Authors: Luke Dittrich
What's true of individual brains is true of brain collections as well. With his Brain Observatory, Annese was setting out to create not the world's largest but the world's most useful collection of brains. Each specimen would, through a proprietary process developed by Annese, be preserved in histological and digital form, at an unprecedented, neuronal level of resolution. Unlike Brodmann's hand-drawn sketches, Annese's maps would be three-dimensional and fully scalable, allowing neuroscientists to zoom in from an overhead view of the hundred-billion-neuron forest all the way down to whatever intriguing thicket they liked. And though each brain is by definition unique, the idea was that as more and more brains came online, the commonalities and differences between them would become increasingly apparent, allowing, Annese hoped, for the eventual synthesis of the holy grail of any neuroanatomist: a modern, multidimensional atlas of the human mind, one that conclusively maps form to function. For the first time, we'd be able to meaningfully compare large numbers of brains, perhaps finally understanding why one brain might be less empathetic or better at calculus or more likely to develop Alzheimer's than another. The Brain Observatory promised to revolutionize our understanding of how these three-pound hunks of tissue inside our skulls do what they doâwhich means, of course, that it promised to revolutionize our understanding of ourselves.
And what could be a better cornerstone for the Brain Observatory, a better volume for Annese's collection, than the brain of Patient H.M.? The boxes filled with the cryogenic vials containing the slices of Henry's brain sat in their own freezers, to the left of the others, under lock and key. Precious cargo. San Diego is earthquake-prone, but there were backup generators and sensors that would automatically dial Annese's home and cellphone in the event of an emergency, so that wherever he was, he could jump into his Porsche, rush over, protect Henry.
Henry, just by being Henry, was helping bring Annese's larger ambitions closer to reality. People who'd read newspaper articles about Annese's work with Henry's brain had already called him up and made arrangements to donate their own. One of them, Bette Ferguson, a feisty ninety-one-year-old who was one of the original flying monkeys in
The Wizard of Oz,
would be dropping by the Brain Observatory soon to get her second set of MRI scans. Annese knew the publicity would continue, hoped it would continue to inspire donation. He had wanted to get the brain of the guy
Rain Man
was based on, but that didn't work out. Eventually he wanted to get somebody really big, a household name, Bill Clinton, someone like that.
But Henry's brain was more than just an attention-garnering curiosity. And it was more than just a proof of concept, something Annese could use to demonstrate to the world the power of his methods.
It was an objectâ2,401 objects nowâthat contained enduring mysteries still waiting to be solved.
The cutting was just the beginning.
Within a matter of months, Annese was planning to release a three-dimensional surface model of Henry's brain, built from the 2,401 high-resolution “block-face” images taken during the slicing. Those images captured the view of Henry's frozen, embedded brain just prior to each pass of the blade. This model would be at least ten times as detailed as anything one could possibly produce with an MRI machine and had the additional benefit of being derived from images of the actual brain rather than a computerized interpretation of it. And then, bit by bit, he planned to supplement that model with imagery of even greater resolution: A custom-built microscope scanner would digitize each of the mounted, stained slides at such a level of magnification that single neurons would be clearly visible. All of this, the resulting petabyte or two, would be accessible for free online, to researchers worldwide. Over the past fifty-five years of his life, Henry was hidden away while a select coterie of scientists gathered more data about him, his abilities and his deficits, than about any human in history. Now, after his death, Annese was poised to release Henry's brain into the wilds of the Internet, and the whole world would be able to reillumine that unprecedented volume of clinical data in the light of an unprecedented neuroanatomical map.
One of Annese's assistants poked her head into his office, told him that some more slides were ready for staining. A few minutes later, Annese held one of the fresh-dipped seven-by-five-inch slides up to the light, letting a purplish dye drip off the glass. The dye had adhered to the slide's cross section of pale, almost invisible brain tissue, darkening it, developing it like a photograph.
A cross section of brain looks a lot like an inkblot, a Rorschach, and this one at first glance gave the impression of the head of a vaguely sinister goat. But then Annese started guiding me through it.
“You can see here,” he said, indicating a spot where the tissue looked darker, the neurons more cramped, “where your grandfather pushed up his frontal lobes.”
