Interactive modeling adds a new dimension to scientific publishing.

Quantitative modeling has revolutionized modern biology. The ability to reduce biological processes to sets of equations enables us to reproduce many features of the living system: complex nonlinear systems can defy intuition, and sometimes the best way to put a given finding into perspective is to simulate it. More importantly, quantitative modeling can yield emergent insights. We do our best to generate a faithful model, alter a parameter, and solve the new model. The outcomes are often surprising, forcing us to reexamine preconceptions. Iterative interactions between the workstation and the laboratory bench motivate new biological experiments to probe the system. The results, in turn, serve to refine the model (which can only be as reliable as the biological data upon which it is based). Scientific publishing has done little to unleash the amazing potential of quantitative modeling. The state of the art has been simply to list sets of equations in print, along with a few snapshot predictions. The field of electrophysiology is illustrative. In 1952, Hodgkin and Huxley1 pioneered the use of modeling to rationalize their theory of excitability, which led to the general acceptance of the existence of discrete ionic currents in excitable membranes. The differential equations were listed in their article, along with selected simulations. Anyone else who wanted to implement the model and play with it had to start from scratch, laboriously translating the equations to a given programming environment before running the simulations. The exchange of information was strictly one-way. Lamentably, the publishing practices prevalent in 1952 remain conventional even today, despite the novel opportunities presented by the advent of electronic communications and the Internet. The present issue of Circulation Research ushers in a new era for scientific publishing by enabling interactive modeling. The online version of the article by Greenstein et al2 contains a live hyperlink to an implementation of the Winslow action potential model. By logging on to this site (http://nsr. bioeng.washington.edu/Software/DEMO/CANINE-AP), you can run selected simulations in real time, and you can also alter various parameters within the model at will and re-run the simulations. In brief, you are no longer just a reader; you have become a modeler. The model is housed on a server at the National Simulation Resource Facility for Circulatory Transport and Exchange, run by James Bassingthwaighte at the University of Washington. The Resource Facility’s simulation analysis systems are used by investigators around the world for interactive quantitative modeling. Because their support comes from the National Institutes of Health National Center for Research Resources, the National Simulation Resource Facility releases its software, models, and modeling systems for general use by the investigative community. More information on this unique facility can be found at http://nsr.bioeng.washington.edu/Software. Circulation Research is proud to inaugurate the use of this technology as part of scientific publishing. We thank Joe Greenstein and Rai Winslow for their willingness to help us push the envelope and the National Simulation Resource Facility for hosting the site. The Editors welcome your feedback on this new feature, and actively solicit your suggestions on other ways that we might expand the utility of scientific publishing.