Unmarked spoilers are ahead, per Spoilers Off rule.
The existence of Banana Fish itself. This is a drug that causes you bad trips after bad trips, trapping you in a nightmarish and painful version of the world created by your own mind. After Abraham "perfected" it, it was used as a way to brainwash their victims and make them believe that someone specific was the source of their pain and fear, prompting the brainwashed to kill innocent people, of course, even when they manage to assassinate their target, the fear remains and the victim of Banana Fish in their desperation kills themselves. Even if you somehow survive, you are still trapped in your own mind by the effects of the drug and there is no cure.
Throughout the story, we see several examples of how this works but the most heart wrenching example is of Shorter. We're talking about a character that did everything they could to protect their friends and family, consequences be damned but Banana Fish destroyed them and Ash was forced to kill them before they could fatally harm Eiji.
And even prior to that we see how is that the serum was put to work on Shorter. They injected him with Banana Fish right in front of Eiji forcing him to watch the pain an horror take over his friend all the while Dawson was screaming over and over that Eiji was the cause of Shorter's misery and fear and that the only way to end the suffering was to kill Eiji. The sheer evil and glee on the scientist's voice and face adds another nightmarish layer to the cruelty of the scene.
The abuse and harassment that Ash had to endure since he was a small child is nothing short of devastating and horrific. Starting with the fact that it all started when he was seven and by the hands of a member of the community that was highly respected and loved, so, no matter what he said, no one believed him and the only reason he was able to avoid getting murdered like many of that man's other victims was because he charged him, a callous advice his dad gave him because he thought it was too much of a bother to actually look into what his son claimed. This is also Truth in Television with many a victim not being able to get justice because their claims aren't believed.
Adding to this is that, even after it was demonstrated the man was a monster, no one bothered to apologize to Ash or tried to give him comfort, but rather he was cast aside and hidden away as if he was a nuisance, which in turn prompted him to leave for the city where new horrors would take hold of him. Dino would take advantage of his youth and beauty and had him prostitute himself for years, even having him be part of porn videos where he clearly suffered at the hand of grown men that only used him for their own sick pleasure.
