No matter how the parasite was actually introduced to Virginia, we know that malaria spread throughout the East Coast, eventually playing a major part in the pageant of U.S. history. Without malaria, slaves would have been less desirable to southern planters: Most people from tropical Africa are resistant to the plasmodium parasite, the product of millennia of evolution in its presence. The disease became especially endemic in the Carolinas, where it crippled the army of British Gen. Charles Cornwallis during the Revolutionary War. England had by that time drained its marshes and largely been freed of malaria. Meanwhile, the colonists had become seasoned. "There was a big imbalance. Cornwallis's army was simply melting away," says J. R. McNeill, an environmental historian at Georgetown University. McNeill takes pains to credit the bravery of the Revolution's leaders. But a critical role was played by what he wryly refers to as "revolutionary mosquitoes." Cornwallis surrendered, effectively ending the war, on October 19, 1781.

By then the Columbian exchange was in full swing. The Atlantic coast was dotted with monoculture fields devoted to such alien crops as wheat, rice, and West Indian tobacco. Black rats from Europe were devouring Indian corn stores from Maine to Florida. Meanwhile, European farmers were adopting New World plants like corn, potatoes, and tomatoes; chili peppers, unknown in Asia before Columbus, were on their way to taking over Indian, Thai, and Chinese kitchens.

No longer maintained by Indian burning, the shrinking forests of the East would become choked with underbrush—the overgrown, uninhabited "wilderness" celebrated by Thoreau. In the 1800s, the great grasslands of the Midwest, once kept open by native burning, began filling with trees. With the Indians vanquished by disease, some archaeologists believe, species they had formerly hunted, such as the passenger pigeon, experienced a population explosion.

On the James River, where the process began, land-clearing sped runoff and increased the river flow, sweeping aside the mats of vegetation that lined its banks in Powhatan's day. With its plantations, tobacco fields, and rolling meadows, the landscape of the Chesapeake Bay had been utterly transformed. It looked more like England than it had when Jamestown began, but it wasn't at all the same. Four centuries ago, the English didn't discover a New World—they created one.