Seattle is home to well-known scientific powerhouses such as the University of Washington and Fred Hutchinson Cancer Research Center.

But most locals would be hard-pressed to name the upstart that bested all U.S. research labs in a recent ranking of scientific clout: the Institute for Systems Biology (ISB).

"For an institution that's only 10 years old, this is nothing short of remarkable," said Dr. Leroy Hood, the maverick biologist and entrepreneur who split from the UW to form ISB.

Hood's ambitious goal is nothing short of a revolution in medicine.

At the institute's complex on the north side of Lake Union, biologists, engineers and computer wizards are working to unravel the intricate web of genes, proteins and biochemical signals underlying human disease.

Hood is convinced the work will lead to better drugs, earlier diagnoses and "personalized medicine" — the ability to more precisely tailor medical treatments to individuals.

Landing on a list ahead of Harvard University, the Massachusetts Institute of Technology and other elite research centers shows ISB's approach is paying off, said co-founder Alan Aderem.

"There were a lot of naysayers when we started."

ISB made national headlines last month for its full-genome analysis of a family of four from Utah. The work pinpointed the mutation responsible for a disfiguring disease that affects the family's two children.

The institute also scored a surprising coup when the tiny European nation of Luxembourg decided to invest more than $100 million to pioneer personalized medicine. ISB scientists will sequence the genomes of 100 Luxembourgers to identify genetic variations linked with disease and drug response.

But one of the main reasons ISB isn't a household name in its hometown is that much of its research has focused on far humbler creatures: yeast, sea urchins and the type of bacteria that thrives in the Great Salt Lake.

That's because systems biology is so mind-bogglingly complex it would have been impossible to start with human studies, Aderem said.

Even Hood struggles to explain the endeavor in simple terms. At its core, he said, it looks at living things holistically, rather than focusing on single genes or pathways.

In the past, Hood has offered analogies to automobiles and football to make the point that the whole is greater than the sum of its parts. These days, he favors the radio.

If engineers wanted to figure out how a radio works, first they would break the machine into its components, he said. Decades of research on the building blocks of life and the sequencing of the human genome have provided an equivalent parts list for biology.

To understand how a radio functions, though, it's necessary to assemble the parts in circuits and see how they interact. In humans, the circuits can include thousands of proteins, scores of genes and multiple environmental factors that interact to cause a disease like diabetes.

Daunting complexity

Until recently, there was no way to sort out such tangled networks. The best scientists could do was to focus on individual genes or the workings of a particular enzyme — an approach that has proved disappointing in terms of medical breakthroughs.

Now, a new generation of lightning-fast machines coupled with unprecedented computing power is providing a big-picture view.

Hood kick-started the era with his development of automated DNA sequencing machines that made the Human Genome Project possible. ISB scientists spend a lot of time designing similar tools to identify and measure the mélange of molecules that are crucial to the way cells function.

One of the institute's most influential projects described a method to identify and measure hundreds of proteins in a drop of blood.

That ability is crucial to one of Hood's objectives: pinprick tests that diagnose disease in its earliest stages by detecting minute changes in a person's blood.

A big chunk of ISB's floor space and energy is devoted to computer processors and the programmers who interpret the blizzard of data churned out by systems biology. To identify "biomarkers" that show up in the blood before the onset of a mad-cow-like disease in mice, ISB scientists analyzed 30 million biological measurements.

"The human mind itself is not capable of integrating that amount of information," Aderem said.

Skeptics of systems biology said it wouldn't be possible to sort through haystacks that big and pick out useful information. Those who remain skeptical note that the field hasn't delivered blockbuster drugs or diagnostic tests.

Systems biology is still in its infancy, Hood admits.

In the early days, he put up $5 million of his money to keep the institute afloat until it could attract funding. ISB still hasn't scored the major endowment Hood sought, but its budget hovers around $50 million a year, mostly from federal grants. At least 100 other systems-biology programs have sprung up around the world in the past decade.

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