Like many students of neuroscience, I first learned of patient HM in a college lecture. His case was so strange yet so illuminating, and I was immediately transfixed. HM was unable to form new memories, my professor explained, because a surgeon had removed a specific part of his brain. The surgery froze him in time.
HM–or Henry Molaison, as his name was revealed to be after his death in 2008–might be the most famous patient in the history of brain research. He is now the subject of the new book, Patient HM: A Story of Memory, Madness, and Family Secrets. An excerpt from the book in the New York Times Magazine, which details MIT neuroscientist Sue Corkin’s custody fight over HM’s brain after his death, has since sparked a backlash. Should you wish to go down that particular rabbit hole, you can read MIT’s response, the book author’s response to the response, and summaries of the back and forth.
Why HM’s brain was worth fighting over should be obvious; he was probably the most studied individual in neuroscience while alive. But in the seven years since scientists sectioned HM’s brain into 2,401 slices, it has yielded surprisingly little research. Only two papers examining his brain have come out, and so far, physical examinations have led to no major insights. HM’s scientific potential remains unfulfilled–thanks to delays from the custody fight and the limitations of current neuroscience itself.
The Grand Model
Corkin, who made her career studying HM, confronted her complicated emotions about his death in her own 2013 book. She describes being “ecstatic to see his brain removed expertly from his skull.” Corkin passed away earlier this year.
She had reason to be emotional. The behavioral tests on HM done by Corkin’s graduate advisor Brenda Milner and then Corkin built the foundation of memory science research. HM made it clear that memory came in different types, and they involved different parts of the brain. He could learn certain tasks like tracing a star through a mirror (procedural memory), even if he was unable to remember names, faces, or events (declarative memory.) And while HM could remember things for about 30 seconds, he could not consolidate them into longer-term memory.
HM transfixed me that day in the lecture hall because his case so perfectly illustrated the ultimate goal of neuroscience: explaining how the stuff that makes us human can be found in the brain’s physical structure. Or as neuroscientist Antonio Damasio put it, “how consciousness may be produced within the three pounds of flesh we call brain.” Most of my neuroscience class–and most neuroscientist’s labs–are focused on granular details like the workings of a particular sodium ion channel or the pattern of light that sets off a certain set of retinal ganglion cells. Those details are all important, but they are far removed from the grand questions of consciousness.
When neuroscientists finally got to look at HM’s brain, it was a chance to study a brain so famous for memory deficits on the level of individual neurons. “The resolution when you’re looking at brain tissue is microns, and with MRIs, it’s millimeters,” says Rebecca Burwell, a memory researcher at Brown who was not involved with that work.
It’s a 1,000-fold difference–but that doesn’t easily translate to 1,000 times as much information. The slices confined and refined observations from earlier MRI scans of HM while he was alive, but they weren’t groundbreaking.
Memory scientists don’t yet know what to do with with all this extra resolution. In other neuroscience labs, scientists are confronting the same problem: They are sectioning and mapping terabytes worth of brain images, with the hope they can lead to new insights. Just what, nobody is sure of yet.
That doesn’t mean there isn’t anything new to learn from HM’s brain. When I asked Matthew Frosch, a neuropathologist who has worked with Corkin to study HM’s brain, about what work remained, he said a group of scientists is now looking at how HM’s brain lesions may have impacted accumulations of a protein associated with certain brain diseases. “This isn’t as much about the role of HM’s lesions in studies of memory as an opportunity to examine the impact of these lesions on other aspects of neuropathologic processes,” he writes. If that’s difficult to parse, well, science at this granular level often is.
Jacopo Annese, the neuroanatomist who sectioned HM’s brain at University of California, San Diego and who was on the other side of the fight with Corkin, told me he expected any additional work to be incremental, too. “We’ll just continue getting pieces of the puzzle,” he says.
Both sides can agree that the custody fight delayed a lot of this research. “Because of aspects of a failed collaboration over the use of tissue,” writes Frosch, “the neuropathologic examination based on sections from HM’s brain was significantly delayed.” Annese had also gotten a $300,000 National Science Foundation grant to put HM’s brain slices online for researchers, but the legal battle with MIT iced it. “It was big mess because we were not able to utilize this grant,” says Annese, who has since left UCSD.
Last year, Annese turned over the physical slices of HM’s brain to Corkin’s collaborator, David Amaral, at the University of California, Davis, per an agreement between UCSD and MIT. The images he took of the slices are accessible online at the website of the Institute for Brain and Society, which Annese founded. Researchers as well the interested public can request access.
Though the images are now readily available, no scientific gold rush has followed. Neuroscience is hard. Annese says he’s unaware of anyone publishing studies based on his set of images so far. UC Davis has a set of the digital data as well, though Amaral could not be reached for comment.
It’s been eight years since HM died, seven since the sectioning of his brain was livestreamed to much fanfare among scientists. That’s not an entirely unreasonable amount of time for science, and the fight over the brain has delayed research. But if HM’s brain once illuminated the link between anatomy and function, its mysteries now show just how much is left to understand about individual neurons connecting to form consciousness and memory and all that makes us human.