Afterward, Jamie explained the failure of the stem cell work to me this way. “If you think of stem cells as a repair crew, ALS is a flood region. Can’t send in repairmen now. The flood is still there.” He thought he and Matt and Paola needed to clean up the glutamate flood before they could put new nerve cells in there and see the cells grow and go to work. That would take his EAAT2 bailers.
According to another view of ALS, Jamie’s explanation was overoptimistic. By the time motor neurons begin to die in ALS, the glutamate flood is probably gone. It has rolled on. It is elsewhere in the spine. The flood is gone, but the nerve cells that it damaged have begun what is known in the jargon as apoptosis, a process in which cells give up and die. The nerves in Stephen’s spine had begun literally killing themselves.
Jamie was beginning to lose his faith in futuristic medicine. He still hoped that his gene therapy could correct Stephen’s problem at or near the source, and stop the last healthy motor neurons from being damaged. Then, someday, in five or ten years, he could use stem cells to replace the nerves that had died. But in Washington, gene therapy was now absolutely untouchable. Paola got massacred when she presented her Canavan protocol at the next RAC meeting, Jamie told me. “People on RAC are posturing!”
Matt decided that they might do well to wait awhile longer before submitting their ALS gene therapy proposal to the RAC. Maybe the world would be calmer in September. If the RAC approved their plan then, Jamie calculated that Stephen might get the EAAT2 gene in the spring of 2001.
“It’s like molasses,” he said. “There are so goddamn many things in the way.”
With Steve Gullans of Harvard Medical School, Jamie had begun to look in still another direction. Gullans was convinced that there might be buried treasure in the medicine chest: They might find cures for the incurable in drugs that were already on the market. Gullans was trying to develop and automate a way to test drug after drug on cells in petri dishes or on mice to see what they might do for orphan diseases. Jamie could go prospecting in the tailings of old gold mines while he fought to open up the new frontiers.
Jamie’s foundation, a few minutes from the Victorian, had about three thousand square feet. On his office wall there was a framed black-and-white picture of Stephen and Jamie as boys, and a photo of his little baby Zoe on his desktop, behind stacks of files. There were also slogans written graffiti style on the glass wall of his office: “Time Is Neurons!” “Trust but Verify!”
He was already thinking of moving again. He needed an animal facility. On a table behind the reception desk stood stacks of plastic cages with rotating wheels. He had designed them himself. Each one had a built-in data collection unit, and a fan to clear out the ammonia from the mouse litter. A company was building the cages for them at cost. With individual data collection and micro-controllers, Jamie thought they could do automated checks of the energy and the strength of the mice as they tried out drugs on them in different combinations.
Jamie kept trying to get me excited about his new idea, but every time we talked I felt sadder.
“So you’re no longer the guerrillas charging the hill,” I said.
“We’re moving away from the guerrilla metaphor. And from Brave New World.” In fact, Jamie told me, he had begun to think about the Model T.
“Henry Ford had this insight: I don’t need to build a Dusenberg. I just need to build a simple car that gets from A to B.” What if the scientists and technicians in his foundation could automate tests of all the drugs ever approved by the FDA, and try them out one after another on ALS mice? If they found something that worked—or a cocktail of drugs that worked in combination—there would be no red tape, no delays, since all these drugs were already approved by the FDA.
Jamie tried to sell me on the Old World the way he had sold the New. “I remember when we were all going to the moon,” he said. “Rockets! I was going! I was born in ’66. Air flight has not changed since that day. Not at all. Military jets have not changed. We’re not in rocket ships.” The Brave New World in medicine was still coming, he was sure of that. It would come as soon as we were ready to make it come. So would the space colonies. “We could build a rocket ship to Jupiter. And medicine will get better. Gene therapy will be done—and it will be just another drug. Not Brave New World. Stem cells—we’ll figure out how to do it. ALS, Parkinson’s, Alzheimer’s will be cured. Not by miracles. You’ll go to the pharmacy.”