We looked at another slide, and he pointed to an area that would have sat a little below and back from Henry's frontal lobes, a portion of the slide where no dye stuck, since there was no tissue for it to adhere to. It was a part of the lesion itself, the little bit of nothing that spawned everything. Though Annese didn't want to go into too much detailânot before his findings were officially publishedâhe told me, sotto voce, that he'd already discovered some surprising new things about what my grandfather destroyed in Henry's brain and what he spared. For years, memory researchers assumed that the hippocampal stump that remained in Henry's brain was completely atrophic and nonfunctioning. According to Annese, however, that didn't seem to be the case. The little that was left of Henry's hippocampus looked like it was in pretty good shape, actually.
According to Annese, this was the sort of revelation that could shake up the field of memory science yet again. In 1953, when my grandfather closed a door in Henry's mind, did he leave it open just a crack? Did this explain the surprising exceptions to Henry's amnesia? So much of our understanding of how memory works is based on our understanding of how Henry's memory
didn't
work. But have we been misunderstanding him, at least in part, all these years? These were the sorts of questions scientists would grapple with and argue over in the years to come as the Brain Observatory went online, as Henry's mind was preserved everywhere and nowhere at once, as his cells were counted and his final mysteries came to light.
Annese put the slide on a rack to dry, and I looked at it again, the blank spot near the middle, the hole you could see right through.
O
ne night, half past midnight, half-tipsy on pink champagne, I stood beside Jacopo Annese and watched him bring a drill down onto a man's exposed skull. The sound of high-rpm machinery filled my ears, the smell of bone dust wafted up to my nostrils, and with a little ecphoric jolt I was reminded of being in a dentist's office midfilling. I was wearing my best shoes, and I stepped back from the body to avoid the splatter. I hadn't expected to be there that night, doing what we were doing.
Earlier in the evening, I'd attended a fundraising cocktail party for Annese's new nonprofit, the Institute for Brain and Society. Annese had conceived of the institute as a sort of complement to the Brain Observatory, one that would engage the public through educational outreach programs and museum exhibits and maybe even a café and gift shop. The money generated by the nonprofit, he said, would then be cycled back into funding the research conducted at the observatory. The party took place at a fancy condominium near Balboa Park, and there were maybe a hundred people in attendance, mingling and munching on “brain-healthy” appetizers, lots of fish and folic acid. Just past the condo's entrance, in the front hallway, framed portraits of several of Jacopo's “donors”âthe men and women who had agreed to give him their brainsâhung on the wall. Some of the donors in the portraits had already passed away, but others, like the nonagenarian Bette Ferguson, were still alive. In fact, when I made my way past the portraits and into the central room of the party, I spotted her sitting in a corner, on a low bench by a window.
“Bette!”
She looked toward my voice, her eyes sort of unfocused.
“It's Luke,” I said, “the writer.”
“Luke!” She grabbed my hand. “Sit down, sit down.”
I'd met Ferguson two years earlier, during my first reporting trip to San Diego. Annese brought me along to her apartment while he conducted one of his periodic interviews with her. A key aspect of Annese's work, and his collection, was the accumulation of as much premortem data about his donors as possible. This data ranged from childhood stories to IQ tests, from MRI scans to the chronicles of their marriages and divorces. So during that first visit I learned a variety of things about Ferguson's past and present. I learned that she collected angel figurines, that she'd been married five times, and that she'd grown up near Los Angeles, where her mother worked for a while as a waitress in a café on the Paramount lot. I learned that when she was fourteen, she auditioned for, and got, a part as one of the flying monkeys in
The Wizard of Oz.
I learned that she was proudly Irish, though she'd never been to Ireland. I learned that she wasn't religious, strictly speaking, but that she believed in something beyond life. When she spoke of death, she didn't use that word. “Graduation” is what she called it.
We'd seen each other a few other times since then, once in Annese's laboratory, where I attended one of her MRI scans, and twice more when she took me to her favorite BBQ joint, a place called Phil's. She was friends with Phil, and everyone there knew her and would whisk her right to a table no matter how long the line was outside.
The last time we'd spoken was on the telephone, a few weeks before the party. She asked how my daughter, Anwyn, was doing, and I told her that she'd just played a munchkin in her school's production of
The Wizard of Oz
and that she'd been excited when I bragged that I was acquainted with one of the real-life flying monkeys. Ferguson suggested I buy Anwyn a kids' book written by Rush Limbaugh called
Rush Revere and the Brave Pilgrims,
and I told her I'd think about it. At the end of the call, I mentioned I might be coming to San Diego for Annese's party, and she said she was looking forward to being there herself, if she hadn't graduated beforehand.
At the party it was clear that her eyes had gotten bad and that people had become walking blurs. Her mind, though, seemed as sharp as ever. When a large guy stood nearby shoveling canapés into his mouth, Ferguson leaned toward me and said in a too-loud voice, “Now, there's a fat man right over there, right?” then laughed, aware she was being inappropriate and clearly not giving a damn.
