Matt and Jamie met in Matt’s office at Jefferson that spring and took stock. The neurovaccine was ready if Jamie wanted to use it. Matt’s paper had been published in Science at last. In it, he and Paola and their colleagues showed evidence that a neurovaccine seemed to have protected rats from stroke damage. Matt told Jamie that he was ready to try the neurovaccine on ALS. But Jamie was still scared of Matt’s neurovaccine. “Back at Advent, we had a rule,” he said. “Only invent one new technique per project. The neurovaccine has a lot of inventions in it.”
So Matt and Jamie decided to try the stem cells while they prepared the gene therapy. Their first test of the stem cell therapy, back in December, had not done any good for their dying ALS volunteer. Steve Fowler thought his speech had improved a little. If so, the improvement was not measurable, and his limbs and his breathing continued to get worse. But at least the stem cells did not seem to have done him any harm.
Doctor Brown was nervous about it, but Stephen told Jamie that he was willing to take the chance. In his apartment building, he took the stairs very slowly now. He planted his left foot on the next step up, hoisted his body up, swung his right foot up. Wendy went up behind him, but Stephen was six foot, three inches tall and that spring he weighed one hundred ninety-five pounds. The stairs were not easy for her either, she writes in her memoirs of life with Stephen. She was showing now: “Every day, I had more trouble hauling a loaded belly (which was pressing on my lungs) up four flights of stairs.”
As they were going out one day, Stephen stepped off the third-floor landing with his left foot and misjudged the distance. Wendy had stopped for him on the second-floor landing, and she watched Stephen pitch forward full length toward her in slow motion. She screamed, and he thudded and rolled down the stairs straight at her.
“After all my imaginary training, all my mental images of catching him,” Wendy writes, “I dodged him.”
Stephen fell into the banister, flattened against it for an instant, and bounced off into the wall. He came to rest on the landing with his feet up on the bottom step and his back wedged into the corner.
Oh my God! Wendy screamed. Honey, are you all right?
His fall and her screams had raised an enormous echoing racket in the stairway. As she helped him stand up, she was glad it was a weekday. There was nobody in the building to help them, but at least none of their neighbors would see them: a woman pregnant by a dying man who could no longer even manage their steps.
What were we thinking?
Stephen and Wendy left Back Bay and moved back into the house on Mill Street; and Jamie decided to give Stephen the stem cells. It was now April 2000, and the gene therapy still looked far away. Jefferson’s IRB ruled that because the procedure was being done to treat an individual patient, not as a research protocol, Matt, Paola, and Jamie were free to proceed. The procedure would be carried out by Fred Simeone, the chairman of Jefferson’s department of neurosurgery—the same neurosurgeon who was prepared to carry out Jamie’s gene therapy. Because the procedure was novel, all of the doctors involved were taking a certain risk.
Jamie sat down with his family in the house on Mill Street and they all talked it over, evening after evening. Stephen said he was sure he wanted to do it. Then Jamie sat down at Jefferson and talked with Simeone. He said, This would be an amazing thing to do for my family. We don’t know if it will work. You need to understand, you can look me in the eye. If Stephen dies on the table you will never get anything but gratitude from us for the rest of your life.
They would have to put 25 million cells in Stephen’s brain to get enough stem cells in there. If they waited until they developed the KDR technique, they would have to put in only three hundred thousand cells. It would be safer and more elegant, and it would be a merchandisable technique.
The way Jamie tells it, he decided he had to withdraw from CNScience. “I pulled over one day and said—I’m out. If I had proceeded to develop KDR, the therapy would have been delayed by eighteen months. So Matt and I closed down the company. I didn’t want profit questions to come between Stephen’s treatment and the right decision. I thought there were one-in-ten odds it would do anything. Which is why it was important not to do it as part of a company, for profit. You couldn’t do it in corporate architecture.
