A Textbook Case

 

Hartford, Connecticut, is a traffic-choked city today, but in the 1930s it was a sleepy town where kids could play in the streets for hours without having to move aside for a passing car. One day in 1934, an eight-year-old boy named Henry Gustav Molaison fell off his bike and struck his head. He wasn’t wearing a helmet, since it wouldn’t occur to anyone for another half century that children needed that kind of protection. Or maybe it happened a little differently: maybe he was on foot and another bike knocked him over. His parents didn’t remember which it was, when they thought about the incident years afterward.

Henry might have lost consciousness for a few minutes, or perhaps not. Concussions were considered a normal part of growing up back then, so nobody would have paid much attention. After the accident, whatever it was, he seemed perfectly normal. If you’d told Henry’s parents at the time that their only child would one day become the most celebrated neuroscience patient in history, and that his obituary would appear on the front page of the New York Times, Gus and Lizzie Molaison—he was an electrician, a Cajun who came originally from Thibodaux, Louisiana; she was a stay-at-home mother whose parents had emigrated from Northern Ireland—would have been convinced you’d lost your mind.

A couple of years after he hit his head, Henry began to have epileptic seizures, and his parents wondered if the bike accident might have been responsible. At first, they were mild, petit-mal seizures. Henry would go into what seemed like a trance for a couple of minutes, then return to normal. By the time he was in his mid-teens, however, he was having grand-mal seizures, in which he would fall to the floor, go into convulsions, foam at the mouth, and bite his tongue. These episodes were so disruptive and so embarrassing that he dropped out of one high school, waited several years, then started again at another school as a seventeen-year-old freshman. He didn’t take the college-prep track, choosing instead the school’s vocational course. After he graduated, at twenty-one, he got a job with a company that built electric motors, then moved on to work at an assembly line, making typewriters.

Throughout his early twenties, Henry’s epilepsy kept getting worse. By the time he was twenty-six, he was taking four powerful medications, any one of which by itself would have kept most patients’ seizures in check. He’d had a series of tests to rule out a brain tumor or some other physical abnormality. The most unpleasant of them, called a pneumoencephalogram, involved draining the cerebrospinal fluid, which normally cushions the brain, then forcing air into Henry’s skull to replace it, which allowed an X-ray to look for any unusual gaps in his brain tissue. That showed nothing. Neither did a much less invasive electroencephalogram, or EEG.

At a loss for how else to proceed, Henry’s doctor, an eminent neurosurgeon named William Beecher Scoville, suggested an operation as a last resort. Scientists understood by this time that neurons, the cells that process and store information in the brain, communicate with one another through tiny electrical signals. They also knew that seizures are caused when these signals go out of control, sending spasms of electrochemical energy bouncing chaotically through the brain. In some cases, the chaotic signals originated in areas that had been damaged by illness or injury. Henry’s parents were right to suspect that his bike accident might have been the cause of his epilepsy.

The tests found no such injuries, but epilepsy can also be caused by much subtler brain abnormalities, which are often genetic. Several relatives on Henry’s father’s side had had epilepsy as well, so maybe that was the explanation. No one knew where these abnormalities were located, but tests on both animals and humans had shown that deliberately stimulating the brain’s medial temporal lobes with mild jolts of electricity could trigger seizures. Scoville himself had removed medial temporal tissue from patients with schizophrenia, hoping to cure their psychosis. It didn’t work, but one patient who also had epileptic seizures saw significant improvement in that illness.

So Scoville proposed to remove large parts of Henry’s medial temporal lobes. “This frankly experimental operation was considered justifiable,” he would write several years afterward, “because the patient was totally incapacitated by his seizures and these had proven refractory to a medical approach.” Scoville made it clear to Henry and his parents that the operation was risky. He thought it was likely to relieve the epilepsy, but there might be side effects. But the seizures were so awful that the Molaisons decided it was worth the risk. Even if the surgery didn’t cure him, Henry said, in giving his consent, it might help others.

On August 25, 1953, orderlies wheeled Henry into an operating room at Hartford Hospital, his skull newly shaved, and the surgery began. Scoville drilled two large holes in Henry’s forehead, each about an inch and a half across, and reached in with an instrument called a brain spatula, which he used to lever the frontal lobes—one on each side—out of the way. This gave him access to the hippocampus. Then he worked the spatula in and down, and began to apply suction to the soft, spongy brain tissue. By the time he was done, Scoville had sucked out big chunks of Henry’s two hippocampi, one on each side of the brain. He’d also removed much of the neighboring amygdalae, which are involved in the processing of emotions. And he’d taken out tissues from the entorhinal, perirhinal, and parahippocampal cortices, which border the hippocampi. He didn’t get all of the hippocampus out on either side, because the far ends curved away, out of reach of his straight, inflexible suction tube. The remaining chunks of hippocampus, however, were now largely disconnected from the rest of the brain. They might as well not exist.

