GH.325 is one of the many drugs derived from the bodily fluid of a corpse codenamed "G.H.". The body was recovered sometime after World War II, and was transferred to a facility known as The Guest House where it was studied intensively. From G.H.'s bodily fluids, scientists were able to synthesize a number of advanced drugs with varying effects on human biology, including the serum GH.325.
After high-ranking S.H.I.E.L.D. agent Agent Phil Coulson was fatally stabbed through the heart by the rogue Asgardian, Loki; S.H.I.E.L.D. director Nick Fury used his connections to allow Coulson to undergo a series of intensive surgeries at the Guest House that brought him back to life after being dead for several days. Among the processes used on Coulson was the administering of the GH.325 serum, which had the effect of completely regenerating his eviscerated heart tissue. However, the use of this serum, along with all other details of his resurrection, were kept secret from Coulson.
Later, during a mission carried out by Agent Coulson's team, Skye, an inexperienced asset recruited by Coulson, was shot twice in the abdomen and left for dead. This event deeply affected Coulson, who felt personally responsible, motivating him to research all aspects of his mysterious resurrection in order to find something capable of saving Skye's life. His search led him and a small team to execute an unwilling raid on the Guest House in search of the drug. While the GH.325 was successful in restoring Skye's health, the raid resulted in the destruction of the Guest House, burying all existing stock of the drugs, along with its source.
Upon learning of the miracle drug's true source, Agent Coulson became extremely apprehensive of its use and possible side effects on himself and Skye, which have yet to be seen. At his behest, Coulson had his team member and S.H.I.E.L.D. scientist Jemma Simmons actively monitor the serum's effects on Skye. Personally interested in how the GH.325 could benefit humanity, Simmons hoped to recreate the drug by repeatedly analyzing Skye's blood. However, she was unable to discover anything unusual in the blood samples, even when comparing them to Coulson's blood. When she asked Coulson to send blood samples to their headquarters] in order to analyze them and mend her lack of available resource, Coulson denied permission, informing her that the Guest House's two guards went down fighting to protect the drug. He tells her to stop looking into the drug until they meet with Director Nick Fury and get some answers.
Agent Simmons continued to research and analyze the drug in secret, eventually gaining access to a better lab at the Hub and receiving help from Agent Antoine Triplett, who used his higher clearance level to help contact Agent Anne Weaver for Simmons to consult on her analysis. Unfortunately, before much progress could be made Simmons was interrupted by the assault on S.H.I.E.L.D. by Hydra sleeper agents.
In response to the Hydra uprising, Skye backed up the data on her blood work along with other technologies onto a hard drive to keep it out of the wrong hand. But when Deathlok forced her to decrypt the drive, Raina was able to reverse engineer GH.325 from the various vials John Garrett recovered from the Guest House. As Garrett's cybernetics were disabled by Fitz's EMP joy buzzer, he had Raina infuse him with the drug, nearly causing an Extremis reaction before he stabilized, claiming to have experience "the Universe." However, the side effect of the drug began to slowly drive Garrett insane as he started to draw alien maps. Coulson later experience the same thing, extensively drawing the map.
GH.325 is a drug known to promote cellular growth that can be used to heal critical conditions and, in some cases, even revive the recently deceased.
In the two known cases of the drug's use, there was no detectable trace of the drug's presence in the patient's body immediately following the period of recovery, making it difficult to properly research the drug's exact effects or to replicate it.