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George Ford and Owen Farrell have been urged to prove their time has come by establishing themselves as England's twin playmakers.
The pair are expected to start the RBS 6 Nations opener against Scotland on February 6 at fly-half and inside centre respectively, reforming an age-grade partnership seen only twice at Test level.
Farrell has profited from the absence of Manu Tuilagi and Henry Slade, who are thought to have been head coach Eddie Jones' preferred options at 12.
Tuilagi is to miss Leicester's next two matches with a hamstring injury, potentially scuppering hopes of fielding him in the latter stages of the Six Nations, and Slade has been ruled out of the entire Championship with a broken leg.
The absentees have given Ford and Farrell the opportunity to demonstrate they are the solution to England's midfield conundrum.
"We saw glimpses of their potential against Uruguay in the World Cup and people are licking their lips about the potential of having two ball players at 10 and 12," defence coach Paul Gustard said.
"They played together as kids, but now they play for different clubs and come into camp for a short period of time so it's up to them to integrate as well as they can. They are good friends and know each other well.
"Their time is now because they are both international rugby players and they are both very good.
"If we can get them both on the pitch - if that was the selection - and they perform then it could be that their time is now."
Offering midfield cover from the bench at Murrayfield will be Ollie Devoto, the Exeter-bound playmaker who will leave Bath at the end of the season due to a lack of game time.
"Some of Ollie's performances last season were stellar. Really good," Gustard said.
"He has had mixed matches this year, so his selection might be a surprise for people from the outside looking in. But we're not Bath head coaches.
"He's been one of the guys I have been most impressed with this week. He's better than I thought, he's a big kid and has a deftness of touch and a strong kicking game with another left-footed option. He's really impressed me."
Gustard revealed that former Australia openside and Test centurion George Smith made his presence felt during a defensive skills breakdown session the Wasps forward conducted at the squad's Surrey training base on Wednesday.
"The way he explained it was refreshing. He hadn't been coached and wasn't thinking like an Anglo-Saxon, where you try to build a process around the tackle," Gustard said.
"The way his body moved, speaking to Chris Robshaw and James Haskell, who have 50 caps, left some of the guys a little bit embarrassed in terms of how poor their body moved compared to his."