Meanwhile he had found an open niche, he said: research that should be done but that most big biotechs would never try. “Because it won’t make Genzyme any money to show that, God forbid, aspirin helps with EAAT2,” he said. “They’re interested in what makes money.”
I tried to feel excited by Jamie’s “back to the past” speech, but I only felt depressed. It was now late summer 2000. Almost a year had passed since I had climbed the ladder to the hayloft of the carriage house with Jamie and Stephen. I remembered how hopeful we had felt and the gallantly sardonic way that Stephen stood up there, with folded arms, and surveyed the ruin: the rotting floor, the smell of rats and rot, the spider-shrouded dormer windows.
“So this is a bit of a death trap,” he said.
And Jamie laughed. “No, it’s not,” he said. “This is our house.”
Thirty-Eight
A Sick King
Each time I visited Providence, my mother looked smaller and stiffer. She was slowly bending over into a question mark. To meet her eyes I had to sit at her feet and look up into her face. When we connected, she gave me a locked stare. In her checkup in the fall of 2000, Doctor Salloway held up a finger in front of her face and moved it to the left and right. Her eyes tracked it. Then he moved his finger up and down. Now she followed it by tipping her head, not moving her eyes. Placing his hand on her head to hold it still, he raised and lowered his finger again and again, and her eyes just stared straight ahead. When he tipped her head forward and backward, very slowly, her eyes rolled so that her gaze stayed dead level, like the eyes of a doll.
Salloway looked at my father. I think I know what this is.
First her rag-doll, forgotten-marionette falls, then the slow stiffening of her body (just getting her outside was a big production now). With that suite of problems, and now this peculiar selective paralysis of the gaze, the diagnosis was clearer. It was not Lewy body dementia after all. She had Steele-Richardson-Olszewski syndrome, also known as progressive supranuclear palsy, PSP.
Steele was the young doctor who had gone to the island of Guam to work with the native Chomorros and study their peculiar epidemic of nerve-death disease, which manifested sometimes like ALS, sometimes like PSP.
In PSP, the gunk in the sick neurons is not made of alpha-synuclein, like Lewy bodies. It is made of tangles of tau, one of the same proteins that accumulate in Alzheimer’s, although it piles up in a different set of cells in the brain. So the vaccine that Matt and I had talked about would have been a long shot at the wrong target. But I did not go back to Matt to talk about tau. By now the experimental neurovaccines were looking almost as uncertain and unready as gene therapy; and if she had ever been a candidate for a trial at the edge, my mother was too far gone now.
Jamie wanted me to keep writing about his foundation. He called often.
“Come down to Duck with us. Everyone in my family read the article. They all love you.”
But I was too sad and demoralized to follow his progress.
Once when we saw each other, I told Jamie that my mother’s disease was probably PSP, but that we would not know until the autopsy. And Jamie laughed. “I’m sorry,” he said. “It’s just all so ghoulish sometimes.”
My title at Rockefeller was writer-in-residence, but I was not really in residence. I still lived out in the country in Bucks County, Pennsylvania. Once a week or so, I went into the city on the bus. Actually, I was not writing, either. I was too depressed. After all our hopes, I saw nothing but bad signs. It was the onset of a time that I and some others remember as a long dark blur. The Interne
t bubble popped, and the biotech bubble popped, too. Matt and Paola, who had been seeing each other secretly, had a horrible public falling-out, and Matt had her escorted from the CNS Gene Therapy Center by security guards. Then, in the middle of a complicated squabble with its department of neurology, Jefferson closed down Matt’s center, and he sued the school for breach of contract. Margaret Sutherland moved her lab from Vanderbilt to George Washington University, and on the way to Washington, Minnie died. Sutherland would not publish anything about the miracle mouse, so a student of Jeff Rothstein’s tried to replicate her experiment. His ALS mice took a little longer to get sick, but they did not live one extra day.
