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One Room, 3,000 Brains

Researchers are on the brink of understanding the biological causes of psychiatric disorders like schizophrenia. The Brain Bank at McLean Hospital has become a key player in what could be a stunning new era of discovery. But for some McLean scientists, making sense of our madness is more than a job. It's personal.

WHEN I PEER DOWN INTO ONE OF THE BUCKETS IN A SINK, I see my first human brain. It's actually half a brain, trailing some stem, and the noodlelike folds are pearly in color, rather than the gray you'd expect. "We don't want the smell to be too strong," says George Tejada, explaining the need to soak the half-brain in water. It has been preserved in formaldehyde, which gives off a powerful stench.

We're standing in the dissection room of the Harvard Brain Tissue Resource Center, a.k.a. the Brain Bank, which is housed on the McLean Hospital campus in Belmont. A few minutes ago, Tejada peeled off a latex glove so we could shake hands. "Don't worry, my hands are clean," he assured me. I did not doubt him. Tejada, the assistant director of tissue processing at the Brain Bank, could pass for the headmaster of a prep school, with his crisp button-down shirt and pressed khakis. The dissection room itself, where human brains arrive and get sliced up at a rate of about one per day, also appears to be disappointingly spick-and-span. Aside from the buckets in the sink -- and the map of the brain regions taped up above the counter -- it would be hard to guess what goes on here.

The institution collects brains from donors and distributes tissue to researchers around the world. The Brain Bank stocks "normal" brains as well as those donated by people who had schizophrenia, bipolar disorder, Huntington's disease, and Parkinson's disease. In part, it is because of the Brain Bank -- and other such repositories -- that neuroscientists are finally beginning to zero in on the genes involved in such mental disabilities, a crucial step needed to speed the development of lifesaving drugs.

Thirty years ago, there were no brain banks in the United States -- at least not officially. Now, more than 100 such repositories exist. Over the past few decades, psychiatry has gone through a monumental transition, away from talk therapy and toward drug therapy. So scientists are sorting, storing, and examining human brains as never before, peering through microscopes at tiny slices of tissue for clues about why we go mad. This is all happening at a time when the proportion of mentally ill people worldwide who receive treatment is "woefully inadequate," according to an unprecedented new study by a World Health Organization consortium and published this month in the Journal of the American Medical Association.

Just this year, McLean researchers announced that they had pinpointed what they called energy deficiencies in the brain cells of people with bipolar disorder, an important insight that could contribute to the development of specific drugs to help the 2.3 million Americans the illness afflicts. It is this type of brain work that marks a profound shift in the way we think about our own thoughts.

Dr. Francine M. Benes, director of the Brain Bank, explains just how powerful this kind of analysis has proved to be. She says, "We're on the threshold of finding the markers for schizophrenia," that is, the genes that contribute to a person's susceptibility to the disease.

And to boost genetic research at other institutions, the Brain Bank has put a database online. It is open to researchers and the general public (it can be found on the Web at national_databank.mclean.harvard.edu). Benes's hope is that scientists who receive tissue from the Brain Bank will submit the results of their research to the database, helping to create a superstorehouse of brain data for the field.

It all sounds very worthy and hygienic, but I must admit that I had come to the Brain Bank hoping to be grossed out, at least just a little. My ideas about what might go on at a facility that houses more than 3,000 human brains had been inflamed by an episode of the original Star Trek in which DayGlo-colored brains order slaves to fight battles for their amusement. And then there is an old sci-fi movie called They Saved Hitler's Brain, in which the Fuhrer's cutoff head, kept alive inside a glass jar, commands what's left of the Nazi empire. Something about iced brains captures the imagination -- after all, no one would bother to make a movie called They Saved Hitler's Liver. The brain seems to contain the essence of the self. Yet, unlike so many other dear and familiar body parts -- our eyes, our arms, our toes -- it exists under wraps. Even as I write that sentence, I'm aware of my own brain dwelling in the loft apartment of my skull, doing who-knows-what up there. It is me, and it is also eerily remote.

"This is a problem that's not going to go away soon," says Benes about the complex feelings people have about their brains and, therefore, about donating that particular organ to science. "It's believed by many that the soul of their loved one resides in the brain, or they see the brain as what gives one a special connectedness in the spiritual." For years, when people donated their bodies to organ banks, brains were not part of the deal. Now, the taboo against collecting brains has begun to relax. The New England Organ Bank and the New England Eye & Tissue Transplant Bank, for instance, have quietly begun to include brains in the roster of donations they collect. The brain is on its way to becoming just another body part.

