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There Is No Cure

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Bob has some kind of affliction or state (broadly speaking) — it might be The Plague, The Virus, a Soap Opera Disease, or it might be a Metamorphosis, Forced Transformation, Transhuman state or other transformation. It doesn't necessarily even need to be something wholly negative or detrimental, as Bob can be Cursed with Awesome. This trope can also apply to an outbreak of The Virus or The Plague if there are efforts to find a cure for the populace. A magic spell can theoretically also be a case of this trope, but this is rare, usually being a downplayed form of this trope at most where there's a Curse Escape Clause or a Celestial Deadline to remove it.
Whatever the type of affliction/state, a cure or reversal method isn't readily available. If Bob and/or his friends want it gone, they'll probably look to Find the Cure! — this trope is not when they succeed in that objective.
This trope is in effect when Bob or his friends are explicitly told there's no way to reverse or undo Bob's affliction and when that's proven to be the case. How Bob will respond to this information varies, especially if he resents his affliction. Maybe he'll learn to accept his fate and spend the rest of his days with his condition wisely, maybe he'll cross the Despair Event Horizon, maybe he'll be in denial and keep on looking, maybe he or his friends will put him down if his condition makes him a danger to others, maybe he'll Take a Third Option via consciousness transferral to an unafflicted new form.
If the affliction is the transhuman/transformation type, there can be overlap between this trope and Metamorphosis, but this trope is specifically where the matter of reversing the change is brought up and the answer to the question is a no. It can overlap with Mistaken for Disease if the reason they can't cure it is it turns out not to be a disease — in fact, the transformative form of this trope might be accompanied by the line, "It isn't a disease" to emphasize why it can't be reversed.
Note that the question of whether or not there's a cure or reversal method must be brought up in some form and the answer must be a clear no in order to be a straight example of this trope. If the matter of a cure is not brought up, no matter how irreversible the affliction seems, then it's an Implied Trope. Instances where Bob does find and take a cure but Status Quo Is God forces him to regain his affliction or suffer a new replacement affliction do not count as this trope.
Contrast Keeping the Handicap, where a "disease"-type affliction or a disability has a cure but Bob chooses not to take it. Compare Too Injured to Save, which is where a character is too severely injured and their immediate medical circumstances too inconvenient for them to survive. Not to be confused with No Cure for Evil, which is where evil is incapable of healing.
It's not unheard of for franchises which run for long enough to initially depict a recurring disease, transformation or transhumanism as incurable, only for a cure to turn up in a later installment, sometimes as a symptom of Flanderization.
This trope unfortunately has a significant grain of Truth in Television to it in regard to many Real Life illnesses and other ailments, so No Real Life Examples, Please!.
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DBTropes
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Abraxas (Hrodvitnon): Monster X at one point begs San-Who-Could-Have-Been/Youngest Brother (Keizer Ghidorah's attached left head) to purge the Many from an infected living Titan to save the latter's life, but San-Who-Could-Have-Been's thoughts reveal he and his brothers can't remove the infection once it's set in even if they wanted to.
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Dragon Age: This is the case for the Blight, which destroys any living thing it touches — even bacteria. The larger a creature is, the longer it takes for them to die, so humans can be ill with the Blight for months. It's also extremely contagious. The Blight has been presumed to be incurable for centuries In-Universe, and the closest thing to a 'cure' is to become a Grey Warden, which extends the lifespan to roughly thirty years and stops it from being contagious, but even then, the body will eventually succumb to it if they aren't killed in battle first. Possibly subverted as of Dragon Age: Inquisition; the Hero of Ferelden (the Player Character from Dragon Age: Origins) is on a quest to find a way to reverse the condition. It remains to be seen how successful they will ultimately be.
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Grimm: After Juliette is turned into a Hexenbiest as a side-effect of a spell involving her, she approaches Henrietta for help, only to be told that her transformation can't be reversed. She slowly but surely goes out of control with her newfound powers from there. Ultimately subverted in the show's last few episodes when Juliette (now Eve) is rendered human after returning to Earth from Another Dimension which was affecting her Woge, with Diana speculating the Hexenbiest part of her got left behind there (a time reset returns her to her Hexenbiest state).
