It's a children's birthday party at a family restaurant and arcade. A teenage waiter, Jack, rushes a birthday cake to a party, ignoring his younger sister, Kama, and her requests for more soda. The restaurant mascot comes out for the traditional birthday dance and Jack vomits all over the table in the middle of dancing. Then his heart stops.
Paramedics rush to the scene and try to shock Jack back to life. Standing with her younger brother, Will, Kama pleads with the paramedics to save their brother. The paramedics advise Kama to call their parents and Kama says that their parents died. Jack is all they have left.
Wilson emerges from his hotel in the morning to find that his car is being seized on Tritter's orders. At the hospital, the team reviews Jack's case with House. He had a heart attack, but an echo showed no abnormalities. Cameron reads from Jack's file: fatigue, night sweats and weight loss preceding heart attack. House wonders about the itchy feet also listed.
Ignoring his team, House writes his diagnosis on a piece of paper, seals it in an envelope and tapes it to the white board. He then announces a game to his team. They get one test each and the clock runs out at lunch. If House is right, Jack lives. If not, well, then it's a very cruel game.
The doctors study Jack's file, with Chase paying particular attention to the page House was on when he wrote down his diagnosis -- the patient history. When his parents died, Jack quit using drugs and quit smoking. Thinking bacterial, Chase plans to do a blood culture. Foreman's going for an MRI. Cameron is keeping her test a secret.
Chase is working on Jack when House strolls into the room. He asks Jack about his itchy feet before inquiring about the drug use. In front of his younger siblings, Jack admits to previous drug use, but says he's clean now. House thinks it's all lies.
Foreman slides Jack into an MRI. House, hovering in the control room, gets on the microphone and again presses Jack about his drug use. Then he asks how Jack managed to go from two packs of cigarettes a day to nothing just cold turkey. Foreman, finding this relevant, asks Jack to answer. Jack explains that he didn't really quit. He just sorta lost the taste for smoking. A smug House asks Foreman if he thinks that's an important bit of information.
Now it's Cameron's turn. She injects Jack with a substance to see if his heart attack was caused by a spasm in the vessels surrounding the heart. House, naturally, pops in on this test as well. House observes that Cameron's injection has had no effect.
Cuddy notices Wilson's late arrival. Wilson testily announces that his car is being held hostage until he rolls over on House for Tritter. Cuddy nervously points out that any conviction for House will cost the hospital. Wilson, still testy, tells her to relax before heading to the pharmacy to find out why all of his prescriptions have been bounced back recently. The pharmacist informs Wilson that his DEA number has been suspended. This is not good.
House confronts his team will the results of the tests. They all whiffed. But Jack did have positive titers for Hepatitis A. House wonders who ordered that particular test. It must've been somebody who knew what persistent vomiting, itchy feet and a sudden distaste for nicotine have in common. That somebody being House. Foreman points out that Hepatitis A doesn't explain the heart attack. But the puking does. And Hepatitis A explains the puking.
Wilson shuffles in with the news that the DEA revoked his prescription privileges. House tells him to relax. Tritter is just trying to squeeze him until he gives in. Wilson tells House he's going to use his team to do his prescribing until everything is straightened out. After ordering his team to start Jack on IVIG and handing his diagnosis envelope to Cameron, House follows Wilson out of the office. Cameron opens and reads what's inside. The note predicts that Chase would do a blood test for bacteria, Foreman would do an MRI and be too stubborn to check the lungs and Cameron would look for a spasm.
The next day, Foreman ambles in to Jack's room with good news. The Hepatitis A has cleared his system so they can unhook the IV and Jack can go home tomorrow. Will asks Jack if his arm hurts and Jack says it doesn't. Will asks why it's bleeding and when Jack holds his arm aloft, blood is pouring down his foreman from the IV connection. Then blood begins to trickle from his ear and nose.
Later, Foreman informs House that a high PT and PTT on Jack's blood panel have confirmed a coagulopathy. House finds it interesting that after they cured the Hepatitis A, something new popped up. He asks what infections cause DIC. Cameron mentions that kids don't wash their hands after using the bathroom. Jack's place of employment is probably teeming with E. Coli, Eikenella and strep. Chase thinks about a food-borne toxin. House orders Foreman to give Jack an LP, Chase to sample some of Jack's vomit from the restaurant and to have Cameron check the place for the diseases she mentioned.
After the meeting breaks up, House pulls Chase aside and asks for a prescription for Vicodin. When Chase resists, House makes it an order. But Chase declines, saying he'd rather lose his job than his medical license.
Wilson has pulled Cameron into his office and is running down his patients and the drugs they need. Cameron balks, saying that she'll need to examine the patients before putting her name on any prescriptions. Especially with Tritter watching them.
Behind the restaurant, Chase goes through the dumpsters with one of Jack's co-workers. The guy explains that they don't use any toxic cleaning products since kids put everything in their mouths, then directs Chase to the bin holding the trash from Jack's last day there.
