As for Karl Pribram, he left the Institute of Living in 1957 and transferred to Stanford University, where he received a joint professorship in the departments of psychology and psychiatry. Pribram’s protégé, Mishkin, left the Institute of Living for the National Institute of Mental Health, in Bethesda, Maryland, where he established his own primate lab, one of the largest in the country. At the NIMH, Mishkin continued to focus on trying to document H.M.-like amnesia in monkeys. He would lesion the monkeys’ medial temporal lobes, then run them through a series of tests, then sacrifice them to precisely measure the dimensions of their lesions.
Lesioning, testing, sacrificing. Again and again.
It took two decades before he found what he was looking for.
—
To get to Mishkin’s office at the NIMH, I had to pass through multiple levels of security, first showing my passport to a guard behind a glass-shielded desk, then passing through a metal detector manned by another guard, then discussing the reasons for my visit with another guard before I was issued a temporary visitor’s pass on a lanyard to hang around my neck. Mishkin’s office was almost a quarter mile from the entrance to the sprawling NIMH campus, and as I walked to it I thought of a book I’d loved as a kid, Mrs. Frisby and the Rats of NIMH, a novel about a group of laboratory animals that are granted extraordinary intelligence, which they use to escape from their cages so they can live in their own world rather than “on the edge of somebody else’s, like fleas on a dog’s back.”
There was another security guard in the lobby of Mishkin’s building, and I showed him my visitor’s pass and my driver’s license and told him I had an appointment. He got on the phone.
“Dr. Mishkin?”
A minute or so later, Mishkin emerged. He looked much the same as the latest picture I’d seen of him, shaking hands with President Obama in 2010 during the ceremonial presentation of the National Medal of Science. During the event, Obama had praised Mishkin for his “contributions to understanding the neural basis of perception and memory in primates.” Mishkin, who had a firm handshake and an interesting, interested face, with bright eyes and a wide smile, led me down a few hallways and through a heavy door into his office space.
“Did all of this security happen after 9/11?” I asked.
“No,” he said. “It happened after I opened my lab.”
Animal rights activists, he explained. All that lesioning, testing, and sacrificing made him and the rest of his laboratory staff, not to mention the lab itself, a target for those who thought humans should keep their hands off their nearest animal kin.
Mishkin wanted me to know that he hadn’t always worked with animals. The first study he ever published, in 1950 while he was still at McGill, was a study of lobotomy patients. “But it was nonsense,” he said. “We were using inkblots to study schizophrenic patients who had lesions to their brains. My god. Inkblots! It was pretty incredible that we were doing things like that. And we knew that it was stupid. But that’s what was being done at the time. I actually refused to continue, it was so silly.” The basic problem, as he saw it, was that nobody knew the functions of the structures they were destroying. Neurosurgeons may have thought they knew, but neurosurgeons were not scientists, even if they sometimes pretended to be. Mishkin knew enough to at least know what he didn’t know. He knew it was a terrible thing to mutilate a human brain on the basis of nothing more than a glorified hunch. Animals were another matter. Whatever you thought about the ethics or morals of animal experimentation, the rationale for it boiled down to a simple statement, one you either agreed or disagreed with: Better them than us.
Mishkin’s office was large and cluttered. There was a phrenological skull on one shelf, next to an assortment of model brains. I noticed that along with the neuro stuff there were also a number of items related to astronomy, including a beautiful framed photograph of an earthrise as seen from the surface of the moon. Mishkin told me that astronomy had always been an avid but amateur interest of his. I took a seat across from him. There was a small framed H. G. Wells quote on the wall to my right: NO PASSION IN THE WORLD, NO LOVE OR HATE, IS EQUAL TO THE PASSION TO ALTER SOMEONE ELSE’S DRAFT. He saw I was staring at it, then pointed out the joke to me: One of the commas, the one after HATE, had been penciled in.
“I added that,” he said.
That’s science, in a way. Each new generation takes the drafts created by the men and women who came before it and revises them, sometimes making small tweaks, adding commas or dropping clauses, sometimes making more drastic changes, discarding chapters altogether or writing entirely new ones. They’re all editors, and all of them, the good ones at least, have to be passionate about altering someone else’s draft if they’re ever going to make any progress.
In Mishkin’s career, one of his most significant edits revised our understanding of monkey amnesia and began to bring it in line with our understanding of the human amnesia suffered by Patient H.M. The discovery hugely strengthened the scientific community’s confidence in its understanding of memory mechanisms. He made the discovery here, at the NIMH, with another series of macaques. After replicating H.M.’s operation by lesioning their medial temporal lobes bilaterally, removing structures including the majority of their hippocampi and amygdalae, he ran the macaques through a new variation of the delayed-response tests that, for decades, had been coming up empty. This variation was called a delayed-nonmatching-to-sample task, and it differed from previous tasks in an important way. Now, instead of Mishkin requiring the monkeys to remember which object concealed food, he concealed the food under an entirely new object each time. So to earn the peanut, the monkey would have to remember which object he had chosen before, then choose the other one. This test protocol was designed to overcome the basic problem with the previous tests, which was the suspicion that a monkey could learn to associate a particular object with a positive reward in an instinctual way without employing what we think of as memory. By contrast, in this new task, as Mishkin wrote, “because the food is always associated with a novel object, the ability to link a specific object to a reward has no bearing on performance. The reward serves merely as an incentive; the test measures recognition memory specifically.”
