WARNING: The following contains spoilers for Boruto: Naruto Next Generations Episode 159, "The Hashirama Cell," now streaming on Crunchyroll.
Boruto's anime has taken quite a drastic turn recently with Kara being introduced as a terrorist cell that's orchestrating a new ninja war. As things heat up, Naruto and company have sent Boruto's Team 7 to the Land of Valleys to track missing scientists, fearing they could be tied to Kara's presence and the creation of new arms.
What they discover, though, runs way deeper mercenaries and rogue ninjas as the DNA of Hashirama, Konoha's most powerful Hokage, is being weaponized and possibly sold on the black market. This could result in the emergence of godlike shinobi — major threats to the ninja world's uneasy peace. As a result of these findings, it's clear the show needs to bring back two fan-favorite former villains.
The first is Orochimaru, the snake-like ninja who battled the likes of Jiraiya and Tsunade as the legendary Sannin. He was a main villain in Naruto, turning on Konoha to try to perfect himself as a god. He tried to use Itachi and Sasuke's bodies and often dabbled in forbidden resurrections, all to improve himself as a weapon. What's interesting is he has always been obsessed with Hashirama's cells and the Wood Technique — a technique that grants one power over the dreaded Tailed Beasts.
It's what made warriors like Danzo, Shin, Obito and Hashirama's archenemy Madara so deadly, as his genes really are something out of this world. What's interesting here is that Orochimaru's genetically-cloned "son," Mitsuki, is actually infected with Hashirama's DNA from when his snake bit the infected Anato. Yubina tends to the boy but, while his body seems to have purified itself, it'd be very interesting to see him taken to Orochimaru for a final checkup — with a twist, of course. The villain was redeemed when he joined Naruto's team to fight off Madara and Kaguya, and has since been working on experiments to better Konoha.
Or so we're led to believe. The fact he engineered Mitsuki says a lot about how much Orochimaru has truly changed. He works in secrecy, so this situation could either see him using Mitsuki's spliced genes for something good — like healing the old and taking care of dying people — or it might result in him using it to create more vessels like Yamato did in the past. In fact, Orochimaru might even upgrade Mitsuki to finish his failed global takeover. Admittedly, he was seen in the Log arc, but this feels like a more natural fit.
This is also why Kabuto should be brought back. He too was a son-like figure to Orochimaru and someone obsessed with the Hokage of old. He worked as an assistant and then ran his own experiments, eventually succeeding where his mentor failed. He'd be just as fascinated with the Hashirama cells, and while he redeemed himself and now runs an orphanage, Kabuto still loves science. He could harness the genes to help mankind or even upgrade himself and make new weapons, returning to his old tricks.
The point is, both men's sinister pasts make them completely untrustworthy, so the situation with the spreading Hashirama infection presents the perfect opportunity for them to come to the fore once more. Not everyone's taking to the cells and increasing numbers of kids are showing up needing attention on Yubina's doorstep. Orochimaru and Kabuto's backgrounds in mad medical science would make them invaluable to Konoha in a time like this, while giving them plenty of room to reestablish themselves as bad guys. Whatever their intentions, they'll surely have fans glued to the series with their unpredictability, which would spice up things when Kara inevitably invades.