Engineers test their designs for automobiles and airplanes on computers, and similar approaches are being used to study cancer in the emerging field of systems biology.

The field is so new and diverse that systems biology means different things to different people. But clearly one goal is to create mathematical models of biological processes, and this can only be done by integrating information about the components of biological systems, such as genes and proteins, and their environments.

"The essence of systems biology is understanding the interplay between environmental cues and the information encoded in the genome," Dr. Leroy Hood, co-founder of the Institute for Systems Biology (ISB) in Seattle, said this summer during a lecture at the Jackson Laboratory in Bar Harbor, Maine.

He and others view biology as dynamic networks that interact with one another and with their environments. Networks change constantly, particularly during development and disease, and a single disruption can reverberate throughout "larger" systems.

Current computational models describe networks of genes and proteins that cooperate in specific tasks, or pathways. But in theory the behavior of an entire cell, groups of cells, or even whole organisms could be simulated - if enough data could be collected and analyzed.

In a study published this past spring, Dr. Hood's laboratory identified gene and protein networks that are disrupted in cells and in tissues affected by prostate cancer. Some proteins in these networks may be secreted into the blood, and the researchers are studying how the secreted proteins, the perturbed networks, and the clinical disease are related.

"The key point of this research is that you need to understand the whole system," says Dr. Biaoyang Lin of ISB, who co-led the study in the April 15 Cancer Research. The field will need new technologies and methodologies, he adds, noting that changes in proteins cannot yet be surveyed in a comprehensive manner.

The field also needs efficient ways to integrate biological information from different sources, such as imaging or microarray studies, in order to build the models.

"These models are where the real power of a systems, or integrative, approach will be utilized," says Dr. Daniel Gallahan, program director of the Integrative Cancer Biology Program at NCI. "The models will begin to transform how we conduct research as they become more sophisticated and accurate."

Though they are approximations of reality, models can generate hypotheses to be tested experimentally, and the results of experiments can, in turn, improve models.

"Modeling is a powerful tool for designing, testing, and refining hypotheses about cancer, and it goes hand in hand with experimentation," says Dr. Thomas Deisboeck of the Complex Biosystems Modeling Laboratory at Massachusetts General Hospital.

Dr. Deisboeck leads an international project to develop a virtual tumor that could simulate the ripple effects of a single mutation on multiple cells and tissues. "We view cancer as a complex adaptive biosystem, and we're using various modeling techniques to study its dynamics at multiple scales in space and time," he says.

The project, which also is developing Web-based infrastructure for the cancer-modeling community, is one of nine supported by NCI's Integrative Cancer Biology Program. Each project will generate computational models that simulate a different aspect of the cancer process, such as communication among cancer cells.

"Some believe that integrative approaches are really the only way to understand biology because biology does not occur in a vacuum," notes Dr. Gallahan. "There is always an environment, whether it's a cell or a tissue or something else."

The interconnectedness of biology is an old idea; what distinguishes systems biology from its predecessors, such as physiology, is the focus on modeling and high-throughput technologies.

A recent editorial in Molecular Systems Biology endorses the new term systems biology - even if physiology could have been revived: "After all, a new generation of scientists enabled all the progress, and a new term always creates hope and stimulates visions."

By Edward R. Winstead