The virtual heart has, in many ways, come alive over the last dozen years. But it still has a long way to go. “We can model a heartbeat over a period of 10 minutes,” says McCulloch. “But we can’t yet model the natural progression of disease-how a cardiac cell gradually proceeds from normal to injured to failed.” One barrier: although hundreds of researchers around the world are exhaustively deciphering the workings of the heart, most biologists haven’t been trained to gather and present data in a rigorous, quantitative way that can feed into the mathematical formulas used to build computer models. “When you talk to them about describing their results as formulas, some of them get very turned off,” says Paul Herrling, head of corporate research for pharmaceutical maker Novartis.
Yet the cardiome is already making contributions to medicine, and one of its biggest may be as a tool to help researchers discover better heart drugs. Novartis, for one, is already using cardiome models to develop drugs by programming in the changes that a compound has been observed to make in a cardiac cell, and then letting the model project how those changes will affect heart rhythm and blood flow. “We’ve been able to make predictions of which ion channels in heart cells to tweak with drugs to reduce arrhythmias,” such as those found in patients who have suffered heart attacks, says Herrling. He emphasizes that the cardiome needs a great deal of additional development before it’s capable of providing detailed, complete, accurate predictions of how the heart would respond to a wide range of potential drugs. “But we’ve had a sufficient number of elements come together to allow getting a good start,” he says. “That tells me it’s worthwhile pursuing the models, even if they’re not perfect yet.”
The virtual hearts are also advancing surgical therapies. For example, about five million Americans suffer from congestive heart failure, and one relatively new treatment that is gaining popularity involves implanting two pacemakers in patients to counter the abnormal heart rhythms typical of the disease. But doctors can have trouble determining the sequence of electrical stimulation that best ensures a stronger heartbeat. So McCulloch has adapted one of his models to simulate a diseased heart with two pacemakers, allowing him to experiment on a computer to find the right placement and timing for the two jolts. “There’s intense interest in the work from pacemaker companies,” he says.
As exciting as these early applications are, the modelers have far greater ambitions. Eventually, biologists and physicians hope, modeling research will give life to an entire virtual patient, with a full complement of simulated organs. That would enable, for example, studying how an experimental heart drug affects the kidneys, or identifying the long-term effects of a high-fat diet within weeks, rather than following human volunteers for years. Taking one small step toward this lofty goal, Hunter is helping to oversee the development of an open-standard programming language called CellML, based on XML, the Web page development language. Over the next two or three decades, CellML and other such standardized tools will give modelers the world over a common language and enable the integration of the cardiome work with computational models of other organs. “We’re all asking ourselves what sort of infrastructure we need to make sure our work is expandable and extensible to other applications at other levels,” says Johnson. “We don’t want the cardiome to be a one-off.”
The flurry of modeling is leading to a promising trade-off: the better we get at creating virtual heart disease, the less we stand to see of the real variety.
Virtual Hearts in Operation
|Artesian Therapeutics (Gaithersburg, MD)||Cardiac models to support drug development|
|Immersion Medical (Gaithersburg, MD)||Whole-heart models for training surgeons|
|Insilicomed (La Jolla, CA)||Whole-heart models for medical-device design|
|Predix Pharmaceuticals (Woburn, MA)||Cardiac cell and tissue models for drug discovery|