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Doctor controls Harvard's brain trust

Bank of gray matter one of world's top research collections

By Neil Osterweil
MedPage Today Senior Associate Editor

Editor's note: CNN.com has a business partnership with MedPageToday.com, which provides custom health content.

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Benes and her staff provide tissue samples for researchers investigating brain disorders.

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BELMONT, Massachusetts (MedPage Today) -- Dr. Francine Benes has more brains than just about anyone else in the world.

She has her own prodigious gray matter, of which she is in full possession, and that of about 6,000 other people who have left theirs in her charge.

As director of the Structural and Molecular Neuroscience Laboratory and the Harvard Brain Tissue Resource Center (known collectively as the Brain Bank) at McLean Hospital in Belmont, Benes is the steward of one of the world's most important medical research collections.

Researchers have used brain tissues stored here to identify the gene that causes Huntington's disease -- the progressive neuromuscular disorder that killed legendary folk signer Woody Guthrie -- and to develop a treatment for Parkinson's disease.

In her investigations, Benes has found compelling evidence that miswiring of neural circuitry may give rise to both schizophrenia and bipolar disorder. Her work has contributed to the current understanding that like Alzheimer's disease, neither schizophrenia nor bipolar disorder is linked to degenerative changes in the brain.

In recognition of her work, she was inducted in 2004 into the prestigious Institute of Medicine of the National Academies, one of the highest honors in medicine.

Benes and her staff routinely supply brain tissue samples to medical researchers investigating the root causes of Alzheimer's and other forms of dementia, Lou Gehrig's disease (amyotrophic lateral sclerosis), autism, bipolar disorder, depression, schizophrenia, Tourette's syndrome and many others.

In addition to collecting, preserving, cataloging and storing the brains of people with identifiable pathologies, Benes and fellow Brain Bank researchers seek donations from people with, for want of a better word, "normal" or "control" brains, for purposes of comparison, and for studies of how the nervous system works in both health and disease.

In other words, if you always wanted to get into Harvard but thought you didn't have the brains for it, here's your chance.

Could-be verse an inspiration

As a child growing up in Queens, New York, Benes had assumed she would go into social work or teaching, but a bit of doggerel and a chance encounter on a ski lift launched her on quite a different career path.

"One of my eighth-grade teachers wrote little poems about everyone in her class," Benes said. "The poem she wrote for me was about me becoming a scientist. I had never thought about being a scientist, but from then on I realized it was something to strive for."

She got her doctorate in cellular biology at Yale University. While attending an annual winter brain research conference in Colorado in the early 1970s, she sat in on a session on schizophrenia, during which a researcher proposed the then-novel concept that schizophrenia and bipolar disorder might share common features involving specific areas of the brain.

"As a young scientist, I was quite taken by the idea," she said.

But when she tried to share her enthusiasm with the neuropathologist sitting next to her on the ski lift the next morning, his reply stunned her.

"He said, 'Oh no, there's nothing there in the brains of patients with schizophrenia. This was looked at by many people in the earlier part of the century, and they found nothing,' " she recalled with an incredulous laugh.

"All I could think of was how could you find nothing? If you really seriously look, you've got to find something, so I just got intrigued with this, and I decided that I was going to devote my career to the study of schizophrenia."

Although it meant abandoning a fledgling career in cellular biology and eight years of work, she went back to school. After graduating from Yale's medical school, she applied to McLean Hospital, a world-renowned psychiatric facility, for her residency.

"McLean was the only place in the country that had a brain bank of any type, the first one in the U.S.," Benes said. "They were collecting schizophrenia brains, and I said, 'That's where I've got to be.' "

Frozen and canned

There are no tellers or toaster giveaways in the Brain Bank, just a couple of offices, laboratories and two rooms where donated brains are stored. One contains rows of freezers chilled to -70 degrees C for storage of whole brains; the second is filled with tiers of orderly shelves stacked with plastic containers full of dissected brain slices floating in a preservative bath in what staffers call "the Tupperware room."

The brain tissues stored here are available by investigators with legitimate research interests. Staffers maintain strict confidentiality, with samples labeled by code numbers to which few have access.

Benes' laboratory is also home to the National Brain Data Bank, a collection of publicly accessible data on the genetic profiles of thousands of brains from people with psychiatric and neurological disorders such as schizophrenia, Parkinson's disease and Alzheimer's disease.

Throughout her career, Benes has worked within a few steps of the Brain Bank, which has provided a rich array of tissues for her explorations into the convolutions and dark passages of the brain and the mind, and their connections to the body.

"I think what surprises me most at this stage," she said, "is not so much the intricacy of the circuits, but that the neurons of the brain are just like any other cells. Because we're looking at gene-expression profiling, we're able to look at metabolic and signaling pathways that are being studied by cancer researchers, diabetes researchers, people who study cardiovascular disease -- we're studying the same genes."

To understand fully what happens in brain disorders, she said, you have to look not just at the wiring and the nerve signal transmission and reception points but also at the basic function of nerve cells themselves.

At the time of her Institute of Medicine induction, Dr. Bruce Cohen, president and psychiatrist in chief at McLean, said that "with each important discovery, Benes continues to provide new hope to the countless individuals and their families whose lives have been robbed of the basic human qualities that most people take for granted -- normal thought, emotions and the ability to cope with daily life."

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