Senator Edward M. Kennedy of Massachusetts, the last surviving brother in a political dynasty and one of the most influential senators in US history, died Tuesday night at his home on Cape Cod after a year-long struggle with brain cancer. He was 77. In nearly 50 years in the Senate, Kennedy served alongside 10 presidents – his brother John Fitzgerald Kennedy among them – compiling an impressive list of legislative achievements on health care, civil rights, education, immigration and more. His only run for the White House ended in defeat in 1980. More than a quarter-century later, he handed then-Senator Barack Obama an endorsement at a critical point in the campaign for the Democratic presidential nomination, explicitly likening the young contender to President Kennedy. To the American public, Kennedy was best known as the last surviving son of America's most glamorous political family, father figure and, memorably, eulogist of an Irish-American clan plagued again and again by tragedy. Kennedy was elected to the Senate in 1962, taking the seat that his brother John had occupied before winning the White House, and served longer than all but two senators in history. 1969 scandal His own hopes of reaching the White House were damaged – perhaps doomed – in 1969 by the scandal that came to be known as Chappaquiddick, an auto accident that left a young woman dead. He sought the White House more than a decade later, lost the Democratic nomination to President Jimmy Carter, and bowed out with a stirring valedictory that echoed across the decades: “For all those whose cares have been our concern, the work goes on, the cause endures, the hope still lives and the dream shall never die.” Kennedy was diagnosed with a cancerous brain tumor in May 2008 and underwent surgery and a grueling regimen of radiation and chemotherapy. He made a surprise return to the Capitol last summer to cast the decisive vote for the Democrats on Medicare. He made sure he was there again last January to see his former Senate colleague Barack Obama sworn in as the nation's first black president, but suffered a seizure at a celebratory luncheon afterward. He also made a surprise and forceful appearance at last summer's Democratic National Convention, where he spoke of his own illness and said health care was the cause of his life. His death occurred precisely one year later, almost to the hour. He was away from the Senate for much of this year, leaving Republicans and Democrats to speculate about the impact what his absence meant for the fate of Obama's health care proposals. Under state law, Kennedy's successor will be chosen by special election. In his last known public act, the senator urged state officials to give Democratic Gov. Deval Patrick the power to name an interim replacement. But that appears unlikely, leaving Democrats in Washington with one fewer vote for the next several months as they struggle to pass Obama's health care legislation. His death came two weeks after that of his sister Eunice Kennedy Shriver on Aug. 11. Kennedy was not present for the funeral, an indication of the precariousness of his own health. In a recent interview with The Associated Press, Kennedy's son, Rhode Island Democratic congressman Patrick Kennedy, said his father had defied the predictions of doctors by surviving more than a year with his fight against brain cancer. The younger Kennedy said that gave family members a surprise blessing, as they were able to spend more time with the senator and to tell him how much he had meant to their lives. “There are very few people who have touched the life of this nation in the same breadth and the same order of magnitude,” Obama said in April as he signed the Edward M. Kennedy Serve America Act into law. Family tragedies Kennedy arrived at his place in the Senate after a string of family tragedies. He was the only one of the four Kennedy brothers to die of natural causes. Kennedy's eldest brother, Joseph, was killed in a plane crash in World War II. President John F. Kennedy was assassinated in Dallas in 1963. Sen. Robert F. Kennedy was gunned down in Los Angeles as he campaigned for the 1968 Democratic presidential nomination. Years later, in 1999, John F. Kennedy Jr. was killed in a plane crash at age 38 along with his wife. It fell to Ted Kennedy to deliver the eulogies, to comfort his brothers' widows, to mentor fatherless nieces and nephews. It was Ted Kennedy who walked JFK's daughter, Caroline, down the aisle at her wedding. Tragedy had a way of bringing out his eloquence. Kennedy sketched a dream of a better future as he laid to rest his brother Robert in 1968: “My brother need not be idealized, or enlarged in death beyond what he was in life; to be remembered simply as a good and decent man, who saw wrong and tried to right it, saw suffering and tried to heal it, saw war and tried to stop it.” After John Jr.'s death, the senator said: “We dared to think, in that other Irish phrase, that this John Kennedy would live to comb gray hair, with his beloved Carolyn by his side. But like his father, he had every gift but length of years.” His own legacy was blighted on the night of July 18, 1969, when Kennedy drove his car off a bridge and into a pond on Chappaquiddick Island, on Martha's Vineyard. Mary Jo Kopechne, a 28-year-old worker with RFK's campaign, was found dead in the submerged car's back seat 10 hours later. Kennedy, then 37, pleaded guilty to leaving the scene of an accident and received a two-month suspended sentence and a year's probation. A judge eventually determined there was “probable cause to believe that Kennedy operated his motor vehicle negligently ... and that such operation appears to have contributed to the death of Mary Jo Kopechne.” At the height of the scandal, Kennedy went on national television to explain himself in an extraordinary 13-minute address in which he denied driving drunk and rejected rumors of “immoral conduct” with Kopechne. He said he was haunted by “irrational” thoughts immediately after the accident, and wondered “whether some awful curse did actually hang over all the Kennedys.” He said his failure to report the accident right away was “indefensible.” After Chappaquiddick especially, Kennedy gained a reputation as a heavy drinker and a womanizer, a tragically flawed figure haunted by the fear that he did not quite measure up to his brothers. As his weight ballooned, he was lampooned by comics and cartoonists in the 1980s and ‘90s as the very embodiment of government waste, bloat and decadence. But in his later years, after he had remarried, he came to be regarded as a statesman on Capitol Hill, seen as one of the most effective, hardworking lawmakers Washington has ever seen. Hardworking senator A barrel-chested figure with a swath of white hair, a booming voice and a thick, widely imitated Boston accent, he coupled fist-pumping floor speeches with his well-honed Irish charm and formidable negotiating skills. He was both a passionate liberal and a clear-eyed pragmatist, willing to reach across the aisle to get things done. Kennedy's speech in accepting defeat to Carter electrified the Democratic convention and turned out to be a defining moment. At 48, he seemed liberated from the towering expectations and high hopes invested in him after the death of his brothers, and he plunged into his work in the Senate. Kennedy served close to 47 years, longer than all but two senators in history: Robert Byrd of West Virginia (50 years and counting) and the late Strom Thurmond of South Carolina, who died after a tenure of nearly 47 1/2 years. Kennedy's career spanned 10 presidencies. Kennedy and his niece Caroline shook up the Democratic establishment in January 2008 when they endorsed Obama over Hillary Rodham Clinton for the nomination for president. Born in 1932, the youngest of Joseph and Rose Kennedy's nine children, Edward Moore Kennedy was part of a family bristling with political ambition, beginning with maternal grandfather John F. “Honey Fitz” Fitzgerald, a congressman and mayor of Boston. Teddy was thrown out of Harvard in 1951 for cheating, after arranging for a classmate to take a freshman Spanish exam for him. He eventually returned, earning his degree in 1956. He went on to the University of Virginia Law School, and in 1962, while his brother John was president, announced plans to run for the Senate seat JFK had vacated in 1960. A family friend had held the seat in the interim because Kennedy was not yet 30, the minimum age for a senator. Devastated by his brothers' assassinations and injured in a 1964 plane crash that left him with back pain that would plague him for decades, Kennedy temporarily withdrew from public life in 1968. But he re-emerged in 1969 to be elected majority whip of the Senate. Kennedy's memoir, “True Compass,” is set to be published in the fall.