WHILE THIS IS A GREAT BOON TO THE BRAIN BANK, in terms of recruiting donors, outreach is only one small part of what goes on here. Most of the work happens after the donor dies, at which time the cells in his or her brain immediately begin to deteriorate. Within hours of getting a call from the donor's family, the Brain Bankers must find a pathologist in the appropriate region of the country, arrange for that pathologist to extract the brain and put it in a special container, and fly the brain to McLean by same-day shipping. After that, the brain will be assigned a number, sliced up and photographed, frozen, preserved in formaldehyde, examined, entered into a database, and distributed to worthy investigators.

The brain in the bucket, in fact, turns out to be the only one I come across here that looks remotely brainlike. Every other piece of tissue has been so carefully preserved and processed that you'd be hard-pressed to say what it is. Tejada shows me into a room full of freezers, and opens a door to reveal plastic bags, each of which holds a brain hemisphere cut into 16 sections. Mist rolls out into the room -- the freezer is kept at 80 below zero. The bags themselves appear to contain flash-frozen shrimp.

When a brain arrives here, usually half of it gets frozen while the other half ends up in formaldehyde -- a system designed to give researchers as many options as possible. In the "Tupperware room," slices of brain tissue marinate in chemicals; each half-brain is stored in the kind of plastic container you might use to microwave leftover pasta. From the looks of the original labels, which still cling to some of the containers, the Brain Bank chose an off-brand rather than genuine Tupperware.

Tejada leads me back to his office and shows me a photo of one of the brains. Such mug shots are made available to researchers, along with other information, in order to help them select which tissue sample they would like to order. The brain in the photo, freshly cut out of the donor's head, gleams with blood. Unlike the brains in sci-fi movies, this one does not look up to the task of issuing commands to Nazi followers. It's just a piece of meat. I'm reminded of what William James said: "The brain itself is an excessively vascular organ, a sponge full of blood." This photo is a powerful argument for using a biological model to understand what goes on in the mind.

"I was part of the shift" toward seeing mental illness as an organic problem, says Benes, who is trim and wears a starched lab coat. We're sitting in her office, and she's holding research on her lap -- a sheaf of papers covered with numbers that represent the gene profiles of schizophrenic, bipolar, and control-group brains.

IN 1973, FRANCINE BENES attended a neuroscience meeting at a ski resort in Colorado. Then a cell biologist, she had no particular expertise in mental illness. Nonetheless, she found herself in a talk on schizophrenia, delivered by Dr. Janice R. Stevens. "I was standing in the back of the room, and it blew me away," Benes says. Stevens proposed that schizophrenia was due to a dopamine disturbance in a part of the brain called the nucleus accumbens -- a radical theory back when psychiatrists were still blaming mothers, who were presumed to have driven their children mad with Joan Crawford-like behavior. Stevens's paper helped to erase that stigma. The illness became a matter of bad wiring rather than bad mothering. "Schizophrenia could now be visualized in terms of the circuitries in the brain," Benes says.

The revelation changed the direction of Benes's life. She returned to medical school to get her MD, and, in 1982, established the Laboratory for Structural Neuroscience at McLean. Early on, "there was me and maybe two other people who were doing postmortem schizophrenia research," she says. By the late 1980s, however, researchers were routinely examining postmortem brain tissue in order to search for the causes of Alzheimer's and Huntington's disease. Using the same methods to investigate mental illness no longer seemed so strange. These days, Benes says, "the stigma is gone, and you have the excitement of getting inside the cells," chasing after the genes that lead to mental dysfunction.

Most exciting, brain scientists have begun to borrow ideas from the colleagues who study problems that affect other parts of the body. "At this juncture, we're starting to move into alignment with cancer research and hematology research," Benes says. "That is going to prove to be the most historic step in this field." Treating the brain as just another part of the body -- vulnerable to high cholesterol, secondhand smoke, and bad genes -- may lead to breakthroughs that were not possible back when the brain seemed to be something special and separate.

"I AM A BRAIN BANKER, asking for a deposit from you," Jill Bolte Taylor sings to me over the phone from her home in Bloomington, Indiana. She's sitting with a guitar in her lap and a phone receiver lying on the floor before her, strumming like a cowboy. "Find the key to unlock this thing we call insanity," she warbles. "Just dial 1-800-BRAIN-BANK for information, please." And then she ends with a whoop worthy of Hank Williams.

