Strategies for the physiome project

The physiome is the quantitative description of the functioning organism in normal and pathophysiological states. The human physiome can be regarded a s the virtual human. It is built upon the morpheme,the quantitative descrip tion of anatomical structure, chemical and biochemical composition, and mat erial properties of an intact organism, including its genome, proteome, cel l, tissue, and organ structures up to those of the whole intact being. The Physiome Project is a multicentric integrated program to design, develop, i mplement, test and document, archive and disseminate quantitative informati on, and integrative models of the functional behavior of molecules, organel les, cells, tissues, organs, and intact organisms from bacteria to man. A f undamental and major feature of the project is the databasing of experiment al observations for retrieval and evaluation. Technologies allowing many gr oups to work together are being rapidly developed. Internet II will facilit ate this immensely. When problems are huge and complex, a particular workin g group can be expert in only a small part of the overall project. The stra tegies to be worked out must therefore include how to pull models composed of many submodules together even when the expertise in each is scattered am ongst diverse institutions. The technologies of bioinformatics will contrib ute greatly to this effort. Developing and implementing code for large-scal e systems has many problems. Most of the submodules are complex, requiring consideration of spatial and temporal events and processes. Submodules have to be linked to one another in a way that preserves mass balance and gives an accurate representation of variables in nonlinear complex biochemical n etworks with many signaling and controlling pathways. Microcompartmentaliza tion vitiates the use of simplified model structures. The stiffness of the systems of equations is computationally costly. Faster computation is neede d when using models as thinking tools and for iterative data analysis. Perh aps the most serious problem is the current lack of definitive information on kinetics and dynamics of systems, due in part to the almost total lack o f databased observations, but also because, though we are nearly drowning i n new information being published each day, either the information required for the modeling cannot be found or has never been obtained. "Simple" thin gs like tissue composition, material properties, and mechanical behavior of cells and tissues are not generally available. The development of comprehe nsive models of biological systems is a key to pharmaceutics and drug desig n, for the models will become gradually better predictors of the results of interventions, both genomic and pharmaceutic. Good models will be useful i n predicting the side effects and long term effects of drugs and toxins, an d when the models are really good, to predict where genomic intervention wi ll be effective and where the multiple redundancies in our biological syste ms will render a proposed intervention useless. The Physiome Project will p rovide the integrating scientific basis for the Genes to Health initiative, and make physiological genomics a reality applicable to whole organisms, f rom bacteria to man. (C) 2000 Biomedical Engineering Society. [S0090-6964(0 0)02208-6].