The fall of 2000 was happy for Stephen and Wendy, at least. Their son Alex was born by cesarean section on September 11, exactly one year before that date turned dark.
As before, I hung around in the laboratories of scientists, and followed their patient work and their more than patient view of time. Günter Blobel and I often talked that year. One afternoon Günter was reclining across two or three chairs at the foot of the conference table in his seminar room, relaxing as he chatted genially and comfortably, rubbing his eyes.
“If we knew the signals, we could replace your heart tissue,” he said. “Say you had a heart attack. I could take stem cells from you, take out the nucleus, put it in one of your heart cells, put it back in your heart. Then all the proteins the cell makes will be your proteins. Then you can repair the damage in your own heart! This has been done with mice, it was published in Nature.
“This will be a very important line of research in the next ten or twenty years. I only regret that I don’t have another thirty years of creative work. I would do another long-range inquiry like in the past. I am always interested in the long-range inquiry—not the bread-and-butter questions that give you answers and that’s the end. But I know I don’t have thirty years of creative work. You have to just face reality and hope for the best. To do science, you must never lose a child’s hope,” he said, a line that became a proverb for me. “You must not fall into the cynicism of old age, that nothing matters. Once you have lost that childish hope, then you have lost a very important element for doing science.”
A long time before, when he was just starting out, Günter had asked a scientist for a letter of recommendation, and the man had written that he was immature. Günter found out about it, and now it amused him vastly to remember that letter. “ ‘Clever, smart, but immature!’ Of course, I didn’t get the job! He mistook my childish enthusiasm—he felt this was immaturity. Probably he had long since lost hope himself. Many do. Psychosclerosis, you can call it. Some have it at age twenty. Many would consider them mature. Probably they are! They have nowhere to go! Other than falling off the tree and being eaten by the worms.”
He leaned his head back, hands clasped behind his head, on the long row of chairs. He wanted me to go to Dresden, he said. I had to see the way the Dresdeners were restoring their ruined city and I had to stand inside the Frauenkirche. “You have never seen a space more magnificent than that space! Reconstruction has spiritual meaning. Buildings are not just brick and mortar. It doesn’t matter if the brick and mortar are five hundred or three hundred years old, or new, what’s important is the spirit.
“Einstein said, ‘Religion without Science is blind. Science without Religion is lame.’ The Communists tried to do without religion and it was a catastrophe. We’ve seen what the Russian rejection has brought their cities and their citizens—total devastation.
“You can make your own religion if you want—and you can look at religions as a struggle to deal with life through metaphor, to deal with what we cannot explain. The great old solutions are worth studying, and their similarities are worth exploring.
“The cell arose three and a half billion years ago! So as we sit here we are really three-point-five billion years old! So for practical purposes we can really speak of eternal life! And the Resurrection!”
I did not see the Heywoods again until May of 2001. That month, the story of Jacques Cohen’s experiment, the project that I had heard about in the Caribbean three springs before, broke at last. It was one of Cohen’s own people at St. Barnabas, the young scientist Jason Barritt, who forced the story to the world’s attention. He was leaving the clinic at St. Barnabas, he was looking for a job, and he published an article announcing that they had been the first to genetically engineer human babies.
The press took up the story in the United States, in Europe, in Asia. The angriest articles were published in Scotland, the birthplace of Dolly. The Scotsman ran a story about Jacques Cohen on May 9, 2001, with the headline “GM Baby Doctor: My Little IVF Experiments.” Next the Scotsman ran an editorial, “Birth of a Crime Against Humanity.” In the twentieth century, the editorial said, political utopias had led to murders. In the twenty-first, would scientific utopias lead to murders?
As the criteria for perfection become ever more narrow, couples who produce ugly children of moderate intelligence through opting for the “outdated” method of conception involving love and luck, will find themselves charged with committing crimes against humanity. Ways will be found to deal with such aberrations.
“It will never happen,” I hear you say, but that’s exactly what we used to believe about GM babies.
