On the other hand, history might point to lower estimates as well, since the 20th century's two other influenza pandemics, the "Asian flu" of 1957-58 and the "Hong Kong flu" of 1968-69, killed fewer people as percentages of the world population. According to the CDC's Web site, the Asian flu killed about 70,000 people in the United States, and the Hong Kong flu killed about 34,000.
"If we were sure it was going to be like history, we would still be unsure," Lipsitch told ABCNEWS.com. "But we can't be sure it will be like historical examples."
Beyond the issue of whether historical precedents will be repeated, there's even more uncertainty.
Marvin J. Bittner, an associate professor at the Creighton University School of Medicine, suggested it may be wrong to predict the lethality of the bird flu solely on the fact that about half of known human cases in Asia have resulted in death.
"The percentage of people who died from bird flu seems to be high when you look at the data from Asia," Bittner said. "However, this could be misleading. Sometimes, when you study a disease, the worst cases are easiest to recognize. … Later on, you learn to recognize milder cases, and so the disease looks less severe.
"You may have had some people who didn't feel sick, didn't feel sick enough to see the doctor, or didn't look sick enough to have tests for bird flu -- yet they had bird flu," Bittner added. "I don't know if this happened, but it's a theoretical possibility."
Regardless of death estimates, Lipsitch said Americans and their government officials should not take the threat from the bird flu lightly.
"Even a mild pandemic kills, in this country, some tens of thousands, and in the world, a lot more than that," Lipsitch said. "And it does so in a wide range of age groups. It's not like a normal flu that kills primarily the elderly. … We obviously need to plan for the worst case, but also know that in a best case our plans could save a lot of lives."