Foreman performs the LP on Jack. After the procedure is completed, Foreman puts his hands on Jack's side to roll him over. One of Jack's ribs snaps and he screams out in pain. When Foreman informs House of this, and explains that he barely put any pressure on Jack, House recognizes osteomyelitis. The infection has spread to Jack's bones.
House, whose pain has been increasing without his Vicodin, has been given a new cane by the hospital physical therapy. A four-pronged metal job. The doctors are quick to mock it when House tracks them down in the lab. Foreman breaks the news about osteomyelitis to his colleagues. Jack has syphilis. But Cameron's blood test shows that he's also positive for Eikenella. As the doctors try to process this, Chase announces that his test for botulism has also come back positive.
The next morning, Foreman informs House that they managed to clear all three infections from Jack's system, but now he's having seizures every few hours. House figures he must be immuno-compromised. But his blood work was negative for HIV and lymphoma. House goes back to drug use. Despite the clean tox screen, perhaps some drugs were trapped in Jack's fat cells. With his vomiting and rapid weight loss, perhaps they've come out to play. If they can make Jack lose more weight, maybe they can trigger another attack.
The doctors sit in the hospital sauna with Jack. He insists that he's off drugs. He was high the night the cops told him about his parents and the first thing he did was laugh. That was enough to clean him up. Jack then falls to the floor and has another seizure. Foreman reports back to House that Jack was completely drug-free at the time of the seizure, and he's still having them every few hours whether he's in a sauna or not. House, figuring that something besides infection is causing the seizures, orders another brain scan.
Foreman gives Jack another MRI. His brain stem is clean. So is the midbrain. But when they cut to an axial view, they realize that Jack's brain is now riddled with tumors. The doctors press House to start radiation treatment, but House has two concerns. First, the radiation would destroy the little immune system Jack has remaining. Second, he finds it hard to believe several tumors just suddenly appeared from nowhere. Maybe it's fungus. He instructs the team to stick a needle in Jack's brain and make an extraction. If it's liquid, he's right. Solid, they're right. With that, House pops his last remaining Vicodin and angrily tosses the empty bottle in the trash.
House barges into Cuddy's office and asks for a Vicodin prescription. Cuddy smiles, knowing if House is approaching her, his staff stood up to his bullying. Cuddy pulls out her pad and writes a scrip, acknowledging that if she cuts him off, the police will assume House doesn't really need the meds. But before she hands over the paper, Cuddy notices House massaging his aching shoulder. That's a change. She asks him what's changed in his life recently. House stops. He's on the verge of an epiphany.
Foreman returns from the brain surgery on Jack. The marks on the MRI were abscesses from a fungal infection. Aspergillis. Thinking that his parents' death could be enough of a trauma to trigger Jack's genetic illness, House begins running down everything that's gone wrong. He decides that they need to introduce new infections and see what happens.
House informs Jack that each of the four possible genetic conditions is most susceptible to a different type of infection. House pulls out a spray bottle from his pocket. Inside is a cocktail of serratia, meningococcis, cepacia and rhinovirus. Whichever germ strikes first will give them their answer. If it's meningococcis, Jack will have another seizure. Serratia will shut down his lungs. Cepacia means a heart attack and rhinovirus means... he'll sneeze. House spritzes Jack's face.
The doctors begin shifts at Jack's bedside. Hours later, his lungs begin to shut down. Serratia wins. The next morning, House pronounces it Chronic Granulomatosis Disease. Jack needs a bone marrow transplant to reboot his immune system. Fortunately, Will is a match. But when Foreman explains the situation to Jack, he's angry that the doctors pressured his younger brother. Foreman tries to persuade Jack to consent to the transplant, explaining that Jack will constantly get sick from the germs he'll contact every day. He'll constantly be in and out of the hospital. Jack agrees to the procedure, but not until Will is 18 and can decide for himself.
House scoffs at Jack's decision. He thinks he's running from something. House brings Foreman back into Jack's room and tells Jack they found a bone marrow match in the registry. No Will, so they can proceed. Jack counters that he could die, but House sees through this. He keeps pushing Jack until he breaks down and admits that he's too young to be a father to Kama and Will. Having proven his point, House leaves Foreman and Jack alone in the room.
That night, House finds Wilson in his office. Wilson announces that he's shutting down his practice and referring his patients to other oncologists. House chides him for overreacting and Wilson erupts, screaming that he can't put his patients on hold while waiting for House to release Cameron from her duty to sign prescriptions. House sarcastically asks if he should turn himself in and Wilson snaps that that's exactly what he should do. Show Tritter some remorse. Promise to get help. House bristles that he doesn't need any help. Wilson tells him to get out.
Elsewhere, a social worker stands in Jack's room with Kama and Will. Jack tries to sell them on the orphanage and promises that he'll still be able to see them. Foreman is crushed as he observes this moment from the hallway.