Cell model from Cell, Vol. 100, No. 1 with permission from Elsevier Science

 Over the last few years, there’s been an explosion of information in biology. The mapping of the human genome gave biologists unprecedented detail about some 30,000 to 40,000 genes. Efforts are also under way to identify the thousands—and potentially millions—of proteins encoded by those genes. Researchers are now pursuing the next logical step in integrating all this data: systems biology.
 

The goal is to understand not just the functions of individual genes, proteins and smaller molecules like hormones, but to learn how all of these molecules interact within, say, a cell. Biologists hope to then use this information to generate more accurate computer models that will help unravel the complexities of human physiology and the underlying mechanisms of disease. The biggest payoff: faster development of more-effective drugs. “This is really opening up a whole new world, a new way of doing things,” says Aram Adourian, director of advanced technologies at Beyond Genomics, a systems biology startup in Waltham, MA.

A handful of academic groups, biotech firms and drug companies are embracing this new approach (see table). Pharmaceutical maker Eli Lilly is scheduled to open its new Center for Systems Biology in Singapore this spring. The center plans to spend $140 million over the next five years to develop more effective drugs using a systems approach. In Seattle, biotech pioneer Leroy Hood has recently founded the Institute for Systems Biology
(see “Under Biology’s Hood,” TR September 2001) with the objective of better understanding complex systems like the immune system, as well as diseases like cancer. Beyond Genomics is using systems biology to identify better molecular targets for heart disease drugs and is collaborating with the Dublin, Ireland-based drug company Elan to develop new Alzheimer’s therapies.

Traditionally, drug researchers might identify a gene that is turned on or off in diseased patients and then develop a drug that regulates that gene or the protein it codes for. But many diseases  involve a number of different genes and proteins, all interacting with each other in unique ways. Systems biology, by examining these complex interactions, could shed more light on how diseases alter cellular processes. This could help researchers hone in more efficiently on the crucial genes or proteins that cause illness, and which are therefore prime targets for new therapies. Researchers could also adjust their models to more accurately simulate the effects of a potential drug before testing it in humans, saving companies millions of dollars.

Systems biology has only recently become feasible with the development of an array of new lab tools—ranging from sophisticated protein identification methods to data-mining software—that allows researchers to process massive amounts of data. Beyond Genomics, for example, collects samples such as blood, tissue or brain fluid and then uses a number of newly developed analytical tools to identify the main genes, proteins and smaller molecules that behave differently in healthy versus diseased patients. And rather than identifying every type of molecule in a sample—“That would be a daunting task,” says Adourian—the company zeroes in on only those that appear to be involved in disease.

The new data are then combined with information from public databases and fed into a computer that maps out the possible interactions between the molecules. This allows the company to spot molecules that are likely to make good targets for new drugs in a matter of weeks, as opposed to the years traditional methods might take.

Even a single cell is an extremely complex system filled with thousands of molecules that researchers have yet to identify. And it could be more than a decade before systems biology is able to construct an accurate model of all these interacting elements in a cell. Yet as the approach evolves, and as databases on genes, proteins and other factors continue to grow, researchers will move closer to that goal—and even a partial understanding could greatly aid the drug discovery process. “I think there are quite exciting opportunities in biotechnology for companies that take on systems biology correctly,” says Hood, acknowledging the technical challenges inherent in this multifaceted research.

Eventually, researchers would like to look at systems even more complex than the cell. Some day systems biology might make it possible to model an organ, like a heart, and ultimately a whole organism. Then the term “holistic healing” would take on a whole new meaning.

The Big Picture
Companies exploiting systems biology