On the return trip from Logan, we stopped at Starbucks to fortify ourselves with cups of espresso, and then headed to Frosch’s Mass General office. The autopsy would be an indelible learning experience for all of us. Henry’s body was safely stored in a large refrigerator in the basement of the hospital’s Warren Building. We gave Matthew a CD with some of the beautifully clear images André had obtained the night before. These pictures gave Matthew guideposts for the removal process. He was concerned about the site of Henry’s surgery: scarring might have caused the brain to stick to its cover, the dura, the tough layer between the brain and the skull. It would be difficult to remove the brain without leaving fragments behind. Losing tissue from the surgery site would hinder our ability to provide definitive evidence of the extent of tissue missing from Henry’s brain. As Matthew looked through the scans, he was reassured to see that a good amount of fluid remained between the brain and the dura in that region. He printed several images to use as a reference in the autopsy room.
Down in the Warren basement, the senior pathology technician wheeled Henry into the autopsy room. Matthew, Jacopo, and the medical student joined him, along with a photographer from the Pathology Department who would document the procedure. So as not to get in the way, I stayed in the “clean room” next door, behind a huge glass window through which I could watch the delicate procedure unfold. I stood on a chair, eager to get the best possible view.
Matthew first made a shallow cut across the top of Henry’s head, from behind one ear to behind the other. He then peeled back the scalp in both directions to expose the skull. At the front of the skull, they could see the faint outlines of the two burr holes that Scoville had drilled decades ago, just above the ridges of Henry’s eyebrows. These plugged holes had healed well, so Matthew was able to cut around them. The next task was to remove the top of the skull, which is the trickiest part because the dura tends to stick to the surface of the skull, especially in older people. The technician made the first pass, using an electric saw to cut all the way around the head at one level, going only partway through the bone. Matthew, a highly experienced neuropathologist, deftly completed the cut without nicking the brain. He then used a chisel to pry off the skull. To our relief, it lifted off smoothly. Although Matthew seemed to proceed with complete confidence, he later admitted that he had deliberately turned his back to the window so that I would not see how much he was sweating.
Matthew pulled back the dura, starting at the frontal lobes. He next lifted the frontal lobes to loosen them from the skull, severed the optic nerves to disconnect the brain from the eyes, and cut the carotid arteries to detach the brain from the circulatory system. The brain was now freed enough from its moorings that he could move it from side to side to view the site of the surgery on either side. He noticed areas where the dura was stuck to the brain, particularly on the right side. Taking a fresh scalpel, he carefully cut the dura from these sections. He then worked to free the back of the brain, a job that was facilitated by the shrinkage of Henry’s cerebellum, caused by Dilantin. Matthew was now able to lift the intact brain out of the skull and place it in a large metal bowl.
At one point during the autopsy, I had left to call Brenda Milner who, at age ninety, was still working at McGill. I told her Henry had died; it was not unexpected news, and she accepted it with equanimity. I asked her not to tell anyone yet, as I wanted the autopsy to be completed before we announced Henry’s death to the world and started fielding calls and emails from the press and the scientific community. When the brain was out and intact, I called Milner again to report our success. Seeing Henry’s precious brain in the safety of the metal bowl was one of the most memorable and satisfying moments of my life. Our planning for this day had evolved over years, and we pulled it off without a hitch. Those of us who witnessed it were elated and smiling; I raised my hands over my head and applauded Matthew.
Matthew transferred the brain into the clean room by passing it through a refrigerator that had a door in each room. The entire neuropathology staff joined us in the clean room, and we all took a good look at the brain while the photographer snapped shots from all angles. Matthew then tied a thread around the basilar artery and secured the thread to the handle of a bucket full of formalin, thus allowing the brain to float in the solution without sinking to the bottom and becoming distorted. The solution would change the brain from its soft tofu-like consistency to something more firm like clay. A few hours later, Matthew transferred the brain to a special formaldehyde solution. He had bought the concentrated paraformaldehyde in advance, stored it in his cold room, and made a fresh bucket’s worth of fixative that morning.
After taking Matthew and Jacopo to lunch, it was time to let the world know of Henry’s death. During scanning the night before, I sat in the control room and typed out his obituary on my laptop. It was the first opportunity I had had to stop and reflect on Henry’s death, and it was also a chance to sum up briefly his enormous contributions to the science of memory. I drove to my office at MIT and emailed the obituary to faculty members in my department, to former lab members who had worked with Henry, and to Larry Altman, a veteran medical reporter at the New York Times. He passed it along to reporter Benedict J. Carey, who wrote an elegant obituary that appeared on the front page of the newspaper two days later, December 5, 2008. The article brought the attention of the wider public to this case so well known in the world of neuroscience. For the first time, Henry’s name was made public, and with the conservator’s permission, we announced to the world that “the amnesic patient, H.M.,” was Henry Gustave Molaison.2
Ten weeks later, in February 2009, Jacopo returned to Boston, bringing a custom-made Plexiglas chamber that would hold the preserved brain during a new round of imaging outside the body, ex vivo imaging. The Martinos imaging team first used the same three Tesla scanners they had used the night Henry died. This set of scans would provide a bridge between the geometry of the brain as it was in life with the final form it would take after being cut into ultrathin slices. The brain tissue could be further stretched or reshaped when sliced and placed onto glass slides. The MRI imaging data would allow us to measure and correct any deformities in the brain slides so they could be mapped back to the original architecture of Henry’s brain.
