In the mid-’90s, when Elizabeth Fenn began researching Pox Americana: The Great Smallpox Epidemic of 1775-82, her chosen topic was gripping but remote in time and place. After all, for the past quarter-century, the world has been free of smallpox—a centuries-old scourge that can kill one-third of infected patients and scar or blind many of those who survive. But that sense of distance ended abruptly on Sept. 11: Medical professionals now worry that smallpox obtained illicitly from Soviet-era stockpiles may become the next weapon of choice for bioterrorists.

Suddenly, Pox Americana was no longer academic; it had become part of current events. “The book reminds us of what the re-emergence of smallpox would be like,” says Fenn, a history professor at George Washington University. “We’re all vulnerable. It would be 1492 all over again: No one would be immune.”

Fenn’s is the first book to reveal the full impact that smallpox had on North America. The 1775-1782 epidemic—actually a succession of interrelated outbreaks all over the North American continent—nearly wrecked the American colonists’ chances of winning the Revolutionary War, until Gen. George Washington decided to inoculate his troops. Compared with vaccination—a more sophisticated method developed by Edward Jenner in 1796—inoculation was risky and scarcely understood, requiring an incision and a deliberate infection that, for some still-unclear reason, led to a less serious case of smallpox followed by lifetime immunity. Long-term freedom from smallpox in the United States was still about a century away.

Little-studied smallpox outbreaks in the 18th and 19th centuries also shaped other parts of the continent, mainly by attacking Native American populations that lacked resistance to the disease. In the Great Plains, smallpox led to the downfall of many sedentary farming tribes and helped the more nomadic Sioux take over the region (at least until white settlers overran them a few decades later). And in Texas and the Southwest, Fenn notes, American Indian deaths from smallpox enabled outnumbered and embattled Spanish settlements to survive and achieve regional dominance.

Fenn, 42, never intended to study infectious diseases. Indeed, she barely made a career of academia; in the mid-’80s, after testing the waters as a graduate student at Yale, she took a job as an auto mechanic. (In her spare time, Fenn had become adept at fixing cars. She continues to pull gigs during summers and school breaks in North Carolina, where she and her husband live when she is not in Washington.) About a decade later, still working as a mechanic, Fenn read The Horseman on the Roof, a novel by French author Jean Giono that is set during a cholera epidemic. “It blew me away—the way he could write beautifully about something so terrible,” Fenn says. She went back to graduate school in 1996 and began studying smallpox.

Fenn notes that one of the most fearsome aspects of smallpox is also one of its most fascinating for historians: The disease can incubate for up to two weeks without symptoms, meaning that infected people can unknowingly spread the virus to faraway populations as they travel. “In mapping the epidemic, you can map how people moved,” Fenn says. “It has no respect for class, gender, or geographic boundaries.” —Louis Jacobson