The Forgetting

by David Shenk

  One essential component of self that Alzheimer’s patients do not come untethered from early on is their own emotional reservoir. From this vantage, it almost seems as though de Kooning contracted just the right disease, the one neurological disorder that would spare his ability to create as it ate away at most of the rest of his abilities.

  Perhaps, then, Alzheimer’s did not dim de Kooning’s art, at least not until much later in the disease. Perhaps Alzheimer’s enhanced his art. Morris Friedell’s observation about the heightening of consciousness in the early stages of Alzheimer’s would seem to apply perfectly to de Kooning and other abstract artists. If Abstract Expressionism exists predominantly as an emotional response to the world, the new freshness of consciousness forced upon early-stage Alzheimer patients could presumably serve as a creative impulse.

  De Kooning himself had complained in the mid-seventies (pre-Alzheimer’s) that his way of working had become “almost a habit,” and critics seemed to agree wholeheartedly. It seems more than a mere coincidence that his art was rejuvenated at precisely the same time he began to succumb to the disease—to lose his ability to follow habits. One reasonable analysis is that the disruption of memories fortuitously dissolved chronic work patterns that had become such a burden. In this way, the disease may have, if only temporarily, rescued de Kooning’s career, granting him an extra few years of creative energy by releasing him from a tired routine.

  “Collectively, the pictures … seem to glow with an inner light,” the San Francisco Examiner’s David Bonetti wrote of de Kooning’s late work. “… They remind you that even during bleak times, art can offer emotional and spiritual solace like nothing else.” Kay Larson, writing in the Village Voice, pared the rejuvenation theory down to its perfect reductionist epithet: De Kooning, she wrote, rounded out his career in a fertile period of “Alzheimer s Expressionism.”

  One does not, of course, want to exaggerate the advantages of a slide toward oblivion. Many important faculties are, in fact, adversely affected early on in Alzheimer’s: constructional abilities, spatial relations, orientation, perspective, and concentration. So even as an abstractionist, de Kooning would have had a somewhat reduced command of his craft after the onset of Alzheimer’s. His ability to execute a desired stroke would in certain ways have been compromised.

  Another important consideration is the impairment of so-called executive function skills, including goal-setting and self-evaluation. A person’s introspection begins to wither away from near the beginning of Alzheimer’s—the constant “How-am-I-doing?” inner dialogue that people with functioning brains take for granted. When introspection begins to break down, so does willfulness—“Here’s-what-I-should-do-next.” As the plaques and tangles proliferate and the brain begins to shrink, a psychic barrier arises between the victim and the outside world. The Alzheimer’s sufferer becomes an island.

  In that isolation, argue some, de Kooning’s art in particular vanished completely. “Art, in the way that de Kooning conceived it, is something that is produced in a conscious dialogue with the rest of art history and culture,” argues art historian András Szántó. “De Kooning is an excellent example of what we call the ‘professional artist,’ one who worked strictly within the context of other art. His was actually a very conceptual, aesthetic agenda, turning the art world upside down, demolishing certain assumptions that were in place up to the 1960s.

  “If, later on in life, we end up with someone who is merely doing things in his head, then de Kooning’s art, as he understood it, is gone. Once the dialogue with the rest of the world is severed, it is impossible to speak of this as art with a capital ‘A.’”

  Amidst stark disagreements about the quality of de Kooning’s eighties paintings, the 1995 panel did not manage to come to a real consensus. “No single point of view predominated,” Garrels politely reported, except for the agreement that the works produced after 1989 could not be counted as “fully realized works of art.” Some panel members felt that the work had lost its essential structure in the mid-1980s—which is roughly when de Kooning passed into the middle stages of the disease. But others agreed with Garrels and MOMA curator Robert Storr that the work up to 1989 stands on its own.

