The novel begins as Charlie follows Doctor Strauss and Professor Nemur’s orders as he writes his first ‘Progris riport’. Charlie introduces himself and speaks about his job working for Mr. Donner as well as his night classes with Miss Kinnian who recommended him to Strauss and Nemur due to his hard work and ambition.
Burt, an assistant in the experiment gives Charlie a series of Inkblot tests to see if they trigger something in Charlie’s subconscious. Although Charlie tries hard to see something in the ink blots, he cannot move past the surface of them being merely ink. Nemur and Strauss choose Charlie as their test subject due to the fact that he’s shown high motivation in his class and they continue to test him.
Charlie learns for Strauss and Nemur that he will be the first human test subject for this experiment and that it has only been performed on animals. The doctors now need permission from a family member to proceed with their experiment on Charlie.
Charlie competes with Algernon the mouse to solve maze tests, but Algernon wins every time. The doctors have Charlie’s estranged sister Norma’s consent for the operation and they begin to explain to Charlie that he will be very smart after the operation. They also discuss that the procedure might fail and the complications of it may lead Charlie to revert back to his current mental capacity if not worse.
Charlie’s ambition to become smarter is motivated by his desire to please others, whether it’s Miss Kinnian or his co-workers, or his estranged family. Charlie desires acceptance from society, and the doctors tell him that he will be famous once this procedure works. After the surgery Charlie becomes impatient and frustrated and resolves to quit, but Miss Kinnian being the voice of reason manages to convince him that he has to be patient and work hard in order to become smart.
Charlie returns to the bakery because he misses his friends. However while Charlie is too innocent to realize, the readers will notice that his friends aren’t good people and only tease him and bully him for their own satisfaction. They aren’t his friends at all. We also learn that Charlie has been working with Mr. Donner for 17 years as a favor to Charlie’s uncle Herman to prevent his mother from sending him to a home for the mentally disabled.
After the operation Charlie resumes classes with Miss Kinnian and professor Nemur gives Charlie a contraption that resembles a TV and tells him to listen to it while he sleeps (the machine is used for subconscious learning and surfacing repressed childhood memories). The device triggers Charlie to recollect memories of his co-worker Joe bullying him for his desire to learn how to read and Fanny Birden defends him. We come to see that Fanny lead Charlie to Miss Kinnian’s classes.
Charlie is invited to a party with his co-workers and they get him drunk and abandon him, Charlie is left feeling ashamed and recalls a feeling of shame from his childhood when he got lost in a store. In the same progress report, Charlie finally beats Algernon and at the same time he develops a critical mind when questioning the way the scientists treated Algernon.
Charlie begins to read more complicated books with Miss Kinnian and he begins to relate to the characters within the books. Although Joe encourages Charlie to work as a dough mixer just for his amusement as it’s “April Fools”, much to everyone’s surprise Charlie excels at his new job.
Charlie begins to excel at grammar and punctuation rules and learns the hard truth that his co-workers aren’t really his friends. Charlie’s repressed childhood memories begin to surface as he remembers all the times he was bullied as well as his unsettling domestic life among his family and his rather daunting mother.
As Charlie’s intelligence increases, he begins to excel further at work and develops a way to help the bakery save more money. His co-workers start to resent him and fear him. It seems he no longer makes them feel superior. Meanwhile, Charlie begins to develop feelings for Miss Alice Kinnian and plans to ask her out but delays it.
As Charlie now has an IQ of over 100, he participates in discussions with college students who pose existential questions. Charlie also begins to go to the library on a regular basis to read autonomously. It seems the more intelligent Charlie is, the more unhappy he is and the more repressed memories he begins to remember.
He remembers his mother’s refusal to admit that he is mentally challenged and she insists that he’ll become normal after his teacher suggested that Charlie be admitted to a special needs school. He remembers his mother physically abusing him and pressuring him to be ‘normal’ which is something beyond his control.
Charlie and Alice have a lovely day out and at the end they both confess their feelings for each other but choose not to make it personal. After that Charlie gets fired from his job due to a unanimous vote (except for Fanny Birden). As he is upset, he seeks comfort with Alice and they kiss but the kiss makes him feel uncomfortable and nauseous.
Charlie’s intelligence has increased to the point where he now participates in discussions with professors. He also becomes aware that professor Nemur treats him like an object (no better than Algernon). Charlie stops writing progress reports for two weeks and Nemur is furious with him for his disobedience as there is a conference coming up in Chicago in which Nemur and Strauss will reveal their creation.
Charlie now has become arrogant and unsympathetic with an IQ of more than 180. His new personality is not the innocent and kind Charlie that Alice used to know and so she admits to him that she can no longer speak to him as he makes her feel inferior. Charlie later flies out to Chicago for the conference in which he looks down on some of the work presented. Nemur shows footage of Charlie when he was mentally disabled and the crowd laughs. With his pride hurt, Charlie sabotages his creator by freeing Algernon and escaping with him to a different life.
Charlie settles down in a new apartment and builds a new maze for Algernon to maintain his progress. Meanwhile he embarks on an affair with his neighbor Fay Lillman who brings in a mouse named Minnie to keep Algernon company. Charlie aims to abandon the realm of education and lead a life of indulgence. Fay belongs to the sensual world and grants Charlie his sexual experience as well.
Charlie remembers where he came from when he sees a mentally challenged waiter drop his tray, he laughs at first but then recalls that he was once in that position. He decides to become selfless and dedicate himself to helping other mentally challenged people. Meanwhile Charlie notices that Algernon has become aggressive and his mental capacity has started to deteriorate. So he resolves to contact Professor Nemur.
Nemur and his foundation agree to support Charlie’s research and him and Charlie discuss the possibility of Charlie’s own deterioration into a lower mental age than before the procedure. They arrange for him to go to a home for the mentally challenged. After that news Charlie spends most of his time researching and observing Algernon.
Alice goes to visit Charlie and meets Fay. To his surprise they both get along and Alice compliments Fay to Charlie. When Charlie escorts Alice out he tells her that he only loves her and not Fay. His relationship with Fay fades and he becomes more concerned with research. At a cocktail party, he drinks too much and causes a scene and accuses Nemur for being arrogant. Strauss confronts Charlie with his own change from being innocent and kind to arrogant and rude.
Charlie then discovers a flaw within the report, he calls it the Algernon-Gordon Effect, in which he explains that the larger the degree of enhanced intelligence, the quicker the deterioration. Charlie presents his findings to Nemur and they are confirmed. Algernon then dies and Charlie is sad.
He resolves to reunite with his family, he has visited his father once before but he didn’t recognize him and Charlie didn’t tell him who he was. Charlie visits his mother Rose and his sister Norma. Rose has dementia and is violent and neurotic, while Norma is kind and asks Charlie to stay with them. Charlie gives Rose his published work and she says she’ll show everyone that she has an intelligent son.
Charlie visits Alice’s class, forgetting that she is no longer his teacher. She cries when she sees the degree of his deterioration, and he also finds out that Alice has been paying his own landlord to look after him and cook for him. Charlie goes back to work but he is clumsy and this time Joe and his co-workers respect him, however there is a new employee named Klaus who bullies him.
Charlie’s downfall is marked with his inability to understand his previous sophisticated, intelligent progress reports. He resolves that he will not work, nor will he depend on other people’s kindness. Charlie says goodbye to everyone and admits himself to the Warren State home and asks someone to put more flowers on Algernon’s resting place.
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