자기 약혼녀를 뇌사 상태로 만들어버린 죄책감 때문에 수술을 멀리하고 당직 의사로서 살아가던 진. 그러던 어느 날, 신분을 알 수 없는 수상한 환자가 병원에 실려 온다. 그리고 진은 갑자기 종적을 감춘 그 환자를 뒤쫓다가 갑작스러운 두통과 함께 계단에서 굴러떨어진다. 잠시 후, 두통과 함께 정신을 차린 진의 눈앞에 보이는 것은 사극에서나 볼법한 모습을 한 사람들이었는데...

신기한 의술로 사람들을 살린 진은 사카모토 료마를 만나게 되고, 그가 원래 있던 세계에 왔던 수상한 환자라고 의심하게 된다. 한편 에도에는 다시 호열자(콜레라)가 돌기 시작하고, 서양의학소의 리더인 오가타는 호열자(콜레라)의 치료법을 찾기 위해 소문 속의 의사 진을 찾아가게 되는데...

호열자(콜레라)에 감염되어 괴로워하는 사람들의 모습을 본 진은 오가타에게 콜레라 치료법을 알려주기로 한다. 하지만 호열자의 효과적인 치료를 위해서는 당시 에도에는 존재하지 않았던 의료 도구가 필요했었기에, 오가타에게 비슷한 도구들을 만들 수 있는지 묻는다. 과연 진과 사람들은 콜레라의 공포에서 에도를 구할 수 있을까?

진은 오가타와 함께 서양의학소에서 강의를 펼치면서 의술에 대한 열정을 불태우고 있었다. 그러던 어느 날, 료마는 마음에 품고 있던 기녀 노카제가 의사를 찾고 있다는 소식을 듣고, 진과 함께 요시와라를 찾는다. 노카제는 진의 약혼자인 미키와 동일 인물이라는 생각이 들 정도로 닮은 모습을 하고 있었는데...

노카제의 부탁으로 진은 매독에 걸린 기녀 유기리를 진찰한다. 하지만 이 시대에는 매독 치료에 필요한 '페니실린'이 없기에 치료를 포기한다. 자신이 이 시대에 페니실린을 만든다면 의학의 시곗바늘이 빨라지게 만들게 되지만 그 또한 자신의 운명이 아닐까 하고 고민하는 진. 과연 그는 어떤 결정을 내리게 될까?

페니실린을 만드는 데 성공한 진과 의학소 식구들. 진의 의술에 대한 소문이 에도 전역에 퍼지면서, 그 소문을 들은 한의학 권위자 타키 겐엔이 진을 만나기를 청한다. 이야기를 나누던 중, 후쿠다가 복통을 호소하여 쓰러지고, 진은 궤양으로 인한 위 천공이라 판단하고 긴급 수술을 펼치기로 하는데...

신기한 의술을 지닌 진의 등장으로 에도 의학계에는 불온한 움직임이 생겨난다. 그 속에서 오가타는 진과 페니실린을 지키기 위해 온 힘을 다한다. 하지만 그러던 어느 날 페니실린 생산을 위해 지어졌던 제조소에 불이 나게 되고, 한순간에 페니실린을 잃을 위기에 처하게 되는데...

서양의학소의 리더였던 오가타가 지병으로 사망하고, 진은 그의 유언에 따라 슬퍼하기보다는 강하게 살아가기로 마음먹는다. 그리고 사키와 여러 연구를 하며 새 페니실린 개발하는데에 성공한다. 하지만 제작에 필요한 지원금 원조를 거절당하고, 본인의 그릇에 대해서 고민하게 되는데...

에도 거리에서 불잽이 신몬 타츠고로를 만나게 된 진. 서로의 용기와 각오에 관해 이야기를 나누다가 불이 나면 사람들을 치료하러 가겠다는 약속을 한다. 한편, 노카제는 측실을 제안받고 요시와라를 떠나게 될 상황에 부닥친다. 진과 떨어져야 한다는 사실에 상심하던 중 마지막으로 진과 시간을 보내기 위해 서신을 보내는데...

노카제의 측실 이야기가 들리고부터 사진 속 미키의 모습이 점점 흐려지는 것을 보고 생각에 잠기는 일이 많아진 진. 그러던 중 스즈야의 주인에게 노카제가 측실로 가기 전에 필요한 검진을 해달라는 부탁을 받게 된다. 노카제의 젖가슴에서 멍울을 발견하지만, 미키의 탄생과 연관이 있어 보여 이야기를 주저하는데...

자객에게 습격당할 뻔한 료마를 구하려다 료마와 함께 절벽에서 떨어진 진은 다행히 구사일생으로 살아난다. 하지만 료마의 모습은 그 어디에서도 찾아볼 수 없었다. 료마는 그 환자가 되어 현대로 간 것일까? 한편 진은 사부리와 함께 노카제의 멍울을 다시 검사하기로 한다. 사부리는 수술을 권하지만, 여전히 주저하던 진은 오가타 선생의 묘를 찾아가는데...

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.