  A year after the panel deliberated, the neurologist Carlos Hugo Espinel published an essay about de Kooning in the British medical journal Lancet. “These paintings [are] not merely the product of someone who had simply retained colour perception and the motor strength to copy,” Espinel wrote. “Even if at times he confused his wife with his sister … De Kooning went on to create. His resurgence is a testimony to the potential of the human mind, evidence for hope.”

  And there was hope—not that de Kooning might somehow recover from his forgetting, but that he could live serenely within it; that we could all live in harmony with the specter of senile dementia.

  De Kooning was, after all, speaking for all of us, and to us. He had spent his long life producing abstract emotional pastiches, painting images from his psyche in the same way that radio announcers would depict a boxing match: in quick, emotional bursts that said something very personal about the artist and, often, also something profound about the human condition. “I am always in the picture somewhere,” he said in 1950. “… I seem to move around in it, and there seems to be a time when I lose sight of what I wanted to do, and then I am out of it. If the picture has a countenance, I keep it. If it hasn’t, I throw it away.”

  In these late paintings, de Kooning was presenting one final series of communiqués to his public, messages of tranquillity and transcendence in decline. It was a message that Emerson, Shakespeare, Erasmus, and others had sent: Senility, while devastating, is also a part of life.

  In his essay, Espinel also briefly alluded to a feature in the late-period de Koonings that every other observer had missed: the unmistakable resemblance between the wispy strokes on his canvases and the neurofibrillary tangles in his brain.

  PART III

  END STAGE

  Chapter 14

  BREAKTHROUGH?

  San Francisco, California: July 1999

  In July, with patents filed and publication pending, Elan Pharmaceuticals finally broke their long silence: They had a new drug that had eliminated plaques in mice. In the next few months they would begin testing it in humans.

  The news caught researchers completely by surprise.

  “It’s wild and amazing,” said Sangram Sisodia, chairman of neurobiology at the University of Chicago.

  “This is a major step forward,” said the National Institute on Aging’s Marcelle Morrison-Bogorad.

  Even officials from the famously cautious Alzheimer’s Association gushed. “It’s a fascinating finding with immense potential,” offered Vice President Bill Thies. This was the first time in the organization’s twenty-year history that it had issued an unqualified statement of optimism about a potential treatment.

  The most surprising part of the news was the type of drug: a simple antibody vaccine, no different in principle from the vaccines for polio, measles, mumps, and diphtheria. Those vaccines work by injecting weakened bits of live virus into the bloodstream, stimulating the immune system to develop specific antibodies that quickly recognize and remove any future virus to come along.

  Antibodies are not limited to virus removal; they can theoretically be programmed to tag and remove any foreign object—beta-amyloid, for instance, the main component of plaques. Beta-amyloid is just as foreign to the human body as any virus. Elan’s new approach was to inject bits of beta-amyloid into the bloodstream the same way that Albert Sabin injected weakened polio virus.

  It seemed like one of those ideas that was too simple to work, so much so that when lead researcher Dale Schenk had first mentioned the concept to coworkers in a brainstorming session a few years earlier, he said, “Everyone looked at me like I was crazy.” The notion seemed dead on utterance; as a demonstration of its apparent absurdity, one of Schenk’s colleagues pinned it to an office bulletin board of outrageo
us comments.

  Now, other Alzheimer’s researchers were admitting they would have had the same reaction. “If someone had suggested that experiment to me,” said the Mayo Clinic’s John Hardy after the breakthrough announcement, “I would have told them not to waste their time.”

  Chicago’s Sisodia said: “I wouldn’t have imagined it could ever work. We haven’t even thought about a vaccine for Alzheimer’s.”

