Friday, May 02, 2008

Biology's Next Breakthroughs

Biotech pioneer Leroy Hood explains how systems biology will impact medicine.

By Katherine Bourzac

Biotech pioneer: Leroy Hood, president and cofounder of the Institute for Systems Biology, in Seattle, invented several tools, including the automated DNA sequencer that helped make it possible to sequence the human genome. Credit: Institute for Systems Biology

In the 1980s, Leroy Hood was something of a maverick. At a time when most biologists wanted nothing to do with the tools and methods of engineering, Hood developed a series of tools that have revolutionized biological science. As a professor at Caltech, he developed four fundamental, automated tools that have helped make possible the comprehensive study of the human genome: a DNA sequencer, a DNA synthesizer, a protein synthesizer, and a protein sequencer. But the Caltech administration wasn't interested in commercializing these technologies, so Hood cofounded a company that became Applied Biosystems. (He has also helped found several additional biotech companies, including Amgen.)

In 2000, after a stint at the University of Washington, he started up the Seattle-based Institute for Systems Biology, where he is president. Traditional biology tends to study one gene or protein or process at a time. Systems biology takes a cue from engineering and treats organisms as complex systems. Systems biologists, often using computer models, try to understand how genes, proteins, cells, and tissues interact to create complex organisms. By mapping out, rather than reducing, biological complexity, systems biologists hope to reach a new understanding of the fundamental processes of life, from embryonic development to normal metabolism to the emergence of diseases like cancer.

The approach has expanded biologists' understanding of simple organisms like E. coli. But dramatic success has been slow in coming. So far, systems biology's successes have been at the level of single cells, not tissues or whole animals. At the Institute for Systems Biology's International Symposium this April, Hood talked to Technology Review about how systems biology will eventually change human medicine and even materials science.

Technology Review: What are the challenges in applying systems biology to human disease?

Leroy Hood: What we've seen with systems biology in the last eight years or so is that it's very powerful in approaching single-celled organisms, be they bacteria or yeast. Their genomes are much smaller, and our ability to manipulate bacteria and yeast genetically, environmentally, and so forth is much, much greater. As a consequence, we've learned an enormous amount about these single-celled organisms, and in fact we've developed very powerful tools for unraveling networks that begin mechanistically to explain how they respond to their environments.

One of the grand challenges in systems biology is to move from simple, single-celled model organisms up to higher organisms--flies and worms, eventually to mice, and ultimately to humans. Those transitions are enormously complex, both because of the greater number of genes and the greater number of combinatorial possibilities.

TR: How are you making this transition to higher organisms?

LH: A powerful approach is to apply these techniques to individual [human] cells. One important reason for doing single-cell analysis is to be able to use some of the very powerful tools we've developed in single-celled organisms. But when you do single-cell analysis, you lose out on the context, the interaction with other cells [that happens in tissues]. One of the fascinating and unanswered questions is, are you going to be throwing the baby out with the bathwater?