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"Numero tres is the father of fallen beasts. (…) You need to bleed an Alpha."

- Bobby tells Dean that they need the blood of an Alpha.

"Oh, here's a tip: I have it on good authority that there's one Alpha still among us. (…) Wily character that Alpha Vampire. Somehow made good his prison break before Cas went nuclear on the place. (…) Needless to say, I keep tabs. He moves around... quite a bit. But I have an inkling I know where to start the Easter egg hunt. Happy trails."

- Crowley tells the Winchesters about the Alpha Vampire's survival.

The Hunt for the Alpha's blood is the conflict surrounding the attempt by hunters Sam and Dean Winchester aided by the ghost of Bobby Singer to get the blood of the Alpha Vampire, an important component in the weapon to kill a Leviathan while also trying to stop the Leviathan Edgar from doing the same thing.

Prelude
During his attempt to find Purgatory, the King of Hell Crowley searches for monsters that would potentially know its location, particularly Alphas. With the help of Samuel Campbell and the Campbell Family, Crowley captures the Alpha Vampire, the very first vampire despite the Alpha Vampire briefly escaping. Despite the prison later being destroyed by the Seraphim Castiel, the Alpha Vampire is able to escape and resume his activities.

In an attempt to win his war with the archangel Raphael, Castiel forms a deal with Crowley in order to locate Purgatory together and gain access to the souls there for power. Castiel succeeds in taking in all of the souls and killing Raphael, but he is corrupted by their power and subsequently declares himself the new God. Unknown to Castiel, as well as all of the monster souls, he absorbs the Leviathans, the first beasts created by God and locked away in Purgatory due to the threat they pose. Though Castiel eventually returns all of the souls to Purgatory, the Leviathans remain within his vessel and subsequently escape into the world.

As part of their plan to turn humans into the perfect never-ending food supply, the Leviathans begin producing an additive that would significantly reduce humanity's intelligence, releasing it first through Biggerson's restaurants. After the Winchesters discover this, Bobby Singer learns of the Leviathans master plan, but is killed by the Leviathan leader Dick Roman before he can reveal it. The Winchesters later learn part of the plan from the Leviathan George, specifically where the Leviathans would cure cancer and Bobby's ghost eventually explains the rest to them, highlighting their need to find a way to defeat the Leviathans. As a result of his murder by Dick, Bobby's ghost begins showing worrying signs of becoming a Vengeful Spirit, particularly when in proximity to Dick, concerning the Winchesters.

Months after the Leviathan escape into the world, the Leviathan leader Dick Roman begins funding archeological dig sites in search of something. With the help of hacker Charlie Bradbury, Sam and Dean are able to intercept the item recovered by the Leviathans which is revealed to be the Leviathan Tablet. Following a conflict with several angels, the tablet is deciphered with the aid of the Prophet Kevin Tran and it reveals the existence of a weapon capable of killing Leviathans. The weapon lists the blood of a fallen angel, the blood of the ruler of fallen humanity and the blood of a father of fallen beasts as three of the necessary components. From Castiel, the Winchesters are able to get the fallen angel blood and are left to search for the remaining components.

Unknown to anyone, when Kevin returns home, his angel guards are killed by the high-ranking Leviathan Edgar and Kevin and his mother are taken captive. Kevin is subsequently forced to translate the tablet by Dick who, understanding what the instructions mean, sends Edgar after the Alpha Vampire to prevent the Winchesters from getting his blood.

Battle
After getting the Leviathan Tablet translated, Sam and Dean are left confused by the instructions on the weapon to kill a Leviathan. Dean guesses that "cut off the head and the body will flounder" means that they have to kill Dick Roman, the Leviathan leader, but they are unsure of what will happen to the other Leviathans if they do.

As Dean washes up in the bathroom, he is visited by the ghost of Bobby Singer who tells Dean that he is stronger than ever and has been thinking about the instructions on how to build the weapon. While Bobby doesn't have any ideas about where they can find a bone from a human as light and good as the Leviathan are hungry and dark, he does have an idea about the other ingredients. Bobby points out that the Winchesters already have the Fallen Angel's blood from Castiel while the second is from the ruler of fallen humanity. Bobby suggests that the ruler of fallen humanity most likely refers to Crowley, the King of Hell.

Bobby goes on to tell Dean that the last is the father of fallen beasts which Bobby believes means that the Winchesters need the blood of an Alpha, the monsters that are the "fathers" of their entire species. Dean points out that they captured all of the Alphas for Crowley and they were all then killed by Castiel. Though Bobby suggests making it Castiel's problem too, Dean points out that Castiel is in no shape to help. Growing angry, Bobby suggests that they turn to Crowley then and snaps at Dean, losing control and causing the bathroom mirror to crack. Calming down, Bobby reassures the worried Dean that he just got a little carried away and he has faith in them.

