The Amnesiac Who Profoundly Changed The Way We Think About Memory

Sam Kean | The Tale of Dueling Neurosurgeons | 2014 | 12 minutes (3,008 words)

For this week’s Longreads Member Pick, we’re excited to share a story from The Tale of the Dueling Neurosurgeons, a new book from science reporter Sam Kean looking at stories about the brain and the history of neuroscience. Here’s Kean:

In our minds, we more or less equate our identities with our memories; our very selves seem the sum total of all we’ve done and felt and seen. That’s why we cling to our memories so hard, even to our detriment sometimesâ€"they seem the only bulwark we have against the erosion of the self. That’s also why disorders that rob us of our memories seem so cruel.

In the excerpt below, I explore one of the most profound cases of amnesia in medical history, H.M., who taught us several important things about how memory works. Perhaps most important, he taught us that different types of memories exist in the brain, and that each type is controlled by different structures. In fact, H.M. so profoundly changed our ideas about memory that it’s hard to remember what things were like before him.

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In the early 1930s a bicyclist in Connecticut struck a small boy, who tumbled and cracked his skull. No one knows whether the accident alone caused his epilepsyâ€"three cousins had it, so he might have been predisposedâ€"but the blow probably precipitated it, and at age ten he started having seizures. Each lasted around forty seconds, during which time his mouth flopped open, his eyes slipped shut, and his arms and legs crossed and uncrossed as if curled by an invisible puppeteer. He suffered his first grand mal on, of all days, his fifteenth birthday, while riding in the car with his parents. More followed, in class and at home and while shoppingâ€"up to ten seizures a day, with at least one major episode per week. So at an age when most people are struggling to find an identity, he was saddled with one he didn’t want: the kid who shook, who bit his tongue, who slumped over and blacked out and pissed himself. The mockery got so bad he dropped out of high school, and he earned his diploma only at twenty-one, from a different school. He ended up living at home and working in a motor shop.

Finally the desperate young manâ€"soon immortalized as H.M.â€"decided to try surgery. When younger, H.M. had dreamed of practicing neurosurgery himself and studying how the brain works. But while H.M. did end up contributing, profoundly, to neuroscience, his affliction ensured that he would never grasp his own importance.

H.M. started seeing Dr. William Scoville around 1943. A noted daredevilâ€"before a medical conference in Spain once, he’d stripped off his jacket and mixed it up with the toros in the bullringâ€"Scoville liked risky surgeries, too, and had jumped onto the American lobotomy bandwagon* early. But he disliked the drastic changes in his patients’ personalities, so he began experimenting with “fractional” lobotomies, which destroyed less tissue. Over the years he basically worked his way around the brain, carving out this piece or that and checking the results, until he finally reached the hippocampus.

Because it was part of the limbic system, scientists at the time believed that the hippocampus helped process emotions, but its exact function remained unknown. Rabies often destroyed it, and James Papez had singled it out for attention. (A poetaster, Papez even penned a ditty to his wife that read: “It’s Pearl, my girl on Broad Street / that I miss… My hippocampus tells me this.”) Scoville was less enamored: he’d seen the mental turmoil that hippocampus damage could cause. So in the early 1950s he started removing the hippocampi (you have one in each hemisphere) from a few psychotics. Although it was hard to be sure in people with such disturbed minds, they seemed to suffer no ill effects, and two women in particular showed a marked reduction in seizures. Unfortunately Scoville neglected to do careful follow-up tests until November 1953â€"after he’d convinced H.M. to try the surgery.

H.M.’s operation took place in Hartford, Connecticut, on September 1, 1953. Scoville peeled back his patient’s scalp, then used a hand crank and one-dollar drill saw from a local hardware store to remove a bottle cap’s worth of bone from above each eye. As cerebrospinal fluid drained away, the brain settled down in its cavity, giving Scoville more room to work. With what looked like an elongated shoehorn, he nudged aside H.M.’s frontal and temporal lobes and peered inside.