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After the Bomb: The Synthetic Plague which led to the apocalypse in the game's backstory. By the time it was created, advancements in genetics and medical technology had gotten to such a point that viral disease was no longer seen as a major problem in any form, but the disease was designed with a copy of the human genome which ensured any cure that targeted the disease would also target the host.
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Teenage Mutant Ninja Turtles (1987): Carter's mutation which gives him the ability to transform into a giant, bio-mechanical creature as a result of exposure to the Turtles' mutagen is considered incurable in the present day. Seemingly subverted in his last appearance when he accepts an offer to go to the future so their technology can cure him.
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 Teenage Mutant Ninja Turtles (1987)
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Justice League: "Injustice for All: Part I" has Lex Luthor discover to his horror that he has terminal cancer as a result of carrying Kryptonite for so long. After blaming Superman for his condition, he demands his doctor for a cure, only to be told there is no cure and there is nothing he can do. This is subverted later when his cancer is mysteriously cured in "Question Authority" and we later find out in "Divided we Fall" that this is because Brainiac was hiding within Luthor and had cured his cancer in addition to giving him Super-Strength.
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Picard himself, in a possible future timeline, gets hit with Irumodic Syndrome that starts causing severe memory lapses. Though there is some level of treatment, there is no cure. Star Trek: Picard later reveals that he does indeed have it, and it proves increasingly difficult to rein in as he goes on an important mission.
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The Wolfman (2010): The gypsies explicitly say just after Lawrence is bitten that there's no cure for lycanthropy. Once Gwen becomes aware of Lawrence's lycanthropy, she looks into finding a cure in the lead-up to the next full moon, and ends up facing the gypsies, who tell her what they told the audience earlier.
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The Witcher (2019): Yennefer gives up her reproductive organs to be transformed into a beautiful woman. Later she wants to have a child and seeks a cure for her infertility, but she is informed by Borch Three Jackdaws that she will never regain her fertility.
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With This Ring: Despite consulting multiple groups of Maltusians, who are billions of years old and are also the universe's experts on emotional spectrum technology, Paul has still not found any way to reverse orange light assimilation. If someone has been turned into a construct, the only option to free them is a Mercy Kill — and it's not even clear whether the person's soul will survive that, so it might not really be freedom.
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Harry Potter:
Lycanthropy has no cure, although people infected with it may drink Wolfsbane potion to temporarily negate its effects.
In Half-Blood Prince, Albus Dumbledore's right hand has become black. In the next book, it's revealed after Dumbledore's death this was because he wore a Horcrux and got his hand cursed. Severus Snape can only state he, with all his knowledge about the Dark Arts, can only slow the curse.
Maledictus are a type of Animagus who can transform into snakes, with a catch; women (and it's always women) who are one will permanently transform into snakes in the long run, and there is nothing that can be done to stop it. According to Word of God, Nagini is a Maledictus. This is shown in full in Fantastic Beasts: The Crimes of Grindelwald.
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Supernatural:
Lycanthropy is portrayed as almost-completely incurable, with the show's first werewolf episode seeing Sam and Dean try and fail to cure a werewolf using a bogus method, and being forced to accept at the episode's end after scouring all their sources that there's no curing the werewolf in question. From Season 12 onward, this is downplayed when it's discovered the British Men of Letters have an experimental cure which can work if the lycanthropy is caught in the early stages of infection.
Transhuman monsters ("monster" meaning the supernatural creatures descended from Eve) are overall implied throughout the show to be incurable unless their infection is caught in the early stages. On top of the aforementioned werewolf treatment, vampires can only be turned back into humans if they're fed a special potion before they feed on blood for the first time.
Dean's future self in "The End" mentions that the Croatoan Virus currently ravaging the world is incurable.
A variation occurs in Season 9 with Sam, Dean and Kevin looking to find a way to reverse the effects of the Fall (which has expelled every angel in Heaven to Earth and has destroyed all angels' wings except for Metatron's and the archangels'). Their efforts reveal that according to God himself, the spell's effects are irreversible. That being said, later episodes reveal there is a workaround for the "angels locked out of Heaven" part.
Subverted with the Mark of Cain. Part of the Season 10 Story Arc is finding a way to rid Dean of the Mark, and when Team Free Will confronts Cain himself on the matter, he bitterly declares there is no cure. However, the Season Finale reveals that Death is capable of removing the Mark from a person in exchange for another bearer taking their place, and there's also a powerful spell that can erase the Mark entirely (at a cost).
