Student Science

Virtual Wounds: Computers Probe Healing

29
Jan
2015

In movies, huge battle scenes no longer rely upon the expensive recruitment and coordination of thousands of extras. Instead, the epic clashes of armies in films such as The Lord of the Rings trilogy use a computational technique called agent-based modeling, or ABM. In ABM, thousands or even millions of individual "agents" are programmed to follow a set of simple rules, which creates complex, realistic behavior at large scales.

A new feature from Student Science, a science magazine aimed at younger readers, focuses on the use of ABM in simulating a different war: the body's immune response to injury. Much of the article focuses on work by CI Senior Fellow Gary An, who creates computer models to study sepsis and inflammation -- conditions where the "collateral damage" of the immune system may be worse than the original injury.

“Let's say that you are a country and you are attacked,” says Gary An. He’s a surgeon and researcher at the University of Chicago, in Illinois. “You would kind of like to only kill the people who are your enemy,” he says. So your immune system drops what An calls “bombs” next to the enemy cells. These bombs are chemicals that break apart the problem cells.

But sometimes the bombs accidentally damage healthy cells, too. “You try to minimize that damage as much as you can,” he says. “But the damage needs to be strong enough to kill the invaders.” All too often, he says, this means “You end up destroying parts of your own country. That's kind of what inflammation is.”

By modeling these immune processes gone awry, An can test the effects of new drugs, or even find new places in the cascade of cellular events that may serve as promising targets for future drugs. This concept of in silico research, with experiments conducted in the computer, can serve as a new link in the chain of discovery, feeding promising hypotheses into laboratory and clinical studies

Using such models, the University of Chicago’s An has uncovered important features about sepsis. Damaged cells send out a special chemical signal. It’s like a distress cry. This signal attracts neutrophils. Some scientists thought they could stop sepsis in its tracks by giving patients a drug to block the signal. And in laboratory experiments, the drug indeed stopped neutrophils from coming.

But using agent-based modeling, An also discovered why the drug would not save a septic patient. “What you get at the end of the time you give the drug is a bunch of damaged tissue,” says An. And, he adds: “It's not like it will fix itself.”

Once the drug wore off, neutrophils returned. Inflammation started anew. “That's the kind of secondary effect that's incredibly obvious once you use the model,” observes An.

If you enjoy the feature, check out our story about An's talk on the medical applications of agent-based modeling at UChicago Alumni Weekend in 2013, or the video of his Discovery Cloud lecture from 2014.