Once Henry came out of the anesthesia, it quickly became clear that Scoville’s invasion of his brain had been largely successful in treating the epilepsy. Henry’s seizures weren’t eliminated completely, but they were dramatically reduced in both frequency and intensity. It was also clear, however, that something else had happened, something awful. Henry recognized his parents. His intelligence, which was above average according to presurgical testing done in the hospital, was intact. So was his personality. He’d been shy, friendly, and good-natured before the operation. He was the same afterward.

But Henry had no clue about who the doctors, nurses, and other hospital staff who came to his room were, even after seeing them repeatedly. He could remember new information for a minute or two—if you said, “Good morning, Henry, my name is John,” and then, right afterward, “What’s my name?” he had no problem giving the right answer. If you asked him again fifteen minutes later, however, he couldn’t do it. He couldn’t navigate his way to the bathroom even after having been there several times. He didn’t know why he was in the hospital. An hour after he’d had lunch, he couldn’t remember eating. He’d eat a second lunch if you put it in front of him, and then a third. He couldn’t remember much of anything about his past—the condition known as retrograde amnesia. And he also had anterograde amnesia: he couldn’t convert his everyday experiences into new memories to be recalled in the future. Until his death fifty-five years later, he never would.

Scoville was appalled. The operation was, he would later acknowledge, a tragic mistake. He’d had no idea that this might happen. He didn’t know at the time that Wilder Penfield, in Montreal, had had a similar outcome with two other patients, known only by their initials, F.C. and P.B. Both men had epilepsy, like Henry (who himself would be known simply as H.M., to protect his privacy, until after he died). Penfield had operated on them in an attempt to cure it. He’d removed medial temporal lobe tissue, including the hippocampus, from one side of their brains only. Penfield had done the same surgery on many other patients; these two were the only ones who developed profound amnesia. It turned out that, unlike the others’, the mirror structures on the opposite sides of F.C.’s and P.B.’s brains weren’t normal. Both men had suffered injuries to those tissues long before Penfield performed his surgery—possibly as early as birth. Penfield’s other patients had backup. They could use the undamaged lobes on the other sides of their brains to take up the slack of memory formation and retrieval.

Scoville read about these two cases not long after he’d performed his surgery on Henry. He was naturally intrigued, and contacted Penfield, who suggested that a young colleague of his named Brenda Milner should come down from Montreal to test H.M., along with some of Scoville’s schizophrenia patients who had also had medial temporal lobe surgery. Milner, born in England and educated at Cambridge, had been a graduate student in the laboratory of Donald Hebb, a pioneer in the attempt to understand how the brain creates and maintains memory. When Penfield began his campaign to cure epilepsy through surgery, he had recruited Milner to help him test patients to see how the operations might have affected their cognitive abilities. She had helped him figure out why F.C.’s and P.B.’s memory functions had been so severely affected, and she was eager to see how this new patient down in Connecticut might fit into the story.

The testing took place in 1955. Milner showed rigorously what Scoville had understood only in general terms: Henry’s intelligence, language, and other higher mental functions were unaffected by the operation. His personality was essentially unchanged. He was described by the scientists who studied him as “gentle, goodhearted and altruistic.” But his memory had been profoundly damaged, in both the past and future direction.

Unlike Scoville’s schizophrenia patients, Henry wasn’t mentally ill before his operation, which would have made it more difficult to disentangle memory problems caused by the surgery from any memory problems that might have been caused by the schizophrenia instead. And unlike Penfield’s patients P.B. and F.C., who still had some function in the memory structures that had been damaged naturally rather than surgically, Henry had virtually none on either side of his brain. Milner and Scoville wrote up the results in a paper that appeared in the Journal of Neurology, Neurosurgery, and Psychiatry. It’s no exaggeration to say that this article, which first established the crucial role of the medial temporal lobe in memory, changed the course of neuroscience.

