chemistry

The Godfather of Really Small Things

Ned Seeman’s nanoscale world

by Matthew Hutson

A disorderly office, however, is apparently an unreliable indicator of a disorderly mind. Amidst this chaos, Seeman, who has been on the faculty at NYU since 1988, works within a new realm of chemistry that he created, called nanotechnology, or the control of matter on the scale of billionths of a meter. It seems an impossibly delicate task, like building a ship in a microscopic bottle. But a wave of researchers is exploring an ingenious shortcut-essentially a way to get trillions of tiny ships in a test tube to assemble themselves-by using the programmable matter of DNA. Seeman recently built an entire assembly line using this technology, inspiring The Christian Science Monitor to call him the “Henry Ford” of nanotech. Earlier this year, he shared the biannual million-dollar Kavli Prize for nanotechnology-the field’s version of the Nobel. “For a long time, there were no other labs working on his ideas,” says William Shih, a chemist at Harvard University who also studies DNA nanotech. “Now it’s a rapidly expanding field.”

Though the ultimate utility of nanotech is still unclear, many scientists, including Seeman, believe it could revolutionize building materials, medicines, and even computers. Imagine an iPod Nano that’s actually nano. “Our goal is to further in a realistic fashion the kinds of things that people have been talking about with nanotechnology for many years, most of which has been bullshit,” says Seeman, who has longish hair, a bushy beard, and no objection to colorful language.

Seeman, who earned his PhD from the University of Pittsburgh in 1970, invented DNA nanotechnology 30 years ago when he was working as a crystallographer at the State University of New York at Albany. He loved the puzzle of trying to figure out the shapes of tiny molecules. Researchers in his lab would shoot X-rays at crystals and decipher what the component molecules looked like by how the structure scattered the radiation. But forming those crystals “is the dumbest experiment known to modern science,” Seeman says, because it’s difficult to control. You fill a container with many copies of the molecule you’re trying to crystallize, concentrate it, and hope they all line up in a repeating pattern. “If you get a glop of crap, you have no idea what you did wrong,” he explains.

One day at the local pub, Seeman was thinking about DNA junctions—created when strands of different DNA double helixes are unzipped and stuck together to form branched intersections—when an image by M.C. Escher popped into his head. The illustration, titled “Depth,” depicts fish swimming in a regular pattern with other fish lined up above, below, in front, and behind. He realized that if he combined the right strands of nucleotides, their sticky ends would meet up and they would automatically conform to a repeating three-dimensional grid of six-arm junctions, just like Escher’s fish.

“When I had that epiphany in the bar, I had been doing a lot of things that to me were really neat, but it wasn’t me,” Seeman recalls. “Crystallography was fun, and I was good at it, but something clicked in me that said, ‘This is what I’ve got to spend the rest of my life doing.’ ” Controlling matter on a fine scale using DNA had the analytical components of crystallography, but he saw considerably more potential for creativity.

Since this epiphany, Seeman’s work has spawned several branches of research now being conducted in more than 50 labs around the world—many of them populated by former students of his. One branch is the construction of intricate self-assembling shapes. In 1991, he and a collaborator built a cube that consists of six loops of DNA. Later he and another collaborator built a truncated octahedron, or eight-sided figure. Other researchers have made a smiley face and a map of the Western Hemisphere, a thousand of which could fit across the diameter of a human hair. There’s no immediate use for any of these shapes, but they were proof of a concept—any design could become a reality.

Seeman also helped give birth to the fields of DNA computing and DNA nanomachines. In the latter, manipulating the DNA strands allows scientists to control their movement like little machines. Years ago he built the first nanoscale inchworm walker. Others have made tweezers. “He invented a somewhat crazy field,” and for years was “a lone voice in the wilderness,” says Caltech researcher Paul Rothemund, who created the smiley faces and maps.

More and more people are listening to the “lone voice.” In May, Seeman’s team reported in the journal Nature that they’d built an entire assembly line out of DNA. A microscopic walker could pivot and move past three other machines, each holding a different cargo of nanoparticles. The scientists could direct whether each machine would reach over and deposit its cargo onto the “chassis” as it marched past. “A new chemistry, I believe, will come out of this in terms of control,” Seeman says. Creating molecules is currently a messy multi stage process that involves adding and removing protective groups of atoms at various stages to avoid volatile interactions among unfinished molecules. But with something like Seeman’s assembly line, researchers will eventually be able to manufacture drugs and who knows what else more easily and cleanly. It’s Detroit in a test tube.

Despite these leaps forward, it was only last fall, after nearly three decades, that Seeman finally constructed the DNA version of Escher’s “Depth”—a project he thought he could accomplish in five years. The path was more difficult than he’d expected. “On the way, we took what we thought of as baby steps,” he says, noting they continued breaking down the process to see why it didn’t work. This led them to discover: “Some of them were, in fact, giant steps.”

Though the ultimate utility of nanotech is unclear, scientists believe it could revolutionize computers. Imagine an iPod Nano that’s actually nano.