And it worked. Meaning that after the lesioning, whatever memory systems enabled normal monkeys to complete the task previously no longer worked. “Their scores fell nearly to chance,” Mishkin wrote. “It seemed, then, that we had created a true memory loss.”
Things had come full circle. Primate research had inspired my grandfather to create Patient H.M., and Patient H.M. had inspired this new round of primate research, which after years of false starts finally began to validate and reinforce the discoveries made about Patient H.M. In the never-complete manuscript that is our knowledge of self, Henry Molaison was acquiring an ever more central role.
Mishkin demonstrated the historic test to me at his desk, using my cellphone as a standin for a peanut.
—
I waited behind the barrier and watched as the guys corralled the bull. Using whoops and slaps, they guided it through a door someone had opened in the ring, into a narrow pen. It was done for the day. Nobody else wanted to take another turn in the ring with it. This was partly because they’d all gone a few rounds already, but it was also because of what had just happened to me, and what that meant.
Imagine a bullring as an experiment.
The bull is the test subject, and its task is to choose between the bullfighter and the bullfighter’s capote. If it chooses correctly, it will receive the reward of satiated rage, horns against flesh. If it chooses incorrectly, it will receive nothing but an impotent thrust against a billow of air. (Although, of course, during a real bullfight, not just a practice session, if it chooses incorrectly it dies. But it doesn’t know that, so that fact is irrelevant to how the experiment plays out.) Today, during the first part of the experiment, the bull chose wrong, over and over again. It charged the capote, the bigger target, which swayed and shimmied enticing
ly.
Once, twice, three times. A dozen, even. Each time it came up empty.
Then me.
The bull turned and saw that dual spectacle, the flagpole and the flag, and was forced once more to make a choice. It charged. Straight at me, straight for me, straight into me. The flag went flying, and so did I. The bull finally made the right choice.
Now again, I’m a lousy bullfighter. I don’t stand as still as I should and I don’t make the capote undulate as appetizingly as I could. But even if it weren’t me in that ring, even if it were Mauro or one of the other students, someone who actually knew how to torear, eventually the bull would have wised up. This is a known fact in the bullfighting community: On any given afternoon, you can only train with a given bull for a certain number of hours before it is, in a sense, spoiled. Even these broad-shouldered brutes adapt to the task at hand, learn to ignore the capote, and target the man.
This is basically a variant of Mishkin’s delayed-nonmatching-to-sample task. The bull isn’t being tasked with learning to associate a certain choice with a positive outcome. Instead it’s being tasked to do something that requires a more complex form of memory: It has to remember that a certain choice it made earlier was unsuccessful, and that it had therefore better make the opposite choice. As enticing as the capote is, the bull has to go against all instinct, girded and guided only by memory, and choose the bullfighter instead.
It did. It chose me. It found success. And once it did so and was rewarded with the satisfaction of trampling me in the dirt, the experiment had effectively come to an end. Because now, were it to choose again, its choice would be simpler. Learning to hit the bullfighter is only difficult until it has done so. Then it’s easy, just a matter of strengthening the association between the choice it made and the reward it received. That sort of association doesn’t require any meaningful form of complex memory any more than does the drool from a Russian dog hearing a dinner bell.
So the bull remembered. That much seems clear. It had access to the events of its past and made a decision based on it.
But here’s another question, one harder to answer:
Does the bull remember me in the same way that I remember the bull?
Even now, more than a decade later, I can see it thundering toward me. I can remember the heat of the sun, the sound of the hooves, the feel of the impact. I can remember a scene, incomplete but not insubstantial.
This ability to create scenes from our pasts may or may not be uniquely human. And we may never know for sure. Elisabeth Murray, one of Mishkin’s younger colleagues at NIMH, wrote an article a few years ago, the title of which sums up the problem: “What, If Anything, Can Monkeys Tell Us About Human Amnesia When They Can’t Say Anything at All?” You could substitute mice or rats or sea slugs or any of the other animals we’ve tried to substitute for ourselves in memory studies. Eventually, any translational research project—that is, one that attempts to translate our understanding of nonhuman memory systems to human ones—crashes into a wall of unreliable interpretation.