In addition, we had the opportunity to image the brain in a scanner with a seven Tesla magnet—one of the strongest magnets currently used with humans. It would provide a more accurate and detailed picture of the human brain than most researchers have ever seen. We did not put Henry in this scanner the night he died because his brain retained two metal clips used to tie off blood vessels in his operation, and we feared that they would heat up in the powerful scanner, creating further damage to his brain. Matthew removed the clips at the autopsy, so they were no longer a concern in the preserved brain. Jacopo had worried that the heat generated by the seven Tesla magnet could harm Henry’s brain, even in the absence of the clips. To reassure him, Allison had run trials with other brain tissue and estimated that the tissue would not heat up more than about three degrees, which was perfectly safe.
The seven Tesla magnet had a smaller head coil (the opening for the head) than the three Tesla. A technical challenge, therefore, was to craft a chamber that was small enough to fit in the head coil but large enough to hold Henry’s brain wrapped in formaldehyde-soaked cotton for protection. The chamber that Jacopo brought from San Diego was the right size, but the cotton surrounding Henry’s brain collected air bubbles. The trapped bubbles turned out to be a technical problem in the ex vivo images because the bubbles appeared larger than their real physical size and obscured the adjacent brain tissue. Unfortunately, these artificial blobs occurred in some interesting temporal-lobe regions.
After three separate scanning sessions over a long weekend, the imaging team had finally gleaned all it could from Henry’s brain, and it was time for it to travel to the University of California, San Diego, for cutting. On February 16, I met Jacopo at the Martinos Center, where
he was waiting in the vestibule guarding a cooler that contained Henry’s brain in its ice-encased chamber. A PBS film crew joined us to document our journey from Mass General to the door of the plane. We all climbed in a van with the producer in the front passenger seat, her assistant driving, and the cameraman in the middle seat facing backward so he could film Jacopo and me in the backseat—the cooler tucked snugly between us for protection.
When the van pulled up to the curb at Logan Airport, a welcoming committee was on hand—representatives from the Transportation Security Administration and JetBlue Airways, and the Director of Communications at Logan. I knew it was critical to pave the way for this unusual piece of carry-on luggage, so a month earlier, in a letter to the Customer Support and Quality Improvement Manager in the US Department of Homeland Security at Logan, I had requested help in transporting a human brain from Boston to San Diego. I explained how the brain would be packaged, that Jacopo would accompany it on the flight, and that upon landing he would take it to his laboratory at the university. The chair of Jacopo’s department also wrote a letter, confirming that Jacopo was a faculty member in his department and underscoring the extreme importance of the mission. Walking through the airport, we felt like celebrities: the film crew tracked our path, and people stared, wondering who we were and why we were being filmed. At the security checkpoint, a uniformed woman approached us and gave us the welcome news that she would carry the cooler around to the other side, so as not to expose the brain to radiation. Relieved, we passed through security in the normal manner and retrieved the cooler.
When it was time to board, Jacopo and I enacted a formal exchange for the camera. I carried the cooler to the door of the gate and placed it on the ground. We smiled at each other and hugged; he then picked up the cooler and walked down the ramp, stopping once to turn around and wave. At face value, Jacopo was just a scientist carrying a cooler with a brain that had been fixed in formaldehyde. But what he was carrying remained precious to me. I felt sad to see Henry’s brain go—it was my last goodbye to him.
As I left the gate with the PBS crew, I looked out at the plane. Henry’s most memorable experience from his childhood was that half-hour plane ride over Hartford. If only he knew that his last trip would be a twenty-five-hundred-mile flight in a big jet, he would have been ecstatic. The moment had an air of finality about it.
On December 2, 2009, a year after Henry’s death, I stood in a laboratory at the University of California, San Diego, where Jacopo was preparing to cut Henry’s brain into slices as thin as a strand of human hair—seventy microns. Normally, brains used in research are cut into large sections or slabs and then sliced thin enough for the tissue to be viewed under a microscope. Henry’s brain would be cut whole, from front to back, with the goal of collecting full vertical planes through the brain, rather than isolated pieces. The brain had been immersed in a solution of formaldehyde and sugar. The sugar soaked into the brain tissue and to prevent ice crystals from forming when the brain was frozen in preparation for the cutting. Before freezing, it was placed in a mold filled with gelatin, which would help this precious organ hold its shape. It was important to maintain a delicate temperature balance throughout the cutting—keeping the brain cold enough that the blade could slice the tissue cleanly, but not so cold that the tissue would shatter.
