The Werther Box was an enchanted vault created by the former member of the Men of Letters, Cuthbert Sinclair. It was created to hold a special codex stolen from the Grand Coven witch Nadia, and ensure that the codex does not fall into the Coven's hands again. However, the warding spell was too powerful and far beyond Men of Letters handling, making it too dangerous and caused two Men of Letters' death. It was also the reason for Cuthbert's expulsion.
The Werther Box came with a "security system" wherein anyone who attempted to open it without the proper ritual was struck with a spell that led to the person killing themselves. The warding spell was so potent that it reached a theoretical rate of 98% lethality. The only way to turn off the protection spell was to use a large amount of blood from a member of the Men of Letters.
In 1973, 17 years after Cuthbert's expulsion (15 years after the Men of Letters Downfall), a girl, Suzie, found the box in her house (a former Men of Letters chapter house) in St. Louis and accidentally activated it, causing her entire family to commit suicide. She survived, but suffered serious trauma and became a recluse, making her social skills "rusty".
In 2015, Sam learned about its presence and wanted to retrieve it so he could obtain Nadia's Codex. With Dean's help, they nearly succeeded but Suzie learned their intentions. This caused Sam's spell breaking ritual to fail, and unleashes the Wether Box's curse once more. Suzie took her own life and Dean was pulled into a near death experience. The box nearly caused Sam to commit suicide, but Rowena came and saved him with a spell.
Later, based from its inscription and Rowena's assistance, they learned how to deactivate the box. Sam sacrificed himself in order to turn off the box. Unfortunately, Sam's blood was insufficient to fully depower the box. Dean, imbued with the Mark of Cain, successfully overpowered the spell. He later added his own blood to complete the ritual to deactivate the box.
It was later smashed into scrap metal by Dean as an added measure.