Taylor, the Brain Bank's spokeswoman for psychiatric disorders, tours the country, exhorting the public and especially those with mental illnesses to donate their brains to science. In just about every talk she gives, "there's this wonderful moment when the audience realizes, 'Oh, my gosh, she wants my brain,' " Taylor says. "The tension in the room gets really thick. Everyone's looking down like we're all in the first grade -- 'Don't call on me, don't call on me.' So I'll pull out my guitar and sing the Brain Bank jingle. It lightens everything up. It's been a wonderful marketing tool."

Taylor hooked up with the Brain Bank in 1993, a postdoc working in Benes's lab, researching the organic causes of schizophrenia. She was determined to prove they existed. Her brother had schizophrenia.

"The thinking in the professional community for decades was that it was a character flaw caused in part by the schizophrenogenic mother -- they blamed the family," she says. Taylor fought against that stigma on two fronts: as a Harvard researcher and as a board member of the National Alliance for the Mentally Ill, a group that pioneered the effort to understand mental illness as a biological problem rather than a failure of the will. "It's only been 10 years really that it has been put out that severe mental illness, schizophrenia in particular, is a biologically based brain disorder," Taylor says. In the mid-1990s, Taylor worked in the lab from Monday through Friday, and then would often hop on a plane over the weekend to deliver lectures around the country, spreading the word about brain donation. "When I first started, we were receiving fewer than five psychiatric brains a year," she says. Now that figure has jumped to 25.

Taylor admits that, back then, she was something of an overachiever. "I had been driven toward excellence by very powerful anger," she says. "And that anger was related to growing up with a sibling who was not normal. You're constantly on guard. You trust him, and then he hurts you emotionally."

On December 10, 1996, Taylor, then 37 years old, woke up to find she had a brain disorder of her own. "Inside four hours, I watched my mind deteriorate in its ability to process incoming information," she says. A fist-sized hemorrhage had formed in the left hemisphere of her brain, between the two centers that process language. Because the hemorrhage had also knocked out the portion of the brain that creates fear, she felt only curiosity as her mental functions shut down. "I learned as much about my brain in those four hours as I had in my whole academic career," she says. "Eventually, my right arm went completely paralyzed, and that's when my brain said, 'Oh, my gosh, I'm having a stroke. I'm having a stroke? I'm a very busy woman. Well, I can't stop this from happening, so I'll do this for a week, learn what I can learn from it, and then I'll get back to work.'"

In fact, recovery took years. "I was an infant in a woman's body," she says. She was unable to wiggle her toes or roll over in bed. "I couldn't understand when I heard other people making language at me. I lost my ability to read and write." It was two years before she could cook and talk on the phone at the same time, and many more before she could hop from rock to rock without planning exactly where to put her feet.

Last summer, year seven of her recovery, Taylor slipped into water skis for the first time since her stroke. As a girl, she'd been a slalomer, so comfortable on the water that her skis felt like part of her feet. Now, as the boat pulled away, she found her balance and began cutting through the glassy water. "All of a sudden, there was this moment when my body took its position, and every cell remembered that it was powerful. Off I went. It was pure bliss. I had recovered who I was before that hemorrhage."

No longer a workaholic, she enjoys a laid-back life in Indiana. She continues to spread the word about brain donations, and she also makes brains -- out of stained glass. Taylor's creations are suitable for hanging against a big sunny window, where you can watch the world through the yellow and blue and green pieces of glass that represent the nuclei and gyri and limbic system.

RIGHT NOW, IN ONE WINDOW of my computer, I'm donating my brain to science, typing information into an online form at www.brainbank.mclean.org/questionnaire.htm. It's no more difficult than ordering a book from Amazon.com. You give your name, address, next of kin, and use a pull-down menu to let the Brain Bank know what kind you've got. For a moment, I linger over that list, deciding how to classify myself: normal control, schizophrenia, bipolar disorder, Parkinson's disease, Huntington's disease. I click on "normal control," knowing that designation could change. That blood-soaked sponge in my head, so soft, so frangible, could be destroyed by any of a number of diseases. I have seen them up close on a computer screen at McLean. There, a helpful man in a lab coat showed me slides of brain tissue that had been eaten away by abnormalities, from the tangles of Alzheimer's to the bloom of melanoma cells.

We hope, of course, that all of this study of brain tissue will lead to the discovery of new pills and treatments. But along the way, perhaps it will offer another benefit, too. The more we know about the neurological disorders, the more likely we are to feel compassion for the people who have those disorders. I'm remembering something that Jill Taylor said about the moment when her brother was diagnosed with schizophrenia: "It was a relief. Finally, I could separate him from the disease. I could forgive him. I could love him again as my big brother."

Pagan Kennedy's latest book is Black Livingstone: A True Tale of Adventure in the Nineteenth-Century Congo. 

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