"When I was younger," Mark Twain quipped near the end of his life, "I could remember anything, whether it had happened or not; but my faculties are decaying now and soon I shall be so I cannot remember any but the things that never happened."
At age seventy-two, Twains memory and wit were intact. But behind his remark lay a grim recollection of another celebrated writers true decline. In December 1877, Twain had come to Boston at the invitation of William Dean Howells, editor of the Atlantic Monthly, to satirize a group of Brahmin intellectuals. Among Twains targets that night was the father of American Transcendentalism, Ralph Waldo Emerson.
It was after midnight when Twain finally took to the floor at the Hotel Brunswick to spin his yarn. He told the venerable crowd about a lonely miner who had been victimized by three tramps claiming to be famous American writers. The literary outlaws stormed into the miners cabin, ate his beans and bacon, guzzled his whiskey, and stole his only pair of boots. They played cards and fought bitterly. One of the tramps called himself Emerson.
The point of the skit was to poke some harmless fun at Emerson by corrupting some of his noble expressions. As they played cards at the climax of the story, the Emerson hobo spat out contorted fragments of his poem "Brahma." A mystical paean to immortality, the original included these stanzas:
If the red slayer think he slays,
Or if the slain think he is slain,
They know not well the subtle ways
I keep, and pass, and turn again.
They reckon ill who leave me out;
When me they fly, I am the wings;
I am the doubter and the doubt,
And I the hymn the Brahmin sings.
Twain twisted the verse into drunken poker banter:
I am the doubter and the doubt
They reckon ill who leave me out,
They know not well the subtle ways I keep,
I pass and deal again.
An elegant master of spoof, Twain was revered around the world as the funniest living man. But on this important night, his material bombed. From the start, Twain drew only silence and quizzical looks, most prominently from Emerson himself. At the finish, Twain later recalled, there "fell a silence weighing many tons to the square inch." He was humiliated. Shortly afterward, he sent a letter of apology to Emerson.
Only then did Twain learn of the hidden backdrop to his performance: Emerson had been present only in body, not in mind. Emersons dead silence and flat affect, Twain discovered, was a function of neither offense nor boredom. As his daughter Ellen wrote to Twain in reply, it was simply that he had not understood a word of what Twain was saying.
At age seventy-four, this was no longer the Ralph Waldo Emerson who had written "Self-Reliance" and Nature; who had said, "Insist on yourself; never imitate"; who had mentored Henry David Thoreau; the Emerson of whom James Russell Lowell had said, "When one meets him the Fall of Adam seems a false report."
This was now a very different man, a waning crescent, caught in the middle stages of a slow, progressive memory disorder that had ravaged his concentration and short-term memory and so dulled his perceptions that he was no longer able to understand what he read or follow a conversation.
"To my father," Ellen wrote to Twain of the performance, "it is as if it had not been; he never quite heard, never quite understood it, and he forgets easily and entirely."
One of the great minds in Western civilization was wasting away inside a still vigorous body, and there was nothing that anyone could hope to do about it.
Taos, New Mexico: March 1999
They came from Melbourne, Mannheim, St. Louis, London, and Kalamazoo; from Lexington, Stockholm, Dallas, Glasgow, Toronto, and Kuopio. From Tokyo, Zurich, and Palo Alto.
Some took two flights, others three or four, followed by a winding three-hour van ride from the floodplains of Albuquerque, up through the high desert terrain of Los Alamos, past the Sandia mountains, past the Jemez volcanic range, past the Camel Rock, Cities of Gold, and OK casinos, up near the foothills of the Sangre de Cristo mountains.
More than two hundred molecular biologists gathered in the small
but sprawling city of Taos, amidst the adobe homes and green-chile
quesadillas, to share data and hypotheses. This high-altitude, remote
desert seemed like a strange place to fight a threatening disease.
But specialists at the biannual conference "Molecular Mechanisms
in Alzheimers Disease" needed a refuge from their routine
For four and a half days they met in Bataan Hall, an old ballroom converted into a civic center. The room had once been used as a shipping-off point for soldiers in World War II, and later named in memory of those same soldiers wretched ordeal in the infamous Bataan Death March. Some five hundred prisoners died each day on that trek, about the same number now dying each day in the U.S. from Alzheimers disease.