“So we had a choice—wait and do KDR? Or go for it now?” The massive but inelegant injection might help. “No reason not to just try it—unless you were intellectually or financially interested in the KDR application—which is why I quit. When I went into a room as president of CNScience everyone wanted an angle.” What’s in it for me? “When I went into the room as founder of TDF, everyone wanted to help.”
So in that way he went into the project with clean hands. But I think Jamie felt almost as worried about stem cells as he did about the neurovaccine. He would have asked Stephen to risk his neck for the gene therapy, but he was nervous asking him to do it for stem cells. Rothstein had some idea how EAAT2 worked; no one knew how stem cells worked. “It’s not a cure,” Jamie worried to me. “I don’t know how effective it will be. It’s lightweight.”
The truth was that stem cells were still more a hope and a promise than a treatment or a cure. Art Caplan was just as discouraging about stem cells as he was about gene therapy. “My skepticism about all this is somewhere between unbounded and enormous,” he told me. “A stem cell effort? Good luck! I mean, stem cells, I’d put that on the five-year plan, not the short-term plan.” Jamie was more likely to hurt Stephen than help him. “You can actually kill somebody,” Caplan told me. “You can actually make them suffer more miserably. Somebody might say, ‘How could you suffer more miserably than by having ALS?’ But you can. Way back when the artificial heart was being developed, in the mid-’80s, I watched Barney Clark, who was dying of heart failure, die instead of nosebleeds, dementia, psychoses. He just had a miserable dying because the device wasn’t ready. They rushed it to save him, and he agreed to try it because he was doomed. He certainly was going to die—faster than this gentleman is. But the fact is that you can be made more miserable—even though it doesn’t seem possible—by interventions.”
As the date for Stephen’s injections got closer, Jamie sounded more frightened. They had given human stem cell injections to two monkeys without doing any obvious harm, but that was almost all the data they had. “This is risky,” Jamie said. “This could be worse than Gelsinger. It’s really borderline. We could cook him. Jeff Rothstein thinks I’m crazy, outside the curve.”
That was true. “Wow, are you kidding?” Jeff Rothstein said when I asked him what he thought of Jamie’s plan. “Putting foreign cells into the cerebrospinal fluid—cells that are not normally there? They could cause an inflammatory response and become horribly toxic. Jamie keeps telling me that this is just a variation on an FDA-approved procedure. Yes, it is, but you put the patients’ stem cells back into their blood. You don’t put them into their spinal fluid. Years ago, some doctors injected formaldehyde in there by accident and killed someone. You don’t put things in there. That’s a sacred space in your body. What Jamie is planning has never been done in a human being before. It’s just ludicrous. I’m appalled. Jamie’s decided he is going to practice medicine on his own for the sake of his brother.”
Rothstein said he hated to sound like a stereotype—like the monstrously overcareful, uncaring doctors you see in the movies. “Of course we care,” he said. “We just have a different view. We recognize that people go into these experiments extremely biased, thinking that no harm could come of them. They say, ‘What’s the harm, I’m going to die anyway!’ But there can be harm.”
On Sunday, May 21, 2000, Stephen and Wendy stopped by the Victorian before they left for Philadelphia. They were driving down with Peggy—Jamie would follow after he took care of some business at the foundation. Stephen gave Jamie and Melinda long hugs. He said, trying to joke, Let’s see if I come back dancing and jumping around.
On Monday, Wendy and Peggy drove Stephen to Je
fferson Medical Center to give blood. Normally the doctors would have taken it from his arm, but Stephen felt so weak that if they stuck him there, he was half afraid he would never be able to flex his arms again. Besides, he did not think he could make a fist. The doctors decided to insert a catheter into his jugular instead. They also gave him a drug that flushed the stem cells out of his bone marrow.
Stephen, Wendy, and Peggy stayed that night at Paola’s three-story row house, with the cat, the rabbit, and Gnocci and Bambi, the German shepherds. Gnocci and Bambi greeted them at the door and were extremely excited to see them. When they put their paws on Wendy’s shoulders, they were taller than she was. She felt protective of her belly. She was almost six months pregnant.
