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The softly-spoken reformist will become the most senior Iranian to visit America in nearly three decades. He is expected to attend the United Nations Dialogue of Civilisations conference in New York next Tuesday, address an inter-faith meeting at the National Cathedral in Washington on Thursday and give a speech to an Islamic group in Chicago.
The highlight could be a meeting with Jimmy Carter, the former American President who heads the Carter Centre in Atlanta, a conflict-resolution organisation.
Iranian and American officials insist that the visit by Mr Khatami and his entourage of aides and family members is purely private. No meetings are planned with members of the Bush Administration and he will not be representing President Ahmadinejad, his hardline successor.
But experts on the region hope that the visit could open a channel between America and Iran, who have no diplomatic ties and whose dialogue is usually confined to public threats and insults.
“This is an important visit because Khatami does still have clout in Iran,” Dr Ali Ansari, an expert on Iran at the University of St Andrews, said. “Much will depend on how the visit is handled. It is a very delicate matter.” Certainly, the former Iranian leader, who tried to improve ties with the West during his tenure from 1997 to 2005, will have his work cut out.
His trip coincides with the expiry today of a UN Security Council deadline on Iran to halt its uranium enrichment work, which it is alleged could be diverted to produce a nuclear weapon. The Iranians have said that they will not halt the programme and a report to be presented to the council by Mohamed ElBaradei, the head of the International Atomic Energy Agency, is likely to accuse Iran of accelerating the enrichment work.
America, Britain and France want the council to move ahead with punitive sanctions against Iran that would target key figures in the regime and ban the sale of nuclear equipment and possibly arms.
China and Russia, the two other permanent council members with strong commercial ties to Iran, favour a more diplomatic solution.
While the outlook appears stark, diplomats involved in negotiations with Iran are convinced that a deal is still possible between Washington and Tehran that could settle all outstanding issues stretching back to the Iranian revolution in 1979, which swept the Islamic regime into power.
By a twist of fate a key figure in mediation efforts could be Mr Carter. He lost his presidential re-election attempt in 1980 in part because of the Iranian hostage crisis, when militant students seized 52 American diplomats and held them for 444 days. Since then he has dedicated his career to conflict resolution and now stands ready to meet Mr Khatami.
But the visiting Iranian former leader will not be welcomed everywhere in America.
The Simon Wiesenthal Centre has started a petition calling on the Bush Administration to block the visit.
“Granting former President Khatami a visa at this time, coming on the heels of both Iran’s proxy war in Lebanon and its refusal to drop its nuclearisation programme, will be viewed by the mullahs as a reward for their policy of confrontation and hatred toward the United States and her allies,” the organisation said.
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