The digital human: towards a unified ontology.

THE EXPONENTIAL INCREASE in biological data resulting from the latest automated experimental techniques and the accelerated availability of molecular sequences has provided an explosion of empirical data and analysis on the molecular foundations of biological structure and function. The complexity of this kind of analysis has grown to the point where biological systems can best be understood by using modern computers. Computers were essential for sequencing the human genome and will be even more important for understanding how genomes work by developing computer simulations of their functions. These tools can also make it possible to visualize the operation of complex systems—how cells assemble miniature machines or how defects in electrical networks degrade the performance of a heart—and allow one to “see” what happens when these system are altered with drugs, surgeries, or other therapies. The ability to simulate biological systems will give us an extraordinary set of new tools that could increase economic productivity while reducing pollution and our need for natural resources. We have reached a critical juncture where model integration using diverse data derived from various biomedical domains can significantly enhance our understanding of complex phenomenon in normal human function and disease states. Integration of all of this data into a “Digital Human” will help biomedical researchers master the staggering complexity of their discoveries, physicians make effective use of their discoveries to improve health, and engineers imitate biological mechanisms to achieve revolutionary change in computing, for the design of artificial organs, robots, and a variety of other applications. The ultimate goal of the Digital Human is construction of a complete, functioning, accessible simulation of the human body—from the performance of DNA and other molecules within individual cells to the operation of entire organ systems such as the heart, lungs, brain, and musculo-skeletal systems. The following example outlines why cell models are essential for the Digital Human and why the Digital Human is a worthy goal. Investigators working in cardiac modeling and simulation provide a particularly compelling example. Sophisticated models of cellular, tissue and organ systems have been built from a variety of data sources: diagnostic images, electrophysiological measures, biomechanics, bioelectric fields, and ionic studies. The teams have used this model to build sophisticated simulations that provide insight into the physiology of the heart not possible from studies limited to a single level of analysis. The models have, for example, allowed a detailed understanding of the mechanisms of heart disease, such as arrthymias, ischemia and myopathy that allow them to explore a range of potential new strategies for therapies. Cell models, many of which are being developed through the BioSPICE effort, are essential for understanding the structure and function of the heart. For example, investigators have shown that a mutation in the SCN5A gene produces a structurally defective sodium channel that causes cardiac arrhythmia when inserted into an integrated, quantitative computer model of a cardiac cell (Clancy and Rudy, 1999). The Digital Human will represent human biology at all physical scales, from organs to tissues to cells and protein. However, for this technology to be realized, researchers need to develop common knowledge