Entrepreneur Isaacman has been formally approved as the next chief of the National Aeronautics and Space Administration, ending an unusual nomination process where Trump put his name forward, withdrew it, and then renominated him.
The 42-year-old, an amateur jet pilot who was the first civilian to undertake a spacewalk, is also the first agency head in a generation to come directly from outside government.
For a significant portion of the space community, the legacy of his time in office will be decided by one crucial test: whether it can land people to the lunar surface ahead of the Chinese space program.
The President has stated explicitly a desire for the America to establish a permanent lunar base, both to enable resource extraction and to serve as a stepping stone for travel to the Red Planet.
On Wednesday, the Senate cleared Isaacman's nomination with a decisive vote.
The President first withdrew the nomination in the spring, pointing to a "comprehensive examination of previous relationships".
At the period, the president was publicly feuding with tech billionaire Musk, one of his biggest supporters, with whom Isaacman has a working relationship.
Isaacman has stated he is now aligned with the administration's goal to harvest the moon, creating a divergence from Musk, who has argued that lunar missions is a detour from the goal of travelling to Mars.
In the current space battle, nations are competing to tap into the moon's resources.
“This is not the time for hesitation but a time for action because if we lag, if we err, we may never catch up, and the consequences could alter the global dynamics here on Earth,” Isaacman told the Senate committee recently.
The billionaire entrepreneur sees bringing in more private sector competition as key to meeting those targets, according to a circulated paper detailing his strategy for the agency.
In his Senate hearing, he stood by the blueprint, which he drafted when he was first nominated, but said it was a developing document.
His openness to competition could also cause friction with SpaceX. Recently, Isaacman praised the issuance of a significant agreement to Jeff Bezos's company, which is one of the few rivals of SpaceX.
In the document, he suggested the agency should increasingly partner with research institutes, positioning the agency as a "catalyst for science".
He pointed to the scheduled deployment of the Nancy Grace Roman Space Telescope as a prime illustration.
"And if we be close to something groundbreaking - like launching Roman - I will leave no stone unturned to see it launched, even providing personal financing if that's what it requires to produce the discoveries," he stated.
According to analyses, his wealth is estimated at around $1.2 billion, made mostly from his payment processing company and the divestment of his firm that provided flight training and operated a collection of military aircraft.
The position of agency chief will be his maiden role in politics, a break from the previous two appointees appointed as head of the agency.
He will replace the former transportation secretary, who has served as temporary leader since the summer.
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