Building a Universe a Molecule at a Time

Of all chemist Michael Sailor’s many prestigious awards, the one that probably describes him best is the small stuffed lamb that sits atop a file cabinet in his office at UC San Diego.

It was given to him by colleagues after his first year of graduate work in 1984--the prize for “best new researcher under the mental age of 3.”

A quick scan of his office shows that nothing much has changed. There’s a Fierce Warrior remote-controlled car (black with orange flames), a gum ball machine, Mr. Potato Head, Elvis bubble gum cards, and Bananas in Pajamas --the lab mascot.

The toys are testimony not only to Sailor’s playful approach toward the material world, but to the nature of the work he does. In a sense, it’s a grown-up version of Tinker Toys.

Except he can’t actually touch the building blocks he uses to make his creations. They’re much too small--molecules, in fact.

If chemists can learn to manipulate molecules like Tinker Toys, they could build a universe of tiny new machines able to crawl inside the human body to do repairs, networks of brain-like computer circuits, sensors that can pack together to put a whole laboratory on a chip.

Building from the molecules up means that scientists could invent whatever materials they need to do the job. Materials that glow, for example, make good sensors because they send a visible signal when something affects them. Materials that conduct electricity are good for switches and circuits.

Across the hall from Sailor’s office, in one of several labs he runs, amid the glassware, computers, lasers and other electrical gadgetry is a small copy of Michelangelo’s famous Sistine Chapel image of God reaching out a holy finger to Adam, bestowing life.

“This is the perfect picture of what we do,” says graduate student Christian Gurtner, who works with Sailor. “Of course, we’re on a smaller scale. But then, we don’t really know how big God is.”

Sailor’s lab is the focus of a new brand of creation science, bringing to life the microstructures behind the future of everything from computers to medical technology.

The driving question for these molecular-scale machinists is: How do you build things from the molecules on up? How do you stack one molecule after another on top of each other when molecules are too small to touch? How do you tell the next molecule where to go?

“People always say, ‘When they made you, they broke the mold,’ ” says Sailor. “But there is no mold that made your nose the way it is, there’s no mold that constructed your eye. It was all built using chemical reactions.”

Building complex three-dimensional structures is something “nature does really well,” says Sailor. “And it’s the one thing that we don’t have the capability to do well.”

If they could learn how to imitate nature’s methods, these creationists could create a micro-world from the ground up that could revolutionize technology.

Sailor, considered a top researcher in the rapidly blossoming field of materials science, sees a future of tiny bio-sensors that can see, feel, smell, do drug screening and DNA analysis and sense antibody levels. “You could put an entire lab on a chip,” he says.

Networks of artificial nerve cells--grown in the lab, molecule by molecule into three-dimensional arrays--could vastly enhance the thinking power of computers, making them work much more like the human brain. “You could rewire your brain if you lost some connections because of head trauma,” says Sailor.

Medical procedures could be simpler, less invasive, he says.

“You could put some little Roto-Rooter thing into the body’s blood vessels,” says Sailor. “Angioplasty right now is done with this big old fat balloon. If you could have these little teeny-weeny machines, you could make these little robots that could climb through your body and clear everything out.”

Since these microstructures are much too small to build with human-scale tools, Sailor figures out ways to seduce the molecules to do the work for him--including molecular-scale Darwinian evolution. “It’s a way of building Lincoln Logs or Legos using chemical tools instead of your hands.”

As a bonus, this world of truly tiny things is overflowing with surprises. Dull silicon, for example, glows when scratched with tiny indentations--a completely unexpected effect. One of Sailor’s claims to fame is a fingernail-size etching of Elvis in silicon that glows orange in black light. “Silicon doesn’t glow in the dark,” he says. “But when you make something small, it behaves differently.” And because the glowing colors change when the porous silicon is exposed to different chemicals, the chips could be used as chemical sensors.

The fertile ground that Sailor explores is the largely unknown territory where physics, chemistry and biology merge into the science of materials. Scientists have learned how to study subatomic particles by bashing them together in giant accelerators and sifting through the debris of collisions for clues to invisible events. They study atoms by looking at the light they give off. On a larger scale, scientists manipulate large hordes of molecules by attaching electrodes to things or they view them through powerful microscopes.

The science of matter on the molecular scale is somewhere in between.

It’s right under our noses, yet, until recently at least, terra incognita. “That’s the neat thing about it,” says Sailor. “No one’s ever really explored this size scale before.”

Until now, scientists haven’t had the proper tools to manipulate this world. When things get really small, you can no longer use a hammer and chisel, Sailor says. You can no longer use photolithographic techniques (of the kind used to etch computer chips), because light can only be focused down to a certain point.

But Sailor knows such tools exist in nature. That’s proved, he says, “by the fact that your brain is sitting inside your head with all these multiple connections. That was all built using just chemical reactions.”

A person starts out as a single fertilized egg that divides and multiplies exponentially. Along the way, intricate structures like eyes and brains and muscles appear, all constructed from the nutrients in the egg’s environment--and later on in the food the person eats. Somehow, each new molecule and atom finds its place in the scheme of things, attaches to the right place at the right time.

If nature can do it, Sailor figures, so can chemists. Working with an active group of postdoctoral, graduate and undergraduate students, he simultaneously takes two quite different approaches to inventing the tools that will one day build his micro-world: systematically studying how nature does it, and just fooling around.