Even if that bull could call me to mind, what then? What could it do with that scene? Could it play with it, muse over it, find the connections between it and other scenes? That’s what we do constantly. I call that memory up, that charging becerro, and other memories sprout from it like spokes from a hub. I think of a series of pictures from an old family album. Black-and-white. My grandfather again, leaning against a wall, a deeply tanned man beside him. In the crook of my grandfather’s arm: a capote. He tried bullfighting, too, during a trip to Spain to attend a medical conference. There are more pictures following it: He’s in the bullring, the cape unfurled, the bull charging. I don’t know whether he was any better than me, or whether his bull ultimately connected, but he was certainly better dressed. He was wearing a good suit, the jacket off, the shirt still tucked in. He didn’t look as afraid as I remember myself being. He was nothing if not daring. Another spoke of the wheel: I remember reading the transcript from a panel discussion on medical ethics. The discussion took place in the seventies, and my grandfather was a panelist. So was Karl Pribram, incidentally, and a man named José Delgado, a onetime colleague of both of theirs at Yale. Delgado is famous for an experiment he did with bulls; that’s why this leaps to mind. In his experiment, Delgado implanted a device into a bull’s brain. It was a remote-controlled device, and he claimed that when activated it would remove all of a bull’s aggression instantly. He demonstrated it in a bullring sometime in the 1960s and invited the press. You can find a clip on YouTube. The bull charges, and Delgado waits until the last possible minute, at which point he presses a button on the remote control and the bull comes to a shuddering halt, looking suddenly confused and uncertain. Delgado liked demonstrations like this and liked saying the most outlandish things. During the symposium, he boasted that the neural implants he was developing promised to revolutionize evolution itself: “The question,” Delgado said, “rather than, ‘What is man?’ should be ‘What kind of man are we going to construct?’ ”
My grandfather responded with uncharacteristic humility.
“With all due respect to Dr. Delgado,” he said, “I work almost wholly on humans, and we are more aware of the disastrous effects that sometimes occur in neurosurgery.”
—
Mishkin told me he had to leave soon to attend a talk by a colleague. The talk was called “FMRI Correlation Maps from Spontaneous Recordings of Single Neurons,” and he tried to explain to me what that meant, but I got a little lost. Earlier, when we were talking about amnesia, he’d complained that his own memory was beginning to fade and that he suffered from anomia, an inability to recall the names of everyday objects. I hadn’t noticed. Instead speaking with Mishkin reminded me of something Brenda Milner had told me when I asked what accounted for the enduring sharpness of her own remarkable brain. “Curiosity,” she said. Every day she woke up with a genuine passion to discover something new, and that’s what kept her mind so quick.
I asked Mishkin if he felt that same driving, undying curiosity. He smiled, nodded.
“It is a really interesting adventure, what we are into,” he said. “Trying to discover how the brain works! How long is it now? Over sixty years. There’s nothing more interesting.”
He laughed and pointed at his earthrise poster.
“Well, except the cosmos,” he said. “The two great mysteries: the cosmos and the brain!”
TWENTY-TWO
INTERPRETING THE STARS
In a quiet conference room in a busy laboratory complex in San Diego, I placed the tip of a ballpoint pen on a piece of paper. A young German research psychologist named Ruth Klaming was at my side, a stopwatch in her hand, telling me what to do. A small metal stand hid my hand from my direct view, though I could see it in a mirror that was propped on the table in front of me. The piece of paper had a single large five-pointed star printed on it. The star had a double outline, and there was approximately a centimeter between the inner line and the outer one. My task, as Ruth explained it, was to trace a line all the way around the star, starting at the top and moving counterclockwise, between the inner and outer borders, trying not to touch either. Ruth pressed start on her stopwatch and I began. I looked at my hand in the mirror and moved it, one short tick, and watched as the pen in the mirror moved in entirely the wrong direction, toward the outer border. Then I stopped. I prepared to move the pen again but when I started and saw the line moving once again in the wrong direction, this time straying outside of the star, my hand froze. I sat there gripping the pen, staring at the mirror, trying to work out the puzzle. Obviously the problem was the mirror. I needed to move my hand in the opposite direction to what it was telling me was the right direction. In other words, if the image in the mirror indicated I should move the pen down toward me, in reality I needed to move the pen away from me. I steeled myself—it was almost physically uncomfortable to go against the visual cues provided by the mirror—and pulled the pen shakily down and to the right for a
n inch or two until it reached the star’s first juncture, its second vertex. Then I froze again, trying to figure out which way to move my hand next. I got it wrong again, breaching the border, before recovering and moving slowly down toward the third point. This process repeated itself for the rest of the journey around the star until I reached the spot where I’d begun. Ruth pressed a button on the stopwatch.
She told me my time, not even bothering to pretend that my score was good. Then she removed the paper and replaced it with a fresh one, and I started over. Four more pieces of paper, four more stars. My times improved slightly with each one, until by the fifth star I felt almost comfortable, almost confident, almost able to overcome the odd disjoint between what I saw and what I felt.
Ruth gathered my papers and filed them in a binder, then placed a fresh sheet in the device. She left the room for a minute and I moved to another seat at the table. When Ruth returned she was accompanied by a man I’ll call Jason, and Jason took my former seat. He was wearing baggy jeans and a red T-shirt with the lightning bolt symbol of the Flash printed on it. Around his waist he had a fanny pack, which was where he kept his smartphone along with a modded Game Boy filled with classic Nintendo games. Jason was in his late twenties and looked younger than that, with a wispy mustache and a hairstyle verging on mulletish.
Ruth explained the test to Jason and gave him a pen, and he placed the point at the top of the star. Then she clicked the stopwatch and he began. His first try was faster than mine—and his second even faster. He improved steadily until by the fifth try he’d made it around the star blazingly fast. Ruth congratulated him, gathered up all the stars, and filed them away in her binder.
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