While she and I caught up, sipping pink champagne, Annese was busy making the rounds, talking to as many attendees as possible, trying to convince them to donate either their money or their brains. At about ten-thirty
P.M.
, he came over and pulled me aside.
“Something's come up,” he said, and explained that one of his donors had died, that the body was about to be delivered to his lab, and that he was going to have to do the harvesting that night. He didn't want to leave the party early, since he'd been planning it for months, but there wasn't any way around it: The brain needed to be removed, stat.
Then a thought occurred to him.
“Do you want to come along?”
When we arrived at the Brain Observatory that night, Jack was already there waiting for us. I suppose you could say someone else was waiting for us, too, though he was lying in a red-zippered bag on a stretcher in the back of Jack's minivan.
Jack was big and friendly, jeans and a Padres jersey, a warm smile and a lazy eye. This was his job, delivering bodies. To the coroner or the medical examiner or the funeral parlor or wherever. His minivan was beige and unremarkable, had no logo or anything else on the outside that would give you a hint as to its contents. He made sure the air-conditioning was always in tip-top shape. Annese opened a rear door to the lab and helped Jack negotiate a tight corner with the stretcher. They rolled the body down a hallway, then turned left into the MRI room. A clock on the wall said it was eleven
P.M.
Annese asked Jack when he'd picked up the body from the hospice, and Jack said he'd had him for about an hour. He'd died that morning at about ten
A.M.
, so that meant he was in cold storage for about twelve hours before Jack picked him up, not frozen but close to it, and had only had an hour to thaw. If the body was too cold it could interfere with the MRI results. They unzipped the red canvas body bag. Inside, a man was swaddled from head to toe in a baby-blue sheet. They each gripped a handful of sheet and lifted him off of Jack's stretcher and onto a second stretcher that was built entirely out of plastic and nonferrous metals so it could be used inside the MRI machine. Annese placed a hand gently on the forehead through the sheet, like a parent taking a child's temperature, and decided that he was warm enough for the scanning.
The MRI room was actually two rooms, the first a sort of control center, with the computer used to operate the machine, and the second containing the machine itself. Annese wheeled the stretcher into the second room and prepared to insert it, body and all, into the hollow center of the machine. Jack said he had to leave but that he'd be back to collect the body later.
“Just let me know when,” he said. “â'Cause I know Luke wants to hit the last call. I'll get you guys a lap dance!”
Annese laughed.
“You have any other cases tonight?” he asked Jack.
“I've got two. Actually, I'm sorry, I've got three. One in Tri-City, up in Oceanside, one in Chula Vista, and one in San Diego. But like I said, whenever I know that I've got a case for you, I try to make sure I set X amount of time aside, so that way when you call I'm ready to go.”
After Jack left, it took Annese another five minutes or so to finish prepping for the scan. He had to position the man's head as close as possible to the dead center of the machine, where the magnetic field was strongest. During the premortem scans, the man could adjust himself somewhat while lying in the machine, shifting up and down or left and right a bit if Annese needed him to. Now Annese had to make sure he was positioned exactly right from the start.
Eventually he came back into the first room, sat down in front of the computer, and began the scan. A loud, abrasive, rhythmic pulse began to sound. This was normal. An MRI machine works in two stages. First the magnet, which was about five thousand times more powerful than Earth's magnetic field, halted the normally chaotic spins of the hydrogen atoms that were the primary ingredient of the man's body, lining them up so that they were locked into place, their protons pointing either in the direction of his head or his toes. The second stage was what caused the loud pulsing sound: A precisely tuned radio signal was bombarding the atoms, knocking the protons briefly out of polarity. Each time the radio signal turned off and the pulse subsided, the protons would snap back into their magnetic formation, like springs that had just been released. This would create a tiny burst of energy, and it was this energy that was becoming visible to Annese now, producing a ghostly, Shroud of Turinâesque image on his computer screen.
The scan took about an hour to complete, the machine making its way slice by virtual slice through the man's skull, mapping its contents. Tissue tends to heat up after prolonged periods in an MRI machine, which means that prolonged periods can be challenging for living subjects, even if lying in a tight tube doesn't bring on claustrophobia, as it often does. For this final scan, however, Annese didn't need to worry about the man's comfort, so he didn't rush things. I sat on a couch and tried to ignore the ornery pulse of the machine.