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Final Fantasy XIV:
In the Stormblood White Mage questline, Sanche suffers from a heart condition that makes exerting herself dangerous and she often collapses from being out of breath while desperately trying to chase off any Gridanians who could meet her daughter Gatty. While the Warrior and Sylphie are able to gain her trust to try to treat her, Master E-Sumi Yan admits Sanche's condition is too severe to save her even with a powerful White Mage and a Padjal conjurer tending to her. Sanche succumbs to her illness at the end of her questline, as a voidsent named Camamotz made her ill to drive Gatty mad with grief and feed on their aether.
In Shadowbringers, the dwarves of Tomra once suffered from a plague known as "stoneblight" that was inevitably fatal and had no cure, forcing the village elders to isolate the afflicted deep in the mines to avoid infecting the rest of the village. This swift and decisive action is said to have saved the Tomran dwarves, who revere the elders' actions as a Shoot the Dog moment a century later. Subverted, as in truth, Lamitt (one of the Warriors of Light from before the flood) was able to venture deep into the ruins of Ronka to devise a cure from the ancient magics there. The formerly stoneblighted dwarves were none too happy about being left for dead and decided to remove their helmets and leave Tomra in protest. To maintain order and their own political standing, the elders exiled Lamitt along with the stoneblighted dwarves, who all perished in the Flood, allowing the Elders to perpetuate their own self-serving narrative.
Primals can 'temper' people enthralling their minds into worshipping them and doing their bidding.. There is no known way to reverse this, and no defense save the Echo, a rare power possessed by the Player Character and a very few others. Tempered individuals are usually put to death to prevent them from empowering the primals with worship. However, in 5.4, Allisae is able to develop a spell to reverse tempering, using knowledge learned from a scholar of souls on the First, and the lost research of an Allagan scientist.
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Notably, the Torchwood episode "Cyberwoman" reveals Ianto has been keeping his half-converted girlfriend Lisa alive in the hopes of getting her restored to full humanity, only for Jack (who has knowledge of Cyber-Empires from The Future) to outright tell him, "there is no cure. There never will be. Those who are converted stay that way." Lisa sort-of gets around this by using the Cybermen's tech to transplant her brain into a fully-organic body, but her brain's Cyber-programming sticks.
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"Cure 4 Psycho" by RedHook is about the singer realising that her awful, gaslighting ex is a psycho, and "There's No Cure For Psycho".
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Superman: The Animated Series: In the episode "The Way of All Flesh", Corben is turned into Metallo by Luthor by having his mind implanted into a bionic body. At first, Corben's happy that he now possesses Super-Strength, can't feel getting shot by the police, and can go toe-to-toe with the Man of Steel himself, especially since he now possesses a piece of Kryptonite. However, when Corben plants a Forceful Kiss on Lois Lane, he realizes that he can't feel anything at all. When he confronts the scientists Luthor hired for the procedure, Corben is told that he has to get used to not feeling anything anymore because the procedure is irreversible. Corben then decides that from now on he'll go by Metallo.
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Terminator Genisys: Having encountered the T-3000 John Connor and knowing it's basically a transhuman, Kyle Reese proposes trying to find a way to restore its humanity. Pops, who has files on the T-3000's development in the future war, points out that having your entire body assimilated and replaced with nanobots cell-by-cell isn't the kind of thing that a human can be brought back from, and he quotes the trope name.
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Dwarf Fortress: Some toxins and curses have no cure nor end, meaning they last until the death of the sufferer. These include mummy curses (less luck for launch) and cave spider venom (permanent dizziness).
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Transistor: The Limiter notes on BadCells notes that their transformation, which is unwanted, "they become something else, something they don't seem to want to be." is irreversible:
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Jackie Chan Adventures: In the series finale, following Drago's empowerment with all eight Demon Chi, Uncle approaches Shendu to ask if he knows of a way to depower Drago. Whilst the Demon Chi were previously removable when they possessed hosts individually of each-other, Shendu's response reveals that once all eight of the Demon Chi are united inside a single host, "nothing can remove them — ever." When Uncle and Tohru's reversal spell begins sucking the Demon Chi and all the extradimensional demons Drago summoned into the Netherworld, the Ice Crew's Demon Chi (one demon's powers for each of them) is pulled out of them, while Drago just gets pulled in with the Demon Chi still inside him.
