It was time for lunch. As we walked toward the revolving doors in the lobby of the building, I was alone for a moment with Stephen because the others had already gone through. Stephen walked slowly. “What do you think of the lab?” I asked him, not very diplomatically, since the next moment we emerged on the sidewalk with Jamie, Matt, Paola, and Wendy waiting there in the sunlight and watching us.
“Good,” Stephen said simply. “A little disorganized, but good.”
The restaurant that Jamie had chosen was Buddakan, one of the best and trendiest places in the city, with a fountain of water running down a stone wall near the front door, and a big statue of the Buddha inside. Jamie asked Paola to order, and when the food came she dished out our portions from the bowls and trays with happy, festive laughs. But when she thought no one was watching her, I saw her stare at Stephen with a moist film in her eyes, as if she were taking a picture of him to go with her photographs of the Canavan babies. I looked across the table and saw the picture she saw: a tall, dark, and handsome man of thirty, beaming at his fiancée.
Stephen saw us watching him and gave Jamie a slow, careless smile, like a young man with all the time in the world. Then he grinned around the table at the rest of us. Still, whenever he was serious, earnest, asking questions, I saw a kind of pain in his face and eyes. And when he was quiet, in repose, he looked very sick.
When the credit-card chit came, Stephen signed it.
“So you are left-handed?” Paola asked.
He gave one of his mordant laughs. “I am now,” he said.
Thirty-Three
Bat Wings in Paradise
At the end of the month, Stephen and Wendy moved into their fourth-floor walk-up on Beacon Street. “The stairwell was wide, with long flights of carpeted steps and heavy, dark-stained wooden banisters,” Wendy wrote later in a journal and memoir about life with Stephen.
“From the fourth floor, the top floor, you could look down through the gap between the banisters and see all the way to the main landing. It was a tight space, but not so tight that one couldn’t fall to his death if he were unlucky enough to lose his balance and go over the banister.”
The day they moved into the building, Stephen’s footsteps were already heavy, uneven, and alarmingly loud on the long flights of steps. The woman on the third floor cornered Wendy on the landing between the third and fourth floors and gave her a piece of advice.
Keep the noise down if you don’t want your neighbors to know your business.
Wendy felt for John when he came to visit, and inspected their two small rooms from the doorway. Even as she opened the door, she could see that he was looking for ways he could lend them a hand. With only two rooms to survey, there was not much John could see to do. There were pictures to hang, of course, but Wendy would hang them herself. They needed a kitchen table, and John offered an old one from the house on Mill Street. Maybe he could help move the couch? “He needed a task and we had none to give him,” Wendy writes in her memoir. Stephen was still capable, and the son needed tasks even more than the father. “So John settled for standing in the entryway, rotating his hat in his hands.”
Every morning Stephen walked down the four flights and walked six blocks to the train, which he rode to Newton, where he was still renovating John and Peggy’s master bathroom. He carried a black shoulder bag across his chest and his right arm swung limply by his side. He used his left foot as an anchor, step-by-step, to lift and drag his right foot along. “In his large body,” Wendy writes, “he swayed down the street like an updated, very handsome version of Frankenstein.”
The Washington Post broke the story of Jesse Gelsinger’s death at that time, and in the last days of September it ran on front pages across the country.
The boy’s father, Paul Gelsinger, told the Post, “I lost a hero.” He also said he did not blame the researchers. “They’re as hurt as I am. They’ve promised full disclosure.”
He told the New York Times, “The doctors are as devastated as I am. It was because of these men that I had my son for eighteen years.” He would stand by them “until my dying day.”
