Dr. Steven Hyman, left, shares a laugh with Vice Chancellor Dr. Harry R. Jacobson at the dinner. The lecture and dinner officially launched the Vanderbilt Brain Institute. (photo by Dana Johnson)
Brain Institute launched
“The brain is the most complex object in the history of human scientific inquiry,” Dr. Steven E. Hyman told the crowded room.
The seats and aisles of Light Hall were filled on a recent Monday evening for a public lecture by the director of the National Institute of Mental Health, marking the official launch of the Vanderbilt Brain Institute. The rapt audience was treated to a far-reaching overview of what is known about genes and the brain, and a view of where brain research is headed.
“Vanderbilt has committed its highest level of support to discovery in neuroscience,” said Dr. Harry R. Jacobson, vice chancellor for Health Affairs, in his opening remarks. “We work together across the University to find answers to the secrets of the brain, working at the level of molecules, cells, circuits, and living beings.”
The brain has thousands of distinctly different types of cells, each having a different shape, size, and function, each playing a part in a remarkably complex—and changeable—signaling circuitry.
“We are still learning how neurological circuits are built: how genes affect their make-up, how the circuits affect physiology, and how physiology affects behavior,” Hyman said. “Circuits are affected continuously over the course of a lifetime.”
For some time scientific dogma held that neurons were not replaceable. It’s known now that the brain is not static, but is changed by experience. Brain cells can be made anew. Synapses—the connections between brain cells—can undergo remodeling, Hyman said, “literally changing the wiring of the brain.”
The experience that changes the brain is memory, conscious and unconscious. When we form memories, we strengthen some synaptic connections and weaken others, grow new synapses or prune existing ones. This remodeling is dependent on the activation of genes in nerve cells for the production of proteins, the building blocks that will be used for new growth.
Genetic advances—including the sequencing of the human genome—have provided powerful new tools to understand the brain in health and in illness. Though it is now estimated that our genome has only around 30,000 genes, Hyman said, the number of proteins encoded by those genes is a “very, very large number.” Regulation of gene expression is complex and results in tremendous variation in our physical traits, including brain structure.
The work of sequencing the human genome has generated a dense map of human sequence variation, showing single letter, or base pair, changes—called SNPs (“snips”)—about every 1300 base pairs. Most of these SNPs are silent, having no effect, but others cause regulatory changes in how genes produce proteins.
Because we are an evolutionarily young species, Hyman said, human DNA sequences have not had much of a chance to move around and recombine in our genome, as is known to have happened in older species such as insects. Consequently, SNPs stay together in blocks of sequence as DNA is transferred during reproduction, carrying risk of disease as they travel.
Researchers can now begin to use SNPs as signposts in determining if certain blocks of DNA are associated with particular diseases. With the use of advanced statistical and mathematical tools, inheritance and risk of disease can be predicted within families and among populations.
It is this variation—between individuals and between ethnicities—that will provide targets for novel drug treatments, once specific differences are shown to be associated with neurological dysfunction or disease.
Chronic brain diseases, including mental illnesses, are complex, having at their root multiple genetic and non-genetic factors working in concert. Hyman pointed out that though it is known that disorders such as schizophrenia or autism run in families, “genes are not fate.”
“If you have an identical twin with schizophrenia, you have a 50-fold risk of also having it,” he said. “However, that also means you have a 50 percent chance of not developing it.”
For every mental disorder, he said, this is true. Genes by themselves do not determine destiny, but instead interact and are influenced by non-genetic, environmental factors, such as diet, smoking, stress, and others.
“A lot of the business end of understanding how the genome builds and operates the brain is still opaque to us, as it relates to these aspects of regulation. The field of neuroscience will not be ending any time soon,” Hyman reassured the students in the audience.
“We are really just beginning this adventure.”