The hippocampus sits at ear level and has the rough shape and diameter of a curled thumb. Hoping to remove as little tissue as possible, Scoville first sparked each hippocampus with wires to find the origin of H.M.’s seizures. No luck, so he grabbed a long metal tube and began cutting and sucking out tissue gram by gram; he eventually removed three inches’ worth of hippocampus on each side. (Two nubs of hippocampal tissue remained behind, but because Scoville also removed the connections between those nubs and other parts of the brain, the nubs were useless, like unplugged computers.) For good measure, Scoville removed H.M.’s amygdalae and other nearby structures as well. Given how deeply all these structures are embedded in the brain, only a neurosurgeon could have destroyed them with such precision.

Post-op, H.M. remained drowsy for a few days, but he could recognize his family and carry on a seemingly normal conversation. And by many measures, the operation succeeded. His personality never changed; the seizures all but disappeared (two attacks per year at most); and when the fog of epilepsy lifted, his IQ jumped from 104 to 117. Just one problem: his memory was shot. Aside from a few small islands of recollectionâ€"like the fact that Dr. Scoville had operated on himâ€"an entire decade’s worth of memories from before the surgery had vanished. Equally terrible, he couldn’t form new memories. Names escaped him now, as did the day of the week. He repeated the same comments over and over, verbatim, and while he might remember directions to the bathroom long enough to get there, he always had to ask again later. He’d even consume multiple lunches or breakfasts if no one stopped him, as if his appetite had no memory, either. His mind had become a sieve.

In light of modern knowledge, H.M.’s deficit makes sense. Memory formation involves several steps. First, neurons in the cortex jot down what our sensory neurons see and feel and hear. This ability to record first impressions still worked in H.M. But like messages scrawled on the beach, these impressions erode quickly. It’s the next step, involving neurons in the hippocampus, that makes memories last. These neurons produce special proteins that encourage axon bulbs to swell in size. As a result, the axons can stream more neurotransmitter bubbles toward their neighbors. This in turn strengthens the synapse connections between those neurons before the memory decays. Over months and yearsâ€"provided the first impression was strong enough, or we think about the event from time to timeâ€"the hippocampus then transfers the memory to the cortex for permanent storage. In short, the hippocampus orchestrates both the recording and the storage of memories, and without it, this “memory consolidation” cannot occur.

Scoville couldn’t have known all this, but he’d clearly sabotaged H.M.’s memory, and he didn’t know what to do. So a few months later, when he saw that Wilder Penfield was about to publish a report on hippocampus damage, Scoville called the renowned surgeon and confessed.

Penfield had recently operated on two patients with hippocampal epilepsy. To be safe, he’d removed the structure on just one side, but unbeknownst to him, the seizures had already destroyed the other hippocampus in each person. So removing the one left both patients without a working hippocampus, and they developed the purest amnesia Penfield had ever seen. Although he was still puzzling through the cases, a graduate student was going to present them at a scientific meeting in Chicago in 1954.

When Scoville called, Penfield reportedly flipped out, berating him for his recklessness. After calming down, though, the scientist in Penfield realized (much as the beriberi doctors had) that Scoville had actually performed an invaluable experiment: here was a chance to determine what the hippocampus did. As part of its mission Penfield’s clinic in Montreal tracked the psychological changes that patients experienced after psychosurgery. So Penfield dispatched a Ph.D. student from the Neuro, Brenda Milner, down to Connecticut to investigate the hippocampusless H.M.

After his memory vanished, H.M. lost his job and had no choice but to keep living with his parents. He spoke in a monotone now and had no interest in sex, but otherwise seemed normal. To the neighbors, it probably just looked like he was loafing his life away. He took a part-time job packing rubber balloons into plastic bags, and did odd chores around the house. (Although his parents had to remind him where they kept the lawn mower every single time, he could actually mow just fine, since he could see what grass he hadn’t cut.) His temper did flare up occasionally: his mother tended to nag, and he cuffed her a few times and kicked her shins. Another time, when an uncle removed a few choice rifles from the family’s gun collection, he flew into a rage. (Despite his amnesia he retained a lifelong love of guns, and always remembered to renew his NRA membership.) But he whiled away most days peacefully, either doing crossword puzzlesâ€"working through the clues methodically, in orderâ€"or flopping in front of the television and watching either Sunday Mass or the old movies that, to him, would never become classics. It was like early retirement, except for the days Milner arrived to test him.

