—including the windows. That was an engineering decision, he told me. His best friends in the department did the same thing. I did not understand the concepts of heat transfer and thermodynamics.)
But now she was sinking fast and he was at least as desperate as I was to find help for her. It made a difference for my father, I thought, that we had a diagnosis now—Lewy body dementia, something concrete and physical, something in the realm of engineering and mechanics, not the shaming realm of mental illness. And if Matt During’s neurovaccine looked like our best hope, I thought he might agree to bring Ponnie in to a laboratory and have her injected with an experimental treatment from the edge of medicine.
I had stopped writing about my mother in my journal. Later I found out that Melinda had quit writing about Jamie and Stephen in hers, too, and Wendy in hers, at about the same time. Melinda’s notes were fewer and ALS crowded everything stiffly out. (“The circus gig is turning out to be quite an ordeal, interfering with our ALS activities….”) I once asked Wendy if she would look through her notes and see if she could find anything at all. After a few days, she wrote back that she had found very little, besides the few, very happy diary entries she had sent me. “Sorry! During the time after Stephen’s diagnosis I found it hard to write about my feelings. It was just too overwhelming to have to put it in writing, as if writing it down gave it some credence, like recorded history, and by not journaling what was happening I could maintain the possibility of miracles.”
Matt During had told me over the phone that he had always been criticized for jumping around—and that now he had reached a stage where he could get away with it. So I was startled to meet a man who looked almost as young as Jamie.
“How old are you?” I asked.
He hesitated. “About forty-two,” he said, and laughed.
We sat down in his office. “It’s an interesting story,” Matt said, in his strong New Zealand accent. “What motivates a lot of biomedical scientists is impersonal, emotionally distanced. It’s unusual to take on a project because someone walks in the door wanting to save his brother.” But he admired Jamie and his willingness to take chances, he said. “There, I’m somewhat similar.”
I knew Jamie worried that Matt might be less than hopeful about his gene therapy for ALS. He sometimes thought Matt was more excited about his own brainchild, the neurovaccine. So I asked Matt what he thought about Jamie’s plan. I expected him to say something cautiously optimistic.
“Most gene therapy to date has had a poor run,” Matt said bluntly. First, there was too much hype. And everyone had been going after diseases where all else had failed, like inoperable cancer. Now they were going after easier targets. The brain made a good target, he said. It is hard for drugs to cross in, and it is hard to target just one part or another. With gene therapy they could select just the parts and cells they wanted. With so many neurological disorders, doctors have drugs that can help, but the drugs are not specific enough to be useful. Drugs can silence the parts of the brain that start epileptic seizures, for instance, but they silence so much else besides that they put the patient into a coma. A gene therapy injected into just the right part of the brain might do better. And neurological diseases often involve highly specific types of cells. In ALS, for instance, only motor neurons die, while the body’s other neurons seem to stay healthy. Gene therapies, unlike
most drug therapies, could be designed to target only the vulnerable nerve cells. “The gene is the most specific way to intervene,” Matt said. And they were getting more sophisticated about switching genes on and off. They could inject a gene, switch it on to do its work, and switch it off when it had done enough. He predicted that gene therapy would have its first success in the next year or two—but not with ALS.
Next I asked Matt what he thought of Jamie’s chances of treating Stephen within six months, while he was still in good shape.
“It’s always hard to predict timetables,” Matt said, just as bluntly. “Jamie’s enthusiasm assumes we haven’t hit any roadblocks. By December we will have some sense of whether we can move into a clinical trial. We need a controlled study.” He wanted many animal tests before injecting DNA into Stephen’s spine. Jamie was very hopeful, of course, Matt said. “How realistic that is—I’m not sure our first foray into this will be successful. I think we’re a long way from understanding this disease, which always puts you on the bad foot. The disease is not simple. There’s no agreement about the starting point.” Naturally, because Stephen’s disease was progressing rapidly, Jamie had “a sense of pushing,” Matt said, but he thought their project would take longer than Jamie wanted. “Not as if I can go out and hire ten or twenty people. Certain techniques take time.” He was not sure Jamie understood that. “He’s trying to accelerate three to five years into one. But I’m not sure it will work.”
That did not mean Jamie’s plan was not worth trying, in his view. These experiments were necessary to advance the field. When parents of Canavan babies all over the world were pressuring Matt and Paola Leone to try again, during the controversy in New Zealand, he had defended himself in a letter to The Lancet: “Our concern for the suffering of the children helped to motivate this project, to offer some hope, not necessarily for these families, but for future generations of children who may have Canavan disease.”
His Brother's Keeper Page 18