When the scan finished, Annese prepared for the harvesting. He grabbed a roll of plastic sheeting from somewhere, and some duct tape, and we headed down a hallway, passing through the book-and-computer-filled front office of the Brain Observatory, through the airtight biosafety door, and into the laboratory itself. The lab was colder than the surrounding rooms and had a vague antiseptic, chemical odor. It was clearly an active workspace, somewhat cluttered, with a lived-in feel, and in a dim, dark corner of the lab I could hear the gentle whir of a machine that had been left to do its work overnight, slowly slicing a frozen brain into thousands of infinitesimally thin sections. On a granite tabletop by a sink there were a variety of items that had been left out to dry, mostly laboratory beakers and pipettes and test tubes but also a couple of martini glasses and one large glass container with a taped-on label that read,
ORCA CEREBELLUM
. Annese had an ongoing arrangement with SeaWorld.
Annese unfurled the plastic sheeting and taped it in place so that it covered an approximately twelve-by-eight-foot area between two rows of cabinets. Behind him, against the far wall of the lab, there was the long bank of glass-fronted refrigerators that contained most of his growing collection of brains, including the remaining slices of Henry's, the slices that hadn't yet been mounted on slides. There was a bit of a backlog, too many brains, too few histological technicians, too much mounting to be done.
A student assistant of Annese's arrived at about midnight, and we returned to the MRI room to retrieve the man inside. Annese and the assistant carefully lifted him from the MRI stretcher back onto the more basic one that he'd arrived on, then wheeled him off to the lab. They stopped in the middle of the plastic-protected area, and Annese took some of the same tape he'd used to affix the plastic sheeting and now used it to bind the wheels of the stretcher so that it would not move back and forth during the harvesting. The task before him was one that required an unusual combination of strength and finesse, in that the brain is a delicate organ, easy to damage, but one that is shielded by the body's most formidable fortress.
Annese armored up. He covered his shoes with stretchable booties, his torso with a hospital smock, his face with a rounded, clear plastic visor. On his hands, rubber gloves; up his nostrils, two wads of cotton. Brains contain so much: memories, ideas, emotions, perceptions, aspirations, desires. They also contain pathogens, dangerous proteins and viruses and bacteria, some found nowhere else in the body. It's important to protect yourself.
He rolled the light blue sheet that covered the man's face down a little ways, to a point where his bushy eyebrows were visible. He had a formidable crop of white hair, unthinned by time. It sprouted densely from his ears as well, in that familiar old-man way. The skin of his forehead and his temples looked waxen and yellowish, thicker and heavier than living skin.
Annese picked up a scalpel, then remembered something and put it down. He walked to a nearby computer, brought it out of sleep, and clicked and typed for a few moments. Mozart's Twenty-fifth Symphony announced itself with a delicate flurry of strings, tinkling out of some speakers positioned in various spots around the laboratory. He always works with music, and music was itself once his work: As a young student abroad, he would play covers of old pop songs on his acoustic guitar in London subway stations, busking for change. Back then, he'd aimed his songs at the audience, trying to read them, their preferences. He did the same thing now, trying to match his own mood with the sensibilities of the person lying before him. A few months before, one of Annese's best friends had diedâRoberto, the owner of an Italian restaurant in San Diego. The two had known each other for only a few years, but they'd become close, bonding over their common heritage and their shared passion for food and wine. Roberto had signed up to be one of Annese's brain donors, and when he died Annese did the harvesting. It was a strangely intimate evening, those last hours with Roberto. He was all alone, hadn't wanted an assistant.
“It feels like a Mozart night,” he said now, returning to the stretcher.
He picked up the scalpel and bent down, using his fingers to part some of the thick white hair, finding the skin below. He placed the point of the scalpel at a spot just where the top of the cartilage of the ear connects to the side of the head, then began to cut, moving upward slowly in an arc, pausing every few inches to part the hair again if he needed a better view. He moved the scalpel up one side of the head, crested the summit, then moved it down the other side, stopping at the top of the other ear. He bent low again, using one hand to pull the hair forward a bit, making the incision visible. There was very little blood. Annese inserted the scalpel underneath the incision, pointing it in the direction of the forehead, and carefully slid it back and forth, severing the binding tissue between the skull and his scalp. Then he put the scalpel down and used his thumbs and fingers to gently roll the scalp down off of his skull. When he finished, the top of the skull was completely exposed. The white towel that had covered all of the man's face had shifted lower and was now just concealing his mouth. His eyes were still invisible, though, since the front portion of his scalp had been rolled down over them.