At 8:00 p.m. on the first evening, Stanley Prusiner, a biologist at the University of California at San Francisco and a 1997 recipient of the Nobel Prize in medicine, rose to give the keynote address. "I cant compete with Monica," he began with a shrug. "But I think we all know that we wouldnt learn anything new."
Barbara Walters much-anticipated TV interview with Monica Lewinsky was starting to air on ABC at that very moment, which further fueled the sense of isolation. The local support staff had just raced home to their televisions to catch the well-lighted promotion for the million-dollar book about the sordid affair with the needy President.
No TVs here. The scientists in this large, windowless chamber were distracted by something else: Alzheimers disease was about to become an epidemic. Known as senility for thousands of years, Alzheimers had only in the past few decades become a major health problem. Five million Americans and perhaps 15 million people worldwide now had the incurable disease, and those numbers would soon look attractive. Beginning in 2011, the first of the baby boomers would turn sixty-five and start to unravel in significant numbers. By 2050, about 15 million people in the U.S. alone would have Alzheimers, at an annual cost of as much as $700 billion.
Other industrialized nations faced the same trends. In Japan, one in three would be elderly by 2050. In Canada, the number of elderly would increase by 50 percent while the working-age population increased by just 2 percent. "We have to solve this problem, or its going to overwhelm us," said Zaven Khachaturian, former director of the Alzheimers Research Office at the National Institutes of Health. Alzheimers had already become a costly and miserable fixture in society. Unless something was done to stop the disease, it would soon become one of the defining characteristics of civilization, one of the cornerstones of the human experience.
They were here to solve this problem.
Chapter 1: I Have Lost Myself
A healthy, mature human brain is roughly the size and shape of
two adult fists, closed and pressed together at the knuckles. Weighing
three pounds, it consists mainly of about a hundred billion nerve
cellsneuronslinked to one another in about one hundred
trillion separate pathways. It is by far the most complicated system
known to exist in nature or civilization, a control center for the
coordination of breathing, swallowing, pressure, pain, fear, arousal,
sensory perception, muscular movement, abstract thought, identity,
mood, and a varied suite of memories in a symphony that is partly
predetermined and partly adaptable on the fly. The brain is so ridiculously
complex, in fact, that in considering it in any depth one can only
reasonably wonder why it works so well so much of the time.
Mostly, we dont think about it at all. We simply take this
nearly silent, ludicrously powerful electrochemical engine for granted.
We feed it, try not to smash it too hard against walls or windshields,
and let it work its magic for us.
Only when it begins to fail in some way, only then are we surprised,
devastated, and in awe.
On November 25, 1901, a fifty-one-year-old woman with no personal
or family history of mental illness was admitted to a psychiatric
hospital in Frankfurt, Germany, by her husband, who could no longer
ignore or hide quirks and lapses that had overtaken her in recent
months. First there were unexplainable bursts of anger, and then
a strange series of memory problems. She became increasingly unable
to locate things in her own home and began to make surprising mistakes
in the kitchen. By the time she arrived at Städtische Irrenanstalt,
the Frankfurt Hospital for the Mentally Ill and Epileptics, her
condition was as severe as it was curious. The attending doctor,
senior physician Alois Alzheimer, began the new file with these
notes in the old German Sütterlin script.
She sits on the bed with a helpless expression.
"What is your name?"
"What is your husbands name?"
Auguste, I think.
"How long have you been here?"
(She seems to be trying to remember.)
It was her second day in the hospital. Dr. Alzheimer, a thirty-seven-year-old
neuropathologist and clinician from the small Bavarian village of
Markbreit-am-Main, observed in his new patient a remarkable cluster
of symptoms: severe disorientation, reduced comprehension, aphasia
(language impairment), paranoia, hallucinations, and a short-term
memory so incapacitated that when he spoke her full-name, Frau Auguste
D, and asked her to write it down, the patient
got only as far as "Frau" before needing the doctor to
repeat the rest.
