Major John Sheppard's team have been visiting the planet Hoff for a day and a half, and have seen technology reminiscent of Earth's 1920's. Once Chancellor Druhin and his people begin to trust the off-worlders, they reveal their most prized discovery: a chemical defense that they believe will prevent the Wraith from absorbing the life energy of any human who takes it.

Dr. Elizabeth Weir is informed of the Hoffan drug, and thinks that if the entire civilization is committed to succeeding in developing a viable antidote against Wraith cullings, Atlantis should help in whatever way possible. Sheppard enlists Dr. Carson Beckett's aid and returns to Hoff. After looking over their work, the team meets Perna, one of the lead scientists responsible for developing the drug. Beckett is immediately captivated by her. She explains the origins of the original anti-Wraith prototype drug. Apparently they've been working for more than 150 years, surviving over three cullings, storing archives of their knowledge (floors and floors of books) deep inside their planet. If one is destroyed, the other archives survive to carry on the works of past generations.

Beckett is more surprised than anyone, but he believes that it's time Atlantis helps the Hoffans carry the drug to the next level. He tells Dr. Weir, saying he has already informed the Hoffans of the "guest" in the brig. Meanwhile, Sheppard talks to the Wraith captive, nicknamed "Steve," inquiring as to how many Wraith hive ships are floating about the galaxy. Steve says that the information they are looking for is only one human away – if he gets fed ...

Beckett admits he has only experimented on the Wraith arm the team brought back from Athos. But because hose cells have already decayed he will require completely active cells. Steve's prison cell is opened, and a Wraith stunner is used to take him down, so that Beckett can get the material he needs. He then returns to Hoff to continue his work with Perna. After five results they arrive at 100 percent cell penetration. All outcomes are nothing short of perfect. There is now a definite hope for a defense against the Wraith.

Beckett is alarmed when he learns Druhin and Perna are eager to take the next step – they want to use the drug on Steve.

Weir talks the matter over with Sheppard. They are talking putting a human in the same room as a starving Wraith. The Geneva Convention would never have allowed this, but Sheppard reminds her that if the Wraith had attended the convention, they would have tried to feed on everyone. The Hoffan test subject who has volunteered for the experiment is terminally ill. Eventually, Weir consents. Sheppard approaches Steve and tells him that if he gives him information of value, he'll allow him to eat. Steve agrees. He is soon bound and taken by Jumper to Hoff.

Merell, the terminally-ill test subject, has long been at peace with his fate, and is ready to face the Wraith. Injected with the drug, he enters Steve's new chamber and faces him. When the creature places his palm on his chest he quickly removes it. Merell survives, and Steve's condition begins to worsen almost immediately. Meanwhile, Druhin congratulates Perna and Beckett. He is eager to administer the drug to the entire population, but Carson cautions that several tests must still be run before that can happen.

Steve soon dies. Beckett determines that the Hoffan serum not only shields the victim from culling, but it is now clear that the antidote is transferred into the Wraith. Essentially, Steve was poisoned. All of his vital organs shut down simultaneously. If the serum was indeed the cause, not only is it a defense – but a weapon. Teyla and Sheppard approach Druhin with this information. When the Wraith discover the danger, they will wipe the Hoffans from existence, as well as anyone they have been in contact with, just to prevent fruition of the drug. But it's too late. The Chancellor has already made his recommendations to the Hoffan council: the serum is being inoculated into the population.

Perna tells Beckett that Merell has been found dead. The cause is still unknown. Beckett urges her to cease the inoculations, but she admits that she cannot be a part of it – she herself was among the first to be given the drug.

Soon the hospitals are overwhelmed with patients. Fifty percent of those inoculated are dying. To Sheppard's dismay, Druhin believes these are perfectly good odds, and says the entire population is going to take a vote on whether or not to administer the drug to everyone. Sheppard cannot believe what he's hearing, but is assured the word of the Chancellor that everyone will have a say, and the majority will win victory in the decision. Meanwhile Teyla informs Carson of bad news: Perna has become one of the sick. Beckett goes to her deathbed. Perna assures him she will die with peace – they have accomplished the unthinkable, and she has no regrets. Beckett stays at her side until she passes away.

The results of the vote are in. Ninety-six percent of the Hoffans are in favor of disseminating the drug among their people, no matter what the cost. Druhin says that when next Sheppard's team returns, they'd like to discuss plans for passing the drug to all the worlds in the Pegasus Galaxy, but John believes that no one will be around when they come back.