New York ? As bad as this year’s flu season is, it hasn’t brought the worldwide outbreak known as a pandemic. But experts warn that a pandemic is coming, it’s just a question of when.

“It’s going to happen,” said Dr. Greg Poland of the Mayo Clinic. “For the American public in particular, I think it will be horrific.”

Many Americans haven’t experienced the overwhelming crush of patients at hospitals and doctors’ offices and the widespread fear a flu pandemic could bring. And by historical pattern, Poland said, it’s about time for the next one.

There have been three in the past 100 years, igniting in 1918, 1957 and 1968. There’s no way to predict when the next one will appear, but the pattern does give experts pause.

It’s all up to a virus that is variable and fickle, constantly changing its genetic makeup, and the time when it hits upon a combination that lets it take off worldwide is a “roll of the genetic dice,” said Dr. William Schaffner of Vanderbilt University.

So the lack of a pandemic in the past 35 years basically means “the genetic dice haven’t been rolled that way,” Schaffner said. “While we’re grateful for that, it makes us nervous.”

There’s plenty to be nervous about. It’s estimated that in the industrialized nations alone, the next pandemic is likely to send 1 million to 2.3 million people to the hospital and kill 280,000 to 650,000.