Everyone in the lab was excited and anxious as the process began. During the cutting, which lasted fifty-three hours, visitors appeared from time to time. Benedict Carey from the New York Times flew out to capture this seminal moment in memory research. Jacopo had also invited several luminaries at his university to view the event, including the famed neurologist Vilayanur S. Ramachandran, neurophilosophers Patricia and Paul Churchland, and eminent neuroscientist Larry Squire. Because the cutting went on endlessly, the conference room was decked out with treats for the lab members and visitors to enjoy—platters of food and a delicious Italian cake. Jacopo had hired a film crew to document the entire procedure. They positioned cameras in the cutting room to stream the events live on the Web, and over the course of three days, 400,000 people visited the site to witness this historic undertaking.
For the cutting, the brain, embedded in its block of frozen gelatin, was secured on an electronic device, a microtome, which acted like an exceedingly precise meat slicer. To keep the brain cool, technicians pumped liquid ethanol through a tube into the surrounding spaces. Jacopo, wearing black gloves, sat in front of the microtome. Each pass of the blade over the block of ice revealed a delicate roll of brain tissue and gelatin, which he gently wiped up with a large, stiff paintbrush and placed in a well in a partitioned container that resembled an ice-cube tray, filled with solution. The front of Henry’s brain faced upward, and a sixteen-megapixel camera mounted above captured and numbered each surface before it was cut. Each slice was placed in a well with the corresponding number. The cutting began at the front of the brain and proceeded back—from the frontal pole to the occipital pole. As exciting as the project itself was, the painstaking work of cutting and securing thousands of brain slices was monotonous. Still, the lack of drama meant that everything was going according to plan.
As of December 2012, Henry’s intact brain has been examined by the neuropathologist at Mass General, scanned by investigators in the Mass. General Martinos Center, and cut into seventy-micron slices at the University of California, San Diego. My colleagues and I continue to advance the coordination of these different studies—both to allow for a final diagnostic neuropathological examination at Mass General and to address the numerous research questions that are waiting to be answered.
Once this work is underway, we will learn with certainty which medial temporal-lobe structures were preserved in Henry’s brain and to what extent. Although the residual nubbins of hippocampus and amygdala were nonfunctional, the remaining portions of the neighboring cortex—perirhinal and parahippocampal—may have been working. Knowing the status of this residual memory tissue will help to explain Henry’s unexpected knowledge, such as his ability to draw the floor plan of the house he moved to after his operation. We are also eager to know the effect of his lesion on the structure and organization of areas that were connected to the medial temporal lobes—the fornix, mammillary bodies, and lateral temporal neocortex. Some brain areas beyond medial temporal-lobe structures are known to support declarative memory in normal individuals, so a further question concerns the structure and organization of those areas—the thalamus, basal forebrain, prefrontal cortex, and retrosplenial cortex—and of preserved nondeclarative memory areas—the primary motor cortex, striatum, and cerebellum. Henry’s MRI scans told us that his cerebellum was severely atrophied, and now we can document the specific areas that were affected.
The 2,401 slices of Henry’s brain have been frozen and are currently stored in a protective solution. Some will be placed on large glass slides, about six inches by six inches, and stained using various methods to reveal details about the cells or the anatomical boundaries of brain structures, such as those around his lesion. Some of these sections will be stained with dyes developed by neuropathologists in the nineteenth and early twentieth centuries to show normal brain structure—identifying the neurons, highlighting their organization and connections, and revealing the white-matter tracts that connect one brain region to another. Other sections will be stained using methods from the late twentieth and early twenty-first centuries that engage antibodies—proteins that detect the abnormal proteins that mark diseases such as Alzheimer and Parkinson. With this combination of approaches, a careful analysis of the abnormalities in Henry’s brain tissue will reveal a vast range of new information. Future research will tell us the kind of dementia he had when he died, the exact locations of his small strokes, and the consequences of his surgery—both for the regions adjacent to the operation site and for distant areas that had been connected to the removed structures.
The digital images captured during the cutting will be used to create a massive three-dimensional model of
Henry’s brain, which will eventually be available on the Internet for anyone to explore. This brain will be the centerpiece in the Digital Brain Library Project at UCSD, which aims to collect and archive the brains and personal profiles of one thousand individuals over the next decade. Even after death, Henry will continue to make groundbreaking contributions to science.
Henry’s legacy has many layers. From studying him directly, we have amassed the largest and most detailed collection of information on a single neurological case—Scoville and Milner’s legendary research, reams of test results collected over decades, our descriptions of his everyday life, the imaging of his intact brain in life and death, and the precious slices of his physical brain. This astonishingly large dataset representing a single brain would in and of itself secure Henry’s legacy as a vital contributor to the history of neuroscience, but his impact goes beyond that. His case inspired thousands of researchers to investigate other kinds of amnesia and disorders related to memory loss. In addition, what we learned about Henry motivated generations of basic scientists to study memory mechanisms, creating a myriad of different approaches with non-human primates and other animals. These huge advances allowed researchers to explore all manner of issues in basic and clinical science. Henry’s case triggered an extraordinarily fertile period in memory research, and the momentum continues to grow.
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