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Step by step, Südhof stalked the devil in the details, snagged a Nobel

Devil on the staircaseIt took him a few decades, but - in league with a handful of colleagues scattered around the world - Stanford neuroscientist Tom Südhof, MD, assembled an impressively complete picture of how each of the roughly 2 quadrillion nerve-cell to nerve-cell connections, or synapses, in our brains work. The synchronized firing patterns of these electrochemical contact points underlie all consciousness, movement, and back-office operations such as sleep-wake cycles.

In the few weeks between Südhof's receiving the Lasker Award (the Nobel Prize's less known but almost equally scientifically prestigious American equivalent) and his winning the actual Nobel a couple of weeks ago, I asked him whether he'd had any "Eureka!" moments when, in a dazzling stroke of insight, he instantly grasped the Big Picture. As I wrote in a story:

Südhof noted that in his experience, science advances step by step, not in jumps. "I believe strongly that most work is incremental," he said.

Südhof's fellow 2013 Nobel laureate, Stanford biomolecular-modeling computer scientist Mike Levitt, PhD, has remarked similarly, that serious scientific pursuits proceed step by step. Each step may itself be highly technical, its importance all too often impossible to explain in a nutshell to nonscientists.

For a simplified summary of Südhof's science, see here. But for now, it's enough to say that a synapse is much more than a simple switch. "A synapse is not just a relay station," he told me. "It is not even like a computer chip, which is an immutable element. Every synapse is like a nanocomputer all by itself."

In painstakingly identifying the manifold molecular mechanisms that control the exquisitely timed events at the synapse, Südhof's research has contributed massively to our understanding of  the healthy brain. It has also shown how disturbances in the detailed and daunting interplay of the numerous proteins involved in that careful choreography can contribute to autism, Parkinson's disease and more.

But, as Südhof points out in a wide-ranging review article just published in Neuron, the devil is in the details:

[U]nderstanding the brain is not like understanding a house where features like air ducts, electrical connections, and window locks are just details that you do not really need to know in order to live in it.... [T]he brain is rather like an assembly of billions of houses - the synapses - each of which has [its] own air ducts, electrical connections, and window locks... Moreover, it is necessary to know how the houses change, as there is continuous construction activity, demolition and rebuilding of houses, or just renovations - a never-ending series of changes... [U]ntil we understand how synapses work, how synapses differ from each other, and how synapses change as a function of use over milliseconds and years, we will not be able to understand how the brain works, no matter how many connections have been mapped... [T]he molecules which make up a biological system are actually more than trivial details but are the system... [S]tudying and understanding them is not just an unfortunate necessity but the only avenue to building the building in the first place.

Previously: The lure of research: How Nobel winner Thomas came to work in the basic sciences, But is it news? how the Nobel Prize transformed noteworthy into newsworthy, and Revealed: The likely role of Parkinson's protein in the healthy brain
Photo by NYCDOT

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