  But to Schenk, his self-described “nutty idea” was the natural outcome of tracing what he already knew about plaques through a number of logical steps. “The absolute levels of production of beta-amyloid in the brain tissue seem to be a critical factor in whether or not you get amyloid plaques,” he explained. “So I was thinking about that one day, and I thought, ‘If there was only a way to tie up that beta-amyloid in the brain, to keep it occupied.’ Then I thought, ‘Well, maybe if we had antibodies there, that would work. It’s too bad that there are no good ways to get antibodies into the brain. You could inject them straight into the brain, but that’s not a good idea.…’

  “And then it suddenly hit me like a stone: Actually, we could put antibodies into the bloodstream, and a small amount would likely leak into the brain. Furthermore, why don’t we just immunize with beta-amyloid? Then the body would be constantly making a ton of antibodies and over time a small amount of that antibody would get in and change the equilibrium.”

  To most scientists, the idea would immediately have seemed like a nonstarter because of the famous blood-brain barrier, the protective mechanism that keeps carbohydrates, proteins, metals, and other impurities out of the brain. While the rest of the body’s organs can easily tolerate a rich and coarse blood flow, the brain’s fine vasculature cannot. Brain arteries are a delicate silk web as compared to the body’s rope artery hammock, and would easily clog and burst under the pressure of such bulky particles.

  The brain does need fresh blood, though, which delivers a constant infusion of oxygen and glucose in order for it to survive. So it relies on a fine mesh filter system—the blood-brain barrier. Schenk was very familiar with the barrier through some recent research he had done—so familiar that he was mindful of something that most other neuroscientists seemed not to be: The blood-brain barrier is not perfect. For whatever reason, it has a tiny built-in leak—about three out of every thousand unwanted particles get in.

  Schenk’s epiphany was that a body constantly manufacturing its own supply of beta-amyloid antibody would produce so much of it that three parts per thousand would be plenty.

  Like so many other breakthroughs in history, his eureka moment capped off years of hard work. Schenk and his colleagues had been researching Alzheimer’s aggressively on several fronts since 1987. With no expectation of near-term profit, they’d invested tens of millions of dollars. “For years, we’ve had a major, major, major commitment to Alzheimer’s research, far more than any single university center,” Schenk boasted. “It has been a giant effort. At one point, we had sixty people working on it at once, and that doesn’t count the labs of our collaborators. It’s not by chance that we came up with the vaccine. It really isn’t chance.”

  For the vaccine experiment, Schenk cordoned off three groups of mice genetically designed to develop plaque-filled brains. The first batch, the control group, received no vaccine. The second group received a series of injections of vaccine beginning at six weeks of age (young adulthood). The third group started getting injections at twelve months (old age)—only after they had started to accumulate plaques.

  After about a year, mice from groups one and two were sacrificed and dissected: Brains from the control group were, as expected, riddled with plaques. Of the nine mice in the group receiving the vaccine from early on, though, seven had virtually no plaques; the remaining two had significantly fewer than the control mice. The results were so dramatic, Schenk says, that when they first looked at the tissue slides, “we thought maybe the animals had been mixed up.”

  They had not. To an extent beyond the Elan team’s wildest expectations, the injected bits of beta-amyloid had evidently stimulated the immune system to attack and dissolve the plaque deposits as they were being formed. It is a two-step process. First, the injected beta-amyloid prompted the immune system to tag all beta-amyloid in the brain for removal. Then white blood cells and another class of cells called microglia, acting as the body’s garbage collectors, swept through and picked up everything that had been tagged. The result: no more plaques. Individual strands of beta-amyloid floating free were nabbed before they could glom on to a plaque.

  Eighteen months after the experiment began, they got even better news. When they sacrificed the third group of mice—those who received the vaccine only as elderly mice—they again saw fewer plaques compared to the control group at that same age. The vaccine not only prevented plaques from forming, but also disassembled and removed plaques already in the brain. It was a true plaque-buster—not just a shield but also an antidote.

  This new drug, temporarily named AN 1792, was not by any means a certain cure for Alzheimer’s disease. First, the company would have to see if it was safe in humans. There was a serious worry among some neuroscientists that the injected beta-amyloid could stimulate a troublesome (possibly even lethal) autoimmune response, wherein the immune system behaves as though the body’s own cells are a foreign enemy needing to be destroyed. (Other autoimmune disorders include psoriasis, rheumatoid arthritis, lupus, diabetes mellitus, and multiple sclerosis.)

