The Illinois senator interpreted the remark as a slam against him but the White House denied that Bush's words were in any way directed at Obama, who has said as president he would be willing to personally meet with Iran's leaders and those of other regimes the United States has deemed rogue.
In a speech to Israel's Knesset, Bush said: "Some seem to believe that we should negotiate with the terrorists and radicals, as if some ingenious argument will persuade them they have been wrong all along.
"We have heard this foolish delusion before. As Nazi tanks crossed into Poland in 1939, an American senator declared: 'Lord, if I could only have talked to Hitler, all this might have been avoided.' We have an obligation to call this what it is — the false comfort of appeasement, which has been repeatedly discredited by history."
Obama responded with a statement, seizing on Bush's remarks even as it was unclear to whom the president was referring.
"It is sad that President Bush would use a speech to the Knesset on the 60th anniversary of Israel's independence to launch a false political attack," Obama said in the statement his aides distributed. "George Bush knows that I have never supported engagement with terrorists, and the president's extraordinary politicization of foreign policy and the politics of fear do nothing to secure the American people or our stalwart ally Israel."
House Speaker Nancy Pelosi also responded during her weekly press conference, saying, "I think that what the president did in that regard was beneath the dignity of the office of president and unworthy of our representation at that observance in Israel."
Video: Obama on Iran "I would hope that any serious person would disassociate himself with the president's remarks," she added.
The White House said Bush's comment wasn't a reference to Obama.
"It is not," press secretary Dana Perino told reporters in Israel. "I would think that all of you who cover these issues and have for a long time have known that there are many who have suggested these types of negotiations with people that the president, President Bush, thinks that we should not talk to. I understand when you're running for office you sometimes think the world revolves around you. That is not always true. And it is not true in this case."
The debate over whether the president should directly negotiate with rogue leaders has been one of the most prominent issue differences in the race for the Democratic nomination. Obama says he would meet with heads of state in places like Cuba, Iran and North Korea. Rival Hillary Rodham Clinton says those meetings could be used for propaganda and her first response will be outreach through other diplomatic channels.
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As Obama inches closer to clinching the Democratic nomination, he's spent far more time assailing Republicans and the GOP's nominee-in-waiting, John McCain, than he has going after Clinton. By assailing Bush, Obama sent a signal that he's strong enough to take on the sitting president and the incumbent party — and counter the notion fueled by Clinton that she would be the stronger Democratic general election candidate.
Bush, for his part, mostly refrained from directly injecting himself into the presidential race through the Republican primary. When McCain clinched the nomination in March, however, the two appeared together in the White House Rose Garden. Since then, he has talked up McCain frequently.
When it comes to the Democratic race, the president typically avoids naming names but he has publicly disagreed with the positions of the Democratic front-runners.
He has, for example, strongly disagreed with Obama's expressed willingness to meet the leaders of U.S. adversaries such as Cuba and Iran. And, McCain has criticized Obama directly and repeatedly for saying that he would meet with Cuba's leader, Raul Castro, without preconditions.
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