The Forgetting Read online

  I love you

  You love me

  We’re a happy family

  Members of the early-stage group occasionally caught a glimpse of the middle-stage group as they passed by to get a cup of coffee. The quiet, desperate hope of everyone in this group was not to end up in the other group. Barring a scientific miracle, though, there would be no avoiding it. The average interval from diagnosis to death in Alzheimer’s disease is eight years.

  In the meantime, there were a hundred small consolations. The early-stage group members had quickly come to rely on one another for help through this very strange ordeal. Sometimes barely able to remember from week to week, they had nevertheless become friends. They shared memories of movie stars and kosher butchers. They talked about travel and passed around pictures of grandchildren. They even talked politics.

  “Greta, any comments on Giuliani?” Judy asked one afternoon.

  Greta swatted an invisible bug away from her face. “Oh don’t get me started about him,” she said. “You know I can’t stand him.”

  “Clinton, then? What does everyone think about Monica?”

  Opinions ran the gamut. Ted, his hands shaking with a Parkinsonian tremor (it is not unusual for people to suffer from both Parkinson’s and Alzheimer’s), suggested that Clinton should resign because he lied directly to the American people. Greta, a lifelong subscriber to The Nation, thought that Clinton probably kissed Monica but that the whole issue was overblown. Sadie thought it was all a Republican scheme.

  Doris had an opinion, too, but with her severe expressive aphasia—an inability to retrieve words—she had great difficulty making it known.

  “Gore … President … I think … good leader … lies …”

  She appeared to be aware of her thoughts and very clear on what she wanted to say. But the words were no longer accessible. This was especially painful to watch because, as everyone in the group knew by now, Doris had a forty-year-old son with cerebral palsy who was deaf The two were very close, and, as it happened, she was the only one in the family to have ever learned sign language. Now Doris’s aphasia was also wiping away that second and more vital language. She could no longer speak to her son, leaving him marooned.

  It was now a few minutes after one o’clock, time to say good-bye for the week. Rides were arranged. Someone went to fetch William’s wife, a volunteer in the middle-stage group.

  Robert seemed to be having a hard time of it. Just a moment before, he had been lucidly telling me about his family and his past. He’d had no problem relating how he was spirited out of Nazi Germany as a young boy, turned over to relatives in England and later in New York. I learned all about his children, their occupations and families, the cities they lived in. But now he was struggling to understand a piece of paper his wife had written out for him about getting home. To the undamaged brain, the instructions were fairly straightforward—Robert will be picked up by the car service at 1:15, and should be driven to his home at ___ Street.…—but he was having a lot of trouble making sense of it. Then there was the other problem. In the last half hour, he had told me how he eventually came to live in the Bronx, where he was introduced to his wife, a distant cousin. He had described how crowded that Bronx apartment was, and where else he had lived in the city as he’d grown older. But now, for the life of him, Robert could not remember where he had put his jacket.

  It was on the back of his chair.

  Very often I wander around looking for something which I know is very pertinent, but then after a while I forget about what it is I was looking for.… Once the idea is lost, everything is lost and I have nothing to do but wander around trying to figure out what it was that was so important earlier. You have to learn to be satisfied with what comes to you.

  —C.S.H.

  Harrisonburg, Virginia

  Chapter 3

  THE GOD WHO FORGOT AND THE MAN WHO COULD NOT

  There could be no happiness, cheerfulness, hope, pride, immediacy, without forgetfulness. The person in whom this apparatus of suppression is damaged, so that it stops working, can be compared … to a dyspeptic; he cannot “cope” with anything.

  —FRIEDRICH NIETZSCHE

  As found in the Pyramid Texts, from 2800 B.C., Ra was the Sun God, the creator of the universe and of all other gods. From his own saliva came air and moisture. From his tears came humankind and the river Nile. He was all-powerful and, of course, immortal—but still not immune to the ravages of time: Ra, the supreme God, became old and senile. He began to lose his wits, and became easy prey for usurpers.

  Throughout recorded history, human beings have been celebrating the powers of memory and lamenting its frailties. “Worse than any loss in body,” wrote the Roman poet Juvenal in the first century A.D., “is the failing mind which forgets the names of slaves, and cannot recognize the face of the old friend who dined with him last night, nor those of the children whom he has begotten and brought up.”

  It took several thousand years, though, for anyone to figure out how memory actually worked. Plato was among the first to suggest a mechanism. His notion was of a literal impression made upon the mind. “Let us suppose,” he wrote, “that every man has in his mind a block of wax of various qualities, the gift of Memory, the mother of the Muses; and on this he receives the seal or stamp of those sensations and perceptions which he wishes to remember. That which he succeeds in stamping is remembered and known by him as long as the impression lasts; but that, of which the impression is rubbed out or imperfectly made, is forgotten, and not known.”

  Later came the ventricular theory of cognition, from Galen (129 – ca. 199 A.D.), Nemesius (fourth century), and St. Augustine (354–430). According to this notion, the three major functions of the brain—sensation, movement, and memory—were governed from three large, round fluid-filled sacs. Vital Spirit, a mysterious substance that also contained the human soul, was harbor to the swirl of memories.