Cohen lives on the Upper West Side of Manhattan, and one morning he stopped by my office at Rockefeller on his way to the clinic at St. Barnabas. He sat on the edge of the sofa, brought out a silver pillbox, and swallowed a few pills. He sounded out of breath, as if he had been running. Not only were the world’s tabloids accusing him of genetically engineering the Brave New World. The Washington Post was now about to announce that several of the babies conceived with the help of cytoplasmic transfer had genetic problems.
“The critics say our kind of work should be risk-free.” He pointed at his silver pillbox. “I’m taking a drug for acid reflux disease. It’s a wonderful new drug, especially for the last two weeks a godsend. Comes with a list of risks. I am the experiment, no? I am the experiment. And who knows what it does to me.
“I don’t think we did anything wrong. I think we did the right thing. This is just bad journalism, irresponsible reporting. PR at St. Barnabas has been working on this seven days a week. And the legal department, too. The reactions of all the journalists! Some of them are claiming that this is the same thing as cloning. In Taiwan that’s what they said. It goes around the world in twelve hours. They only talk about cloning. I’m ‘Mister Cloning.’ It’s almost a joke. What we do is separate from cloning. But psychologically it seems the same to people. It’s all needles and eggs. And scientists are all mad and irresponsible,” he said, with a sudden tightening of his voice, as if his chest were caught in a vise. “They throw it all in the same heap. And of course the majority is fertile. So the infertile have very little say.”
“You have my sympathy.”
Cohen gave me a trapped, hunted-animal smile. He looked like a man who has been tortured in a stone cell, and then is told to get dressed and have a candlelit dinner with his torturer. There was a strained, battered look on his face and in his whole manner. Yes, you are being nice to me now, but are you going to hit me again?
Fortunately, Cohen said, even when a scandal is global, most people on the planet do not hear about it, even the parents of the babies in question. “I spoke to two mothers, they had absolutely no idea what had happened. Because they have two-year-olds—how do they know what happened! Mothers of two-year-olds do not watch the news! And it is nice to find that some of my colleagues have not heard of it. It is actually a pleasure.”
“Do you still have patients coming in, this last couple of weeks?”
“The last couple of weeks? Hundreds, maybe thousands. Why, do you think the news scared them?”
“Yes.”
“It might have scared me and you, but it didn’t scare patients.”
I walked Jacques out through the stone gate at 66th Street. As we were crossing York Avenu
e, I said, “Do you ever think about this, Jacques? Here you are making these decisions case by case, for the good of patients right in front of you. But when you see the babies that you have helped to make, do you ever think that somewhere down the road, this work, or even these very babies, could be the start of a whole new line of the human species? That this could be the beginning of a transformation?”
“No. It is too day-to-day. It’s day-to-day. It’s this hour, this patient, these clients, their wishes, this baby. I don’t look past that.”
“But you do sometimes take the long view,” I said, thinking of the retreat on the Galaxy. “Don’t you think it is somewhat eerie that you may be playing a role in some altered future?”
“No. Each one of us is such a small pea in the process. Every scientist makes such a small contribution. We are all part of a very large process. And so one doesn’t think of oneself as playing any large role in that.”
And the truth is that you can spin that project of his either way: as just another surgical procedure, or as the cosmic beginning of the transformation of the human race; as one more modest way for a doctor to help a patient, or as a new, revolutionary, and possibly fatal means for human beings to play God.
We were passing a big elementary school, PS 183, with a great stone lion above the arch of the doorway and wire mesh on the windows. We could hear children shouting and laughing inside. A computer-printed sign on the door hoped they would have a good summer. Abruptly, although we had not reached his car, he shook my hand and said goodbye. I had upset him. It was one thing to talk about the fate of the species on a Love Boat out in the Caribbean. Now he was in a global scandal. He was standing on 66th Street, watching his back. He looked terribly nervous.
“Well, it is a fascinating story,” I said. “You will certainly get past this.”
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