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Arthur: In "Paradise Lost", Kate and Pal are devastated to find out that as they get older, they will understand each-other less and less to the point where Kate will eventually forget she could even talk to Pal. When they seek advice to reverse or at least stop the process before it gets worse, they're told the process is irreversible and there's nothing they can do about it. However, they feel better when they talk to Grandma Nora's dog, who tells them they don't need to have full conversations to communicate, and just a few words, barks and body language are enough to let each-other know what the other is trying to say and how they feel.
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Druuna: Druuna spends much of the comic trying to find a cure for the Morbus Gravis plague that took the life of her lover Shastar and many others, horribly mutating them into barely-sentient monsters. By the end of Aphrodisia, she deciphers a message from the ghost of Captain Lewis that Morbus Gravis cannot be cured. Despondent, she goes back into the dreamworld she just woke up from, praying that someday it will be different.
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Star Trek:
The Next Generation:
When Vulcans reach around 200 or so, a rare few develop a condition called Bendi Syndrome, where every emotion they've bottled up gets telepathically transmitted to everyone within range, causing them to act violently and angry. Sarek is revealed in the titular episode to experience this condition, and continues to decay when he boards the Enterprise-D for a diplomatic mission. Since there is no treatment or cure, all Picard can do is willingly mind-meld to take the brunt of these emotions on himself until Sarek can complete his mission. Sarek later succumbs to the disease in Season 5.
In the episode "Reunion", Klingon Chancellor K'mpec reveals that his enemies have poisoned his bloodwine. He's rather cavalier about there being no cure, since he keeps drinking it even as he talks to Picard about it.
Picard himself, in a possible future timeline, gets hit with Irumodic Syndrome that starts causing severe memory lapses. Though there is some level of treatment, there is no cure. Star Trek: Picard later reveals that he does indeed have it, and it proves increasingly difficult to rein in as he goes on an important mission.
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Gargoyles: In one episode, the villainous gargoyle Demona starts the episode by hitting the main cast's human friend Eliza with a poison dart, then tells Eliza to have Goliath face Demona if he wants the cure. Eliza was actually protected thanks to the dart bouncing off her badge that was under her shirt, but Goliath goes to meet Demona anyway since he wants information. The entire night turns into a lethal game of cat and mouse as Demona tries to kill Goliath. The next day, frustrated by being unable to kill Goliath, Demona flees rather than continue fighting, but first screeches that there never was a cure for the poison and Eliza is surely dead by now. Goliath and company decide it's best not to correct Demona about Eliza being alive.
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Charlie and the Chocolate Factory: After Wonka demonstrates his Wonka Vision machine that transports huge, oversized chocolate bars (as in several square feet and weighing dozens of pounds) to a person's TV as regular sized candy bars, Mike TV excitedly goes into the machine because he gets to be on TV (the 2005 adaptation shows Mike jumping in because he hates Wonka's Mundane Utility for a matter teleporter). However, Mike comes out a few inches tall, and when he and his father tell Wonka to just teleport him back so he'll return to normal size, Wonka says that the teleporter's resizing works one way (big things can be made small, not small things made big). The only solution is to take Mike to the taffy room and stretch him, and he's last seen coming out of the factory, not normally proportioned but looking very tall and very skinny.
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Being Human (UK): Season 2 sees Nina join up with Kemp's organization as a volunteer for their experiments in the belief that they can cure her lycanthropy. When she goes to George about this, he at first denies that any cure for their condition exists, but eventually joins Nina. In actuality, it's more of a treatment than an actual cure which suppresses a werewolf's transformation during the full moon — and even then, it has fatal side-effects which Kemp intentionally allows so that he can covertly murder supernaturals. Overall, the possibility of turning vampires, werewolves, ghosts or other supernaturals back into humans isn't really touched upon, implying that they're all incurable — the Series Finale has the main cast seemingly rendering themselves human when killing the Devil break their curses, but the ending hints and a bonus episode confirms that this is actually a Lotus-Eater Machine.
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NCIS: The Yersinia pestis bacterial bioweapon which infects Tony in "SWAK" is a mild case. When Gibbs confronts the people responsible, it turns out there is no cure, but the bacterium has a short lifespan, and Tony's immune system subsequently fights the symptoms off on his own.
