by David Shenk
That same morning, Schenk shared the fine points with fellow researchers in the hotel’s underground ballroom. Reviewing the data from follow-up studies on mice, guinea pigs, rabbits, and monkeys, he said it was now clear that the vaccine was working exactly as they predicted: The injected beta-amyloid was prompting the immune systems to produce targeted antibodies, a small portion of which were crossing the blood-brain barrier and binding directly with beta-amyloid in the brain. Then the offending substances were effortlessly being cleared away as cellular trash.
Even though most of these scientists had known something about the vaccine for almost a year, many still seemed startled to hear Schenk’s presentation. Just a few years earlier, no one could have even imagined that anyone would be talking about a potential cure so soon. It was as if President Kennedy had called for a moon landing within a decade and NASA soon reported back that they were about to land men on Mars.
After the talk, as everyone filed out of the large ballroom to head for the smaller specialized sessions of the day, one researcher turned to another and asked, “So if this thing works, is the game over?”
On the surface, of course, that was the big question: Will clearing the plaques abolish this disease? Going deeper, though, there was a more fundamental question raised by this vaccine’s sudden emergence: Why had Dale Schenk been the only person on earth to think of it? And why had he been laughed out of the room when he first shared his thought?
It was a variation on the recurring theme of outcast scientists. Why was Stanley Prusiner vilified for years over his unusual—but as it turned out, correct—idea about infectious prions? Why was Allen Roses denied grants for follow-up research to his important ApoE discovery? Why was Ruth Itzhaki ignored in her pursuit of herpes simplex virus 1? Why was Meta Neumann ignored? Alois Alzheimer? Why does the culture of science seem to so often punish the most inventive?
Science is ultimately a human endeavor. Its language is uniform, its methods are strict, but the questions posed and the analysis applied are as idiosyncratic as love affairs and operas and football games. There is, thus, an organic incongruity. Scientific discovery is, and always will be, an inherently clumsy matter as scientists attempt to fit the round peg of humanity into the square hole of objectivity.
The most adventuresome of these scientists, pushing against the limits of comprehension, are inevitably bruised by the friction. They are threatening existing power structures and, perhaps more dangerously, jeopardizing people’s basic understanding of the world around them. They are casting doubt on “truths” on top of which people have built their careers, and around which they have oriented their lives. If a scientist named Galileo suggests in the early seventeenth century that the earth revolves around the sun, the veracity of that statement does not matter nearly as much to his peers as how its consideration may immediately affect their lives. So Galileo is forced to recant. That particular truth will have to wait.
The persistent challenge of science, and all edification, is to minimize the friction: to encourage the pursuit of new ideas while helping to sustain the integrity of people’s lives.
Other enticing developments were revealed at the July 2000 conference. Researchers from the Mayo Clinic had just produced the first knock-out mouse with both plaques and tangles. Several drug companies had isolated the brain enzyme that seems to convert harmless APP into malicious beta-amyloid; perhaps a drug could arrest that process. “There’s a smell of success in the air,” said the NIA’s Marcelle Morrison-Bogorad.
Hundreds of more mundane, if still important, presentations were also taking place. In the Jefferson Room, New York University’s Yaakov Stern was comparing the hippocampal memory network with the prefrontal memory network; in the Monroe Room the University of Texas’s Rachel Doody was reviewing the limited success of Aricept and other similar drugs.
The real heart of the conference, though, was in the free-for-all poster sessions at midday. In a vast, low-ceilinged room, the entire community of researchers came together every day at noon to eat bland sandwiches and browse the hundreds of large bulletin board presentations lined up in long rows. These were novel bits of research from experiments, many of which were still in progress. It was old-fashioned science, with data open for review and critique. Charts were pinned next to graphs, were pinned next to microscopic photographs, were pinned next to project summaries, were pinned next to tentative conclusions, were pinned next to contact information. Gerontologists from Sweden huddled in front of one poster, right next to a group of microbiologists from New Orleans. There was barely enough room to squeeze through.
The variety of material was fierce.
