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Nearly everyone in Massachusetts is waiting for Joseph P. Kennedy II to make up his mind.

It is hard to imagine this state without a Kennedy in the U.S. Senate. But it seems that Joseph P. Kennedy, 56, an entrepreneur and former congressman who has avoided politics for more than a decade, is the only family member seriously mulling a run for the seat that his uncle, Edward M. Kennedy, held for 47 years.

For Massachusetts, with its top hospitals, universities and research centers that counted on the federal dollars that flowed from Edward M. Kennedy’s influence on Capitol Hill, the stakes extend far beyond its deep emotional connection with the senator. People here are starting to grapple with the big political question: How to replace their irreplaceable senator, whose decades of relationships in Washington made Massachusetts a prime beneficiary of the things he believed in.

“With Joe, a lot of those ties would come back quickly,” said David Gergen, a professor at Harvard’s Kennedy School who has advised both Democratic and Republican presidents. “There would be an army of people who worked for his uncle who would want to work for him.”

Several people close to the family said that pressure on Joe Kennedy was not coming from inside the family, which is still grieving over the loss of its patriarch, but from within Joe himself, and from various stakeholders in Massachusetts – mayors, labor leaders and others — who view him as the candidate most likely to inherit enough of his monumental influence to take care of their needs.

Friends said that Joe Kennedy, who has the trademark Kennedy toothy smile, is agonizing over whether he truly wants the job, and he is depending almost exclusively on his second wife, Beth, for counsel.

“It’s not about ensuring that someone named Kennedy stays in the seat,” said one friend of the Kennedy family, who requested anonymity, citing the private nature of the discussions. “It’s going to be a very personal decision based on whether or not this fits into Joe’s life right now.”

And until he makes a move, political observers say, no other possible contender — with the exception of Martha Coakley, the state attorney general who announced Thursday — is going to declare for the primary, scheduled Dec. 8.

“This is almost a unique situation in which Joe Kennedy has the right of first refusal to the seat,” Gergen said.