The super soldier serum had a horrendous effect on Johann Schmidt in Captain America: The First Avenger, turning him into the Red Skull, but why didn't that happen to Steve Rogers? In the 2011 movie, it was established that HYDRA leader Johann Schmidt, played by Hugo Weaving, injected himself with a version of the super soldier serum prior to Steve Rogers' transformation into Captain America. The serum increased his physical capabilities as intended, but it also gave his face the appearance of a red skull.

Created by German scientist Dr. Abraham Erskine (Stanley Tucci), the super soldier serum is a formula designed to turn a person into the perfect warrior by increasing their strength, speed, reflexes, agility, and more. After it turned skinny Steve Rogers (Chris Evans) into the muscle-bound Sentinel of Liberty, others in the MCU have tried to replicate it, but without the same results. Years later, an obviously imperfect recreation of the serum transformed Emil Blonsky (Tim Roth) into the Abomination in 2008's The Incredible Hulk. It's possible that different versions of it will appear in The Falcon and the Winter Soldier and be administered to U.S. Agent (Wyatt Russell) and Isaiah Bradley.

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The first known character to receive the serum was the Red Skull, and how it affected him was drastically different from what happened to Steve Rogers. This was explained in Captain America: The First Avenger when Dr. Erskine told Steve that the serum wasn't ready when Schmidt injected himself. It was far enough into development to give him the strength boost he wanted, but Erskine had yet to work out the adverse side effects. Schmidt's impatience is what caused his head to be so terribly disfigured. It resulted in the complete loss of hair, the skin all over his face to deteriorate and fall away, and his head to develop a red discoloration.

It's possible that the super soldier serum would have had the same effect on anyone who used it at that time, but it could be that this particular effect was unique to Schmidt, based on other comments made by Erskine. Erskine told Steve that the serum amplified the good and evil that was within the person who used it, which would mean that the evil head of HYDRA was transformed into something even worse than what he already was. In a way, his ugly physical appearance is a reflection of his true self.

This origin story differs greatly from the explanation that was offered for the comic book Red Skull. In Marvel Comics, Johann Schmidt was not a super soldier when he was introduced. Red Skull's face really was just a mask in the beginning, but it stopped being just a disguise when one of his weapons, a chemical called the Dust of Death, got on his face and caused his skin to decay and ruin. The MCU made a change to this, and brought his origin story closer to Captain America by making Johann Schmidt Steve Rogers' evil counterpart.

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