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Tuesday, Dec. 23, 2008 | In the summer of 2006, Jacopo Annese flew from San Diego to a Connecticut nursing home to have lunch with the world’s most famous amnesic.
The visit was short and rather uneventful. The 80-year-old “H.M.,” who was known only by his initials, was pleasant and peaceful, but in failing health and not lucid enough to hold a conversation. Nonetheless, Annese was glad he made the trip. It gave him a chance to get to know H.M. — if even just a little — before the day came when he would take his brain.
That day is close at hand. H.M., who now can be identified as Henry Molaison, died on Dec. 2. Next month, Annese, a University of California, San Diego neuroanatomist, will make another trip east. He’ll return with perhaps the most anticipated brain since Albert Einstein’s.
The final destination for H.M.’s cerebrum will be The Brain Observatory, Annese’s laboratory in Sorrento Valley. There, the brain will undergo a two-month cryoprotection process, and then be frozen.
Then Annese and his team will begin slicing the brain into 3,000 fraction-of-a-millimeter thin sections that can be placed on oversized microscope slides and scanned into a computer. Finally, the scientists will construct the first ever three-dimensional, high-resolution digital map of a complete human brain.
The end result will be something like Google Earth, except instead of zooming in on a driveway in Normal Heights, users will be able to zoom in to individual neurons in H.M.’s brain. The brain map will be put up on the web, giving the scores of researchers who studied H.M.’s memory during his life the opportunity to finally validate the hypotheses they made regarding different types of memory and where in the brain they are controlled.
“I see it in a romantic way — I think I am writing a biography,” Annese said. “We will revisit his life by slicing through this brain and studying those structures that gave him the life he experienced.”
H.M. was 9-years-old when he suffered a traumatic brain injury after being in a bike accident in his neighborhood near Hartford, Conn. By the time he was in his late teens, he was having seizures with such regularity that he couldn’t attend school or hold down a job. By age 27 he was having as many as 11 seizures a week.
In 1953, brain surgeon William Beecher Scoville performed an experimental operation in which he removed much of H.M.’s hippocampus, a seahorse-shaped part of the brain that plays a major role in the consolidation of memories. The operation was successful in reducing the seizures, but it killed his ability to form new memories. H.M. could, for example, be introduced to someone, and if that person left the room and came back moments later, he would not remember meeting them.
And though H.M. could remember big events in his past like World War II, he had problems remembering his own past. Scoville, horrified by the outcome of the surgery, never tried it again, nor did anyone else. H.M. became unique in the annals of medicine, and the most studied brain patient in the world.
It was through the study of H.M. that neuropsychologist Brenda Milner and her student Suzanne Corkin first discovered that memory is not a single system, and that different aspects of memory are controlled by different parts of the brain. H.M., for example, never forgot how to ride a bike. And if taught a skill, such as golf or piano, he would not remember taking lessons, but would continue to get better at whatever he was being taught.
Leading brain researchers say the importance of H.M.’s brain cannot be understated. “The number of patients with memory impairment who have been studied carefully in life, and then studied post mortem can be counted on one hand,” said Larry Squire, a neuroscientist at the UCSD Medical Center and VA San Diego Medical Center.
Squire and other researchers are hopeful that the study of H.M.’s brain will lead to a better understanding of diseases like Alzheimer’s, which attacks the same structure of the brain that Scoville damaged when he operated on H.M. A subject of much interest is the length of the lesion in H.M.’s brain, which should help explain why he had such extreme memory impairment.
In the middle of it all will be The Brain Observatory, which Annese started in 2005. The observatory is located in a non-descript office complex off the UCSD campus, but its interior is far homier than the usual laboratory. The so-called dry side of the lab, where the offices and computer workstations are, has an espresso machine and a trendy couch. On a table next to the couch is an antique camera. A guitar sits in the corner of Annese’s office.
All of this is on purpose. Annese describes his creation as a not just a laboratory, but a library for the brain. “My original idea was that it would be an institute where artists, scientists and writers would consult and gain a better understanding of the brain,” said the 42-year-old who grew up in Florence, Italy.
He believes this approach attracted Corkin, the Massachusetts Institute of Technology professor who has supervised the research of H.M. for the past five decades, and had the most say in where his brain would end up. Annese met Corkin in 2003 when he was working at University of California, Los Angeles, and he said she followed his progress with the lab. Corkin, who is currently writing a book on her experiences with H.M., couldn’t be reached for comment.
It also didn’t hurt that Annese procured grants from the National Science Foundation and The Dana Foundation for the project. And that he and his staff custom built a large cryostat in the lab. With this device, a whole human brain can be sliced into sections that are mounted on five-inch-by-seven-inch microscope slides. The slides are then stained and scanned into the computer with a customized, computer-controlled microscope.
“In the end there is not anyone else who could have done H.M.’s brain,” said William Bradley, chairman of the UCSD Medical Center’s radiology department, and the man who hired Annese. “Jacopo saw a research opportunity and pursued it — pretty much under everyone’s radar.”
Annese estimates that it will take several months and many terabytes of digital storage space to build the model of H.M.’s brain. He hopes that researchers, and anyone else, will be logging on to The Brain Observatory’s website to study H.M.’s brain by summer.
He is banking on H.M. drawing attention to the observatory’s other projects, most notably the study of the effects of HIV infection on the brain. Long-term HIV patients have been developing neurological conditions that create dementia-like symptoms.
Annese also hopes that the project will raise awareness for the need for normal brains in neurological research. Brains are not part of typical organ donation programs, because the programs are intended for transplants. And, Annese said, people in general — even those who will donate other organs to science — are skittish about donating their brains.
“The way we approach the brain of H.M. will lead others to entrust cases to us,” Annese said. “It could be seen as a beautiful thing that your brain becomes a book in this library.”