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The Elder Scrolls:
Bosmer who undergo the Wild Hunt transform into horrific monsters from the Dawn Era in order to protect Valenwood, but once they've done so they completely lose their minds and, according to the Bosmer Gomini, they're unable to transform back; forcing their brethren to kill them if they don't kill each other first. According to one Bosmer, every monster that currently exists has its origins in a Wild Hunt.
Subverted and exploited with vampirism and lycanthropy. Both are widely believed throughout Tamriel to have no cure, but in actuality, knowledge of how to cure either affliction is suppressed; partly because most of the curing methods are unpleasant at best or immoral at worst, and partly to discourage wannabes from getting themselves turned.
Zig-zagged in Morrowind. Dagoth Ur is spreading the Corprus Disease, created from the divine power of the heart of the series' dead creator god, which turns its victims into insane Body Horror Plague Zombies... while also making them The Ageless and immune to all other diseases. It is said to be incurable and, naturally, the Nerevarine catches it partway through the main quest. With the help of a 4000-year-old wizard Divayth Fyr, they are "cured", but only of the disease's negative effects. This actually makes them eligible for the plot's driving prophecy, as "neither blight nor age can harm him". However, they still have the disease, and the "cure" fails on every other patient Fyr tests it on, ultimately zig-zagging the trope.
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In Wish (2023), once Magnifico uses forbidden magic, he's bound to it forever and there's no way to reverse it.
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Whoniverse:
Conversion into a Cyberman, once it's occurred, is usually considered irreversible.
Notably, the Torchwood episode "Cyberwoman" reveals Ianto has been keeping his half-converted girlfriend Lisa alive in the hopes of getting her restored to full humanity, only for Jack (who has knowledge of Cyber-Empires from The Future) to outright tell him, "there is no cure. There never will be. Those who are converted stay that way." Lisa sort-of gets around this by using the Cybermen's tech to transplant her brain into a fully-organic body, but her brain's Cyber-programming sticks.
In "The Doctor Falls", after Bill is converted into a Cyberman but fights off the programming, the Doctor vows that he'll fix her. He later admits when she brings this up that he wasn't being entirely truthful: he has hope that she can go Beyond the Impossible with what he said, but it's unlikely that she'll ever be human again. Bill finds another way when Heather removes her consciousness from her Cyber-converted husk and turns it into a "pilot" (long story).
One of the reasons why Captain Jack wants to find his way back to the Doctor after becoming immortal is to find out if his immortality — granted by a Humanoid Abomination with temporal power accidentally "bringing him back forever" and turning him into a living anomaly — can be removed. The Doctor simply tells him there's nothing even he can do about it. That being said, a couple Expanded Universe materials have introduced one or two things that are stated to be capable of removing Jack's immortality, and the show's Miracle Day season sees the same force which rendered all humans on Earth immortal in turn apparently render Jack mortal (although Word of God speculates that it probably only removed Jack's Healing Factor and not his immortality). Then there's the hint that Jack will slowly transform into the eons-old Face of Boe (who apparently dies for real in the year 5,000,000,000) if his immortality makes him live for long enough.
In "Evolution of the Daleks", the Doctor tells Laszlo that he can't reverse the latter's partial conversion into a Pig Slave — something which has forced him to live in the sewers since escaping the Daleks and causes his girlfriend a great deal of distress when she finds out in the previous episode — but he can extend his formerly-shortened lifespan later on. The episode ends with Laszlo finding a place to belong despite his appearance in Hooverville.
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Disney Villain Songs (Lydia the Bard): In Anna's Villain Song story, the ice magic in Anna's heart, instead of turning her to lifeless ice, is giving her ice powers like Elsa's but also corrupting her personality — and unlike in canon, Grandpappy informs Anna and Kristoff when they go to him for help that there's no curing it.
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Blade (1998): Discussed and averted. When Karen tells Frost she cured herself of vampirism, Frost and Mercury scoff at the notion and Frost tells her there's no cure, to which Karen counters she's discovered there is a retroviral cure if a vampire was originally human.