Milner would take the night train down from Montreal to Hartford, arriving at 3 a.m. and spending the next few days with H.M. Her battery of tests confirmed Scoville’s basic observations pretty quickly: H.M. had little memory of the past and no ability to form new memories going forward. This was already a big advanceâ€"proof that some parts of the brain, namely the hippocampus, contribute more to forming and storing memories than other parts. And what Milner discovered next redefined what “memory” even meant.

Rather than keep asking him questions he couldn’t answer, she started testing H.M.’s motor skills. Most important, she gave him a piece of paper with two five-pointed stars on it, one nested inside the other star. The outer star was about six inches wide, and there was a half-inch or so gap between them. The test required H.M. to trace a third star between the two with a pencil. The catch was, he couldn’t see the stars directly: Milner had shielded the diagram, and he had to look at them in a mirror instead. Left was right, right was left, and every natural instinct about wheren to move his pencil was wrong. Anyone taking this mirror test for the first time makes a messâ€"the pencil line looks like an EKGâ€"and H.M. proved no exception. Somehow, though, H.M. got better. He didn’t remember any of the thirty training sessions Milner ran him through. But his unconscious motor centers did remember, and after three days he could trace the star in the mirror fluently. He even commented near the end, “This is funny… I would have thought it would be rather difficult, but it seems I’ve done pretty well.”

Milner remembers the star test as a eureka. Before this, neuroscientists thought of memory as monolithic: the brain stored memories all over, and all memory was essentially the same. But Milner had now teased apart two distinct types of memory. There’s declarative memory, which allows people to remember names, dates, facts; this is what most of us mean by “memory.” But there’s also procedural memoryâ€"unconscious memories of how to pedal a bicycle or sign your name. Tracing the stars proved that H.M., despite his amnesia, could form new procedural memories. Procedural memories must therefore rely on distinct structures within the brain.

This distinction between procedural and declarative memories (sometimes called “knowing how” versus “knowing that”) now undergirds all memory research. It also sheds light on basic mental development. Infants develop procedural memory early, which explains why they can walk and talk fairly quickly. Declarative memory develops later, and its initial weakness prevents us from remembering much from early childhood.

Another distinct type of memory emerged from Milner’s tests as well. One day Milner asked H.M. to remember a random number, 584, for as long as possible. She then left him alone for fifteen minutes while she had a cup of coffee. Contrary to her expectation, he still knew the number when she returned. How? He’d been repeating it under his breath, over and over. Similarly, H.M. could remember the words “nail” and “salad” for several minutes by imagining a nail piercing some salad greens and reminding himself over and over not to eat the impaled leaves. Any distraction during those minutes would have ejected the words clean out of H.M.’s mind, and five minutes after the test ended, even the memory of having to remember something had vanished. Nevertheless, as long as H.M. concentrated and kept refreshing his memory, he could hold on. This was the first clue that short-term memory exists; moreover, it showed that short-term memory (which H.M. had) and long-term memory (which he lacked) must utilize different brain structures.

After Milner’s discoveries, H.M. became a scientific celebrity, and other neuroscientists began clamoring to explore his unique mind. He did not disappoint. In April 1958, five years after the operation, H.M. and his parents moved into a small Hartford bungalow. In 1966 a few American neuroscientists asked him to draw the home’s floor plan from memory. He succeeded. He didn’t know the bungalow’s address, but walking through its six rooms over and over had tattooed the layout into his brain. This proved that our spatial memory systems, while normally reliant on the hippocampus, can circumvent it if need be (probably via the parahippocampus, a nearby navigation center).

