We may be witnessing the biggest political upset since Truman defeated Dewey.

With 60 percent of the vote in, Republican Scott Brown is ahead of his heavily-favored Democratic opponent, Martha Coakley, in a special election to fill the remainder of Sen. Ted Kenney's unexpired term

The Massachusetts Senate seat has been held by the Kennedys since the early 1950s.

With 60 percent of precincts reporting, Brown has 53 percent of the vote to 46 percent for Coakley.

The Associated Press calls the race "a referendum on President Barack Obama's sweeping health care overhaul and his first year in office."

From the wire service:

A loss — or even a narrow victory — by the once-favored Coakley for the seat that the late Sen. Edward M. Kennedy held for nearly half a century in this Democratic stronghold could signal big political problems for the president's party this November when House, Senate and gubernatorial candidates are on the ballot nationwide.

More immediately at stake was a critical 60th vote for the Democrats' supermajority, which is needed to save their health care legislation and the rest of Obama's agenda. The Democrats can't afford to lose a seat because a 41st Republican in the 100-member Senate could allow the Republicans to use procedural maneuvers to block votes on legislation.

The election transformed reliably Democratic Massachusetts into a battleground state. One day shy of the first anniversary of Obama's swearing-in, it played out amid a backdrop of animosity and resentment from voters over persistently high unemployment, industry bailouts, exploding federal budget deficits and partisan wrangling over health care.