Systems Biology Is Taking Off

There is a revolution occurring in the biological sciences. It took off just a couple of years ago and is now clearly visible in the literature. Some scientists in the field like to refer to the devel- opment as the birth of systems biology, whereas others prefer not to put a label on what is happening. Modern molecular biology was born with the discovery that genetics is based on nucleic acid chemistry (Watson and Crick 1953), and one way to define it is to say that molecular biology is a large box of tools to do genetics by manipulating DNA. This definition may sound disheartening, but its positive side is that the tools can be applied to all aspects of biology to solve essen- tially all scientific problems that may arise. One result of molecular biology is large-scale sequencing of genomes from a rapidly growing number of organisms. Genome sequencing is not possible without the use of computers with large memory and tools to handle the enormous amounts of data that are generated in the massive sequencing efforts. The need for data handling led to another box of tools, called bioinformatics, which is now an established part of molecular biology. However, when all this sequence data got into computers, it became obvi- ous that the genetic blueprints by themselves tell us very little about the functional behavior of cells and multicellular organ- isms; that is, about what we really want to know about biological systems. In this way, the human genome project, which is per- haps the most spectacular success of molecular biology, also meant that a vast space of future research of a radically different kind became visible. To understand the causal connections be- tween genotype and phenotype will require a very significant expansion of the traditional toolbox used by molecular biolo- gists. It must include concepts and techniques from many other scientific disciplines such as physics, mathematics, numerical analysis, stochastic processes, and control theory. Many novel tools that do not exist today must be forged to understand how dynamic, adapting, and developing systems can emerge from the information buried in the genomes. The development of such an extended toolbox for quanti- tative reasoning about the dynamics of living systems, and the application of its contents to solve a variety of scientific prob- lems, is one way to define systems biology, analogous to our definition of molecular biology above. It is our belief that systems biology will enrich the biological sciences and transform our thinking about biological problems, in analogy with what has been happening in molecular biology during the 50 years that have passed since the discovery of the double helix. Systems bi- ology will always bring the functional aspects into focus, some- times close to genomics and sometimes far out in areas not vis- ited before. Below will follow some examples of what we consider significant developments of systems biology, which is still in its infancy but has great future promise. The selection of topics is limited by the format of this mini-review, and many important contributions could therefore not be covered.