Moment by moment, a movie captures the action as a group of immune cells scrambles to counter an invasion of tuberculosis bacteria. Rushing to the site of infected lung tissue, the cells build a complex sphere of active immune cells, dead immune cells, lung tissue, and trapped bacteria. Remarkably, no lung tissue or bacterium was harmed in the making of this film.

Instead, each immune cell is a computer simulation, programmed to fight virtual tuberculosis bacteria on a square of simulated lung tissue. In their computer-generated environment, these warrior cells spontaneously build a structure similar to the granulomas that medical researchers have noted in human lungs fighting tuberculosis.

The simulation, created by Denise Kirschner of the University of Michigan in Ann Arbor, is an example of an emerging technique called agent-based modeling. This new tool in the world of medical research relies on computing power instead of tissues and test tubes. A growing cadre of researchers, including Kirschner, predicts that agent-based modeling will usher in a broadened understanding of complex interactions within the human body.

The agents in the models are individual players--immune cells in the tuberculosis example. Each player is programmed with rules that govern its behavior. Computer-savvy researchers then set the agents free to cooperate with, compete with, or kill each other. Meanwhile, the agents must navigate the surrounding environment, whose properties can vary over space and time.

Scientists can manipulate disease progression within the models by changing the agents or their environment and then watching what happens. As opposed to traditional, biologically based in vivo or in vitro experiments, these computer trials are dubbed "in silico." The results can suggest biological experiments to test the models' findings and may eventually lead to new medical treatments.

Even simple rules assigned to agents can give rise to surprisingly complex behaviors. When many independent agents interact, they create phenomena--such as the granulomas--that can't necessarily be predicted by breaking down the system into its separate components, says complex-systems specialist John Holland of the University of Michigan.

You've got to study the interactions as well as the parts," Holland says.

In-silico modeling differs from traditional mathematical modeling, which uses differential equations to understand how molecules or cells behave in an averaged, continuous way. Instead, the agents of in-silico modeling make independent decisions in response to situations that they encounter. As a result, unusual activity of even a small number of cells can change the entire system's behavior.

Computers can now calculate thousands of interactions with ease, says Alan Perelson of Los Alamos National Laboratory in New Mexico. "Agent-based modeling has only come into its own with the arrival of really powerful computers sitting on people's desktops, within the last 10 or 15 years," he notes.

Pioneered for economics and population-dynamics studies (SN: 11/23/96, p. 332; www.sciencenews.org/pages/ sn_arc99/4_10_99/mathland.htm), agent-based modeling has only recently plumbed the inner workings of the human body, Perelson adds. That's partly because new imaging and genetic techniques are providing crucial data on which agents' rules can be based.

"Agent-based modeling represents a new frontier with respect to how we do science," says surgeon Gary An of Cook County Hospital in Chicago. "In medicine in particular, all the diseases that we're now dealing with are complex problems: sepsis, cancer, AIDS. All these things are disorders of the system as a whole."

INFLAMMATION SIMULATION An, whom Kirschner calls an in-silico "groundbreaker," got into agent-based modeling to help people survive traumatic injuries and major infections.

A leading cause of death for patients in intensive care units, An explains, is a syndrome called systemic inflammatory response syndrome/multiple organ failure (SIRS/MOF), also termed sepsis when it occurs in response to an infection. In this syndrome, the body's inflammatory response rages out of control after a severe injury or bacterial infection. Excessive inflammation can kill a patient by attacking and shutting down vital organs. More commonly, the runaway inflammation paralyzes the rest of the immune response, and the patient then dies of secondary infections.

During the 1990s, researchers performed clinical experiments in an attempt to develop drugs that dampen an overwhelming inflammatory response to injury, An notes. Only one drug, activated protein C, appeared to help patients with SIRS/MOF. An suggests that trials of other drugs failed because they were planned using data representing individual components of the inflammatory response rather than the interactions of the immune system as a whole.

An says, "It's kind of a Humpty Dumpty syndrome, where after you break the system apart, you can't put it back together."