The Forgetting
David Shenk
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ISBN 978-0-385-49838-8
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We are the sum of our memories. Everything we know, everything we perceive, every movement we make is shaped by them. "The truth is," Friedrich Nietzsche wrote, "that, in the process by which the human being, in thinking, reflecting, comparing, separating, and combining . . . inside that surrounding misty cloud a bright gleaming beam of light arises, only then, through the power of using the past for living and making history out of what has happened, does a person first become a person."

The Austrian psychiatrist Viktor Frankl made much the same point in Man’s Search for Meaning, his memoir of experiences as a concentration camp inmate. Frankl recalled trying to lift the spirits of his fellow camp inmates on an especially awful day in Dachau: "I did not only talk of the future and the veil which was drawn over it. I also mentioned the past; all its joys, and how its light shone even in the present darkness. [I quoted] a poet . . . who had written, Was Du erlebst, kann keine Macht der Welt Dir rauben. (What you have experienced, no power on earth can take from you.) Not only our experiences, but all we have done, whatever great thoughts we may have had and all we have suffered, all this is not lost, though it is past; we have brought it into being. Having been is a kind of being, and perhaps the surest kind."

Emerson was also fascinated by memory–how it worked, why it failed, the ways it shaped human consciousness. Memory, he offered about a decade or so before his own troubles first appeared, is "the cement, the bitumen, the matrix in which the other faculties are embedded . . . without it all life and thought were an unrelated succession." While he constructed an elaborate external memory system in topical notebooks, filling thousands of pages of facts and observations that were intricately cross-referenced and indexed, Emerson was also known for his own keen internal memory. He could recite by heart all of Milton’s "Lycidas" and much of Wordsworth, and made it a regular practice to recite poetry to his children on their walks. His journal entries depict an enchantment with the memory feats of others.

He kept a list:

• Frederic the Great knew every bottle in his cellar.
• Magliabecchi wrote off his book from memory.
• Seneca could say 2,000 words in one hearing.
• L. Scipio knew the name of every man in Rome.
• Judge Parsons knew all his dockets next year.
• Themistocles knew the names of all the Athenians.

"We estimate a man by how much he remembers," Emerson wrote.

Ronald Reagan was never particularly admired for his memory. But in the late 1980s and early ’90s, he slowly began to lose his grasp on ordinary function. In 1992, three years after leaving the White House, Reagan’s forgetting became impossible to ignore. He was eighty-one.

Both his mother and older brother had experienced senility, and he had demonstrated a mild forgetfulness in the late years of his presidency. Like many people who eventually suffer from the disease, Reagan may have had an inkling for some time of what was to come. In his stable of disarming jokes were several about memory troubles afflicting the elderly. He shared one at a 1985 dinner honoring Senator Russell Long.

An elderly couple was getting ready for bed one night, Reagan told the crowd. The wife turned to her husband and said, "I’m just so hungry for ice cream and there isn’t any in the house."

"I’ll get you some," her husband offered.

"You’re a dear," she said. "Vanilla with chocolate sauce. Write it down–you’ll forget."

"I won’t forget," he said.

"With whipped cream on top."

"Vanilla with chocolate sauce and whipped cream on top," he repeated.

"And a cherry," she said.

"And a cherry on top."

"Please write it down," she said. "I know you’ll forget."

"I won’t forget," he insisted. "Vanilla with chocolate sauce, whipped cream, and a cherry on top."

The husband went off and returned after a while with a paper bag, which he handed to his wife in bed. She opened up the bag, and pulled out a ham sandwich.

"I told you to write it down," she said. "You forgot the mustard."

It seems clear enough that Reagan was increasingly bothered by personal memory lapses. In a regular White House checkup late in his second term, the President began by joking to his doctor, "I have three things that I want to tell you today. The first is that I seem to be having a little problem with my memory. I cannot remember the other two."

Did Reagan have Alzheimer’s disease in office? Yes and no. Without a doubt, he was on his way to getting the disease, which develops over many years. But it is equally clear that there was not yet nearly enough decline in function to support even a tentative diagnosis. Reagan’s mind was well within the realm of normal functioning. Even if his doctors had been looking intently for Alzheimer’s, it is still likely that they would not have been able to detect the disease-in-progress. A slight deterioration of memory is so common among the elderly that even today it is considered to be a natural (if unwelcome) consequence of aging. About a third to a half of all human beings experience some mild decline in memory as they get older, taking longer to learn directions, for example, or having some difficulty recalling names or numbers.

Alzheimer’s disease overtakes a person very gradually, and for a while can be indistinguishable from such mild memory loss. But eventually the forgetting reaches the stage where it is quite distinct from an absentminded loss of one’s glasses or keys. Fleeting moments of almost total confusion seize a person who is otherwise entirely healthy and lucid. Suddenly, on a routine drive home from work, an intersection he has seen a thousand times is now totally unfamiliar. Or he is asking about when his son is coming back from his European vacation, and his wife says: "What do you mean? We both spoke to him last night." Or he is paying the check after a perfectly pleasant night out and it’s the strangest thing, but he just cannot calculate the 20 percent tip.