James Wilson told a reporter for the Times that he and his team were conducting an investigation of the cause of death. “We owe it to the field and to the patient, who really wanted to participate and wanted us to learn,” he said. At first, Wilson and his team told reporters that they had no warning of trouble. As a reporter for the Philadelphia Inquirer put it, “The first and only serious side effect in the trial was Gelsinger’s death.” Then Wilson said there had been one case of liver damage but that no one in the set of three just before Gelsinger’s had any side effects. But the FDA pointed out that one volunteer in the group before that one, a woman named Tish Simon of Union, New Jersey, had shown liver enzyme levels that were five times higher than what is considered healthy—levels that should, according to the rules, have been reported to the FDA. The FDA made much of Wilson’s lapses—while saying very little about its own.
Immediately, officials with the RAC, the Recombinant DNA Advisory Committee, began looking into fifty other gene therapy trials around the country that also used the cold virus.
What made the young man’s tragedy agonizing was that he himself had not needed the gene therapy. He might have lived a long life with careful diet and fifty pills a day. He had joined the trial purely in a spirit of altruism and adventure.
The University of Pennsylvania stopped the trial. The FDA issued a clinical hold on it. The RAC sent out a warning letter to the laboratories that were using cold virus.
Jamie followed the news through Matt and Paola in Philadelphia. At home in the peeling Victorian he sat down with the paper and held it in front of his face. Day after day, night after night, he could not help cutting her dead—Melinda and most of his old friends, too. He had no time or energy for anything but the saving of Stephen. They could understand that, or not. On November 1, Jamie came home from a brunch with Katherine Evans and told Melinda that he would be paying Katherine $2,500 a week to work full-time writing the FDA protocols for the gene therapy project. Melinda had thought Katherine was out of the picture. She heard Jamie and thought: More money we do not have, and yet another person working at a desk in our house.
She wrote a little later in her journal: “I did not react in an exemplary, supportive & adoring wife fashion—he became very angry & left the room abruptly, I heard a loud bang in the other room which I assumed to be his foot kicking the door but which was his head banging itself into the wall.”
She went after him to apologize but they had a terrible fight. Jamie said, How can you worry about defending your boundaries when they get in the way of saving Stephen’s life?
Melinda scrawled in her journal and wept. “I love Stephen more than anything. I love your family. You absolutely have my support & always have, every step of the way…. I have a perfect right to worry about boundaries & protect my peace of mind—I’m also PREGNANT, by the way, and my desire to have my own private space is doubly compounded by that. Boundaries are closing in on me, dissolving, at every turn—my body’s boundaries are shifting—hormones have taken me over—another entity is growing within me—there are 7 people in my house, in my kitchen, around the house on any given day—using my dishes, eating my bread, drinking my tea…. I have to stay upstairs with the fan on to block out noise from downstairs…. It has grown too big.”
And the Jesse Gelsinger scandal grew. On November 21, Wilson flew to Tucson to talk with Jesse’s father, Paul, and try to explain his son’s death. Wilson traveled there with a reporter, Donald C. Drake, of the Philadelphia Inquirer, and Drake described the scene at the close of another front page story about the death.
Wilson had never met the father and he had met the son only once. When he arrived at Gelsinger’s small house, he found the man waiting for him outside. Paul was standing next to a dirt bike he had bought that year for Jesse. A reporter had just told Paul one of the first of the nasty revelations in the case: The pharmaceutical house Sch
ering-Plough had seen side effects with cold-virus gene therapy and reported them to the FDA, but the law had required the FDA not to tell Wilson’s group about it. As Paul saw it, he and his son’s doctors had been wronged.
“He didn’t have to die. My kid is dead so they could make billions more,” he said. “Love of money is what killed my kid. You guys would have stopped if you knew about what happened.”
The father was so wound up that he talked on until dark. At last when he felt he had said what he had to say, he let the doctor go over his theories about the cause of death. The father was still loyal to the doctors.
“You guys are baffled, aren’t you?” he said.
By then the papers were reporting that Wilson himself stood to get rich if he could make a success of gene therapy. To Paul Gelsinger that was offensive innuendo. He was still convinced that he and the doctors were on the same side. He asked James Wilson for the truth and Wilson gave him a very soft answer. Yes, he had started a small biotech—many researchers did that these days. But he had only nonvoting stock, and he consulted for the company only one day a week, for which he was paid nothing.