Emerging from the bathroom, Dean tells Sam about his encounter with Bobby and that he has some ideas about the weapon. Sam informs Dean that Bobby's help might be just in time and shows Dean an article revealing that Dick Roman has acquired SucroCorp. The company manufactures additives, particularly high fructose corn syrup which is in everything. Dean realizes that Dick is using SucroCorp to expand his spread of the Leviathan additives beyond just restaurants such as Biggerson's and into everywhere. When Dean asks what they can do to stop it, Sam informs him that aside from destroying all of the SucroCorp trucks and manufacturing plants, they can't do anything. Angry at the news, an invisible Bobby slams Sam's laptop lid shut. Worried about Bobby's growing anger, Dean tells Sam about Bobby's ideas for getting the remaining components for the weapon.

In order to get the ruler of fallen humanity's blood, the Winchesters summon Crowley and inform him about their discovery of the Leviathan Tablet and what they learned from it. Interested by the news, Crowley agrees to give them his blood, but he will only do it last once they have all of the other components. Crowley tells them that if he gives them a vial of his blood now and it falls into the wrong hands, his enemies can use all sorts of nefarious spells against him with it. Crowley expects the Winchesters to have the hardest time getting the Fallen Angel's blood due to their role in the Apocalypse, but the Winchesters dodge the matter and don't tell him that they have already gotten it. As Crowley prepares to depart, he reveals that the Alpha Vampire escaped his monster prison before Castiel destroyed the place and Crowley keeps an eye on him. Stating that he has a good idea where they can start looking, Crowley teleports away and burns the words Hoople, North Dakota into the tabletop, annoying Dean with his antics.

At a gas station, Sam has Dean leave Bobby's Flask in their car so they can talk without being overheard. Sam asks Dean about Bobby's state of mind and is worried when Dean tells him that Bobby was angry, despite feeling that its understandable. Sam is further worried to learn that Bobby feels stronger than ever and tells Dean that the stronger Bobby gets, the closer he gets to becoming a full Vengeful Spirit, a state in which he could cause great harm.

As the Winchesters discuss Bobby, Dean notices a man pouring massive amounts of mustard over a hot dog and points out his weird behavior to Sam along with the strange behavior of other people in the store who appear to be stoned. Sam realizes that its the corn syrup in the food being sold in the store and that its laced with Leviathan additive which is beginning to dumb people down as per the Leviathans' master plan. As a result, the Winchesters are forced to buy only fruit and water to eat and drink so that they don't become affected as well.

That night, the Winchesters and Bobby locate the house that the Alpha Vampire is using as his nest, but see no sign of light or movement inside. As the Winchesters debate what to do, Bobby decides to use his invisibility as a ghost to scout out the house to determine their next move. After a moment, Bobby returns with the news that the house is clear, but there is something that they need to see. Entering, the Winchesters are shocked to find three dead vampires on the table with burns around their mouths, but otherwise unharmed. The three are confused as the only way they know to kill a vampire is decapitation and the vampires all still have their heads attached.

As they discuss the situation, Sam notices an oddity in a nearby wall and Sam and Dean begin searching for a way to open it while Bobby simply passes through the wall to find a bedroom with a young woman inside. Sam finally finds a button to open the door hidden behind a book and the Winchesters enter, startling the girl, Emily. Emily tells them that when she was eight, she was abducted by the Alpha Vampire who said she was the prettiest girl on the playground. Emily explains that the other vampires keep her ready for when the Alpha Vampire comes as virgins are a delicacy and the Alpha Vampire always keeps one on hand. Sam promises to help Emily get back to her mother, but Emily expresses doubts that her mother will remember her and admits to not remembering her mother.

At the Winchesters prompting, Emily tells them that the dead vampires take care of the Alpha Vampire whenever he comes. A week before, they captured three humans for food that came very easily to them. When the vampires ate, they died in agony and the only vampire that didn't eat is currently out hunting for animals for food instead. While confused, the hunters realize that the most likely explanation is the Leviathan additive in the corn syrup is fatal to monsters. The gas station was "lousy with stoners" that would've been great pickings for the vampires and would've fit Emily's description of an easy hunt for the vampires. Sam asks if Emily has any idea where the Alpha Vampire has gone and she tells him that he has most likely gone to his retreat, a place he goes to when something is wrong. While Emily doesn't know where it is, she remembers things that might help the Winchesters find it.

After the Winchesters, Bobby and Emily leave, the final surviving vampire returns to the nest to discover Emily gone and the Leviathan Edgar waiting for him. Edgar demands to know where the Alpha Vampire is and easily overpowers the vampire when he tries to fight Edgar. The vampire refuses to tell Edgar where to look so Edgar shapeshifts into the vampire's form and gains access to his memories. Edgar learns from the vampire's memories that the Alpha Vampire is in Missoula, Montana. Satisified, Edgar rips the vampire's head off with his bare hands, killing him.

Trivia

 * Before the Winchesters leave, the Alpha Vampire quips that he will "see you next season," effectively breaking the fourth wall. However, the Alpha Vampire doesn't return until Season 12's The Raid where he is killed by Sam with the Colt.
 * These events are briefly referenced by Sam in Season 12's The Raid when he tells the British Men of Letters, who had believed the Alpha Vampire to be in Morocco for at least a decade, that he met the Alpha Vampire in Hoople, North Dakota five years before. However, Sam has the location wrong when he told them that as Hoople is where the Winchesters and Bobby Singer found the dead nest and Missoula, Montana is where they met the Alpha Vampire.