“So what were saying is that, um, there’s clear electrical evidence of involvement of the lower motor neurons—”
“Uh-huh,” said Stephen.
“Fairly widely in the body. And then there’s a suggestion of briskness of reflexes, which is a token of abnormalities of the upper motor neurons. So that points to some dysfunction up here, too.”
“So you’re sort of saying they’re highly primed,” said Jamie.
“I’m saying the reflexes are very brisk,” said Doctor Brown, with a faint testiness in his voice. Jamie kept breaking in just as he was about to give Stephen the diagnosis. But that was all right, of course. Jamie had a right to ask. “Yeah,” the doctor said, more patiently. “And that often correlates with trouble in the upper motor neurons.”
Stephen could see that Brown was about to break the bad news. He felt intensely alert. He could read it all in Brown’s face. John Donne wrote on his sickbed, “I observe the Phisician, with the same diligence, as hee the disease; I see he feares, and I feare with him: I overtake him, I overrun him in his feare, and I go the faster, because he makes his pace slow; I feare the more, because he disguises his fear, and I see it with the more sharpnese, because hee would not have me see it.”
Nothing has changed since Elizabethan times, the terrible theater of two, or three, or four, in which things are spoken aloud as if for an audience, with formality, as if forever, the doctor proceeding in a slightly stilted, formal voice, almost like a judge at a sentencing, with no condemnation, of course, but with all the finality of a hanging sentence. It is one of the most private moments in a life and it is also somehow like a piece of public theater. The doctor, the patient, and the family are marshaling the evidence almost ceremonially, in a ritual, to announce what they all dread to speak and hear, the words that, as they are pronounced, will condemn one man to death.
Stephen felt acutely aware of it all. Even his doctor’s use of all those spacers, the ums and ahs, were deliberate. They were for kindness, to signal that something big is coming and to let it come a little more slowly.
“So, um, you know,” said Doctor Brown, “the, uh, diagnosis, uh, that unfortunately—that all of this points toward—is motor-neuron disease, or it’s Lou Gehrig’s disease, or all these terrible terms in ALS. Um. Our job is to work with you to do everything we can humanly do. First of all, to see if we can find something treatable here, and then to find a way to manage the problem if that’s the corner we’re painted into.”
“OK,” said Stephen.
“And, uh, you’ve had a pretty compulsive set of studies,” Doctor Brown said, meaning comprehensive. He walked Stephen step-by-step through all the tests that he had now undergone, and listed all of the lesser medical conditions the tests had ruled out. Compared with ALS, even brain cancer is a lesser condition.
Stephen followed every syllable of Brown’s speech, nodding to show that he knew, he understood, that he had expected this. Later on when Melinda listened to the tape and transcribed it for Jamie, it broke her heart to hear Stephen’s strong voice, his effort to say with every breath, I’m all right.
Doctor Brown drew a few more diagrams of Stephen’s brain and nerves, to explain everything the tests had ruled out. Stephen kept repeating that he understood. At last Brown said, “I think the real question is where to go with a diagnosis that I’m afraid we’re not going to be able to escape.”
“Yes,” Jamie breathed from the doorway. He glanced at Peggy. She looked as if she were sitting in a prison cell in outer space.
When Doctor Brown had finished talking, Jamie could not help broaching the subject of EAAT2, although he could tell as soon as he began that it might be the wrong moment.
Stephen listened. He knew from long experience that he was hearing the start of one of Jamie’s adventures, although he had no way to guess then how far this adventure would go. After a few minutes of Jamie’s gibberish—Eat Two, Eat Two, Eat Two—he decided that it was time to wrap things up. He had to get Jamie back under control. (“I do that with Jamie a lot,” Stephen told me later. “Which I shouldn’t always do.”)
“So this afternoon I think I’m going to have to go buy a Harley!” Stephen said. It was not much of a joke, but they all laughed anyway. Then Stephen said, “I think Jamie also wants to know whether it’s appropriate to call when he has occasional questions.”