Paul wanted to know if Wilson would have made money if the trial had worked. Wilson gave him another soft answer. He talked about the years it takes for a biotech to get a drug through the pipeline. His company, Genovo, still did not have a single product, he said.
That satisfied Paul Gelsinger. The doctor, the handyman, and his son were victims together, he said.
“What you guys were doing was pure.”
When I heard the news of Jesse Gelsinger’s death, I called Art Caplan, the bioethicist. He had served on the Penn internal review board that had approved the study. Caplan said Jamie and Stephen Heywood should drop their project. “You may have a year or two to live, and some of that time you may think of as just more miserable than you can endure, but you may not want to die in the morning,” Caplan said. He knew and respected Matt During, he said, but he doubted Matt’s ALS project would be approved by Jefferson’s internal review board, much less by the RAC or the FDA. “Everybody’s gun-shy about gene therapy now,” Caplan said.
So was Caplan. “I don’t think gene therapy is quite entrails and, you know, bat wings, and the inner gonadal parts of monkeys. But closer to that,” he said, “than it is to penicillin. We’re still so early on. I understand the desire to want to take charge and do something and pursue something, but racing to find the first cure from gene therapy for a complicated disease is really—that’s not just long odds, it’s google-number long odds.”
As I listened to Caplan, I felt vindicated in my fears for Stephen; but at the same time I felt furious at Caplan for judging the Heywoods without even knowing them. I felt glad that I had not put my mother under the needle and the knife; but I felt outraged that the world had made these new medical experiments so charged that they had a supernatural aura, and now a single failure in a clinical trial could slow or stop them all. I wanted Caplan to tell me the right thing to do, but at that moment I hated him for sounding as if he believed that he could. As a professional I admired his confidence. But it was like calling a talk show psychologist. How could he shoot them down when he did not even know them?
“Well,” I said, “if you were talking to Jamie Heywood, what would you say? Would you try to talk the family out of doing this?”
“Yep. And by the way, I can give this speech, because I’ve given it. Not quite as coldly as this, but I’ve given it. I’d say the best thing you can do for your brother is try and prepare”—he paused—“for the worst outcome. To line up appropriate spiritual support, and psychological support, and do everything possible to prepare for, ah, death.”
When I told Jamie what Caplan had said, he was so enraged that my pen stopped and I did not write anything down.
“What does he think of us? Does he think my family is stupid? Does he think we don’t know what is happening here? Prepare for death!” Jamie cried, in a voice thick with rage and tears. “What does he think we’re doing?”
Later, he said, “It’s a good thing Stephen is not Art’s brother.”
With the Gelsinger scandal, Jamie’s job became much harder. He panicked. It was the same terror that he had felt at the very start of his race, he said, “just sort of sheer panic as you try to describe something into existence again.” He was still meeting with potential donors and investors and he was still trying to decide whether to go profit or nonprofit, but every conversation was harder. “Sometimes you wonder what great wealth gives you, and I think maybe it gives you the ability to skip this part,” Jamie said. “You take on a lot of responsibility, and you know how shaky everything you are describing is, because you are the only one who knows where the strong parts are and where the weak parts are. It is sort of like pure force of will.”
The safety record of gene therapy was still far better than the record of most other kinds of drug development, he said. Its efficacy rate was truly abysmal, but its safety record was good.
“I don’t know if anyone realizes quite how hard this is to do,” Jamie told me. “It was much easier for me to talk about putting together Internet companies. This time it is just much more. I wonder if people are always this scared. I met with this CEO—I didn’t get the sense that he was that scared.
“There is also this sense of being an impostor. ‘What the hell are you ever doing here, Jamie, there’s fifty brilliant doctors trying to cure this disease, what are you doing here?’ I mean, I know I can answer that question. But if Jeff Rothstein screws up, there is no loss for him, he’s still a professor at Hopkins and he works hard. If I screw up—I feel like I’m walking twenty-four hours on a plank.”
