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Mertesacker, a native of Hannover, became a youth player at Hannover 96 and eventually made his first-team debut for this club. Mertesacker had an unlucky start for his home club, breaking his nose and scoring an own goal soon after, but established himself as one of the most promising young defenders in the Bundesliga. His type of game was unusually clean, him being rarely booked (as of July 2006, only twice in 74 games) while regularly neutralizing his opponents. The slender Mertesacker was soon dubbed "the Defense Pole" (die Abwehrlatte) by German tabloids. In August of 2006 he moved to Werder Bremen in a €5 million transfer deal after a highly impressive performance in the 2006 World Cup, in which Germany finished 3rd.
Mertesacker got his first red card in his professional career in the match between Werder Bremen and VfB Stuttgart in Season 07-08, which Werder lost 3-6.
In September 2004, Jürgen Klinsmann, manager of Germany, called Mertesacker up to the October 9, 2004 game against Iran. At the age of 19, he became one of the youngest ever debutants for the German national team. With his quiet but effective game, he established himself as a defensive stalwart, pairing up with Robert Huth and later, Christoph Metzelder.
In the 2006 World Cup, he was violently attacked by Leandro Damián Cufré, an unused Argentine substitute, after Germany won the penalty shoot-out against them in the quarterfinals. He suffered minor injuries to his thigh and a kick to the groin. After Germany's loss to Italy in the semifinals, Mertesacker had surgery on one of his legs (not related to the attack above, but an injury he had been dealing with during previous matches) and missed the third place play-off.