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Zig-zagged in Morrowind. Dagoth Ur is spreading the Corprus Disease, created from the divine power of the heart of the series' dead creator god, which turns its victims into insane Body Horror Plague Zombies... while also making them The Ageless and immune to all other diseases. It is said to be incurable and, naturally, the Nerevarine catches it partway through the main quest. With the help of a 4000-year-old wizard Divayth Fyr, they are "cured", but only of the disease's negative effects. This actually makes them eligible for the plot's driving prophecy, as "neither blight nor age can harm him". However, they still have the disease, and the "cure" fails on every other patient Fyr tests it on, ultimately zig-zagging the trope.
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Ninjago: Subverted. During the final battle of Season 14, Nya decides to merge with the ocean using her powers in order to defeat the main villains. This action is irreversible, and Nya is forced to say goodbye to the Ninja as she must stay there for the rest of her life. However, in Season 15, Nya gets Aspheera to take her powers away, thus breaking her connection to the ocean and making her a normal human.
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Warhammer: Mutation from Chaos exposure is both irreversible, even to healing magic, and a death sentence in polite society. Some Back-Alley Doctors discreetly remove the cosmetic effects where possible, but other effects of the mutation persist. Some heretical Shallyans believe that the goddess can cure mutation, but haven't had any luck actually doing so.
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Afflicted: Derek seeks out the vampire who turned him, and when he confronts her he asks her about a cure, only for her to say there's no cure, making it very clear that if there was a cure (or even a way of killing herself), the centuries-old vampiress would have readily taken it long ago.
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Person of Interest: The Victim of the Week in "In Extremis" is poisoned with a lethal dose of a radioactive isotope. There is no cure. Reese is able to arrange it, however, so that the man who poisoned him is given a dose of his own medicine, and the victim dies peacefully with the satisfaction of knowing that his murderer is going out the same way he did.
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The Ultimate Evil: The binding ritual which permanently connects one to their natural Other is an irreversible process. In the second story, Valerie approaches her Other Shendu to ask how a binding can be severed, and he replies that it can't be undone by anything. The first story's ending did indeed demonstrate that not even the Book of Ages' reality-rewriting power can undo a binding between Others.
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Deadpool (2016): The title character is hunting the movie's villain Francis so that he can make him reverse the Body Horror that turning Deadpool into a mutant left him with. As it turns out, to Deadpool's ire, Francis was lying earlier when he said he could fix Deadpool's scarring. Fortunately, Pool's girlfriend decides she can live with him this way after a brief adjustment period and a bunch of drinks.
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The Witches (2020): Agatha tries and fails to synthesize a cure to the witches' Mouse Maker potion which has transformed her grandson and other children into mice, meaning the mice children are stuck that way for the remainder of their lives.
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The Buffyverse is a pretty big Fantasy Kitchen Sink, but one of the few transhuman conditions that's truly considered to be incurable is lycanthropy. It can only be treated (or altered by exposure to Another Dimension), not cured.
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In Half-Blood Prince, Albus Dumbledore's right hand has become black. In the next book, it's revealed after Dumbledore's death this was because he wore a Horcrux and got his hand cursed. Severus Snape can only state he, with all his knowledge about the Dark Arts, can only slow the curse.
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Vampire: The Masquerade - Bloodlines: One of the Thin-Bloods holds out hope that he can cure his vampirism with a blood transfusion or by killing an imaginary "head vampire". You can tell him the truth gently or sell him bogus equipment for the "cure", potentially getting him killed.
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The Green Flu in Left 4 Dead. It's not for lack of trying; the virus mutates too frequently and erratically to pin down, making the paternal "carrier genome" the closest thing to immunity.
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The Next Generation:
When Vulcans reach around 200 or so, a rare few develop a condition called Bendi Syndrome, where every emotion they've bottled up gets telepathically transmitted to everyone within range, causing them to act violently and angry. Sarek is revealed in the titular episode to experience this condition, and continues to decay when he boards the Enterprise-D for a diplomatic mission. Since there is no treatment or cure, all Picard can do is willingly mind-meld to take the brunt of these emotions on himself until Sarek can complete his mission. Sarek later succumbs to the disease in Season 5.
In the episode "Reunion", Klingon Chancellor K'mpec reveals that his enemies have poisoned his bloodwine. He's rather cavalier about there being no cure, since he keeps drinking it even as he talks to Picard about it.
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The following is a list of statements referring to the current page from other pages.

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Indexitis
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Transhuman
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There Is No Cure
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There Is No Cure
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