Time passes … On a day, two years since Minakata Jin went back in time to the closing days of the Tokugawa shogunate in the Edo era, Jin visits Saki’s family home after noticing that she has been looking down. He is told by her older brother, Kyotaro, that their mother, Sakae has beriberi (a nervous system ailment caused by a deficiency of vitamin B1) . According to Kyotaro, Saki, who has been worried about their mother’s health, had visited the Tachibana residence a few days ago and advised Sakae to consult a doctor. However, Sakae would not even allow Saki to set foot in the Tachibana house and turned her away because she still has not forgiven Saki for breaking off her engagement. Hoping to help Sakae in some way, Jin attempts to administer treatment by making a kind of confection since she loves sweets, but … … At that moment, Sakamoto Ryoma comes up from Kyoto to enlist Jin’s help.

One day after the an donut (fried donut filled with bean paste) which Jin had conceived as a confection to treat beriberi had created a sensation in Edo, he is asked by Matsumoto Ryojun of the Institute of Western Medicine and also the doctor to the shogun, to present the donut to Princess Kazunomiya, who is suspected to have beriberi. It is a big honour. But while Saki and the others at Jinyudo are overcome with joy, Jin broods alone as he has qualms that it could change history again … Meanwhile, Jin is reunited with Nokaze, who was driven out of her tenement house and is seeking a job. Concerned for Nokaze, he encourages her to work at Jinyudo. Saki who has been managing the financially troubled Jinyudo also cheerfully welcomes Nokaze. Jin later decides to present the donut. Accompanied by Saki, he visits Princess Kazunomiya, who has travelled incognito to watch Sawamura Tanosuke’s play.

The an donuts that Jin and Saki had presented to Princess Kazunomiya are suspected to be laced with arsenic and they are put into the Kodenmacho jailhouse on charges of attempted poisoning. Because it is the princess who was poisoned, the matter has to be dealt with in absolute secrecy or it would jeopardise the union of the shogunate and the Imperial family, and plunge the shogunate into a crisis. Everything will be blamed on Jin and Saki in order to bury the matter. Jin, who is sent to the great jailroom, is subjected to unrelenting treatment by the head of the prisoner’s group and his underlings. Before long, 100 ryo in bribes is paid for Jin by a mysterious man who is described to have the appearance of a merchant. With that bribe, Jin’s life might be spared … … But when he declines an offer by the the head of a prisoner’s group to promote him to one of his attendants and instead dares to ask that everyone’s tatami mats be spread out, the man attempts to instigate the rest of the common criminals to kill Jin. That unexpectedly backfires. Sick of killing people on his orders, the common criminals turn against him. One even strikes him in the chest, and he crumples to the ground unconscious. Guessing that he may have a ventricular tachycardia, Jin thumps hard on his chest and saves his life. In awe, the prisoners reverentially get down on their knees one by one and bow to him. What awaits Jin next is brutal physical torture by government officials. He eventually resigns himself to death and to face Heaven’s judgment. Meanwhile, Katsu, Ryoma and Kyotaro enlist Shinmon Tatsugoro’s cooperation and attempt to intercede with the shogunate to rescue Jin. Although a merchant, Shinmon is close to Tokugawa Yoshinobu because his daughter is one of the shogun’s concubines.

Time passes … Now under the supervision of the Satsuma domain, Ryoma sets up a maritime shipping company called Kameyama Shachu with his buddies. He also meets Nakaoka Shintaro, a fellow Tosa samurai who has left the domain and is under the supervision of the Choshu domain, and they hit it off. The two of them run around with their sights set on a reconciliation between the Choshu and Satsuma domains. One day, Taki visits Jin who is searching for a way to make powdered penicillin. The shogunate has expressed a desire for Jin to treat Ehime, the wife of the feudal lord of Kawagoe domain, for a lump. Jin accepts the request and heads for Kawagoe with Saki. They stop by at an inn along the way and encounter a girl called Ohatsu. In that moment when Jin comes into contact with Ohatsu, he has a strange sensation as if electricity were running through him … Upon their arrival at Kawagoe, Jin tries to treat Ehime immediately, but is rejected by her. “Treatment is no use,” she tells him.

