It took only a few months—until the 7th month of 1850—for the vaccine to go extinct in Ōno domain. Such interruption was not unusual; almost all entities in Echizen and surroundings that had received a transmission from Kasahara failed to perpetuate it on first attempt (Yanagisawa 2020, 54-55). Ōno’s vaccinators blamed this failure on a lack of volunteers and received a second transmission from Kasahara Ryōsaku in the 11th month (“Shutō shōrei ni tsuki furegaki,” 1851, in Fukui-ken 1992, 458–59). But suddenly their fortunes turned. In the winter of 1850/51, the “southern mountains” exclave of Ōno domain, 30 km from the castle town, was ravaged by the smallpox virus. This sad event turned into an unexpected boon for Ōno’s vaccinators because it convinced skeptical villagers that the cowpox vaccine was effective at protecting children from smallpox.

In a letter to Kasahara, Ōno's domain physicians Nakamura Taisuke and Hayashi Unkei explained that the disease had spared vaccinated children in the village of Motodo, where they had inoculated “five or seven” children in the summer of 1850 (see the header image for a photo of Motodo's former village site, and the map below for its location). According to the letter, village officials in the affected area had then begun to turn to the rural intendant to request more vaccinations and gathered about a hundred volunteers. The letter stated that townspeople and villagers had finally understood the value of the vaccine, and that “we have now escaped the trouble of searching for children to be vaccinated” (1851.2.25, in Kasahara, Hakushinki, 144–45). This vaccination boom occurred two years before Fukui domain experienced a similar effect in the winter of 1852/53. It was widely advertised throughout the domain by Ōno's domain government.

What made Motodo such a compelling case? It was located in a remote, thinly populated valley about a day’s journey (30 kilometers) from Ōno's castle town. Did Ōno's vaccinators deliberately select Motodo to take advantage of the villagers' ignorance to turn them into a test case or perhaps to keep the vaccine alive? Or did they try to vaccinate villagers across Ōno's countryside in the summer of 1850? The fact that only a handful children in the area were vaccinated suggests that most parents had remained hesitant at the time. But while the exact circumstances remain uncertain, it is clear that Motodo represented a place on the periphery in the imaginative geography of Tokugawa-style Confucian rule. Much later, in 1883, the domain lord's official chronicler looked back on that era and wrote how remarkable it was that even obstinate and benighted people in such a remote and impoverished area had agreed to receive vaccinations (Yoshida, "Ryūin kiji," 377). The trope of the ignorant mountain villager, far removed from civilization, served as the perfect foil for highlighting the lord's benevolence.

The village’s secluded location probably amplified the impact of the 1850/51 smallpox outbreak. It was not uncommon for smallpox to hit different parts of the same region at different points in time. In addition, data from other parts of Japan suggest that remote villages were not visited by the virus as frequently as other communities, but tended to experience higher fatalities when the virus did strike because there were many cohorts of newborns who had failed to build immunity (Jannetta 1987, 100-104).

Motodo’s success story does not mean that Ōno’s physicians had solved their perpetuation problem. In the early 1850s there were only three physicians in the domain who were capable of administering vaccinations, and villages such as Motodo had to have regular access to vaccinate every newborn, either by bringing their children to the castle town or by having vaccinators visit their valley once with carrier children in tow and then a second time after seven days. In the winter, such visits would have been particularly daunting because mountain roads were blocked by heavy snow. Moreover, their optimism in 1851 notwithstanding, Ōno’s vaccinators had not yet fully convinced the local people of the benefits of their treatment.

Beside the case of Motodo (and the Nishikata exclave), it is unfortunately unknown how and to what extent Ōno's domain government went about vaccinating its rural subjects. People on the Ōno plain might have been asked to visit the clinic in the castle town, but most mountain villagers of the domain would have had to walk for a day or more to reach the clinic.