Borrowing from nature is the most straightforward method. A living organism builds its parts out of the proteins created according to instructions encoded in DNA. Those proteins, says Sailor, are “the palette of molecules that the organism has available to it to build its structures.”

But how is the growth directed? “When a nerve has to grow out of the brain to try to enervate a muscle, how does that neuron know where to go?” Or take a shell, he says. Some are flat, some are corrugated. How does it know which shape to take?

“There are a few tricks that living systems use.”

For example, sending out growth hormones encourages structures to grow toward places where the hormones are concentrated--because the hormones are catalysts that speed up reactions.

Another trick is to provide a template for growth. Sailor’s first attempts to grow crystals into skinny sticks inside tiny channels has already produced a major surprise: Crystals can be trained to grow in one direction, even after they have left the “track.”

But by far the most successful trick borrowed from nature’s toolbox is what Sailor calls the “Darwinian” method. As in Darwinian evolution, changes in structure that are useful for the organism tend to survive over time while others disappear.

For example, a nerve that connects to another nerve in a useful way gets reinforced. “It gets nourished because it stays active,” says Sailor. “A nerve that goes from your eye down to your toe doesn’t do anything for the system, so it dies off.”

He first applied Darwinian methods to growing organic polymers--long strings of molecules that naturally branch out like nerve cells--to try to make brain-like arrays of neural connections. The problem was that they branched out in every odd direction, making a mess of “wrong,” or unwanted, connections. “We had no way of directing it,” says Sailor, “and we had no way of correcting the mistakes.”

So Sailor set Gurtner to work on growing little crystals that spread out from platinum electrodes like porcupine quills. Unlike polymers, the crystals can be dissolved--giving the scientists a way to “kill off” useless connections through a kind of guided natural selection.

In Sailor’s lab, survival of the fittest works by switching voltage--and therefore direction of electric current--between two fine wires each as thin as a human hair. Gurtner grows crystals between two platinum electrodes immersed in a yellowish solution the scientists call “our spinal fluid.”

Depending on the voltage between the two wires, the crystals take different shapes. Some grow like needles, others like tangled spaghetti. Others curl up at the ends or crisscross like cracked ice. “Most of these things are totally useless,” Gurtner says.

The crystals reach out randomly until, every now and then, one touches another. At that point, a tiny electrical circuit is made. Then Gurtner reverses the voltage, which shrinks all the crystals except the ones that connected. The one that made the connection gets reinforced, while the others die off.

“You’ve rewarded this one for making its contact,” says Sailor. Ultimately, he hopes to use this technique to grow electrical connections between wires that reach out to each other like the 3-D arrays of neurons in the brain, or atom-sized electrical circuitry for tiny robots and other molecule-sized machines.

There’s a lot more work to do--and a lot of it is far less goal-directed than the Darwinian growth scheme. This second approach to research, says Sailor, is a lot like butterfly hunting: nosing around to see what there is to see and catching whatever flies by. So far, his playful approach to discovery has paid off handsomely.

For example, one of his graduate students, Will Green, mixed together some chemicals and serendipitously discovered a kind of glowing “sand,” reported recently in the journal Science.

Glowing materials are more than just pretty; they are necessary for everything from digital clock readouts to computer monitors. The new phosphors could be substitutes for the toxic metals now used to produce the greens, blues and reds in color TV screens. The new material, Sailor says, “is basically sand.” Chances are somebody did make it [decades ago], he says. “But they never put it under a black light [ultraviolet] to see if it glows.” Successful butterfly hunters have to know where to look--and what they’re looking at once they have found it.

The unexpected turns and fast changes are what Sailor likes best about his field. “The style of research I have is suited to the TV generation. If I can’t do it in 15 minutes, I lose interest. I’m not going to spend my entire career looking for one particle. . . . Any question in materials science has lots of different solutions. Whereas if you ask, what’s the mass of the top quark, there’s only one correct answer.”

Materials science is also spilling over with questions that scientists--and industry--would like to ask.

For example, Sailor keeps the Fierce Warrior around as a demonstration of the limitation of current batteries. “They don’t last long enough. And you can’t recharge them indefinitely.”

Coming up with better solutions requires collaboration with scientists in many different fields. In fact, says Sailor, materials science is not a field at all, but a conglomeration of physics, chemistry and math. And although he’s officially a chemist, he spends more time in other departments. “I’m down in the physics and engineering departments. I’m their token chemist,” he says.

The thing he likes best is the prospect of beating nature at its own game. “Nature’s figured out how to do all this stuff, through evolution. But there are things we modern people want to do that aren’t necessarily what nature wants.

“Nature doesn’t care if we have glowing sand or laboratories on a chip. There’s no evolutionary pressure for that. But it sure would be nice to have.”

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Profile: Michael J. Sailor

* Born: May 18, 1961

* Residence: San Diego

* Education: Postdoctoral fellow at Stanford University and Caltech; doctorate from Northwestern University; bachelor’s degree from Harvey Mudd College

* Career highlights: UC Presidential Award for Excellence, 1995; Alfred P. Sloan Fellow, 1994-95; National Science Foundation Young Investigator Award 1993

* Interests: Biking, snorkeling, molecules, toys

* Family: Married