As Milner and her colleagues found during later rounds of testing, Henry did retain some memories of his past, but they were almost invariably general, not specific. They were along the lines of “I remember that I went to X high school,” in contrast to “I remember that crazy time in French class when Jimmy let the hamster loose and Monsieur Picard screamed ‘sacre bleu!’ ” The former are what neuroscientists now call semantic memories; the latter are episodic memories, since they record specific episodes in our lives rather than generalities. Henry knew where he’d grown up and where he’d gone to high school. He knew that his mother and father used to take him on vacations along the Mohawk Trail, a scenic highway that cuts across the Berkshires in western Massachusetts. But he couldn’t remember a single specific event from one of those Mohawk Trail vacations, for example, or something unusual that happened in high school, or a gift he’d gotten on a particular birthday.

There were just two exceptions. In 1939, when Henry was thirteen, Gus and Lizzie bought him a ride in a small plane as a junior high school graduation present. This adventure was so profoundly exciting, it was as though it had burned itself into Henry’s memory too deeply for even surgery to cut it out. Decades after the operation, he could still recall and describe the flight—what it looked like, what it sounded like, how it felt—almost moment by moment, in detail. Henry also retained a vivid memory of the first time he ever smoked a cigarette, which happened when he was ten. Presumably, it was as unpleasant as the plane ride was thrilling.

Aside from these two events, the only memories he had were semantic. That applied not just to memories of his own life, but also to his general knowledge about the world, which is also part of semantic memory. You almost certainly know that Paris is located in France, but you probably don’t know when you first learned that fact. There’s no specific experience, no episode you can point to where the information first entered your head. Similarly, you probably also know where your parents grew up. You know what an orange tastes like. You know that the United States fought against Germany and Japan in World War II. But you probably don’t know exactly when or how you came by these bits of information.

Semantic and episodic memories are different, but they both share this feature: you can describe them in words. Other memories are impossible to articulate, since they don’t involve conscious thought. Riding a bicycle, hitting a tennis ball, driving a nail, and playing a musical instrument are all things you remember how to do after you’ve learned, but you can’t really explain what it feels like to do them. People sometimes call this sort of thing “muscle memory,” because it seems as though your muscles, not your brain, are doing the remembering.

Neuroscientists now call those two broad categories of memory declarative, which refers to things you can describe in words, and procedural or implicit, things you simply know or know how to do without being able to describe them (retrieving the words to construct a sentence is another example). Until Henry came along, nobody really knew whether procedural and declarative memories were formed or stored or retrieved from the same part of the brain, or different parts, or how the whole process worked.

Thanks to the purity of his memory loss, however, which was untainted by any accompanying mental illness or loss of other cognitive abilities—understanding speech, for example, or recognizing objects—H.M. became what Suzanne Corkin, the MIT neuroscientist who worked under Brenda Milner and went on to study Molaison for more than four decades, calls the “gold standard for the study of amnesia…the yardstick against which other amnesic patients were judged.” In the scientific literature, she writes, they were typically referred to as being “ ‘as bad as H.M.’ or ‘not as bad as H.M.’ ”

Over decades of careful study, Corkin, who died in the spring of 2016, either performed or directed hundreds of research studies to probe the tiniest nuances of Henry’s memory loss. Once a month or so, on average, starting in 1966 and continuing until the mid-2000s, Henry would be driven from Hartford up to MIT, where Corkin had settled after doing graduate work with Milner in Montreal. Corkin herself, one of her graduate students or postdocs, or one of dozens of independent scientists who worked with Henry over those decades would put him through a battery of tests. Many of the tests had been created just for him.

Over that time, Henry became more than just a subject. “He was a friend,” Corkin told me, sitting in her MIT office one afternoon. “And not just to me. He was a member of our lab family.” For the first few years after the operation, Henry continued to live with his parents—and then, when his father died, in 1966, with his mother. After she came down with dementia, he moved in with a relative and, finally, in 1980, into a nursing home near Hartford. After that, Corkin said, he had nobody to visit him or look after him. “We sort of filled in the gaps as best we could. We used to send him presents for Christmas and we’d send him pictures of our dogs and stuff like that.” When a health issue came up, Corkin had the nursing home call her. “I don’t do this with other patients,” she said. “If something happens with them, they go and see their doctor, but with Henry, I wanted to make sure that he was well taken care of and that his needs were met, medical and otherwise.” She meant this literally. The last time she visited Henry, in the fall of 2008, she asked his caregivers what he needed. White socks, they told her. So this eminent neuroscientist at one of the most prestigious universities in the world drove over to Costco, bought a pack of socks, and mailed them to Connecticut. She would never see Henry alive again.

The Perpetual Now

By Michael D. Lemonick