The carnage was breathtaking. Over the course of the five-day epidemic, bodies in various states of decay piled up in city squares. Travelers unwittingly carried the virulent pathogen from rural villages to urban centers and back again. Through their efforts to help their own fellows, first responders on the scene unintenionally spread the highly contagious disease as they rushed from victim to victim. As the outbreak continued to rage out of control, social chaos ensued.

“Most of the time, when there is a threat to society, bonding together helps,” Nina Fefferman says. “But in the case of infectious disease, the threat comes from society. The threat and society are the same thing.” PHOTO: ADAM KRAUSE

This doomsday scenario didn’t happen in our world. It happened in World of Warcraft, an online role-playing game to which some 9 million people subscribe. The uncontrolled plague that broke out in September 2005 was a virtual one, intentionally programmed by the game’s designers, and made the game a perfect laboratory in which to study infectious disease, says Nina Fefferman, co-director of Tufts University’s Initiative for the Forecasting and Modeling of Infectious Diseases (InForMID) and a research assistant professor in the Department of Public Health and Family Medicine.

Most models of disease, says Fefferman, G05, fail to account for social behavior in any detail because it is so hard to study. It would be unethical—not to mention an expensive logistical nightmare—to induce an outbreak or run controlled studies on people during naturally occurring plague times. Warcraft, however, offers a completely safe means of observing the range of human responses during epidemics. “That’s the beauty of Warcraft. It models social behavior,” adds Fefferman, who is also an assistant research professor at Rutgers University. “Most epidemiologists presuppose human behavior, or collectively throw up their hands.”

First released by Blizzard Entertainment in 1994, the World of Warcraft game franchise has been around since the dawn of the Internet. Players of the game create characters, known as avatars, that can make friends and fight enemies in the virtual world. Through their adventures and quests, players accrue power, prestige and health—or lose it all in one epic battle.

The intentionally introduced infection—known as Corrupted Blood—was meant only to challenge high-ranking players as they battled a powerful winged serpent named “Hakkar.” But several factors that parallel real-life outbreak scenarios led to the pathogen’s uncontrolled spread through the World of Warcraft, wrote Fefferman and Eric Lofgren, a graduate student at the University of North Carolina at Chapel Hill, in a recent issue of the British medical journal the Lancet Infectious Diseases.

Although only high-ranking players could enter the infectious area of the game to battle Hakkar, they exposed susceptible lower-ranking players to the disease upon their return to busy urban centers populated by players at all levels. In a scenario akin to Europeans bringing smallpox to the New World, many of these weaker players died almost instantly.

The Enemy Within
Other true-to-life aspects of the game perpetuated the disease. As in real life, many game players own pets. The game penalizes players whose pets die, so players often dismiss their pets from battle scenes until the threat is averted. In the case of Corrupted Blood, some players unwittingly dismissed infected pets. When they called them back—often into bustling urban environments—the pets triggered new outbreaks of the disease. According to Fefferman and Lofgren, pets were the major means of transmission, much like the livestock and vermin that have been implicated in plague and influenza outbreaks throughout human history.

In the case of Corrupted Blood, some players endowed with healing abilities (like real life EMTs or ER docs) attempted to revive their fallen comrades. Their altruistic behavior wound up spreading the disease by sending infected characters back into the game to interact with other characters. By contrast, some players who became infected seem to have intentionally spread the disease out of spite or curiosity.

“Most of the time, when there is a threat to society, bonding together helps,” Fefferman notes. “But in the case of infectious disease, the threat comes from society. The threat and society are the same thing.”

Of course, Fefferman acknowledges, she and her colleagues have no idea if people respond to infectious outbreaks in a virtual world the same way that they would in real life. Some may act out socially unacceptable fantasies online; some may take risks with an avatar they wouldn’t take with their own lives—what Fefferman dubbed “the stupid factor.” But these differences between real life and e-life can be quantified. Fefferman cites work under way at MIT’s Media Lab, where researcher Dan Ariely studies “eRationality,” how people behave and make decisions in electronic environments, and Judith Donath investigates identity and society in the online world.

Based on their work and her own experience, Fefferman suspects that most players probably do behave in Warcraft much as they would in the real world. Many players maintain the same avatar for years—and may develop strong relationships with other online characters. (Fefferman, who doesn’t consider herself a real “gamer,” has had a Warcraft character since before the game had graphics, in the earliest days of the Internet.) It’s this inclusion of spontaneous human behavior that could make the game an extraordinarily useful tool for epidemiologists.

Looking for Patterns
“Prediction has a long history,” says Elena Naumova, associate professor of public health and family medicine and founder and director of InForMID, the interdisciplinary collaboration of experts from the medical school and their colleagues around the world. “But the explosion of computing has allowed us to design analytical tools that are more flexible, more responsive, more sophisticated than ever.”

Naumova, a biostatistician, specializes in statistical models, which start with data observed in the real world. With enough information, statistical models can predict the number of new cases of an infectious disease over time—say, the number of cases of the flu in January versus the number in May. Statistical models provide answers, usually in the form of numbers. Meanwhile, Fefferman makes mathematical models, which she calls the “exact complement” to statistical models. “Mathematical models give you a why, a logical story that you tell yourself.”

InForMID began as an informal network of researchers from various fields who shared an interest in forecasting diseases. In 2005, Naumova secured a $6 million, five-year grant from the National Institutes of Health to formalize the group, which today includes about 50 researchers around the world, from the Dana–Farber Cancer Institute in Boston to the National University of Singapore. The experts—specialists from fields like applied mathematics, ecology, public health and urban planning—all bring different perspectives to the study of infectious disease, says Fefferman. Their collaboration could help solve some enduring epidemiological mysteries, like why certain illnesses occur more during specific seasons of the year.

“There are a bunch of theories, none good enough to explain everything,” Fefferman admits. “What would happen if you pulled an immunologist and a virologist and get them to work on the same paper? It would be cool to get that perspective.” Bringing those experts together is exactly the goal of InForMID, says Naumova, who adds that the interdisciplinary research generates not just novel answers, but novel questions to pursue.

This story, which ran in the February 2008 issue of the Tufts Journal, is excerpted from a longer version, which appeared in the Winter 2008 issue of Tufts Medicine. Jacqueline Mitchell is a senior health sciences writer in Tufts’ Office of Publications. She can be reached at jacqueline.mitchell@tufts.edu.