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Why an Economist Needs One of These Laser-Powered, Super Resolution Microscopes

Eighty-two years ago, when a young and struggling painter named "Henri Cartier-Bresson":http://motherboard.vice.com/2012/8/22/henri-cartier-bresson-the-father-of-street-photography-would-have-been-104-today--2 first saw Martin Munkacsi's photograph...

by Lawrence De Geest
Nov 14 2012, 8:11pm
Image of a different Leica microscope booth via AFTE

Lawrence DeGeest attended the 2012 Society for Neuroscience Conference for Motherboard. Read his previous dispatches here.

Eighty-two years ago, when a young and struggling painter named Henri Cartier-Bresson first saw Martin Munkacsi’s photograph “Three Boys at Lake Tanganyika,” he said “Damn it” (or something equivalent in French) and immediately went to the street with his Leica. He went on to become the father of modern photojournalism, before returning to art. Those years of photography, he felt, made him a better painter. This may have been on my mind as I marched with an economist colleague, who was inspired by one of the many neuroscience posters she’d just seen, to the Leica stand in the SfN 2012 exposition center to inquire about a microscope.

Before we get there, you might ask what a pair of economists are doing at a neuroscience conference in the first place. Well, a love of science and post-conference drinks is one thing, but neuroeconomics is a burgeoning field aimed at studying the roots of decision making. Neuroeconomics has made efforts to identify possible neural correlates to economic theory institutions such as utility, and pinpoint mechanisms behind why we choose what we do, which has obvious importance to economics. If we (ruthlessly and recklessly) distilled distill the essence of economics down to the study of people’s monetary decisions, what’s more important than the brain?

The exposition center resembled a bazaar specializing in high tech gadgetry. Some company representatives are scientists themselves, but others are plain salesmen with an eye for a researcher with grant money to spend. “You sir, that’s a handsome fountain pen I see in your pocket, allow me to demonstrate the precision of our lasers with an engraving of your name.” “Can’t quite edit genomes in your monkey’s brain just right? Look no further than GeneArt!” Best of all was the representative for Life Technologies, who brought his pitch home with a ten minute magic show to an applauding crowd. Meanwhile, graduate students floated from stand to stand, collecting free mugs, t-shirts, and tote bags, which one starving student filled with a year supply of pens.

Leica reps, dressed in khakis and black polos, were leaning against their equipment when my colleague approached and said, “Gentlemen, your microscopes please.” After the director from Mannheim quizzed her research purposes – she was unsure, saying only that she had inspiration, which was true, and had just come into a grant, which was not – he called over the resident expert on confocal microscopy.

“This economist likely needs to examine brain slices,” the director told the expert, who was confused. So I, in support of my dear colleague, offered: “I believe what she wants is to get down to the bottom of things like never before.” Inordinately vague, sure, but it was enough to convince the expert to tour us through the latest in microscopy, a spectacular machine called the Confocal Laser Scanning Microscope Leica TCS SP8, which looks like something Apple designed, and which we called Lucy for short. But before presenting Lucy, the expert, who had the presence of Paul Simon telling songwriting stories, first wanted to talk about Leica’s history.

“Before cameras, we made microscopes,” he said. “It wasn’t until 35mm film was introduced that we started with cameras. There were these Germans who wanted to film the effects of a flood, but because 35mm film was too expensive to risk unusable footage, they took single frame shots as tests. That spurred the development of 35mm camera film. The rest is history.”

I asked the expert if he was familiar with Cartier-Bresson. “Do I not have his pictures of New Orleans pasted onto my office wall in Illinois?” he said.

Having declared his love for what can be seen with a good eye, our expert presented Lucy, who he said was well-endowed with a relatively new imaging technique, Stimulated Emission Depletion (STED), a method of super-resolution. Looking into the eyepiece while the expert flicked a switch that activated the laser and turned a knob that focused the objective, I observed what appeared to be a neon-green orange slice against a black backdrop. It was a dyed cell nucleus, filled to its borders by minuscule dots. These were extremely fine intra-cellular particulate matter, each approximately ten microns in diameter, and they almost had a fuzzy glow. This occurrence is what the expert, after a lengthy explanation involving optics, physics, and perhaps voodoo for good measure, eventually called noise.