Poster #40, presented by Tohru Hasegawa, discussed the potential preventative effect of Japanese green tea.
Poster #96, presented by R. Distl & V. Meske, revealed that microdensitofluorometrically determined free cholesterol is higher in tangle-bearing neurons than in tangle-free neurons.
Poster #168, presented by Jennifer W. Catania et al, reviewed the genetics of Alzheimer’s disease in the Caribbean Hispanic population.
The paradox of these poster sessions, and of the entire scientific portion of the conference, was that amidst all the data and ideas the disease was nowhere to be found. Science had fragmented it into almost unrecognizable shards—cholinergic transmitters, vascular risk factors, nicotinic receptors, aspartyl proteases, synaptic plasticity in mice, and on and on. The crowd had the patina of a large cohesive community, but was really a collection of superbly focused specialists—most of whom barely knew how to talk to anyone outside their constricted microfield. In the name of science, good science, they were far too close to the trees to see the forest.
It would take a trailblazer to try to show them the panoramic view. On the last day of the conference, in the last row of the poster session bazaar, the very final display stood out from the others. It had an entirely different flavor:
#1231
POTENTIAL FOR RREHABILITATION IN ALZHEIMER’S
Standing beside #1231 was a man in a brown tweed coat and a graying beard: Morris Friedell, the college professor from Santa Barbara. Struggling to maintain his dignity and his wits as Alzheimer’s slowly advanced, he had made the long journey from out west to present his ideas to the community of scientists. Until now, conversations about his ambitious ideas had mostly been limited to fellow victims, caregivers, friends, and family. His dream was to share them with professionals. He thought he might be onto something important. From his poster:
Central hypothesis:
The typical qualitative symptoms of mild to moderate Alzheimer’s, gross forgetfulness, disorientation, and loss of abstraction and judgment, stem from quantitative decrements in processing capacity underlying these functions. Since patients retain substantial strength in procedural memory and memory for emotionally significant events, there is major potential for rehabilitation through relearning activities using a greater number of simpler steps.
The complex presentation contained fragments of neurobiology, sports psychology, and spirituality. There were quotes from Frankl, Thoreau, and Lao-tzu (“In the pursuit of learning, every day something is acquired. In the pursuit of Tao, every day something is dropped.”) There were poems from victims, a color copy of a de Kooning from 1984, and a diagram from the psychologist A. R. Luria demonstrating rehabilitation of a brain-damaged patient. Morris’s own PET scan report was also pinned up on display. Appended to the conclusion was a note: “I welcome feedback and discussion. I’m staying at.——. Phone is——. E-mail is——.”
But his poster drew almost no interest. Researchers peered at it for a second and moved on. They didn’t know what to make of this unorthodox exhibit, and seemed anxious to find something more technical and less ambiguous—something closer to their own specialty. There was, of course, no one at this conference—or any conference—who specialized in rehabilitating Alzheimer’s patients. That’s just why Morris was there.
He gently looked around at th
e sea of researchers passing him by. “I feel like I’m living a dual life right now,” he said quietly. “On the one hand, I feel like a kid at a science fair. But I also feel like a kind of a ghost, hovering here as an afterthought.”
Selfishly, I was happy that he was there. It was our first face-to-face exchange ever, after about a year of long-distance interaction. We had corresponded via E-mail mostly, except for the one day several months before when Morris called to talk. On the phone, we had spoken for a while about his disease and my book. I had thanked him for his many insights, for introducing me to Viktor Frankl and tipping me off to Emerson’s dementia. He seemed interested in my aim to write a biography of the disease, and eager to help. We agreed to stay in touch, to keep exchanging ideas.
Now I was eager to continue our discussion. The poster scene, though, was a little too chaotic for a real conversation. We agreed to meet the next day for lunch.
Over sandwiches and coffee at a grill across town, we climbed back into some of our shared curiosities, starting with rehabilitation. He was of course not talking literally about beating this disease with brain exercises, but about minimizing and slowing the cognitive loss by adapting to it.