  Another possible scenario was that the vaccine could prove safe but ineffective. It might not clear away human plaques as effectively as mouse plaques.

  Finally, of course, the vaccine might work brilliantly but not end the disease. No one could say for sure that clearing away the plaques would be enough to beat Alzheimer’s.

  These were serious hurdles, but all the same, Elan’s announcement seemed to have inaugurated a new era in Alzheimer’s research: the beginning of the end. This particular drug might not be the cure, but at least it was the first contender.

  Yesterday when I visited my mother at the new home, she had taken her outer garments off and was taking a nap in someone else’s bed (alone). Her personal teddy bear was in someone else’s room. This is one of her best friends, and she used to constantly carry it around and talk to it. I rescued it and put it in her arms as she slept. I realize that residents take things from others’ rooms, but feel bad that her teddy bear was not close by her.

  The old house had five to eight residents. This new one has sixteen. She has sixteen closets to hide in. The staff is cautious when opening closets, because Mother will jump out and “boo” them.

  —J.T.

  Cross Plains, Wisconsin

  Chapter 15

  ONE THOUSAND SUBTRACTIONS

  The late years of Ralph Waldo Emerson’s senile dementia were probably about as peaceful as anyone could have hoped. “He suffered very little,” wrote his son Edward, “took his nourishment well, but had great annoyance from his inability to find the words which he wished for.… He went to his study and tried to work, accomplished less and less, but did not notice it.” Emerson became intermittently confused about where he was, lost his ability to write letters and to understand what he was reading and much of what was said to him, and lost grasp entirely of many important figures in his life. Within a week of Henry Wadsworth Longfellow’s death, in the spring of 1882, Emerson could not be made to understand who his old friend was. The entity of “Longfellow” in Emerson’s mind had comprised a broad constellation of synapses, and that particular constellation was now inaccessible. Did it still exist? Only as cellular residue.

  By far the most vivid account of Emerson’s late-stage dementia comes to us via the efforts of an industrious and conniving young man named Edward Bok. A Dutch immigrant who settled in New York City with his family in 1870, when he was seven, Bok quickly became smitten by the unrelenting American can-do spirit, and particularly seduced by the allure of celebrity. By his early teens, a
s an office boy at Western Union Telegraph and a budding freelance reporter, he developed an ambition to meet and interact (however superficially) with the most popular public figures of the time. Emerson was near the top of Bok’s wish list.

  After easily engaging former President Ulysses S. Grant and then-President Rutherford B. Hayes, Bok traveled to Boston to make more famous “friends” and collect their autographs. Just eighteen, he was already savvy enough to understand how one association could lead to another, and planned his visits accordingly. Over the course of just a few days in November 1881, Bok parlayed a meeting with Oliver Wendell Holmes into one with Longfellow; the Longfellow interaction begat an audience with the Episcopal bishop Phillips Brooks (composer of “O Little Town of Bethlehem”). Brooks, in turn, advised Bok on how to see Emerson. “I don’t know whether you will see him at his best,” he warned the young man in polite understatement. Bok had no idea what he was talking about.

  The next day Bok went to Concord, where he managed to enchant Little Women author Louisa May Alcott. Now nearly fifty, Alcott had grown up with Emerson as a neighbor and uncle figure. “Our best and greatest American,” she called him in her journal, “… and the man who has helped me most by his life, his books, his society.” Alcott agreed to make an introduction for Bok, while also warning him that Emerson was not the man he once had been.

  When they arrived at the house, though, Ellen Emerson politely declined to show them in. “Father sees no one now,” she said, “and I fear it might not be a pleasure if you did see him.” Bok was prepared for this contingency. At just the right moment, he expertly dropped in a line from his previous day’s conversation with Phillips Brooks, and once again a door opened.