Pokémon: Detective Pikachu is now in the theaters and the story of the movie has been revealed to the audience. It turns out that the film follows the plot of the Detective Pikachu video game a lot closer than anyone realized, which in itself used an item from Pokémon Gold & Silver as a major part of its story.
*Mild Spoilers For The Overall Plot Of Detective Pikachu Going Forward*
In Detective Pikachu, the protagonist discovers a vial of a gaseous substance that drives Pokémon crazy and turns them aggressive, to the point where they will even attack human beings. It's later discovered that this substance is referred to as "R" and it's used by competitors in underground Pokémon fight clubs. It turns out that R is a substance that can only be extracted from the body of Mewtwo. R (and its connection to Mewtwo) also appeared in the Detective Pikachu video game for the Nintendo 3DS.
The idea of there being a substance from Mewtwo's body that can drive Pokémon into a rage actually comes from Pokémon Gold & Silver.
In Pokémon Gold & Silver, when the player returns to Kanto they can travel to Cerulean City. The Cerulean Cave where Mewtwo is found in Pokémon Red & Blue has collapsed and cannot be explored. If the player searches the water near the entrance to the Cerulean Cave, then they can find a held-item called the Berserk Gene.
The Berserk Gene is an item that is consumed after a single use, which has the ability to raise a Pokémon's Attack stat by two stages but leaves them confused for the duration of the battle. The fans had speculated that the Berserk Gene was a remnant of Mewtwo that had been left behind, but the connection between the two wasn't confirmed until the Detective Pikachu video game.
The strange thing about the Berserk Gene is that it has only ever appeared in Pokémon Gold & Silver. The Berserk Gene has never returned in any of the other Pokémon games, including the remakes of Pokémon Gold & Silver. Despite its limited appearances in the Pokémon series, the Berserk Gene would go on to be a major part of the Detective Pikachu video game and would be part of the Detective Pikachu movie.
Pokémon: Detective Pikachu is in theaters now.