Scientists also discovered that time worked differently for H.M. Up to about twenty seconds, he reckoned time as accurately as any normal person. After that, things veered wildly. Five minutes lasted, subjectively, just forty seconds for him; one hour lasted three minutes; one day fifteen minutes. This implies that the brain uses two different timekeepersâ€"one for the short term and one for everything beyond twenty seconds, with only the latter suffering damage in H.M. Once again, H.M. allowed scientists to break a complex mental function down into different components and to link those components to structures in the brain. Eventually more than one hundred neuroscientists examined H.M., making his probably the most studied mind in history.

All the while H.M. got older, at least physically. Mentally, he remained stuck in the 1940s. He remembered not a single birthday or funeral after that time; the Cold War and sexual revolution never registered; new words such as granola and Jacuzzi remained forever undefined. Worse, a vague sense of uneasiness often bubbled up inside him, and he could never quite shake it. The feeling, Milner reported, was “like that fraction of a second in the morning, when you are in a strange hotel room, before it all falls in[ to] place.” Only for H.M. it never did.

In 1980, after H.M.’s father died and his mother got too sick to care for him, he moved into a nursing home. He walked a little gimpily by that point: years of taking heavy-duty epilepsy drugs had withered his cerebellum, and his wide, shuffling gait resembled that of kuru victims. He also got pretty portly after too many forgotten second helpings of cake and pudding. But overall he was a fairly normal patient and lived a (mostly) placid life. He loafed through the nontesting days reading poems or gun magazines, watching trains rumble by, and petting the dogs, cats, and rabbits the facility owned. He learned how to use a walker, thanks to his intact motor memories, and he even attended his thirty-fifth high school reunion in 1982. (Although he recognized no one there, other attendees reported the same problem.) When he dreamed at night, he often dreamed of hillsâ€"not of struggling up them, but cresting them and being at the top.

Still, the old, volatile H.M. did flare up now and again. He sometimes refused to take his medsâ€"at which point his nurses scolded him, warning him that Dr. Scoville would get angry if he disobeyed. (That Scoville had died in a car crash didn’t matter. H.M. always fell for it.) He got into fights with other residents as well. One harpy at the nursing home would erase his bingo card midgame and taunt him. H.M. sometimes responded by running to his room and either banging his head on the wall or grabbing his bed and shaking it like a gorilla would its cage. One fit got so violent that his nurses called the police. These were moments of pure animal frustrationâ€"and yet in some ways they seem like his most human moments. For a few seconds a real person broke through the dull, bovine exterior. He was reacting the way we’d all want to if dealt his fate: he raged.

As soon as a nurse distracted H.M., he forgot his torment, of course. And aside from those flare-ups he lived a quiet life, albeit in declining health. He finally died in 2008, aged eighty-two, of respiratory failureâ€"at which point scientists revealed him to the world as Henry Gustav Molaison.

The world of neuroscience mourned Molaison: his death led to numerous tributes about his patience and kindness, as well as scores of puns about his being unforgettable. And his brain is still providing insight today. Before his death, his nursing home had started stockpiling ice packs in preparation; when he passed, employees ringed his skull with them to keep his brain cool. Doctors soon arrived to claim the body, and that night they scanned his brain in situ and then liberated it. After two months hardening in formalin, it was flown cross-country in a cooler (which got the window seat) to a brain institute in San Diego. Scientists there soaked it in sugar solutions to draw out excess water, then froze it to solidify it. Finally, they used the medical equivalent of a deli slicer to shave Molaison’s brain into 2,401 slices, each of which they mounted on a glass plate and photographed at 20x magnification, to form a digital, zoomable map down to the level of individual neurons. The slicing process was broadcast live online, and 400,000 people tuned in to say goodbye to H.M.

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Excerpted from the book The Tale of Dueling Neurosurgeons by Sam Kean. Copyright © 2014 by Sam Kean. Reprinted with permission of Little, Brown and Company.

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