A debate between Democratic nomination hopefuls in South Carolina took questions not from studio audience members or a professional news anchor but from citizens around the country who had recorded their messages using webcams under the partnership, announced by the companies in June.
Candidates have become increasingly adept with the tools of user-generated content production, with the likes of Hillary Clinton and Barack Obama having announced their candidature using online video.
But the two-hour CNN show, which saw editors from the news network select questions from the 30-second YouTube submissions sent to a special website, was among the first instances of the video network being used to create dialogue.
The televised presidential face-off gained currencies in the US in 1960, when Richard Nixon was deemed to have lost a debate with John F. Kennedy thanks to his pallid complexion and poor aesthetic performance.
Viewers who watched last night's CNN/YouTube debate began posting their own video responses to candidates' performance.
A second such project will be staged in September, when YouTubers can ask questions of Republican nominees.
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