Together with Saki, Jin frantically treats Ohatsu even as it seems like his own body is going to disappear. He vanishes before Saki’s eyes and in that moment, he sees something … Back in Edo, Jin’s struggle has been in vain. Ohatsu loses her life … and he is overcome by a feeling of hollowness. Jin returns to Jinyudo with Saki, where they learn from Katsu that Ryoma had been attacked at Teradaya. Painfully aware of his own powerlessness, Jin is alarmed by Ryoma’s looming assassination … Meanwhile, Tanosuke visits Jin at Jinyudo to entreat him to examine his senior apprentice, Bando Kichijuro, who has been bedridden as a result of illness. Because Kichijuro has Raynaud’s syndrome (a disorder of blood circulation in the fingers and toes which aggravates with exposure to the cold), his fingers and toes have become ulcerated and need to be amputated in order to prolong his life. However, Kichijuro wishes to stand on stage and perform a play one last time.

Jin delivers a lecture at the Seitokukan in Nagasaki in order to promote penicillin. In fact, he has come all the way to Nagasaki not just to popularise penicillin, but also because he has made up his mind to see Ryoma and tell him about the assasination. However, he is not able to meet Ryoma. Just when he has half given up hope, Ryoma suddenly appears in front of him. Jin is overjoyed to finally meet Ryoma, but the Ryoma he sees is not the man he knows. Ryoma has been obtaining weapons from Glover and making money selling them to Choshu, which is at war with the shogunate. A troubled Jin visits Choshu with Ryoma. What he sees over there are a large number of dead and wounded among the shogun’s army. They are believed to have been shot with the guns Ryoma had sold. Ryoma had coldly watched that battle … Darknes edges closer and closer to Ryoma.

Jin returns to Edo from Nagasaki in disagreement with Ryoma. At that moment, Kyotaro, who has been ordered by his superior to investigate all matters related to Ryoma, visits Jinyudo repeatedly in order to probe. Jin tries once again to recall when Ryoma was assassinated but cannot remember accurately. Then he is overcome by a headache once again. At that moment, a letter addressed to Jin and Saki from Nokaze is delivered. She is to be legally married to Lelong and would like the two of them to come for the wedding ceremony. So Jin and Saki head to Yokohama to attend the wedding, but when they arrive down there, they are told by Nokaze that there is a patient who needs to be examined.

In the autumn of 1867, political power is returned to the the emperor in a step toward the restoration of imperial rule. Ryoma runs about every day. On the other hand, Ryoma weighs on Jin’s mind while he worries about Nokaze who is hospitalised at Jinyudo. Her lump is metastatic and she is waiting to give birth. Saki also visits a midwife for Nokaze’s sake and goes through a period of hard work so that she can help with the birth as much as possible. However, Kyotaro is ordered by by his superior to continue investigating Ryoma’s movements … One day, it is learnt that Nokaze’s foetus is in a breech position and that it would prove to be dangerous for her to give birth as things are now. With the assistance of everyone at Jinyudo, Jin tries to turn the foetus through chiropractic theraphy and moxibustion (a traditional Chinese medical practice that involves burning mugwort over an acupuncture point near the toes).

The restoration of imperial rule, which is Ryoma’s earnest wish for ‘Japan’s rebirth’, comes into effect. This brings about the end of 260 years of history of the shogunate. On the other hand, Jin recalls how Miki had previously said that Sakamoto Ryoma died on his birthday, and realises that they are just one month away from the day of the assassination. Ryoma’s assassination draws closer. Jin, who has decided that he will make sure he saves Ryoma with his own hands, sets off for Kyoto together with Saki and Saburi. Meanwhile, Kyotaro is ordered by his superior to do something … Jin and the rest try to meet Ryoma as soon as they can, but have a hard time locating him despite searching the streets of Kyoto. Then the day of Ryoma’s birthday, 15 November, comes.

Ryoma is finally slashed just like in the events in history. While he is watched over by Otose, the female proprietress of Teradaya, and others, Jin prepares himself for a major surgery with the help of Saki and Saburi.

The new government army centred around Saigo enters Edo. Calling themselves ‘Shogitai’, the old government army (retainers of the shogun) that had served the Tokugawa family assemble at Ueno to wait for an opportunity to rise in revolt. Even though Kyotaro has been recommended by Katsu to study in France at a time like this, he agonises over his role in setting in motion Ryoma’s assassination and the path he should continue to take as a vassal of the shogun. Meanwhile, Jin, whose condition has been deteriorating, is asked by Matsumoto to instruct the Institute of Western Medicine at a time when Edo is under a full-scale assault. Aware of the time he has left, Jin tries to pass on his entire medical knowledge to the doctors at Jinyudo. Then the next day finally comes. Kyotaro, who has heard that the new government army will launch an offensive against the old government army, makes a decision.