Why shouldn’t Alzheimer’s patients get as much conditioning as stroke victims, for example? The disease’s ultimate mortality should not automatically annul patients’ expectations of living the fullest possible life for the longest possible time.
Alzheimer’s is a very slow disease, and there was no particular reason to settle for a passive approach of managing loss—which was often tantamount to hospice care in slow motion. If drugs like Aricept could lead to marginal improvements, it was tantalizing to imagine what a professional rehabilitation program could do. Intensive rehab, in the spirit of what knee and hip surgery patients go through routinely, had just never been considered before in Alzheimer’s disease. In the new era of people discovering their disease very early on, the idea made abundant sense.
Morris’s proposal was not a first draft. “My previous approach to rehabilitation,” he said, “was to substitute intense meaning and emotional organization for [cold analysis], refining your sense of what’s important to compensate for your inability to deal with everything.
“I’ve revised that. If a person has a block in problem solving and it gets too emotional then their memories can get more scattered.
“Most of the focus on brain injury has to do with the frontal lobes—auto accidents with younger people and such. People with mild Alzheimer’s still have frontal lobes that are functioning very well. They know what they want to do, but they are not able to learn anything from the attempts. There is some work with the Montessori approach to problem solving with people with dementia that’s been encouraging. Rather than relearning to pay attention to the problem, I suggest a reeducation vaguely inspired by Montessori: Do something that’s extremely simple, just to get into a confidence mind-set—stringing one or two beads, or something like that. And gradually learn to solve problems in new, simpler ways.
“The spirit of feng shui is interesting. I tell other early-stage patients, ‘The practical application of my theory is to start getting rid of your clutter,’ and this strikes a chord in the way that my other ideas haven’t. Eliminate physical clutter as a path to get rid of mental clutter. I’m saying, ‘simplify, simplify, simplify’—just like Thoreau.”
We talked for two hours. Some of his ideas I understood, some I did not, entirely. Morris sometimes paused for a while, and had to occasionally struggle to stay on track. There was no question that he was slowly succumbing to the disease. Mostly, though, I was left with the impression that he was onto something important, that he did understand his own unraveling in a way I would not have ever imagined possible when I first started to learn about this disease. Throughout our lunch, I repeatedly encountered a frisson of realization that in several years of research, the most thought-provoking discussions I’d had about Alzheimer’s were with one of its victims.
I realized that, in a peculiar way, Morris had rehabilitated me—and my understanding of Alzheimer’s. When I started my research, I conceived of a book that might, on the one hand, catalogue the horrors of Alzheimer’s, and on the other, relay the hopeful story of the race to cure the disease.
I still respected that dichotomy, still feared the disease, and still hoped for a cure, of course—as did Morris. But I also now realized that the story of Alzheimer’s is in some ways exactly the opposite of my original premise: It is a condition specific to humans and as old as humanity that, like nothing else, acquaints us with life’s richness by ever so gradually drawing down the curtains. Only through modern science has this poignancy been reduced to a plain horror, an utterly unhuman circumstance.
It wouldn’t be fair to say that I had transcended the disease in the same way that Morris obviously had, or in the way that Emerson and de Kooning admirably had. After all, I was still only an observer. But it’s worth noting that, personally, I migrated over several years’ time from morbid fascination and dread of Alzheimer’s to a new kind of peace and reconciliation.
As this realization unfolded, I thought of another presentation at the conference, given by the social worker and author Lisa Snyder. In the Indonesian island of Bali, she reported, there is a powerful myth of life cycles that centers on memory:
Babies are born with no memory. They gather memories as they grow. As they get old they lose these memories so that they can be reborn again in a void.
All of these things I was thinking about as I drove Morris back to his hotel room. I told him again how much I appreciated his ideas, and wished him well.
Then, just before I dropped him off, Morris asked me if we’d ever spoken before today.
EPILOGUE
I cannot promise you everlasting life, but I can promise you life
RIGHT NOW.
