Dancing with molecules

Nicknamed the "paper machine" by Matthias Roth GS, chemistry professor Herschel Rabitz has collected an astounding 653 publications for nearly four decades of work in the fields of chemistry, physics, engineering and biology.

Rabitz, predominantly a theoretician, seeks to push the boundaries of what we can control.

He's working on "manipulating the motions of atoms and molecules using lasers to make the molecules dance."

"We want them to dance to our tunes," Rabitz said.

His ultimate goal is to pull apart atoms and use lasers as a "molecular pair of scissors."

This problem has fascinated scientists for 40 years, Rabitz said, but they have primarily approached it through the limited approach of intensely focusing a single wavelength of laser — red or blue, for example — on a molecule.

But that idea is too simple, he explained, because molecules move in complicated ways.

"You don't make a Beethoven sonata by playing one key of the piano because you're sensitive to the sounds. Likewise, a molecule responds to many different frequencies," Rabitz said. "If you want to control a molecule with broad frequencies, you need a laser with many colors and the ability to control them simultaneously."

The technology that enables this work comes from recent developments in the telecommunications industry, specifically the optical fibers that carry signals between phone connections.

Designing the lasers necessary for molecular manipulations involves a quantitative understanding that did not exist in the past, though. Rabitz developed an algorithm to control the equipment to run experiments.

This invention enables humans to direct computers that may be more effective at designing experiments than humans alone.

"A photonic reagent, shaped light that interacts strongly with molecules, can create a reaction that happens in a fraction of a second," he said. "By putting a computer in the loop, it can then predict the next appropriate experiment so that we can hone in on the target, fine tuning the molecules to make them dance."

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To stay at the cutting edge of science, Rabitz said, "You have to work very hard." He comes in every weekday at 5:30 a.m. and stays until 6 p.m., usually continuing his work at home at night.

"Someone has to make the first pot of coffee for the building, and indeed I do," Rabitz said.

Molecular patterns

Rabitz was awarded the WE Lamb Medal for Laser Science and Quantum Optics "for inventing the learning algorithm approach to the coherent control of quantum phenomena with important and wide-ranging impact," according to a plaque that rests in his office.

This patented algorithm also has applications in the pharmaceutical industry's efforts to discover biological molecules.

Organic chemists involved in drug design synthesize compounds that target enzymes to offer therapeutic value for patients. But there are hundreds of possible chemical compounds that can be substituted to create different molecules with different properties and levels of reactivity.

Scientists must ask the question, "Is there a pattern among the properties of the molecules we have made and possibly even those we have not made?" Rabitz said.

By making a small subset of the compounds and measuring their chemical properties, such as ability to bind to proteins, researchers can generate data that can be graphed in a number of ways.

Rabitz's algorithm involves pattern recognition that reflects the regularity involved in discovering molecule possibilities. "You may have discrete things, but there is a way of sorting them out," he said. "Whether you are developing ways to more effectively discover drugs or looking for chemical fluxes to manipulate in biological systems or shaping a laser pulse, all of these efforts are related through taking a systems perspective as problems of control."

The technology could have powerful implications in biological systems, which are basically complex chemical factories themselves. The introduction of chemical fluxes will enable scientists to similarly "steer" in vivo functions, Rabitz said.

"We are looking into the possibility of neural manipulations to arrest diseases like Parkinson's," he said.

All work and no play?

Rabitz attests to long hours and constant diligence, but he says that the students in his group work hard too. He recalled an amusing exchange with graduate student Lillian Pierce '02. When she had offered to meet him at any time, Rabitz jokingly suggested 3 a.m. and was shocked when she agreed.

This playful outlook and sense of humor may have contributed to his tremendous success. Pierce said, "I've always remembered him chuckling about how wonderful it is to be a theoretician, because you can be anywhere — standing on a street corner, waiting for the light to change — and at that moment you can be working on a problem in your head."

Rabitz's example "conveyed the idea that research isn't 'work,' so much as it is a pursuit of insight, a constant game that you can play wherever you are," she said.

Roth, who also studies the applications of laser technology, attributes Rabitz's success to his eagerness and "ability to get other groups involved, even if they are the competition," he said. "In the end, it helps to push the research forward."

Rabitz has collaborated with scientists such as Joshua Rabinowitz in the genomics arena, developing "mathematical descriptors for what's going on in living systems," Rabinowitz said. Specifically, they have studied cellular metabolism and its function in synthesizing DNA.

Rabitz is unique in his ability to use mathematics in "computer algorithms that are robust enough to apply to the real world, which makes him extremely helpful to experimental scientists like me," Rabinowitz said.

Though predominately a theoretician, Rabitz works with students in a program to interface with experimentation. "It's a fantastic program and is a wonderful experience for the students because it involves a mix of many fields, which only works because we all come together," he said.

Boris Russ '06, who worked with Rabitz on computer simulations for biological systems, described him as a "really funny and intelligent guy who was always available for discussions." Rabitz explained everything clearly, Russ recalled, from the very simple to the most complex of ideas, and derived everything he described from scratch.

Similarly, Pierce recalled from her undergraduate studies in Rabitz's lab that "it was a really nice experience to work with a scientist who not only thought about science at the most complicated level of abstraction, but who also appreciated how important it is to translate deep concepts into graspable, memorable language — and who enjoyed bringing out the playfulness and beauty of science."

What Rabitz finds most rewarding about his job is the opportunity to create and to discover things that no one had seen before.

He also enjoys drawing "together different fields where the sum is larger than the individual fields." Emphasizing the importance of interdisciplinary work, he said that the laser would never have worked if all the pieces didn't fit together.

"We're after the fundamentals," he said. "This is Princeton, not an industrial laboratory, and we want to not only make it work, but to also peel back the layers and understand how it works."