He spoke her name again. She wrote "Augu" and again stopped.
When Alzheimer prompted her a third time, she was able to write
her entire first name and the initial "D" before finally
giving up, telling the doctor, "I have lost myself."
Her condition did not improve. It became apparent that there was
nothing that anyone at this or any other hospital could do for Frau
D. except to insure her safety and try to keep her as clean and
comfortable as possible for the rest of her days. Over the next
four and a half years, she became increasingly disoriented, delusional,
and incoherent. She was often hostile.
"Her gestures showed a complete helplessness," Alzheimer
later noted in a published report. "She was disoriented as
to time and place. From time to time she would state that she did
not understand anything, that she felt confused and totally lost.
Sometimes she considered the coming of the doctor as an official
visit and apologized for not having finished her work, but other
times she would start to yell out of the fear that the doctor wanted
to operate on her [or] damage her womans honor. From time
to time she was completely delirious, dragging her blankets and
sheets to and fro, calling for her husband and daughter, and seeming
to have auditory hallucinations. Often she would scream for hours
and hours in a horrible voice."
By November 1904, three and a half years into her illness, Auguste
D. was bedridden, incontinent, and largely immobile. Occasionally,
she busied herself with her bed clothes. Notes from October 1905
indicate that she had become permanently curled up in a fetal position,
with her knees drawn up to her chest, muttering but unable to speak,
and requiring assistance to be fed.
What was this strange disease that would take an otherwise healthy
middle-aged woman and slowlyvery slowly, as measured against
most disease modelspeel away, layer by layer, her ability
to remember, to communicate her thoughts and finally to understand
the world around her? What most struck Alzheimer, an experienced
diagnostician, was that this condition could not fit neatly into
any of the standard psychiatric boxes. The symptoms of Auguste D.
did not present themselves as a case of acute delirium or the consequence
of a stroke; both would have come on more suddenly. Nor was this
the general paresismood changes, hyperactive reflexes, hallucinationsthat
can set in during the late stages of syphilis. She was clearly not
a victim of dementia praecox (what we now call schizophrenia), or
Parkinsons palsy, or
Friedreichs ataxia, or Huntingtons disease, or Korsakoffs
syndrome, or any of the other well-recognized neurological disorders
of the day, disorders that Alzheimer routinely treated in his ward.
One of the fundamental elements of diagnostic medicine has always
been the exercise of exclusion, to systematically rule out whatever
can be ruled out and then see what possibilities are left standing.
But Alzheimer had nothing left.
What the fifty-one-year-old Auguste D.s condition did strongly
evoke was a well-known ailment among the elderly: a sharp unraveling
of memory and mind that had, for more than five thousand years,
been accepted by doctors and philosophers as a routine consequence
History is stacked with colorful, poignant accounts of the elderly
behaving in strange ways before they die, losing connection with
their memories and the world around them, making rash decisions,
acting with the impetuousness and irresponsibility of children.
Plato insisted that those suffering from "the
influence of extreme old age" should be excused from the commission
of the crimes of sacrilege, treachery, and treason. Cicero lamented
the folly of "frivolous" old men. Homer, Aristotle, Maimonides,
Chaucer, Thackeray, Boswell, Pope, and Swift all wrote of a distressing
feebleness of mind that infected those of advancing years.
"Old age," wrote Roger Bacon, "is the home of forgetfulness."
Known as morosis in Greek, oblivio and dementia in Latin, dotage
in Middle English, démence in French, and fatuity in eighteenth-century
English, the condition was definitively termed senile dementia in
1838 by the French psychiatrist Jean Étienne Esquirol. In
a depiction any doctor or caregiver would recognize today, Esquirol
wrote: "Senile dementia is established slowly. It commences
with enfeeblement of memory, particularly the memory of recent impressions."
But that was senile dementia. What was this? Alois Alzheimer wanted
to know. Why did a fifty-one-year-old appear to be going senile?
How could Auguste D. be suffering from the influence of extreme