Billionaire entrepreneur Jared Isaacman will lead three fellow spaceflight novices into a SpaceX falcon rocket for a three-day mission.
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"It is the first time that a global superpower has sent people up into orbital space, and I think should send a message of all the things to come," Isaacman said.
The civilian crew members have ties to St. Jude Children's Hospital.
Chris Sembroski won a seat in a sweepstakes that drew 72,000 applicants and has raised over $100 million in St. Jude donations, while Hayley Arceneaux is a bone cancer survivor turned St. Jude physicians' assistant.
"This is definitely not something I ever imagined would happen, but I think that's what makes it so fun for me," Arceneaux said.
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The four crew mates have spent the past five months undergoing rigorous preparations, including altitude fitness and simulator training.
The rocket will blast off from Cape Canaveral and splash down in the Atlantic.