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His travel series sparked popular and critical acclaim, with a second season coming. In March, three weeks before his own Mark Twain ceremony in Washington.

Deborah Rutter, president of the John F. Kennedy Center for the Performing Arts, in a statement called O'Brien “a master of invention and reinvention, consistently pushing the envelope in search of new comedic heights."

O’Brien offered his own tongue-in-cheek assessment, saying in the Kennedy Center statement that he would be “the first winner of the Mark Twain Prize recognized not for humor, but for my work as a riverboat pilot.� He will be honored on March 23 in a special ceremony in which he will receive a bronze bust of Twain, the iconic American writer and satirist whose real name was Samuel Clemens.

Mark Twain recipients are honored with a night of testimonials and video tributes, often featuring previous award winners. The ceremony will stream on Netflix at a later date yet to be announced.

O'Brien leaped into the spotlight from near-total obscurity in 1993, when he was chosen to replace the legendary David Letterman as host of “Late Night� despite no significant on-camera experience. The former Harvard Lampoon editor had spent the previous years as a writer for and “The Simpsons,� appearing on camera only as an occasional background extra in “SNL� skits.

Bringing a skittish, awkward energy that contrasted with Letterman's deadpan persona, O'Brien constantly made fun of his own gangly appearance and inappropriateness for the job. He went on to host “Late Night� for 16 years, longer than any other host.

In 2009, O'Brien's career and persona took a turn. He became the man who publicly gained and lost his dream job while America watched.

O'Brien was tapped to replace Jay Leno as host of “The Tonight Show� despite that Leno wasn't ready to cede the throne. After seven months of declining ratings, NBC executives brought Leno back for a new show that would bump “The Tonight Show� back. O'Brien refused to accept the move, that ended with a multimillion-dollar payout for O'Brien and his staff to exit the network in early 2010.

The aftermath split the comedy world, with Leno cast as the villain and O'Brien as the victim who was set up to fail.

In on his final “Tonight Show,� O'Brien described himself as lucky and refused to sound bitter.

“Every comedian dreams of hosting 'The Tonight Show,' and for seven months I got to do it," he said. "I did it my way with people I love, and I don't regret one second.�

He ended with a sort of generational rallying cry.

“All I ask is this one thing, particularly of young people that watch: Please do not be cynical,� O'Brien said, his voice cracking. “Nobody in life gets exactly what they thought they were going to get, but if you work really hard and you're kind, amazing things will happen.�

O'Brien reemerged later in 2010 with a new talk show on the cable station TBS. Despite the channel's lower profile, while he launched parallel ventures like the podcast “Conan O'Brien Needs a Friend� and the travel show “Conan Without Borders,� a precursor to his current show.

Other comedians receiving the lifetime achievement award include both Letterman and Leno, along with George Carlin, Whoopi Goldberg, Bob Newhart, Carol Burnett and Dave Chappelle. , the 2009 recipient, had his Mark Twain Prize rescinded in 2019 amid multiple allegations of sexual assault.