  From this model came cerebral localization, the theory that the various functions of the brain were each controlled by specialized “modules.” This model of specialization turned out to be generally correct (if radically different in the details from what Galen had imagined). In the early twentieth century, it emerged that the brain wasn’t really an organ so much as a collection of organs, dozens of structures interacting with one another in dazzling complexity. Deep in the center of the brain the amygdala regulates fear while the pituitary coordinates adrenaline and other hormones. Visual stimulus is processed in the occipital lobe, toward the rear of the skull. Perception of texture is mediated by Area One of the parietal lobe near the top of the head, while, just to the rear, the adjacent Area Two differentiates between the size and shape of objects and the position of joints. The prefrontal cortex, snuggled just behind the forehead, spurs self-determination. Broca’s area, near the eyes, enables speech. Wernicke’s area, above the ears, facilitates the understanding of speech.

  The more researchers discovered about localization, though, the more they wondered about the specialized zone for memory. Where was it? If vision was in the back of the brain, texture on top, and so on, what region or regions controlled the formation of lasting impressions and the retrieval of those impressions?

  Part of the answer came in 1953, when a Harvard-trained neurosurgeon named William Beecher Scoville performed experimental surgery on a twenty-seven-year-old patient known as H.M. He had been suffering from violent epileptic seizures since childhood, and in a last-ditch effort to give him a chance at a normal life, Scoville removed a small collection of structures, including the hippocampus, from the interior portion of his brain’s two temporal lobes. The surgery was a great success in that it significantly reduced the severity of H.M.’s epilepsy. But it was also a catastrophe in that it eliminated his ability to lay down new memories. The case revolutionized the study of memory, revealing that the hippocampus is essential in consolidating immediate thoughts and impressions into longer-lasting memories (which are in turn stored elsewhere).

&
nbsp; Time stopped for H.M. in 1953. For the rest of his long life, he was never again able to learn a new name or face, or to remember a single new fact or thought. Many doctors, researchers, and caregivers got to know him quite well in the years that followed, but they were still forced to introduce themselves to him every time they entered his room. As far as H.M. was concerned, he was always a twenty-five-year-old man who was consulting a doctor about his epilepsy (he had also lost all memory of the two years immediately prior to the surgery). H.M. became perhaps the most important neurological subject in history and was subject to a vast number of studies, but he remembered none of the experiments once they were out of his immediate concentration. He was always in the Now.

  In the clinical lexicon, this was a perfect case of anterograde amnesia, the inability to store any new memories. Persons with incipient Alzheimer’s disease exhibit a slightly less severe form of the same problem. The memory of leaving the car keys in the bathroom isn’t so much lost as it was never actually formed.

  In a healthy brain, sensory input is converted into memory in three basic stages. Before the input even reaches consciousness, it is held for a fraction of a second in an immediate storage system called a sensory buffer.

  Moments later, as the perception is given conscious attention, it passes into another very temporary system called short-term (working) memory. Information can survive there for seconds or minutes before dissolving away.

  Some of the information stirring in working memory is captured by the mechanism that very slowly converts into a long-term memory lasting years and even a lifetime.

  Long-term memories can be either episodic or semantic. Episodic memories are very personal memories of firsthand events remembered in order of occurrence. Before the baseball game the other day, I put on my new pair of sneakers, which I had gotten earlier that morning. Then we drove to the stadium. Then we parked. Then we gave the man our tickets. Then we bought some hot dogs. Then we went to our seats …

  Now, days later, if I notice a mustard stain on my shoe, I can plumb my episodic memory to determine when and how it happened. If my feet start bothering me, my episodic memory will help me figure out whether it happened before or after I bought my new shoes.

  Semantic memories are what we know, as opposed to what we remember doing. They are our facts about the world, stored in relation to each other and not when we learned them. The memory of Neville Chamberlain’s “peace in our time” is semantic.

  They are separate systems—interrelated, but separate. An early-stage Alzheimer’s patient who cannot retain memories of where she put her keys has not forgotten what keys are for, or what kind of car she drives. That will come much, much later, when she starts to lose old semantic memories.

  The experience with H.M. taught researchers that the hippocampus is key to long-term memory formation. Without that tiny organ, he was totally incapable of forming new, lasting memories. Alzheimer’s patients suffer the exact same systemic loss, but over several years rather than one surgical afternoon. For H.M., there were no new memories after 1953, period. In later years, he was unable to recognize his own face in the mirror. Real time had marched on, 1955 … 1962 … 1974, but as far as he was concerned, he was still twenty-five years old. If you are a young man, alert and intelligent, and you look into an ordinary mirror only to discover the face of a sixty-year-old perfectly mimicking your expressions, perhaps only then do you know the real meaning of the word horror. Fortunately, the extreme distress H.M. suffered during such world-shattering incidents was always immediately and completely forgotten as soon as his attention could be distracted by something happening in the new moment. Not remembering can sometimes be a great blessing.

