Harvard Brain Bank Faces Shortage of "Normal" Brains

Bijal P. Trivedi
National Geographic Today
August 28, 2003
There is a shortage of "normal" brains at the Harvard brain bank, scientists say.

The bank, officially known as the Harvard Brain Tissue Resource Center and located at McLean Hospital in Belmont, Massachusetts, is the world's largest brain repository, distributing tissue to neuroscientists in the United States and internationally for research.

The federally funded brain bank keeps 3,000 brains—most from people who suffered from neurodegenerative diseases like Parkinson's, Huntington's and Alzheimer's, and neuropsychiatric disorders like schizophrenia and manic depression.

But the nature of research requires that scientists need "normal" brains, too, from healthy people of all ages. Neurological disease can strike at any age. For example, schizophrenia and bipolar disorder, also known as manic depression, can occur in the late teens and early 20s. Huntington's afflicts adults mainly between the ages of 35 and 65; Alzheimer's, people 65 and older.

Since its founding in 1978, the bank has collected almost 6,000 brains. Every year it receives about 240 diseased brains but only 30 normal brains. The challenge is to encourage healthy people to consider brain donation, according to Francine Benes, a professor of neuroscience at Harvard Medical School in Boston and the bank's director.

"The problem is that families with members who have a brain disease are working with private foundations and already thinking about brain donation and research and so it is easier to reach out to them," says Benes. "But there is no foundation that advocates for a normal brain."

What's An Ideal Brain?

The ideal normal brain, according to Benes, comes from an individual without a history of head trauma, seizure, dementia, delirium, or drug or alcohol abuse. This normal tissue serves as a basis for comparison.

Brain tissue is essential to research. Techniques like functional Magnetic Resonance Imaging (fMRI) or Positron Emission Tomography (PET) scan the brains of living people, watching the brain at work. But fMRI and PET can't peer into nerve cells.

Understanding the chemistry of cells in diseased regions of the brain—what proteins are present, which genes are active—can help scientists determine what went wrong, and develop diagnostic tests and treatments.

To identify the chemical calling card of disease, scientists need a supply of fresh brains.

A donated brain must be received within 24 hours of death. Scientists divide the brain into its left and right hemispheres. One hemisphere is placed in a preservative for anatomical studies; the other is sliced in sections and frozen, a process that preserves all the chemicals, protein, and DNA for biochemical and genetic analysis.

At the brain bank, Benes and other scientists analyze brains to determine what she calls their "gene expression profiles."

These profiles analyze more than 30,000 genes, revealing which ones are turned on or off in specific regions of the brain, in particular disorders. Erratic gene activity can lead to disease.

In October the bank will launch a national databank for these profiles, with free access for scientists worldwide.

Making A Withdrawal At The Brain Bank

Research progress depends largely on "the availability of quality brains," says Lynn Selemon, an anatomist and research scientist specializing in brain structure in the neurobiology department at Yale University in New Haven.

Selemon, a specialist on schizophrenia and Huntington's disease, credits brains from the Harvard bank for helping her achieve a breakthrough in her research.

Imaging studies, she explains, had shown that the prefrontal cortex—the region of the brain above and behind the eyes—was slightly smaller in individuals who were schizophrenic.

Selemon examined tissue samples from schizophrenics, and discovered that their prefrontal cortex was smaller because the cells were packed more densely. She also deduced that much of the machinery that connects nerve cells was missing, thus hampering the cells' ability to communicate.

John Trojanowski also uses the brain bank. He directs both the Institute on Aging and the Alzheimer's Disease Center at the University of Pennsylvania School of Medicine in Philadelphia. By examining glial cells from brains from the bank, he and his colleagues identified the molecular defect in patients with Multiple System Atrophy, whose symptoms resemble Parkinson's disease. He found that the glial cells—which produce the fatty insulation on nerve cells—in MSA patients were filled with cellular garbage that prevented them from working.

"The brain bank, and any bank that contains biological samples, is a driver for research," Trojanowski says.

A mind is a terrible thing to waste. For information on donating a brain to the Harvard Brain Tissue Resource Center, call (800) 272-4622.

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