On Tuesday, she and Peggy took Stephen back to the medical center, where doctors drained blood from the catheter they had implanted in his jugular. Stephen watched movies on a VCR while his blood drained, Peggy wrote thank-you notes for the foundation, and Wendy read, read, read—she was trying to read as many books as possible before the baby arrived. In a separate laboratory the doctors extracted what they needed from Stephen’s blood and then returned the rest through the catheter. Meanwhile, with the extract, they stripped away as much as they could to concentrate the stem cells. Simeone, the surgeon, had stopped by the row house and given Stephen a statement to sign:
May 23rd, 2000
Stephen Heywood’s Statement
I Stephen Heywood voluntarily write this statement to:
Dr. N. Flomenberg
Dr. A. Freese
Dr. M. During
Dr. P. Leone
Dr. F. Simeone
I was diagnosed with ALS in December 1998 and the disease has progressed rapidly in my body. I have been following the research being done in different laboratories on Stem Cell transplants…. I request that you transplant my own [stem] cells into the intrathecal space of my brain and my lumbar spine.
Because what I ask is a novel procedure I take all risks for any possible outcome and I will be responsible for any personal and/or institutional liability for the result of the procedure. I am personally asking for this procedure and do so under no pressure or duress and I personally take all responsibility for the consequences.
I also understand that any novel procedure involves risks and that in this case though there is no known reason to believe there will be negative consequences it is possible that unanticipated consequences could result in partial paralysis or even death. I am conversant in the technology and operations involved. I understand the potential risk is real and I choose to accept it as reasonable. I also understand that side effects of the operation can include spinal infections, headache and a potential blockage of the spinal fluid. I choose to accept these risks.
With this statement I also fully agree to allow post mortem analysis on my brain and spinal cord in case death would occur as a consequence of this procedure.
At the bottom of the page, Stephen Heywood scrawled his initials with his left hand. Jamie Heywood witnessed the signature.
I talked to Jamie on the phone that night. I had never heard him so nervous. “We have no clue it will do any good,” he said. “And there’s some risk.”
In his fear, Jamie sounded almost as skeptical of his own project as Art Caplan. “Everyone wants one thing that will do it—like acupuncture,” he told me. He pronounced the word with the same contempt that Caplan had used when he compared gene therapy to entrails and bat wings. That night Jamie felt terrified of stem cells. He was asking Stephen to risk his life for something that would probably do him no more good than a placebo.
“But,” Jamie said, at last, “if he believes it’s powerful…”
On Wednesday, May 24, Stephen was taken into the fluoroscopy room at the medical center for the procedure, which would take two hours. Paola and Matt assured Wendy and Peggy that the neurosurgeon who would inject the stem cells into Stephen, Simeone, had performed more spinal operations than anyone in the world. They would not let Wendy stay with Stephen, and she hovered outside the door of the fluoroscopy room. At one point the door opened and she saw Stephen lying on his side on a gurney with his back to her. She saw Jamie, too. Jamie, who always had a way of getting where he wanted to go, was hovering above Stephen with a video camera, taping the procedure. The room was tinted green from the fluorescent lights. The door closed again, and for the first time Wendy felt a thrill of horror instead of hope.
Simeone, the surgeon, injected 20 million stem cells into Stephen’s spinal fluid. Then, using a spinal needle that he guided with the fluoroscope, he injected more stem cells into the cisterna magna, a big space in the back of the brain where a surgeon can insert a needle with relative safety. It is at the back of the lower part of the skull, right where the skull and spine meet. Stephen felt fine when they were done, but he had to stay at the hospital overnight, and the hospital rules would not allow Wendy to stay with him. She went back to the row house, said good night, lay in the dark and could not close her eyes. She wanted Stephen spooning her in the bed, telling her that he loved her, and telling her that they were going to be fine.