The first few slips get chalked up to anxiety or a lousy night’s sleep or a bad cold. But how to consider these incidents of disorientation and confusion when they begin to occur with some frequency? What begin as isolated incidents start to mount and soon become impossible to ignore. In fact, they are not incidents; collectively, they are signs of a degenerative condition. Your brain is under attack. Months and years go by. Now you are losing your balance. Now you can no longer make sense of an analog clock. Now you cannot find the words to complain about your food. Now your handsome young husband has disappeared and a strange elderly man has taken his place. Why is someone taking your clothes off and pouring warm water over you? How long have you been lying in this strange bed?

By 1992, the signs of Reagan’s illness were impossible to ignore. At the conclusion of a medical exam in September, as the New York Times would later report, Reagan looked up at his doctor of many years with an utterly blank face and said, "What am I supposed to do next?" This time, the doctor knew that something was very wrong.

Sixteen months later, in February 1994, Reagan flew back to Washington, D.C., from his retirement home in Bel Air, California, for what would turn out to be his final visit. The occasion was a dinner celebrating his own eighty-third birthday, attended by Margaret Thatcher and twenty-five hundred other friends and supporters.

Before the gala began, the former President had trouble recognizing a former Secret Service agent whom he had known well in the White House. This didn’t come as a total shock to his wife, Nancy, and other close friends, but it did cause them to worry that Reagan might have problems with his speech that night.

The show went on as planned. After an introduction by Thatcher, Reagan strolled to the podium. He began to speak, then stumbled, and paused. His doctor, John Hutton, feared that Reagan was about to humiliate himself. "I was holding my breath, wondering how he would get started," Hutton later recalled, "when suddenly something switched on, his voice resounded, he paused at the right places, and he was his old self."

Back at his hotel after the dinner, Reagan again slipped into his unsettling new self, turning to Nancy and saying, "Well, I’ve got to wait a minute. I’m not quite sure where I am." Though the diagnosis and public announcement were both months away, Reagan was already well along the sad path already trod by his mother, his brother, and by Auguste D.

The doctors who diagnosed Reagan in 1994 knew with some specificity what was happening to his brain. Portions of his cerebral cortex, the thin layer of gray matter coating the outside of his brain, were becoming steadily clouded with two separate forms of cellular debris: clumpy brown spherical plaques floating between the neurons, and long black stringy tangles choking neurons from inside their cell membranes. As those plaques and tangles spread, some neurons were losing the ability to transmit messages to one another. Levels of glucose, the brain’s sole energy source, were falling precipitously, weakening cell function; neurotransmitters, the chemicals that facilitate messages between the neurons, were becoming obstructed. The tangles in some areas of the brain were getting to be so thick it was like trying to kick a soccer ball through a chain-link fence.

Ultimately, many of the neurons would die, and the brain would begin to shrink. Because the brain is highly specialized, the strangulation of each clump of neurons would restrict a very specific function–the ability to convert recent events into reliable memories, for example, or the ability to recall specific words, or to consider basic math problems. Or, eventually, to speak at all, or recognize a loved one. Or to walk or swallow or breathe.

We know about plaques and tangles because of Auguste D. and Alois Alzheimer. After four and a half years in the hospital, Frau D. died on April 8, 1906. Her file listed the cause as "septicaemia due to decubitis"–acute blood poisoning resulting from infectious bed sores. In her last days, she had pneumonia, inflammation of the kidneys, excessive fluid in the brain, and a high fever. On the day of her death, doctors understood no more than they had on the first day she was admitted. They could say only this about Auguste D.: that a psychic disturbance had developed in the absence of epileptic fits, that the disturbance had progressed, and that death had finally intervened.

Alois Alzheimer wanted to learn more. He wanted to look at her brain.

Standing apart from most doctors at the time, Alzheimer was equally interested in both clinical and laboratory work. He was known for his tireless schedule, his devoted teaching, and his own brand of forgetfulness. An inveterate cigar smoker, he would put a half-smoked cigar down on the table before leaning into a student’s microscope for a consultation. A few minutes later, while shuffling to the next microscope, he’d light a fresh cigar, having forgotten about the smoke already in progress. At the end of each day, twenty microscopes later, students recalled, twenty cigar stumps would be left smoldering throughout the room.

But Alzheimer did not forget about the woman who had lost herself in Frankfurt. Though he had since moved to the Royal Psychiatric Clinic, in Munich, to work for the renowned psychiatrist Emil Kraepelin, he sent for Frau D.’s central nervous system as soon as she died. Her brain, brainstem, and spinal cord were gently removed from the elaborate bone casing, that flexible yet durable wrapper that allows us all to crouch, twist, and bump into things without much concern. The exposed contents were then likely wrapped in formalin-soaked towels, packed carefully in a wooden crate, and shipped by locomotive 190 miles southeast to Munich.