“Sure,” Doctor Brown said kindly. “Sure.”
“Because he has a much better theoretical understanding of things than I do,” Stephen said. “And I’m not necessarily going to plan on having a theoretical understanding of this stuff,” he went on. “Because I don’t—”
“He’s very good at delegating!” Jamie put in from the doorway.
But Stephen refused to let Jamie interrupt again. “Because I don’t think it’s critical to do so,” he concluded, with a soldier’s dignity.
Doctor Brown had already ruled out Parkinson’s disease and stroke. But to make absolutely sure that his diagnosis was correct, he recommended one more MRI. The two brothers and their mother had lunch near Doctor Brown’s office, where Jamie could not quite keep himself from crying. Then they went for the MRI. There was one other family in the waiting room, and the parents were hysterical because their child might have a brain tumor. But Jamie and Peggy chanted softly to each other, “Brain cancer, brain cancer, brain cancer.” With cancer at least there was some chance of a cure. With ALS there was no chance at all.
That evening back in Newtonville, in the old house on Mill Street, after his parents had gone to sleep upstairs and Stephen had gone down to the Cave, Jamie sat up late with an old friend of his from high school and MIT, Bjoren Davis, a software engineer. Back at MIT the two of them had worked together in one of Jamie’s first entrepreneurial efforts, Heywood Associates. They had designed Amtrak’s train arrival and departure display at Boston’s Back Bay Station, and it was still in use.
They drank beer in the solarium with the dark sky and the bare trees overhead in the glass ceiling. Jamie told Bjoren everything he knew about the EAAT2 protein. The one key element that every ALS patient shared was that this EAAT2 protein was missing.
Bjoren looked at Jamie. He said, Well, why don’t you just put the damn protein back?
At that moment, Jamie says, he began to lose his photographic memory and began to think like an engineer again. For the first time, he began to feel the can-do techie spirit returning. He saw exactly what he had to do. It was not so different from what he had been doing all along since MIT, putting together teams to do a job. Only now he needed a dream team, and he had almost no time.
On January 16, Jamie Heywood traveled for twenty-four hours to get back to California. Plane after plane was delayed or rerouted. In Atlanta and again in Cincinnati he slept on airport floors.
Melinda wrote in her journal: “Jamie sobbed and sobbed when he got home, wept like I’ve never seen before, overtaken by the emotions he had kept in check all week in Boston. He shook and heaved, and my tears came to join the party. Stephen has some rule that says no two people can cry at once in his presence but he wasn’t there to police us.
“Then Jamie took a shower and went to work.”
Fourteen
A Forced Journey
I was not in on the Heywoods’ story from the beginning. Late one morning in February 1999, just after Jamie got back from Boston, Ralph Greenspan called me from the Neurosciences Institute.
“Have I got a story for you!”
“That would make two,” I said.
Ralph Greenspan had led me to the book that I had just finished writing, Time, Love, Memory, which is about genes and behavior. The book was on its way to the printers that day. I had a dummy of the jacket propped up on my desk where I could stare at it.
“This one would be a little more poignant than the last,” Ralph said. “And also a little more compelling.”
It was then that Ralph told me the story of Jamie Heywood, the brilliant young engineer at the institute whose
brother had been diagnosed with a rare and fatal neurodegenerative disease. Even though Jamie was not a biologist himself, Ralph told me, he had hit on an intriguing idea for an experimental treatment. Now he was going to top-notch authorities on ALS, people at Harvard and the National Institutes of Health and other capitals of the biomedical empire, to build a consortium of people who might test his gene therapy and try to save his brother.
“It’s a great idea,” Ralph said, “and the clock is ticking, so there’s urgency. His last day here is one week from now, on Friday the twelfth. He’s moving back to Boston, where his brother is.”
“How much time do they have?” I asked.
Ralph explained that with ALS the rate of decline is unpredictable. Jamie hoped to save his brother before he was paralyzed. “They may only have a year or so.”
