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Five Questions

Michael Greenberg on The Coming Revolution

Michael Greenberg, chair of the Department of Neurobiology, Harvard Medical School<br/><br/>Photo by Joshua Touster

This has been called the century of the brain. How accurate will that label prove to be?

Very. We’re poised for a revolution of discovery. Many neurological and psychiatric diseases still need to be understood, and many treatments and cures need to be developed. With proper investment, we’ll see astounding discoveries unfold, enabled by microscopy, imaging, and genomic technology. I expect progress in neuroscience to accelerate in this century, just as cancer biology and molecular biology did in the second half of the last.

What role do you expect Harvard Medical School to play in that revolution?

A key to the neurobiology department’s future lies in its past: One of the most profound neuroscientific discoveries of the twentieth century was made here, when David Hubel and Torsten Wiesel showed, in the visual system, that our interaction with our environment helps shape the development and function of the nervous system.

This department will continue to work at the frontier of discovery. Our broad research goal is to understand the development and function of the brain at the level of basic science, but with an eye toward finding therapies and cures for neurological and psychiatric disorders, such as Alzheimer’s, Parkinson’s, and schizophrenia.

What are the most common misconceptions about the brain?

One assumption has been that you’re born with a finite number of neurons, and as you age those neurons die. We now know that to be false; we grow new neurons throughout life.

Another mistaken belief has been that neurological disorders result primarily from neuronal cell death. We’re learning, though, that this might not be true for many diseases. We suspect that in some cases neuronal loss is the result of a loss or malfunction of synapses.

A third misconception, one that’s just now changing, is that developmental disorders of the nervous system—such as Rett syndrome and Fragile X syndrome—are so devastating that no treatment could ever help. We believed that once the brain failed to develop normally, we couldn’t do anything. But evidence now suggests—especially in disorders resulting from a disruption of experience-dependent aspects of brain development—that the brain is waiting for a signal. It’s almost as though the brain is frozen in time.

If we can figure out how to trigger that signal, devise an alternative route, or bypass it, we can make progress. I was recently talking with a friend whose brother-in-law has been incapacitated by Fragile X syndrome for decades. I was able to tell her about a drug being tested in mice that might eventually help him.

What are the greatest challenges?

One key challenge is understanding how neural circuits work—not just the synapse, but also the rules for circuit formation and function. We also need to expand our understanding of how experience shapes our brain by delving into the mechanisms of gene activation and expression.

What would readers be most surprised to learn about you?

I guess it would be that I didn’t train as a neurobiologist. My doctoral and postdoctoral work was in cancer biology. But I sometimes view my nontraditional path to neurobiology as an advantage. Unencumbered by the assumptions of classical training, I can bring a fresh perspective to the field. As a result, not many researchers are taking the approach my lab is taking to understanding the brain.

Also surprising, I suppose, is that I come from a family of artists and teachers. I didn’t grow up with a fascination with science; I wasn’t the kid pulling apart bugs. But when I first learned how DNA works, I became hooked, and science became my passion.


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