—BRUCE SPRINGSTEEN
Two blocks from my home in Brooklyn is the main entrance to Prospect Park, an arrow-shaped 526-acre retreat from urban intensity. It is a wondrous place, with a mile-long hilly green meadow, a great lake, and the last surviving natural forest in Brooklyn. There is a working nineteenth-century carousel, a band shell for concerts, picnic tables and barbecue pits, a horse trail, plenty of swing sets, and wild geese. About six million times a year, people come here to find themselves.
The park was designed by Calvert Vaux and Frederick Law Olmsted from 1865 to 1873, just after the pair had completed their work on Central Park in Manhattan. They had planned to link the two parks with a ten-mile-long, tree-shadowed “parkway,” but could not sell that part of their vision. Still, Olmsted considered his Brooklyn park to be a crowning achievement. “I am prouder of it than anything I have had to do with,” he remarked on a later visit.
Olmsted was a champion of urban beautification in the mid-to-late nineteenth century and is now considered the founder of American landscape architecture. He is responsible for an astounding number of treasured urban American refuges, including Chicago’s Jackson Park, Boston’s Emerald Necklace, and Louisville’s Cherokee Park. “The further progress of civilization is to depend mainly upon the influences by which men’s minds and characters will be affected while living in large towns,” Olmsted argued. A city park, he insisted, must help the resident escape “the devouring eagerness and intellectual strife of town life.”
He was abundantly influenced by Emerson, whom he read avidly and met with early in his career. His was an unflinchingly Emersonian notion. “What we want to gain,” said Olmsted, “is tranquillity and rest to the mind.”
A year or so after Olmsted finished his work on Prospect Park, he moved to Washington, D.C., to design the grounds of the U.S. Capitol, which he worked on for fifteen years, up until 1889. Not long after that, as he neared seventy years old, he started to have memory problems, very subtle at first and then, gradually, more disabling. On the way to pivotal meetings, he would ask his sons to remind him of key names and project details. Then, in North Carolina,
he was discovered writing virtually the same letter over and over again to his patron George Vanderbilt, his short-term memory apparently obliterated.
In 1895, at age seventy-three, he wrote his son John, his devoted right hand for twenty years: “I see that I ought no longer to be entrusted to carry on important business for the firm alone.” Olmsted retreated into seclusion in Maine (in a house designed by Emerson’s cousin, William Ralph Emerson). As John attempted to keep his father tangentially involved in the firm’s projects, he made a firm, practical suggestion. “It would be well for you,” he wrote his father, “to review the letters we have written you since you went to Deer Isle each time before you write your daily letter to us.… [you should] constantly bear in mind that your memory for current events is no longer a working basis for your thoughts.”
Things became much darker. Olmsted became paranoid, accusing John of executing a “coup.” In 1898, at age seventy-six, it got bad enough that he had to be moved into McLean Asylum, in Waverly, Massachusetts, where he would remain confined until his death in 1903.
Alzheimer’s is, in itself, a sort of mental confinement—the sufferer is incarcerated within the collapsing neural structures that he has taken a lifetime to build. But Olmsted, through his own work, inadvertently lived out the metaphor in literal terms. He was imprisoned not just within his own collapsing mind, but also in his own design: Olmsted had created the 275-acre grounds for McLean two decades before. At first, he was bitterly aware of the irony. But by the time he died, he had forgotten not only about his design of McLean, but also about landscapes altogether.
We have not forgotten about him. It has been the great triumph of civilization to compensate for the limits of human life and memory, to extend the fruits of one person’s intellect beyond its natural life. Olmsted’s magnificent creations have lasted a full century since his decline and are set to last many more. Part of the further progress of civilization will be to help care for those who are truly losing themselves—not to overcome their humanity, but to help them find comfort in it. Just to the right of Prospect Park’s main entrance is Prospect Park Residence, a large old apartment building that has recently been renovated and transformed into an assisted-living facility. Many of the residents are in one or another stage of progressive dementia. Through the windows of their apartments and especially through their daily walks into the large park, the residents who are forgetting themselves are finding the peace that they so desperately need in their decline. Through Olmsted’s natural landscapes, in a way beyond what he had imagined, they have found tranquillity and rest to the mind.