I do not remember what I said to that, but Ralph must have heard the doubt in my voice—so little time. He told me again that Jamie was doing amazing work for someone who had started his race with so little biology.
“He sounds like a prodigy,” I said.
“I’ll be very sorry to see him go,” Ralph said. “Jamie’s a delightful guy. He flies in twenty directions at once. He’ll switch topics quickly. Your note-taking hand will get sore.”
Ralph and I had spent many days talking about time, love, memory, DNA, the future of biology. He knew that when I am reporting, I scribble until my right hand can hardly hold a pen. Later on that year, when Stephen and I were riding around Newton in the cab of his pickup truck, with Stephen driving and talking and me scribbling notes, the weakness of my right thumb and forefinger would give me a small hint of what he must have felt when he stood outside his house with the key in the door.
“The whole family is colorful,” Ralph went on, wooing me into the story. “The brother is a carpenter….”
Ralph had no way to know how much the Heywoods’ story was already stirring me. In those days, though my mother had been sick for some time, I rarely talked about her illness, and only with my closest friends. Even then I felt guilty, because my father was outraged and anguished that I would let our family secret that far out into the world. I knew that Ralph had to feel more than he was saying, too. His wife, Dani Grady, is a survivor of breast cancer and a national patient activist. So Ralph and Dani were bound to be moved by the Heywoods’ crisis.
I hesitated. Then I asked Ralph, “What chance do they have?”
“Overall the chances are not great,” he said, with a balance in his voice of pity and professional judgment. “But I don’t think it’s futile. Assuming it’s not harmful to do this gene therapy, the idea could actually work. They won’t know until they try it.”
Ralph explained a few of the steps and hurdles that lay ahead for the Heywoods. Injecting DNA is a routine procedure in biology and biotechnology. A student in a fly lab let me try it when I was writing Time, Love, Memory, and it was as easy as playing a video game. He put a fly embryo in a video microscope so that I could see it in front of me on a big television screen. In the screen’s lower right-hand corner I could see the tip of a very fine glass hypodermic needle. I had a joystick in my right hand, and when I jiggled the joystick, the needle moved around on the screen.
Slowly, I maneuvered the needle until it touched the embryo’s rear end. Then I pressed a foot pedal. On the screen, I saw a shimmer above the needle tip, like hot air above a candle. And that was it. If any of that syringe-load of DNA found its way inside the right cells of that embryo—if a strand of DNA wriggled into one of the young cells that would become that fly’s sperm or eggs—then the DNA I had just injected might pass into that fly’s children. In principle, if the fly had a genetic disease, then in the fly’s children the gene might correct the defect.
That kind of procedure is called germ-line gene therapy, because the DNA finds its way into germ cells—into sperm and eggs. With the same foot pedal, joystick, and microscopic needle, I could have performed germ-line gene therapy on a worm, a mouse, or a human being.
The procedure that Jamie was inventing for Stephen is called somatic gene therapy, from the Greek word for body, soma. In somatic gene therapy, the injected DNA finds its way into muscle cells or liver cells or nerve cells. But injecting DNA into just the right cells in a sick human body can be much more complicated than injecting an egg or an embryo. No one can do it alone. Jamie would need a big team of specialists.
“Putting together teams is Jamie’s forte,” Ralph said. “He’ll be the catalyst. He’ll approach people to make things happen. It’s not easy to get scientists to line up like this. That’s part of what’s interesting. It’s all quite unusual. Normally, ideas from outside are amorphous and rarely work. This idea is such a good one.
“A reporter could be helpful to the project.”
I told Ralph that he might be showing me the future once again—or at least the next few years of my own. That feeling had been growing as we talked. Behind our science-fiction conversation about injections of DNA, I could hear classical music—all through the phone call, the rise and fall of passionate strings.
“Is that chamber music?” I asked at last.
“Yes, a Brahms trio. And fittingly enough for a phone call from the future, it’s playing on my computer.”