On Thursday, May 25, Wendy and Peggy picked up Stephen from the hospital, brought him to Paola’s, and set him up in an upstairs room, away from the dogs. Then Wendy and Peggy walked down South Street, where they bought a thank-you gift for Paola, a tall white orchid. Carrying the orchid back to Paola’s, Wendy stopped in front of a store. In the window she saw a huge steel canopy bed. She was in such a state by now that the bed seemed like a sign. She and Stephen wanted a bed just like it. They had been shopping in Boston for just that bed. Stephen had even begun to think he would have to make it himself. The bed in the window had handsome two-inch-thick industrial steel tubing, and it was high enough that her husband with his long legs could get in and out of it easily. Even the price was right: only $600. Wendy is not a matter-of-fact atheist like Stephen. She is a doubter, an agnostic who often argues and pleads with God, and back at Paola’s that night as they all drank wine, she talked about the bed in the window almost as if it might signify a miracle.
Matt and Jamie played pool. Stephen watched and teased. But Paola found the celebration almost too poignant to bear. She and Matt had no reason to think the stem cells would do more for Stephen than they had for their first volunteer back in December. This was just one of the first incremental steps the world would have to take in developing stem cells into useful treatments. The amount they had to figure out was more than the amount they knew, and so much could go wrong. And even so, Paola hoped and believed. It was quite typical of her to have hosted the Heywoods in her home, with her dogs, cat, rabbit, with more stuffed animals and stick-figure drawings like the ones she kept at the lab—gifts from toddlers with a year to live. Paola puts no walls between herself and her patients, as Matt does, and she suffers like one of the family.
On Friday morning, when Stephen, Wendy, and Peggy sat down in the kitchen for breakfast, they found an envelope on the table: “To Wendy and Stephen.” Inside was a card from Paola and a check for six hundred dollars.
Thirty-Seven
The New Model T
John and Peggy Heywood helped the newlyweds buy a little Cape Cod three-bedroom house in Newton on Beverly Road, just a few minutes’ walk from the Victorian and the carriage house. They were still paying for those, and they were bankrolling Stephen’s work on the carriage house.
The whole family helped them move into the house. Stephen and Wendy had fun assembling their steel bed, and like any expectant parents they threw themselves into renovations and decorations. But Stephen noticed no improvement in his condition. Bob Brown examined him at Massachusetts General, and he saw no improvement either. Stephen’s right hand and foot were still weak, and still getting weaker.
The baby was due in September, and Wendy could not help feeling frightened now. On most days she did not panic about the one big thing—she panicked about many little things. She was still working at a Harvard biological laboratory,
and she came home fretful every evening. “Dear God,” she scrawled in her journal, “Why are you killing Stephen?”
Stephen himself stayed calm. He kept his sardonic sense of humor, and he did not lose his perspective even now. The two of them were still there, and the baby was coming soon. Whenever Wendy said, a little overearnestly, Stephen, there’s something I want to talk about, he said, mock-anxiously, You’re pregnant?
Six years before, Wendy had started and abandoned work on a master’s degree at Southwest Missouri State University in Springfield. It was an MA program in English, with an emphasis on writing. Stephen urged her to call the school and find out what she had to do to finish. With his encouragement, she proposed a project that might qualify as her thesis. And that is how she came to begin her memoirs of life with Stephen. Stephen’s suggestion was inspired. Instead of fretting in the long summer evenings, Wendy could celebrate their story, and their family’s, and she could haul a few of their neighbors in Back Bay before the court of literary justice.
One more ALS patient, a forty-seven-year-old woman, tried the stem cell injections. Once again the injections had no measurable benefits. All three patients went on getting worse, and none of them chose to repeat the procedure. But at least nobody seemed to have been hurt, and all three of them felt that they had helped the cause of regenerative medicine.
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