Imagine, now, that lifeless brain on a passenger train. A coconut-sized clump of grooved gelatinous flesh; an intricate network of prewired and self-adapting mechanisms perfected over more than a billion years of natural selection; powered by dual chemical and electrical systems, a machine as vulnerable as it is complex, designed to sacrifice durability for maximal function, to burn brightly–a human brain is 2 percent of the body’s weight but requires 20 percent of its energy consumption–at the cost of impermanence. Enormously powerful and potato-chip fragile at the same time, the brain is able to collect and retain a universe of knowledge and understanding, even wisdom, but cannot hold on to so much as a phone number once the glucose stops flowing. The train, an elementary device by comparison, can, with proper maintenance, be sustained forever. The brain, which conceived of the train and all of its mechanical cousins, cannot. It is ephemeral by design.

But there was nothing in the brain’s blueprint about this sort of thing, as far as Alzheimer could infer. This was a flaw in the design, a molecular glitch, a disease process, he suspected, and it was important to see what that process looked like up close.

It was also now actually possible to do this for the first time, thanks to a whirl of European innovation. Ernst Leitz and Carl Zeiss had just invented the first distortion-free microscopes, setting a standard in optics that survives today. Franz Nissl had revolutionized tissue-staining, making various cell constituents stand out, opening up what was characterized as "a new era" in the study of brain cells and tissues. (The "Nissl method" is still in use. Nissl, a close collaborator and friend of Alois Alzheimer, became a medical school legend with his instructions on how to time the staining process. "Take the brain out," he advised. "Put it on the desk. Spit on the floor. When the spit is dry, put the brain in alcohol.")

Dr. Alzheimer’s assistants prepared for microscopic examination more than 250 slides from slivers of the outer lining (the meninges) of Frau D.’s brain; from the large cerebral vessels; from the frontal, parietal, and occipital areas of the cerebral cortex (locus of conscious thought); from the cerebellum (regulator of balance, coordination, gait) and the brainstem (breathing and other basic life functions); and from the spinal cord, all chemically preserved in a cocktail of 90 percent alcohol/10 percent formalin, and stained according to a half-dozen recipes of Alzheimer’s contemporaries.

Having fixed, frozen, sliced, stained, and pressed the tissue between two thin pieces of glass, Alzheimer put down his cigar and removed his pince-nez spectacles, leaned into his state-of-the-art Zeiss microscope, and peered downward. Then, at a magnification of several hundred times, he finally saw her disease.

It looked like measles, or chicken pox, of the brain. The cortex was speckled with crusty brown clumps–plaques–too many to count. They varied in size, shape, and texture and seemed to be a hodgepodge of granules and short, crooked threads, as if they were sticky magnets for microscopic trash.

The plaques were nestled in amongst the neurons, in a space normally occupied by supporting tissue known as glial cells. They were so prominent that Alzheimer could see them without any stain at all, but they showed up best in a blend of magenta red, indigo carmine, and picric acid. Alzheimer had squinted at thousands of brain slides, but he found these clumps "peculiar" and had no idea what they could be.

A different stain, invented just four years earlier, revealed the other strange invasion of Auguste D.’s brain. In the second and third layers of the cortex, nearly a third of the neurons had been obliterated internally, overrun with what Alzheimer called "a tangled bundle of fibrils"–weedy, menacing strands of rope bundled densely together.

The tangles were just as foreign to Alzheimer as the plaques, but at least the ingredients looked familiar. They seemed to be composed of fibrils, an ordinary component of every neuron. It was as if these mild-mannered, or "Jekyll," fibrils had swallowed some sort of steroidal toxin and been transformed into "Hyde" fibrils, growing well out of proportion and destroying everything within their reach. Many affected neurons were missing a nucleus completely, and most of the rest of their cell contents. A good portion of the neurons in the upper cell layers of the cortex had disappeared. They just weren’t there. Alzheimer’s assistant Gaetano Perusini wrote of the neurofibrillary tangles in Frau D.’s brain:

It is impossible to give a description of all the possible pictures: there are present all the variable and twisted formations that one can imagine; at times large fibrils seem to lie only on the periphery of the cell. But on focusing untangled fibrillar agglomerations are found. Changing the focus again one has the impression that the single dark-coloured fibrils unwind into an infinite number of thinner fibrils . . . arranged as balls of twine or half-moons or baskets.

Connecting a camera lucida to the top of the microscope, Alzheimer and Perusini both drew pictures of the tangles.

The menacing drawings perfectly convey the ghastly significance of their discovery. Here was the evidence that Auguste D. had not lost herself. Rather, her "self" was taken from her. Cell by cell by cell, she had been strangled by unwelcome, malignant intruders.

What were they, exactly, and where did they come from?

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