Mr. George Mitchell, the special U.S. envoy for Middle East peace, has thrown in the towel. Of course, neither Mr. Mitchell nor the U.S. government would characterize his resignation last week as giving up, but there is no mistaking his frustration with the peace process.

It is a dispiriting end to a remarkable political career, and a signal of just how intractable the problems of the Middle East. The violence that erupted Sunday at Israel’s borders is the counterpoint to Mr. Mitchell’s resignation: a reminder that failure to make progress means that more lives will be forfeit.

Mr. Mitchell was appointed by U.S. President Barack Obama in January 2009 on the second day of his administration, a signal of the priority afforded resolution of the Israel-Palestine problem, an assignment that Mr. Obama called “the toughest job imaginable.” Few negotiators were better suited to the task.

Mr. Mitchell is a former Senate majority leader. For those who remember how U.S. politics used to work, that means he was the man who brought both sides of that body together to pass legislation and he was quite successful at it. He followed that career by brokering a peace agreement in Northern Ireland, a situation that looked every bit as insoluble as that involving Israelis and Palestinians. He then headed the investigation of the use of steroids in professional baseball in the United States, a job that probably meant the most to most Americans—and one that may have best tested Mr. Mitchell’s skills.

Yet even that skill set and list of accomplishments were not enough to break the impasse between Israelis and Palestinians. There was hope that Mr. Obama’s election would transform Middle East dynamics and that his administration would commit more resources to that intractable conflict. Neither proved true. Israelis looked at the new president with suspicion, and the promised diplomatic push never materialized.

Instead, whatever promise might have existed foundered on the intransigence that has blocked progress. By all accounts, the breaking point occurred last year when the United States could not persuade the government of Israeli Prime Minister Benjamin Netanyahu to freeze the construction of settlements on territories claimed by Palestine. Negotiations broke down and Mr. Mitchell lost patience. He has not visited the region since December.

The resignation comes at a bad time. This is a busy week for the president. Mr. Obama met Jordan’s King Abdullah II on Tuesday, will deliver a major address on the Middle East on Thursday and will then meet Mr. Netanyahu on Friday. This occurs in the context of the unrest that has ricocheted throughout the region, overturned governments in Tunisia and Egypt and threatens administrations in Libya, Syria, Bahrain and Yemen, and follows the killing of Osama bin Laden. Even though Mr. Mitchell’s resignation letter was dated April 6, its timing suggests that there is less opportunity in this moment than many assume.

Officially, Mr. Mitchell committed to only two years in his post and, at 75 years old, he has earned his retirement. But this is the man who famously noted that he had “700 days of ‘no’ in Northern Ireland and one ‘yes.'” That one yes was nowhere in sight in the Middle East.

Recent developments may have pushed it further off. Earlier this month, the two rival Palestinian factions, Fatah, which controls the West Bank, and Hamas, which controls the Gaza Strip, signed a reconciliation agreement. Since the Israeli government (like the U.S. and the European Union) considers Hamas a terrorist organization, that effectively kills any negotiations, at least until Hamas accepts basic principles laid down years ago, such as renouncing violence and recognizing Israel. Hamas refuses to take that step.

Weighing on every calculation is the impact of the Arab Spring. In theory, the overturn of authoritarian governments was supposed to create a flowering of democracy that would in turn lay a foundation for peace.

So far, theory has been confounded. The most notable foreign policy developments in the aftermath of the changes in the region have been the readiness of the new government in Egypt to talk to an Iranian government that supports Islamic militancy and to push the Palestinians together. The Arab Street looks less amenable to a deal with Israel than the autocrats.

Not surprisingly, Arab governments under pressure appear to be trying to channel and exploit that sentiment. Last weekend, thousands of people in Lebanon, Syria, the West Bank and Gaza demonstrated at their areas’ borders with Israel to mark “the Nakba,” the anniversary of the seizure of Palestinian territory by Israel. It was the first coordinated protest among Palestinians and it resulted in violence when border checkpoints were overwhelmed and Israeli forces shot at the invaders, leaving at least 10 dead.

Such incidents are a welcome distraction for the besieged government in Damascus, and the Palestinian leaders, both of whom would otherwise have to respond to growing demands for political rights and economic answers. It is far easier for them to refocus domestic anger on Israel than deal with those problems.

As a life-long politician, Mr. Mitchell understood the appeal of that approach, but as a peacemaker he recognized its futility. Until other regional leaders prove to be as farsighted, peace in the Middle East will remain a distant dream and the graveyard of diplomatic careers.

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