On Friday, December 3, after working a few back-to-back twenty-four-hour days, Matt During, Paola Leone, and Jamie Heywood submitted a proposal for a clinical trial for ALS gene therapy to the internal review board of Jefferson Medical College. They asked the review board to approve their trial in spite of the scandal. In reaction to the death in Philadelphia, the FDA had ruled that it would not review a gene therapy protocol without its first being submitted to the RAC, and the RAC would not review a protocol unless it had been approved by an internal review board, an IRB.
IRBs were mandated in 1974 by federal law after scandals in which doctors had badly abused patients in the name of science. The most notorious case was the Tuskegee syphilis study. There, doctors in Alabama deliberately did not treat black men so that they could watch the syphilis progress until it killed them. The disease spread to some of the men’s wives and children, and still the doctors let the study go on.
The institution of the IRB is clearly needed; but the board members are usually unpaid and badly overstretched. One government report found that in a typical university medical center IRB, the board went through agenda items at a rate of less than two minutes per item for two and a half hours. Now Matt During asked his university’s IRB to hurry because the next RAC submission deadline was January 13,2000. If they missed that deadline, the next would come three months later. Jamie and Matt would lose those three months.
On December 8, the fifteen members of a RAC panel, mostly scientists and ethicists, met for a three-day session. The meeting was a sad circus of news conferences, reporters and scientists and cameras, and representatives of government and the biotechnology industry. Wilson spoke to reporters in the company of a press aide and a lawyer. He and the others on his team said the problems with their study came down to technicalities and judgment calls. W. French Anderson, the doctor who is usually called the father of gene therapy, told a reporter for the Times that in a big laboratory like Wilson’s, “sometimes things fall through the cracks.” Jesse Gelsinger’s father sat in the back of the hearing room. He was still supporting the doctors: “These guys didn’t do anything wrong.”
Meanwhile, on December 9 Matt met with a small subcommittee of Jefferson’s IRB to present their case. He pointed out that unlike the notorious trial at the University of Pennsylvania, t
hey were proposing to treat people with a fatal, incurable, rapidly progressive disease. Their virus, unlike the virus used in the Gelsinger tragedy, had been shown again and again to be safe. It had been used, for instance, in genetic therapy trials for cystic fibrosis and hemophilia. In those trials there were hints that gene therapy might be working at last.
The board would not reply for a month. There was nothing to do but wait. I called Steve Gullans, a professor at Harvard Medical School who knew and admired Jamie, and I asked him what he thought the IRB should decide. “This is a tough call, a judgment call,” Gullans said. “No doubt breakthroughs are rare, and they are all preceded by naysayers saying it will never work. But with gene therapy, you have two one-in-a-hundred shots. First that the virus will get the gene in, and second that the gene will help. If there were just one long shot, I’d be happier. But two—”
Jamie was nervous waiting and he was also nervous about the New Yorker story. He called me almost every day. He had found a publicist in Boston who spent a weekend with the Heywood family for free, coaching them on how to make the best of the press attention that would follow the article. “You’re not going to let me see it, are you,” he said one day. “I asked for this, but this is scary. This is very scary. Should I be scared?”
I said he had nothing to worry about, but he did. The money question hung between us now. I was so worried about it that one day I called Ralph Greenspan in La Jolla to ask if he thought I should abandon the story. It was a Sunday afternoon, and we talked for an hour while he did his laundry. Ralph said my worries mystified him. Jamie was an entrepreneur. He was trying to save his brother with all the tools of the entrepreneur. What was the problem?
But I was hugely relieved a few days later when Jamie called to tell me that he had decided to donate all the proceeds of his gene therapy patent and project to the foundation. He had decided at last, he said, in a strained voice. Anything that came from it would belong to the nonprofit, just as he had pledged in his speeches to Robert, Melinda, and Peggy down in the basement.
His Brother's Keeper Page 28
