The Physiome Project: A progress note for the IFMBE
Introduction by Prof. Fumihiko Kajiya
The word Physiome is coined from physio, life or nature, and ome, as a whole entity (Bassingthwaighte, 1992). It is a successor to the Genome project which has been an immense step forward in understanding, fostering new qualitative and quantitative approaches in the biological sciences.
However clear each gene and the amino acid sequence of its associated protein may become, it is hard to infer physiological function, from gene and/or protein, not resulting in solving the puzzles of (human) physiological functions. This is, I think, the very reason why the Physiome Project was thought of. The Physiome Project is certainly integrative work, consisting of two main parts (i) the databasing of biological information and (ii) systematic approach obtaining the schema of interaction, quantitative description of interrelationship and modelling. I believe that IFMBE members can contribute greatly to this growing project.
The idea
The Physiome Project is a loosely integrated multi-centric program to design, develop, implement, test and document, archive and disseminate qualitative and quantitative information, databases and models of the functional behaviour of organelles, cells, tissues, organs, and organisms. It is a successor to the Genome Project. The focus of the Human Physiome Project is on the human organism, its physiology and pathophysiology, to eventually provide full working models of physiological systems that integrate the observations from many laboratories into quantitative, self-consistent, comprehensive descriptions.
The goal is to provide to the community of scientists, physicians, teachers, and manufacturers functional descriptions of human biological systems in health and disease. A major feature of the project is the databasing of observations on all organisms for retrieval and evaluation. A network of Physiome Centres would comprise an adaptable international resource for integrated physiological systems, structured for accessibility via the Internet, for the immense databases of information on methods, data and models.
The plan
There is a growing effort to raise consciousness about integrative biology and to provide a setting for the results that are flowing out of laboratories concerned with genomics. molecular and cell biology, and medicine and biology in general. For those with a primary interest in therapeutics, the Physiome Project can provide a framework for determining the effects of pharmaceutical or genetic interventions on target molecules and functional systems through a deep, comprehensive understanding of biology at the level of the cell, the tissue, the organ and the organism. The Project will need to be supported by the development of databases that follow upon those developed from the Genome and the Proteome. Physiological modelling may be considered to include the dynamics of protein folding, molecular dynamics in general, protein-protein interactions of all sorts, from solutes in competition for binding sites on enzymes and receptors to antigen-antibody reactions. Integration at the more structured levels, organelles, cells, and broader, may not always be based on (reductionist) approaches, but will often have to be explained at molecular level as well as at the system level.
The Progress Meetings in 1997 and 1998 are summarised at either the Physiome website or the given pointers there. These were:
- "Genomics to Physiology and Beyond: How Do We Get There?" Feb 23-26, 1997 at Coldspring Harbor, NY. Organised by Allen Cowley, Pres. Am. Physiol.Soc. It is sponsored by APS. Speakers included James Watson, Tom Caskey, James Schafer, Victor Dzau, Oliver Smithies, Monica Riley, David Cox, Ken Chien, Gary Nabel, and James Bassingthwaighte.
- Genomics to Physiology" A half day Symposium within the Experimental Biology meeting, April 4th, 1997
- "Functional Consequences of Gene Expression in Health and Disease." April 1997, in Washington DC. A workshop-discussion sponsored by the Dept. of Energy and organised by Drs. Ari Patrinos and Ludwig Feinendegen of DOE and Henry Wagner, Johns Hopkins.
- "Integrative Physiology and Evolutionary Design" 5 July 1997 at XXXII Cong. Physiol Sci, St. Petersburg, Russia under the auspices of the Committee on Integrative Physiology of IUPS, organised by Ewald Weibel and Jared Diamond. Speakers include Weibel, Denis Noble, Bassingthwaighte, and others.
- "On designing the Physiome Project" July 5 to 8, 1997 at Petrodvorets, Russia (near St. Petersburg), a satellite of the IUPS Congress, sponsored by the Commission on Bioengineering. Speakers included Leroy Hood, Ewald Weibel, Denis Noble, Allen Cowley, James Bassingthwaighte, Jeremy Levin, Peter Macklem, Evgeni Selkov, Jos Spaan, Hans van Beek, Aleksander Popel, Charles Michel, Judy Vaitukaitis, and Bill Raub.
- Endotheliome Conference, February 7, 1998, Kurashiki, Kurashiki City, Japan, organised by Masao Goto and Fumihiko Kajiya.
- Bioengineering Research: Building the Future of Biology and Medicine, February 27-28, 1998, at the National Institutes of Health, organised by John Watson and Dov Jaron. Speakers included Harold Varmus, and Sen. William Frist.
- Bioengineering and Functional Genomics, Am. Inst. Med. Biol. Eng., March 1-3, 1998, at Washington Marriott Hotel and National Academy of Sciences, Washington D.C. Organised by Murray Sachs. Speakers included William Hendee, John Linehan, James Bassingthwaighte.
- The Microcirculation Physiome Project: Working Group Meeting, April 16-17, 1998, ANA Hotel, San Francisco, organised by Andrew S. Greene, and Aleksander Popel. Speakers included Philip Bourne, Axel Pries, Ken Fasman, Klaus Ley, Tom Skalak, and Andrew McCulloch. (www.bme.jhu.edu/news/microphys/)
The prospects
The Physiome Project combines engineering applications to biology, informatics and databasing, and large scale systems analysis. It is potentially a vehicle for discovery and invention. Its growing popularity is an invitation to IFMBE members and bioengineers in general to embark on collaborative enterprises worldwide.
Government agencies are demonstrating a clear interest (particularly NIH, NSF, NASA, and DOE). A program announcement inviting applications were distributed, e.g. PA98077 from NIGMS on 4 June 1998. More recent announcements from NHLBI were also distributed.
This is a good subject for society-sponsored conferences which would provide an open forum for scientific presentations and advancement of plans, much as in the style of the Gordon Research Conferences in the US. The topics covered would be both on the logistics of specific aspects of the Physiome Project and on its strategies and scientific advances.
In parallel, we need meetings with officials from government agencies to discuss funding mechanisms. One that I feel is important is to obtain better national funding for those agencies which are appropriate to supporting a 'set of networked research resource facilities' to take on specific aspects of the program in various countries.
Further information
- Website: http://nsr.bioeng.washington.edu/NSR/physiome/
- Simulation websites: pointers at http://nsr.bioeng.washington.edu
- Bassingthwaighte, J. B., R. Friesner, B. Honig, C. F. Starmer, and V. Z. Marmarelis. Modeling and Simulation. Bethesda MD: NIH/NCRR Workshop on Technologies for the Future: Biomedical Computing for Visualization, Modeling and Decision Support, April 12-13, 1991, pp. 1-15
- Bassingthwaighte, J. B. Fractal vascular growth patterns. Acta Stereol.11 (Suppl. 1), pp. 305-319, 1992.
- Bassingthwaighte, J. B. Toward modeling the human physionome. In: Molecular and Subcellular Cardiology: Effects on Structure and Function, edited by S. Sideman, and R. Beyar New York: Plenum, 1995, pp. 331-339
- McCulloch, A., J. B. Bassingthwaighte, P. Hunter, and D. Noble. Computational Biology of the Heart: From Structure to Function Progress in Biophysics and Molecular Biology Volume 69, 151-572: Elsevier/Pergamon, 1998.
|
University of Washington |
 |