I read over my scribbled notes, and thought about Providence, which is only a short drive from Newtonville. Ralph had told me that the month before, Stephen had been diagnosed in Boston by Robert Brown of Harvard and Massachusetts General, a world authority on ALS. That same week, my mother had been examined by another neurologist there, Dennis Selkoe, a world authority on Alzheimer’s and its relations, like Lewy body dementia.
Selkoe agreed with the neurologist my mother had already seen, Stephen Salloway, that she might have Lewy body dementia (LBD), and I had forced myself to read a few papers about it. Lewy bodies are tangles that clog neurons in the brain until the victim suffers falls and hallucinations. For some reason, people with LBD often see crowds of little elves or fairies who sit on the couch with them, or scurry around their ankles, run up and down the halls, dance on top of the couch cushions, and chatter to them. Patients do not seem particularly upset by these hallucinations; they do not even get upset if their families tell them there are no elves on the couch cushions. The English language actually has a word for what people with LBD believe they see: a smytrie, a collection of numerous small individuals.
I suspected that my mother’s delusions were closer to garden-variety paranoia. When we were alone in the kitchen in Providence one day, I asked her if she ever heard or saw any little people around her. She said no. No smytries in her life. I was afraid my questions would make her angry, but she seemed almost flattered by my interest.
People with LBD can suffer from delusions other than smytries, and also from depression and a tendency to fall. Some of them also walk with an odd shuffling gait, as my mother began to do a little later on. All those symptoms did fit her condition. But as far as I could tell from the literature, doctors were not sure if those smytries were part of the same syndrome. It was shocking how little they did know. LBD was a fairly recent diagnosis. Although more and more doctors believed in it, LBD was not included in the International Statistical Classification of Diseases (ICD-10) or in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
In any case, my mother and Jamie’s brother had been at Massachusetts General for their diagnoses at the same time. I still think about that: Stephen and Ponnie passing each other in the hall, a tall carpenter with a square jaw who looked as if he would always be young, and a small woman in a tailored blazer who looked as if she would never be old.
I was working with an editor at The New Yorker on an excerpt of Time, Love, Memory. He had asked me to propose another story for the magazine when we were done. I paced around my office. Then I sat down on the carpet with my back against a filing cabinet, rereading my notes from Ralph’s call. Finally, I dialed the number that Ralph had given me: Jamie Heywood’
s office at the Neurosciences Institute.
The voice that answered the phone sounded very young to me, but husky and roughened by exhaustion. Jamie told me that he had just gotten back from another trip home to see his brother and to arrange for the move back east. “Typical pissing Boston weather,” he said.
Jamie sounded nothing like the scientists I usually interviewed. He was all business and he talked at warp speed, just as Ralph had said. He told me he was maneuvering, wheeling and dealing, talking about patents and “heavy-duty intellectual property.” He was meeting with ALS activists and with people in biotech companies like Cell Genesys, trying to get the ball rolling. His voice had a quality that I thought I recognized. It was a voice that sounded strong from having taken in the worst and still resolved to fight for the best. I heard what we are always trying to define: grace under pressure, action in the face of suffering, the will to hope in the teeth of despair, courage.
“The landscape is very complicated,” Jamie said. “This is a forced journey into a new world. A lot of amazing people in it.”
Even though we had not met, I found myself caring about him. “How are you holding up?”
“I’m in a slight depression right now. I’m trying to align people’s interests in a way that won’t hold up time—because the only thing that matters to me is time.” Then I heard his spirits rebound—or rather, I listened as he talked his way back up, as if he could buoy himself by an act of will, or sell himself hope by selling it to me. There was theater in this: By showing us both how well he could sell hope, he was showing that he could sell others. It was that very power to sell hope that was the story. That theatrical power of Jamie’s was now, in fact, Stephen’s only hope.
“When I started, I had a million-to-one odds of getting something off the ground,” Jamie said. “Then, OK, maybe ten-thousand-to-one odds. Now I’m maybe ten to one, or five to one. So I’m feeling pretty good. This is my kind of problem. I like this! Stops you from thinking about things.”
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