book reviews

285NATURE CELL BIOLOGY VOL 5 APRIL 2003 www.nature.com/naturecellbiology

Systems biology and elephants

Foundations of Systems Biologyedited by Hiroaki Kitano

Paperback, £31.95/$47.95

MIT Press • 2002

John Aitchison and Benno Schwikowski

I n an ancient Indian story, a group ofblind men attempt to explore an elephantby touching one of its parts. The man

who feels the trunk has a very different ideaof the beast than does the man who feels hisears and so on, and the elephant as a wholefails to emerge. This allegory captures ashortcoming of the traditional reductionistapproach to the biological sciences thattoday’s genome-scale datasets make uspainfully aware of: high-level properties ofbiological systems are frequently not easilydiscernible from observation of its elementsin isolation. Systems biology is an approachto tackle this problem in dynamic and inte-grated biological systems. In the bookFoundations of Systems Biology, HiroakiKitano provides the reader with a collectionof scientific contributions that representthe state-of-the-art in this burgeoning field.

Tremendous technical advances inmolecular biology have provided us with anunprecedented amount of data: we knowthe genetics lists for an increasing numberof organisms; DNA microarrays and massspectrometry allow us to measure concert-ed cellular responses to defined genetic andenvironmental perturbations on a globalscale; and large scale studies are beginningto identify the potential interactions amongcellular components. This virtual treasuretrove of data is the biologists dream, butalso presents the enormous challenge ofunderstanding how these componentsfunction together to endow the organismwith its system properties.

Systems biology takes aim at this chal-lenge with an ultimate goal of, as Kitanoputs it, “the computer simulation of life”.With this lofty goal in mind, the author usesthe introduction to describe some of thetremendous opportunities this provides forbiology and medicine. In his view, newhigh-throughput experimental and compu-tational technologies will continue to devel-op, and the sciences of biology and chem-istry will assimilate elements of engineeringand system sciences to accomplish this aim.Kitano also proposes a coordinated “sys-

teome project” on the scale of the humangenome project, directed towards the“assembly of systems profiles for all geneticvariations and environmental stimuliresponses”. Kitano argues that a single,problem-independent, albeit large, set ofexperiments can yield a comprehensiveunderstanding of complex circuit dynamicsand ultimately allow precise medical diag-noses and treatments.

The remaining thirteen chapters of thebook arose from conference contributionsat the First International Conference onSystems Biology in Tokyo, November 2000,and highlight various aspects of systemsbiology and the current research in thefield. What is striking from the book is thatcomputing accurate models of even simplesystems is an enormous computationalchallenge. Pedro Mendes discusses thecomputational problems in optimizing theparameters of a simple three-enzyme path-way and John Koza et al. illustrate howunravelling the topology of a similarly sim-ple biochemical pathway demands massivecomputational resources. A significantchallenge for the future of systems biologyis to build on these studies and establishtechniques that can also cope with experi-mental errors, and scale to larger systems ofproteins. This aspect is addressed in thearticle by Jörg Stelling et al. By analogy to

how biologists generally deal with the com-plexity in biological systems, their modelingapproach is built on a hierarchical view ofthe cell, comprised of functional units withspecific inputs and outputs that communi-cate with other modules and can themselvesbe composed of functional units. In princi-ple, the hierarchy extends from small mole-cules to entire organisms. Yet another fun-damental problem faced by modellers isthat many biological processes rely on theinteractions of small numbers of molecules.As such stochastic processes are inadequet-ly described by differential equations,Thomas Simon Shimizu and Dennis Braydevelop a modeling approach in whichmolecules are represented as individualentities whose behaviors are governed byprobabilities rather than rate laws.

While the book is an exceptional repre-sentation of the present challenges andachievements around formal modeling inSystems Biology, it falls short of represent-ing the current state, or future, of the othertechnical challenges of systems approaches,as outlined in the author’s introduction. Tomake the strongest impact on our under-standing of living systems, new and emer-gent technologies are needed to reliably andquantitatively measure the hierarchical lev-els of biology in increasingly higherthroughput, and ultimately at the level ofsingle cells.

Even the current aspects of systems biol-ogy are so diverse that it seems virtuallyimpossible to tie them together in a collec-tion of individual research papers. So, iron-ically, Foundations of Systems Biology alsosuffers from the elephant problem.Nonetheless, the book will serve as an excel-lent source book to engineers, mathemati-cians and biologists who want to grasp thestate of the art, or are seeking to acquaintthemselves with the mathematical chal-lenges of modeling biological systems.John Aitchison and Benno Schwikowski arein the Institute for Systems Biology, Seattle,WA, 98103, USAe-mail: jaitchison@systemsbiology.org

…the book is an

exceptional representation

of the present challenges

and achievements around

formal modeling in

Systems Biology…

© 2003 Nature Publishing Group