Suddenly finding himself in the Edo period, neurosurgeon Jin Minakata tries to return to the present day. But an oddly familiar stranger intervenes.

As Jin struggles to process the startling reality of his situation, a resurgence of a mysterious illness frightens residents across the city of Edo.

Just as Jin learns the shogunate will support his efforts to treat cholera patients with new techniques, he suddenly shows signs of infection.

Jin meets a courtesan with a striking resemblance to his fiancée in present-day Tokyo. She asks him to perform a life-saving operation on her father.

Jin takes on the ambitious task of producing penicillin to help Nokaze’s sister, a patient suffering terribly during the final stage of syphilis.

While visiting an eminent doctor of traditional medicine, Jin is pressed about his medical background — and soon gets an opportunity to prove himself.

When Jin learns of a patient with a terrible burn, he wants to help her. But the treatment requires a skin graft and a large amount of penicillin.

Nokaze asks Jin to treat a sick courtesan, but he needs stronger penicillin to cure her. Kyotaro gets an idea to secure the funds required to make it.

With both Nokaze and Saki developing strong romantic feelings for Jin, bells ring out across Edo warning of a dangerous fire engulfing the city.

When Jin visits Yoshiwara to examine Nokaze before her impending marriage, he notices something concerning during the exam but chooses to stay silent.

Jin wonders whether Ryoma might have traveled into the future during their tumble from the cliff. Saburi and Jin reexamine Nokaze’s symptoms together.

Jin examines Saki’s ill mother after learning that she may have beriberi disease due to malnutrition. Ryoma arrives from Kyoto seeking Jin’s help.

Jin considers the risks of interfering with history by treating an imperial princess with suspected beriberi. An old acquaintance appears before him.

Locked away in prison for a crime he didn’t commit, Jin endures harsh conditions and torture. Ryoma and Kyotaro fight to prove his innocence.

As the Jinyudo doctors continue trying to create penicillin in powder form, Taki asks Jin for help in treating a noblewoman from an important family.

Jin does all he can to help a renowned kabuki actor suffering from severe lead poisoning and limb paralysis to perform on stage one last time.

While visiting Nagasaki to teach other doctors about penicillin, Jin catches up with Ryoma but senses that something about him has changed.

After receiving a wedding invitation from Nokaze, Saki and Jin go to Yokohama for the occasion. But during the visit, Nokaze wants Jin to examine her.

As Ryoma fully devotes himself to achieving a return to imperial rule, Jin battles to protect the lives of both a struggling Nokaze and her child.

As Jin rushes to Kyoto with Saki and Saburi to prevent Ryoma’s assassination, Kyotaro heads for the same destination with a very different mission.

Jin, Saki and Saburi perform a major surgery to try and save Ryoma’s life. The Jinyudo doctors face charges of teaching how to create fake penicillin.

Sensing he has little time left, Jin resolves to pass on his entire medical knowledge to the Jinyudo doctors. Kyotaro makes a difficult decision.