American Scientist

Biology watchers are accustomed to seeing the periodic, rapid evolution of new taxa in the field of life science. Biochemistry begets molecular biology which begets a litter of -omics that now lend novel coloration to departmental letterheads. The names of the new branches in the evolutionary tree have been troublesome. Molecular biology under the nomenclatural x ray seems to mean the same thing as biochemistry. So what do we make of the emerging discipline of systems biology? We can begin by visiting the terrain where it hunts.

The Institute for Systems Biology (ISB) in Seattle, Washington celebrates its 10th anniversary in 2010. The institute is the brainchild of Leroy Hood (Lee to everyone), who cofounded it with immunologist and cell biologist Alan Aderem and cell biologist and proteomics pioneer Ruedi Aebersold. Hood’s specialty is harder to pin down; call it paradigm change. He has been a central figure in the evolution of instrumentation, the human genome project, cross-disciplinary biology, systems biology and his current project, inventing healthcare for the 21st century by using a systems biology approach to create a regime of personalized, predictive, preventive medicine. In presentations, Hood often says, “In 10 years...” According to Hood, in 10 years patient care will be based on rapid, inexpensive sequencing of individual genomes, analyzed using the high-horsepower information science techniques to assess the combinatorial interactions among thousands of variant genes—billions of data points for each patient. In short, a systems biology approach.

What is the fitness of this new link in the scientific foodchain, systems biology? The SCImago Institutions Ranking generator, based in Spain, analyzes the output and impact of the top 2,000 research institutions in the world. They determined that ISB research has the highest scientific impact in the United States and the third highest in the world.

So what is a systems biology approach as defined by ISB? “A whole new way of doing science,” according to faculty member Nitin Baliga, whose expertise includes microbial genetics, extremophile biology and gene regulatory networks. “Each faculty member brings a different expertise to the table. There are geneticists, molecular biologists, chemists, engineers, mathematicians, computer scientists. What brings them together are biological questions.” The founding idea was to use information science to decipher biological complexity, developing the necessary technological tools along the way to capture, rather than reduce, the inherent complexity, then to use computing power to discover what the amassed data can tell us. High throughput is a recurring theme, applying to both data collection and analysis. Advances in microfluidics, nanotechnology and other fields create vast new data sets—for example, extraction of 2,300 protein measurements from a single droplet of blood. Multiply that by expression patterns, chemical modification, half-life and known interactions with myriad other molecules in the cell. Repeat for several hundred million individuals. Stir in new mathematical and computational techniques to make sense of it all. Add fearlessness and a culture of collaboration and you get systems biology at ISB.

Dedication to interdisciplinary science is evident in the very architecture of the ISB facility. “If you take a walk through ISB, you see very few walls. This is done on purpose to allow people from different groups to talk to one another and set up collaborations across groups,” says Baliga. The size of the institution is a calibrated part of the experiment, with just 14 faculty and 300 staff members. Says Baliga: “There is a critical mass. When you cross the critical mass, you tend to decay into departments.”

Is systems biology a paradigm change? Says Hood, “When you change paradigms, you can talk about it until you’re blue in the face. What convinces people is success.” Based on the impact ranking of ISB, systems biology is taking over its niche.