COVER STORY

Your Beautiful Brain

Dispatches from the frontiers of neuroscience.

by Bill Retherford '14JRN Published Winter 2016
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Just as neurons need to commingle, apparently so do scientists. The stereotype of a lone researcher experiencing a eureka moment in a secluded little lab survives only as a science-fiction trope. In real life, discovery hardly ever happens that way. “These are complex problems, and we have not broken them,” says Richard Axel ’67CC, a Zuckerman Institute codirector and Columbia professor of biochemistry, molecular biophysics, pathology, and neuroscience. “The ability to understand will require looking at a problem through a multiplicity of eyes.” The relocation to the Greene Science Center collects researchers from more than twenty disciplines throughout Columbia: neuroscientists, data scientists, molecular biologists, stem-cell biologists, electrical engineers, biomedical engineers, psychologists, mathematicians, physicists, theorists, and model builders. “If you only talk to people who work on the exact same thing you work on, you probably don’t generate as many new ideas as you could,” says Bruno. “Getting together people with different expertise, very different research programs, but a common purpose of understanding the mind — yeah, that’s fabulous.”

The stereotype of a lone researcher experiencing a eureka moment in a secluded little lab survives only as a science-fiction trope.

Scientists don’t necessarily put a premium on luck, but they do subscribe to serendipity — of which proximity is a catalyst. “Science is a completely social interaction,” says Eric Kandel, the third Zuckerman Institute codirector, and a professor of neuroscience, psychiatry, biochemistry, and biophysics at CUMC. “I met Richard Axel in the late seventies. He became interested in the brain and nervous system. I wanted to learn molecular biology. Axel knew nothing about the brain. I knew nothing about molecular biology. And so we started to collaborate. He moved full-time into the brain, and I became comfortable with molecular biology.” Since that collaboration began, both men have become Nobel laureates.

Eric Kandel says that when he came to Columbia, in 1973, "almost everything you learned was something new." / Photograph by CUMC

At the Greene Science Center, a neuroscientist could, and almost certainly will, run into an electrical engineer or stem-cell biologist in a hallway, engage in conversation, and — eureka, ideas collide — that brief exchange may kindle new research, which may lead to collaboration, and after years or decades, maybe a cure. Like neural connections, discovery happens for one reason. Someone gets excited.


Kandel, eighty-seven, has been at Columbia forty-three years.
On his office desk sits Principles of Neural Science, a textbook he coauthored in 1981, and now in its fifth edition. This particular copy, hardly conspicuous, lays beneath his computer monitor and serves as a screen booster.

“Look, I’ve been in the field for sixty years,” says Kandel. “We’ve made a lot of progress. But we’re at the beginning.”

Back in 1952, when Kandel was an NYU medical student, science really, really didn’t know much about the brain: “We didn’t know how smell worked. How taste worked. We knew nothing about learning and memory and emotion.” During the fifties, says Kandel, the only major brain lab in New York City was Columbia’s. Even the word “neuroscience” wasn’t coined until 1962. He recollects the first annual meeting of the Society for Neuroscience in 1971; 1,400 scientists showed up. Today, more than thirty thousand from eighty countries attend. “And now you can’t walk down Broadway without running into a half dozen brain researchers,” Kandel says, half joking. He joined Columbia in 1973, but even then: “So little was known. Almost everything you learned was something new.”

That is still true today. “There are so many psychiatric and neurological diseases that we just don’t understand and don’t treat successfully,” says Kandel. “This is a phenomenal problem facing humanity.” Among the more common brain disorders: Parkinson’s, Huntington’s, Tourette’s, epilepsy, narcolepsy, depression, panic attacks, anxiety, ADHD, OCD, and PTSD (there are hundreds more). “You have to be an optimist in this field,” says Jessell. “It’s big and it’s complicated. It’ll take time to achieve satisfying answers to some of the bigger questions.”

But an imposing technological apparatus, which may help fast-track potential treatments, is arriving. One example: in the basement of the Greene Science Center will be an array of eighteen two-photon microscopes. With them, scientists will see neuronal communities talk to each other in real time; researchers will record those glinting images and replay them endlessly for study. Five years ago, none of this was possible. The amount of data generated by the two-photon is immense, even when the experiment is a simple one. Put a lab mouse on a treadmill, scan the neurons twinkling in its hippocampus for a half-hour — and a terabyte of information emerges, enough to keep Zuckerman Institute mathematicians and statisticians decoding for weeks.

Two-photon microscopy is state-of-the-art, but perhaps only for the moment. Fortified with a $1.8 million grant from the National Institutes of Health, Zuckerman Institute principal investigator and biomedical engineer Elizabeth Hillman is developing SCAPE, a microscope that widens the view from small neuronal groups to whole brains. “With SCAPE, we can see the entire brain of an adult fruit fly in real time as it walks, crawls, even as it makes decisions,” says Hillman; SCAPE’s three-dimensional images generate ten to one hundred times faster than the two-photon. “This advance,” says Jessell, could “unlock the secrets of brain activity in ways barely imaginable a few years ago.”

And it could lead to cures. Already, researchers routinely manipulate individual neurons with electronic nudges, and can even turn off the genes inside a fruit fly’s motor neurons (a nifty trick, given that a fruit fly’s entire brain is barely bigger than the tip of a toothpick). Now, after shutting off the relevant genes, scientists may use SCAPE to look for the fly’s motor impairments, identify its faltering genes — then (one day) map the results onto the counterpart human genes. Somewhere therein could be clues to curing ALS, a grim and currently irreversible motor-neuron disease. “Science goes schlepping along,” says Zuker. “Then breakthroughs come that let you jump the steps. You go boom, you jump — boom, you jump — and a mega-barrier is lifted. How soon can discoveries be brought to patients? I cannot tell you. But we are far closer than we were before.”

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