Drop a briefcase of cash at Leica’s door and they’ll set you up with your own STED ’scope.

“When you look at something extremely close up the tiny things will may dominate your view,” said the expert. “That’s noise, and you want to remove it so you can see what you are after.”

Image noise removal will be familiar to any of you that are into photography, but it’s not exactly easy to use Photoshop for a microscope. What makes Lucy incredible is that she removes noise in real time. With this in our minds, the expert activated the STED laser to commence the noise-removal demonstration that is Lucy’s prize quality. I was asked to stop investigating his press badge with the microscope, while my colleague listened attentively.

“How much an instrument like the human or a microscope can produce an image of an object is limited, and what can’t be accurately detailed is the noise,” said the expert. “But what we can do by super-resolution is average many images of the same object, which smoothes out the effect of the noise on the aggregate image.”

STED then achieves higher detail by minimizing noise, in a process that superficially sounds similar to image stacking in HDR photography. The science behind STED goes way back to Einstein discovering stimulated emission, a process in which an electron interacting with an electromagnetic wave transfers energy in the form of a photon to the ambient electromagnetic field. When the transfer of energy exceeds absorption, optical enhancement of the field occurs. Did our dear Einstein have this in mind all along? Fiddling equations alone in a humble home office in Vienna, wondering how to see the details of the universe like Galileo before him? Who knows, said the expert. “You can invent the future, but you can’t predict where it will go.”

We watched the cell nucleus come into focus on the computer monitor as STED went into action. On the left hemisphere of the monitor were controls that controlled the STED laser loading images into the monitor’s right hemisphere. Once one image was loaded, another would be loaded on top of it, and as this happened there was a line running down the image space from from top to bottom, like the line that ran down old television screens when you adjusted the antenna to get better resolution. The super-resolution process happened very fast. Within thirty seconds all the noise from the orange slice was removed and all that remained was a clean, clear image of the vast emptiness of a cell nucleus. The expert said it was a neural cell from the hippocampus, the memory region of the brain.

A comparison between confocal and STED imaging, via the Max Planck Institute

“See anything that interests you in there?” he asked my economist colleague, and indeed it did.

Neuroeconomic work is driven by research utilizing functional magnetic resonance imaging (fMRI), which can chart activity in the brain. Perhaps there indeed are parts in the brain that drive economic behavior. Or perhaps it is closely connected to other behavior and the job is to understand such connections. But what cannot be seen, at least not yet, is intra-cellular communication, or information sharing between cells in the brain that could reveal how the many regions of the brain work in cooperation or conflict with each other.

This type of theorizing is a long way from paper and pencil, so what an economist would ever need a microscope for was beyond our expert. My colleague did not know either. What she knew was that what happened in the brain would happen whether or not academics categorized them by terminology that changed from field to field. Your brain doesn’t care what a particular researcher calls its processes, it just does what it does. “Why should it be that one field has the answer and the rest are unnecessary?” said the look on her face as she gazed into the empty cell on the computer monitor.

“How much does it cost?” she asked.

“$120,000.”

“That is ten-thousand times what I paid for lunch,” she replied. In any case, the pair exchanged information – maybe her advisor would suddenly decide to build an economics laboratory – and wished each other a good conference.

Everyone has a purpose to find or, if things went bad, to rediscover. Our economist walked out the conference center, where her colleagues were waiting for her at the Howling Wolf. Economists believe that preference is revealed by choice and for this they are sometimes labeled shortsighted by neuroscientists who believe that preference is revealed by deep-rooted neural processes not always expressed by actions. But who’s to say definitely that either, or both, is correct? I say let them all have microscopes and brains. Then, at least, they will have something to laugh about together at the bar.