Throughout the movie, Leonard narrates a story of Sammy Jankis to an unknown phonecaller. Sammy Jankis is a guy who developed anterograde amnesia after a minor car accident. Sammy couldn't learn any new skills since he forgot everything he learned after the accident. Learning through repetition did not work for him, and since it is a 'muscle memory' that uses different part of the brain from the short-term memory, Sammy's condition was determined to be psychological rather than physical. Leonard explains that he and Sammy are essentially different because he can learn through conditioning.
Leonard believes that he and Sammy are different since he can learn through conditioning. This seems to be true, because Leonard somehow knows that he must learn something by looking at his tattoo, or multiple notes in his pockets. If he were like Sammy, then he shouldn't know why he has tattoo on his body, since he got his tattoo after the accident.
"Conditioning didn't work for Sammy, so he became helpless. But it works for me. I live the way Sammy couldn't. Habit and Conditioning. Acting on instinct."
But is Leonard really learning things through conditioning? There are few scenes when Leonard looks at a tattoo on his hand that says “Remember Sammy Jankis”, and he tries to remove it as if he does not know of its existence. This tells me that every time Leonard starts his new memory, he must learn every single clue again. This is not impossible, but seems highly unlikely to me. I think he somehow subconsciously knows that he has to follow clues by looking at his tattoo or notes. At the end of the movie the viewers learn from Teddy that Sammy Jankis story is actually Leonard’s own. There is a debate as to whether Teddy is reliable person, but I believe that at least that part of the story should be trusted.There is a scene where Sammy is staring at people in the hospital, and as a person passes by, it quickly changes to Leonard. 
This scene confirmed that Leonard must be Sammy, (or part of Sammy story must be his) and that Leonard must have entered the mental institution because of his condition.
One of the flashbacks shows Sammy’s wife asking Leonard his honest opinion about Sammy’s condition. Leonard first tries to send her back, but later confesses that he thinks Sammy is physically capable of making new memories. I thought this statement was very interesting, because we already know that Leonard originally believed his problem to be psychologial. If we assume that Sammy=Leonard, then Leonard must be (at least subconsciously) knowing that he is capable of making new memories.
However, if we were to believe that Leonard story=Sammy story, then how could he able to distort his own memory that Leonard and Sammy are two different people? We have to assume that Leonard disguises his memory so that he can escape from the fact that he killed his own wife. However, in order to do that he must remember that he killed his wife. If he did have amnesia, then this should be impossible since Leonard should not remember anything that had happened to him after the accident.
This suggests two things:1) Teddy lied2) Leonard is actually aware of everything that happened to him since the accident. He just tries to avoid the truth by distorting his own memories.I would say that second theory is more plausible and makes most sense. In fact, it is possible that Leonard doesn’t actually have amnesia. His amnesia comes from his own belief; the accident really does not have anything to do with the amnesia. There is a major drawback to this theory though. If Leonard did not actually have amnesia, but imagined one in order to avoid the truth that he killed his own wife, then how could he have killed his wife? His wife died because Leonard forgot that he had already injected insulin. But if he did not have amnesia, then he should have remembered that he indeed did inject insulin, and therefore his wife should never have died.Because of this, I came to conclusion that Leonard did have amnesia, but it healed at some point while he was in a mental institution. He was horrified that he killed his own wife, and that is why he tried to seal his memory by believing that he still has amnesia. This belief ultimately becomes truth, at least in his own world. Leonard says at the end:
“I'm not a killer...but right now I need to be. Maybe I'm not finished yet. Maybe I need to be sure that you won't ever use me again. You're a John G.? Fine, then you can be my John G. Do I lie to myself to be happy? In your case, Teddy..yes, I will.
I have to believe in the world outside my own mind. I have to believe that my actions still have meaning, even if I can't remember them. I have to believe that when my eyes are closed, the world's still there. We all need mirrors to remind ourselves who we are. I'm no different.” Leonard himself says that he has to believe in the world outside his own mind. But this really means that he needs to believe in the world where there is still something to be motivated for. As a solution, he refuses to accept Teddy's story and creates his own world, where everything exists according to his belief. We learn that Teddy dies at the end because Leonard deliberately plants an idea (the belief that becomes the truth) that John G is Teddy. However, just because he is killing the wrong guy, it does not mean that his acts have been meaningless (at least to Leonard himself). He needs to believe that the world is still here. By repeating the cycle of murder, he finds a motivation in his life and knows that he still has a reason to live. Also, the actual truth does not really matter because Leonard’s belief is truth, at least in his simulacrum.
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