Dr. Andrea Grubb Barthwell had been deputy director of the Office of National Drug Control Policy since January 2002. Federal law barred her from seeking the Republican nomination while she worked for the government.
The drug-control office announced her resignation in a written statement. If Barthwell is chosen to face off against Democrat Barack Obama, it would be the first time in U.S. history that two black candidates have battled for a Senate seat.
The original Republican nominee, Jack Ryan, dropped out of the race two weeks ago after the release of embarrassing sex club allegations in his now-public divorce records.
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