Nature and nurture

New techniques and insights reveal the amazing complexity of the human brain

Editor’s Note:  A professor of Pharmacology, Levitt studies the molecular and developmental basis of neuropsychiatric disorders.

Pat R. Levitt, Ph.D.
Director
Vanderbilt Kennedy Center for Research on Human Development
Published: November, 2003

A professor of Pharmacology, Dr. Levitt studies the molecular and developmental basis of neuropsychiatric disorders.
Photo by Dean Dixon
Nothing, perhaps, in biology better illustrates the interaction between “nature” and “nurture” than the development and functioning of the brain.

Early experiences, both in the womb and after birth, can have profound effects on the way in which genes and their protein products orchestrate the formation of circuits that control our mood, our ability to endure stress, our thought processes, our ability to learn new information, and our recall of important memories. It is the combination of these forces – genetic and environmental – that underlies the development of devastating brain disorders such as schizophrenia and autism, and functionally milder ones such as attention deficit hyperactivity disorder (ADHD).

While I have been studying some aspect of brain development since my college days, I began the process of integrating nature and nurture in 1986, after a visit to the intensive care nursery at the Medical College of Pennsylvania, where I was a young assistant professor. My colleagues wanted me to get involved in a new research project to study the effects of prenatal exposure to cocaine on brain development. I resisted; drug exposure research would only distract me from my mission of finding and describing neuro-development genes. Well, the images of the infants, struggling in a new world, possibly carrying the legacy of an altered wiring diagram for the rest of their lives, was more powerful than I had imagined.

I began a new scientific journey, transforming my own laboratory into one in which we became more and more engaged in multidisciplinary efforts with other scientists to investigate the interaction of genetic and environmental factors in the developing brain, how genetic susceptibility translates into disorders, and how intervention can alter the course of development to improve outcomes.

Donald Hebb, who proposed our modern view of the biological mechanism of learning and memory in the 1940s, once made the analogy that the debate about whether nature or nurture is more influential on brain development and functioning is like arguing about whether the length or the width of a rectangle is more relevant in determining its area. Like the rectangle, the trick regarding brain development is to determine how nature and nurture interact to influence the emerging properties of developing brain systems.

Fluorescence microscope image of neurons (nerve cells) in the cerebral cortex, or outer portion of the brain, which is involved in conscious experience, including perception, emotion, thought and language.  The round center of each neuron represents the cell body, and the extensions are the dendrites that receive connections from other neurons.  The neurons are colored with different dyes.
Courtesy of Gregg Stanwood and Pat R. Levitt, Vanderbilt University
If genes were the sole force in brain development, it would be difficult to explain the profound difference between the mind of human beings and the nervous system of the worm, C. elegans, which serves as a model system for studies of the development of neuronal “wiring.” The worm has 19,000 genes, only about 11,000 fewer than human beings, yet the 302 neurons of the worm are far outnumbered by the trillions of nerve cells in the human brain.

What, beyond the sheer number of genes, could explain the quantum leap in neurobiological complexity between a human being and a worm? One key lies in how these genes are “packaged” in human versus worm nuclei. The human genome includes long stretches of non-coding DNA that regulate gene expression cell to cell. This extra genetic material provides an organized, highly complex and flexible molecular network capable of driving the computational genius of human brain circuitry, and capable of responding to extrinsic cues (sounds, sights, touch, food, light, drugs, toxins, cruelty, abuse) perhaps in a more limitless fashion than in simpler species.

In 2002, the opportunity to build new research relationships led me from the University of Pittsburgh, where I was chair of the Department of Neurobiology, to Nashville to direct the Vanderbilt Kennedy Center for Research on Human Development. The center has a rich history of embracing interdisciplinary approaches to study brain disorders. Nicholas Hobbs, Lloyd Dunn, Susan Gray and their colleagues at the Peabody College believed that they could create assessment tools to describe better the nature of a particular brain disorder and through this improved characterization, develop cutting-edge strategies for intervention and treatment. These visionaries imagined the possibilities of doing bio-behavioral research and intervention at a time when technologies had not caught up with their imaginations.

Today, scientists here have at their disposal an armamentarium of tools capable of describing the clinical and genetic details of neurodevelopmental disorders like autism, literally peering into the brain of an individual with schizophrenia, or hunting for single base changes among billions of DNA molecules, which could correlate with increased risk of ADHD.

We at the Vanderbilt Kennedy Center are attempting to take advantage both of our history and the recent technology revolutions that have brought tools to assess our genome, or to view the brain in action, monitoring both with high temporal and spatial resolution. We’re creating more opportunities for clinician-scientists, basic scientists and interventionists to co-habitate, in a sense, to interact at a level at which a common problem of great interest to each scientist serves as the basis for launching multidisciplinary research, training and educating.

Imagine the possibilities for discovery as brain imagers, geneticists, basic developmental neuroscientists and neurophysiologists sit together with developmental and clinical psychologists, psychiatrists and neurologists, special educators and interventionists. Imagine faculty in special education working with the tools of modern brain imaging or with the sophisticated molecular methods of human genetics to solve the mysteries of cognitive or behavioral disorders in children. Imagine a mouse neurobiologist attending an autism clinic to gain a better sense of the fine details of social dysfunction in an attempt to produce a better model in the laboratory.

Can we imagine that this is what Donald Hebb had in mind when he was trying to unravel the mysteries of the human learning machine? We’re not debating nature versus nurture; we’re embracing them both, and indeed, doing it very well at Vanderbilt.

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