President Obama learned about Kennedy's death at 2 a.m. Wednesday, according to a senior administration official. Obama later called Kennedy's widow to offer condolences.

In a statement, Obama says: "An important chapter in our history has come to an end. Our country has lost a great leader, who picked up the torch of his fallen brothers and became the greatest United States Senator of our time."

Kennedy, nicknamed "Ted," was the younger brother of slain President John F. Kennedy and New York Sen. Robert Kennedy, who was gunned down while seeking the White House in 1968. However, his own presidential aspirations were hobbled by the controversy around a 1969 auto accident that left a young woman dead, and a 1980 primary challenge to then-President Jimmy Carter that ended in defeat.

But while the White House eluded his grasp, the longtime Massachusetts senator was considered one of the most effective legislators of the past few decades. Kennedy, who became known as the "Lion of the Senate," played major roles in passage of the Civil Rights Act of 1964, the Voting Rights Act of 1965, the 1990 Americans with Disabilities Act and the 1993 Family and Medical Leave Act, and was an outspoken liberal standard-bearer during a conservative-dominated era from the 1980s to the early 2000s.

"He was probably best known for the ability to work with Republicans," said Adam Clymer, Kennedy's biographer. "The Republican Party raised hundreds of millions of dollars with direct appeal to protect the country from Ted Kennedy, but there was never a piece of legislation that he ever got passed without a major Republican ally."

Kennedy recently urged Massachusetts officials to change a law to allow for an immediate temporary replacement should a vacancy occur for one of his state's two Senate seats.

Under a 2004 Massachusetts law, a special election must be held 145 to 160 days after a Senate seat becomes vacant. The winner of the election would serve the remainder of a senator's unexpired term.

Kennedy asked Gov. Deval Patrick and state leaders to "amend the law through the normal legislative process to provide for a temporary gubernatorial appointment until the special election occurs," according to the letter, dated July 2.

Kennedy suffered a seizure in May 2008 at his home on Cape Cod. Shortly after, doctors diagnosed a brain tumor -- a malignant glioma in his left parietal lobe.

Surgeons at Duke University Medical Center in Durham, North Carolina, removed as much of the tumor as possible the following month. Doctors considered the procedure a success, and Kennedy underwent follow-up radiation treatments and chemotherapy.

A few weeks later, he participated in a key vote in the Senate. He also insisted on making a brief but dramatic appearance at the 2008 Democratic convention, a poignant moment that brought the crowd to its feet and tears to many eyes. Kennedy died one year to the day after that appearance.

"I have come here tonight to stand with you to change America, to restore its future, to rise to our best ideals and to elect Barack Obama president of the United States," Kennedy told fellow Democrats in a strong voice.

Kennedy's early support for Obama was considered a boon for the candidate, then a first-term senator from Illinois locked in a tough primary battle against former first lady Hillary Clinton. Kennedy predicted Obama's victory and pledged to be in Washington in January when Obama assumed office -- and he was, though he was hospitalized briefly after suffering a seizure during a post-inaugural luncheon.

Kennedy was one of only six senators in U.S. history to serve more than 40 years. He was elected to eight full terms to become the second most-senior senator after West Virginia Democrat Robert Byrd.

He launched his political career in 1962, when he was elected to finish the unexpired Senate term of his brother, who became president in 1960. He won his first full term in 1964.

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