  The discovery of hippocampus-as-memory-consolidator was critical. What memory specialists have been trying to figure out ever since then is, once formed, where do these long-term memories actually reside? Are memories stored up in the front of the brain in the prefrontal cortex? On top, in the parietal lobe? In the brainstem at the base of the brain? Where?

  One tantalizing theory emerged in the late 1950s: memories were everywhere, stored in discrete molecules scattered throughout the brain. A stampede to confirm this notion was set off by a 1962 Journal of Neuropsychiatry article, “Memory Transfer Through Cannibalism in Planaria,” in which the University of Michigan’s James McConnell eagerly reported that worms could capture specific memories of other worms simply by eating those worms. McConnell had trained a group of flatworms to respond to light in a noninstinctive way. He then killed these worms, chopped them up, and fed them to untrained flatworms. After eating their brethren, McConnell claimed, the untrained worms proceeded to behave as though they had been trained—they had somehow acquired the memory of the trained worms. It was the unexpected apotheosis of the old saying, “You are what you eat.”

  Out of this report numerous research grants were born, some of which yielded tantalizing results. Three years after McConnell’s initial study, four California scientists reported in the journal Science that when cells extracted from the brains of trained rats were injected into the guts of untrained rats, the untrained rats picked up the learned behavior of the trained rats. These experiments apparently showed that specific, concrete individual memories were embedded as information in discrete molecules in the same way that genetic information is embedded in DNA, and that these memories were transferable from brain to brain. A later experiment by Baylor University’s Georges Ungar was the most vivid yet: Brain cells from rats that had been trained to fear the dark were transferred to untrained mice (ordinarily, neither mice nor rats fear the dark), who suddenly took on this new fear. Ungar even isolated a peptide comprising fifteen amino acids that he said contained the newly created memory. He called the transmissible fear-of-the-dark memory molecule scotophobin.

  The theory that emerged out of these experiments was of memory as a distinct informational molecule that could be created organically in one brain, isolated, and then transferred to another brain—even to the brain of another species. Its implications were immense. Had this cold fusion of an idea been validated rather than widely discredited not long after Ungar’s paper was published in Nature in 1972, it is clear that ours would be a very different world today: Memory swaps. Consciousness transfers. Neurochemical behavioral enhancements that would make Prozac seem like baby aspirin. The rapid decoding of a hidden science of memory molecules might well have spawned a new type of biochemical computer that could register, react to, and even create memory molecules of its own. Laptops (or cars or stuffed animals) could be afraid of the dark or partial to jazz or concerned about child abuse. Memories and feelings could be bottled and sold as easily as perfume.

  But that world did not, and cannot, emerge. The memory transfer experiments, while entertaining and even seductive—DNA pioneer Francis Crick was among the many prestigious scientists on board for a while—were ultimately dismissed as seriously misguided). The idea of transferable memories strained credulity to begin with; to suggest that one animal’s specific fear could travel through another animal’s digestive tract, enter its bloodstream, find its way to the brain, and turn itself on again in the new host mind was an even further stretch.

  And then there was the problem of physical mass. Skeptics calculated that if specific memories were contained in molecules the way Ungar suggested, the total number of memories accumulated over a lifetime would weigh somewhere in the vicinity of 220 pounds. The brain would literally be weighed down by thought and ideas.

  After a decade or so, the notion and burgeoning industry of memory molecules crumbled into dust. It is now one particularly humiliating memory that many neuroscientists would just as soon not retain. What has grown up out of that rubble over the last thirty years is a very different understanding of memory—not as a substance but as a system. Memories are scattered about; that part the memory molecularists had right. Memory is everywhere. But it is everywhere in such a way that it is impossible to point to any one spot and identi
fy it with an explicit memory. We now know that memory, like consciousness itself, isn’t a thing that can be isolated or extracted, but a living process, a vast and dynamic interaction of neuronal synapses involved in what Harvard’s Daniel Schacter elegantly terms “a temporary constellation of activity.” Each specific memory is a unique network of neurons from different regions of the brain coordinating with one another. Schacter explains:

  A typical incident in our everyday lives consists of numerous sights, sounds, actions, and words. Different areas of the brain analyze these various aspects of an event. As a result, neurons in the different regions become more strongly connected to one another. The new pattern of connections constitutes the brain’s record of the event.

  The power of the constellation idea is reinforced by the understanding of just how connected the 100 billion neurons in the brain actually are. A. G. Cairns-Smith, of the University of Glasgow, observes that no single brain cell is separated from any other brain cell by more than six or seven intermediaries.

  The molecular basis for these synaptic constellations that can be reignited again and again (though never in precisely the same configuration), is a biochemical process called long-term potentiation (LTP) that intensifies the affinity between specific neurons after a significant connection is made. Think of an ant farm, with worker ants constantly building new tunnels among one another; once a tunnel is built, transport becomes many times easier; an easy, natural connection has been created between those two points. With memory formation and retrieval, pathways are at first built and later simply used. Each notable experience causes a unique set of neurons to fire in conjunction with one another. As a result, those connections become chemically more sensitive to one another so that they can more easily trigger each other again. With that unique constellation of synapses, one has created a permanent physical trace of the original sensation. Neurologists call these memory traces “engrams.”