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In 2050 a mad scientist was shut down by his superiors after conducting bizarre biological experiments. However soon after, his lab exploded and the scientist himself mysteriously disappeared. Now several years later there are new buildings on top of the forgotten slum where the experiments took place and suddenly a genetic virus has started to spread among the tenants turning them into vicious mutants. The two protagonists return to town after having been away for a long time and upon seeing what is happening they take it upon themselves to clean the town up before the mutants spread across the nation. Along the way they come across not just the mutants but also mechanically modified foes that the mad scientist has created to stop them.
One or two players fight their way through the five levels of various mutated and mechanic enemies, each level containing one or more sub-bosses before an actual boss appears at the end of each stage. The game plays close to the usual beat 'em up mold allowing the player to utilize various combos, jumping attacks, throws and special moves to utilize on the opposition. Rather than the standard fare of allowing players to pick up objects to use as weapons against the enemy however, Mutation Nation instead uses a system where the player can pick up one of four elemental spheres that allows the player the ability to unleash screen filling super attacks. There are also neutral spheres that will give life back to the player and increase the number of super attacks that they can use.
These are the various elemental spheres that can be picked up by the player and used for special attacks. Each sphere is represented by a letter and color that helps the player tell them apart. If the players don’t have any spheres available they can instead sacrifice part of their life meter to unleash a flurry of attacks.
- Light - Red with the letter A written on it. The light sphere unleashes the fastest but also least damaging attack in the game. The player explodes into two bodies of light that shoot out in opposite directions before coming back together to reform the body after the enemies have been knocked down.
- Fire - This sphere is represented by the letter B and has a reddish color. It unleashes a large explosion from the players hands which does heavy damage to everything on screen.
- Lightning - The lightning sphere has a blue color and the letter C. The attack it produces is by far the slowest attack in the game but it doesn't matter much because the player is invincible for the duration of the entire animation. The character will jump up off screen and come down a few moments later hitting the ground to create lightning streaks that go off in all directions for moderate damage.
- Wind - The last sphere is green and has the letter D on it. It unleashes the most powerful attack in the game where the player turns into a massive green tornado that will travel back and forth over the screen, mowing down everything in its path often hitting more than once for massive damage.
- The English manual for the Mutation Nation AES home version.
- The Neo Geo AES technical manual.