Making systems biology work in the 21st century

The idea of systems biology is not new: as long ago as 1968, the mathematician and engineer Mihajlo Mesarovic regretted that "in spite of considerable interest and efforts, the application of systems theory in biology has not quite lived up to expectation". But what of systems biology today? Does it now look more likely to lead to the expected benefits? These questions are of particular urgency in the UK at a time when the Biotechnology and Biological Sciences Research Council (BBSRC) is planning to create six new centers for systems biology over the next two years, investing ￡6 million in each. It was in the hope of answering them that a one-day meeting exploring the nature of systems biology and its potential was organized by the Biochemical Society early this year.In the 1950s the geneticist and biochemist Henrik Kacser was already urging biologists to take systems seriously: "The problem is ... the investigation of systems, i.e. components related or organised in a specific way. The properties of a system are in fact 'more' than (or different from) the sum of the properties of its components, a fact often overlooked in zealous attempts to demonstrate 'additivity' of certain phenomonena. It is with these 'systemic properties' that we shall be mainly concerned...".To most people, however, 'systems biology' is still just a combination of words they encounter with increasing frequency in the literature - a search of PubMed on 3 January 2005 produced 11 hits for the new year, more than for all the years before 1998, suggesting that the total of 316 mentions in 2004 will easily be exceeded this year. The range of opinions expressed at the Sheffield meeting was enlightening, but might leave the outsider none the wiser. It would be an exaggeration to say that each speaker offered a distinct and incompatible opinion about what systems biology is, but there was certainly less unanimity about the nature of the subject matter than there is at most research meetings. One spe