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Researcher believes there's an art to his science

Regan Thomson reached for pieces of red and black plastic and began snapping them together into a form that would seem abstract to the untrained eye. As he worked, he spoke about his philosophy, drawing heavily on the principle that restraint leads to creative breakthrough.

To an outsider, Thomson might appear to be an artist. But he's a scientist, and the model he was building represented a molecule found in a Chinese herb that he hopes to create soon in his laboratory.

Previously focused on the synthesis of plant molecules, the Northwestern University researcher now aims to use his knowledge to help develop cancer-killing drugs that won't make patients sick. This year, the Illinois division of the American Cancer Society awarded Thomson $720,000 as part of a program to support the work of young scientists.

Many drugs kill cancer cells, but they also attack healthy ones, said Thomson, 36. That is what leads to hair loss and other side effects experienced by chemotherapy patients. Thomson wants to design a better compound based on an understanding of how molecules form and behave.

The shape of the molecule in a drug matters, he said. The better the match between the molecule and a protein that regulates the behavior of a cancerous cell, the more likely that the molecule will bind to the protein, disrupt its function and kill the cell. The match he's looking for is "like a hand in a glove," he said.

It is a time-consuming, high-risk approach, though the payoff could be enormous.

Elizabeth Jablonski, director of research for the Illinois Division of the American Cancer Society, said the group expressed interest in Thomson's work because it isn't disease specific.

"We always try to look for research that is novel, has the greatest impact and that can influence as many cancers as possible," Jablonski said. "Regan is looking at one of the problems with traditional cancer therapies: the terrible side effects."

For Thomson, the struggle that comes before success is a big part of the scientific process. For inspiration he looks to contemporary American artist Matthew Barney and an idea called "drawing restraint."

"It comes from this idea that creativity comes from putting yourself in a constrained environment," said Thomson. "If you put yourself in this constrained environment, then you're sort of forcing yourself to have to adapt in it."

That limitation can drive discovery, he said.

"I like to work on compounds that I perceive as being very challenging to make because that forces us, at some level, to confront what our limitations are as scientists," he said. "That also means that, generally, more unexpected things happen, and you open yourself up to other interesting discoveries."

Thomson, a New Zealand native, received his Ph.D. at the Australian National University under the supervision of chemistry professor Lewis Mander, who called Thomson among his students "the best of the lot."

"I felt at the time that he could easily have taken over the supervision of the whole group," said Mander. "I am very sorry that we have probably lost him from this part of the world."

Thomson will be promoted to associate professor with tenure at Northwestern beginning in the fall, according to the university.

In his office, the model of the molecule buckled and flexed in Thomson's hands as he worked. Rings of black pieces representing carbon atoms joined to create a tangled, three-dimensional model interspersed with red and white pieces representing oxygen and hydrogen.

The complex design of the molecule, which extends in three directions, makes it ideal for binding with a specific problematic cell, Thomson said. He wants to synthesize it in the laboratory to give chemists more control over their experiments and because not enough of the molecule exists in nature to be practically useful.

"If you only rely on things available, you are limited to the amount that is made by nature," Thomson said.

But synthesizing molecules can be a time-consuming process, plagued by trial and error.

"The power of organic synthetic chemistry is that, in principle, we can make whatever we want," he said. "But we are limited by the tools that we have at our disposal as chemists."

Some of the oldest and most extensively used cancer therapies were derived from natural products, said Edith Glazer, an assistant professor of chemistry at the University of Kentucky. "They were isolated from a natural source and scientists had to develop the synthesis."

Enter academic researchers like Thomson.

"He's got a long and illustrious history of synthetic chemists making these natural products to work as (medicinal) agents behind him," said Glazer.

The scientific community is moving to re-examine large collections of natural compounds in hopes of uncovering previously overlooked molecules that could be used to fight cancer, according to Dr. Louis Weiner, director of the Lombardi Comprehensive Cancer Center at Georgetown University and an adviser to the National Cancer Institute.

"Placed in this context," he said, "the work that (Thomson) is doing is quite contemporary and an area of intense interest at a local, regional and national level."

Although he wouldn't call Thomson's work "out of the box" or completely unprecedented, Weiner praised the American Cancer Society and Northwestern for investing in young scientists and their new ideas.

"It's critically important that we make it possible for the next generation of great scientists to emerge because that's the only way we'll make progress," he said.

Now directing his own research group, Thomson's success among his peers may come down to one trait: persistence.

"We're in a society where we expect things to be at our fingertips and just be there instantly," Thomson said. "My experience is that a bit more time can lead to more answers."

Copyright © 2014, The Baltimore Sun
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