Exeter Chiefs centre Henry Slade is the latest big name player forced to withdraw from England's 36-man Nations squad just six days out from the opening game of the 2023 tournament.
Slade suffered a hip injury in Exeter Chief’s game against Castres in the Heineken Champions before last week’s training camp, and has not recovered sufficiently to be available for selection.
Slade, 29, missed England's summer tour of Australia after having surgery on his shoulder but returned in the Autumn Nations series to play all four internationals as he earned his 52nd cap for his country.
His absence ahead of the Calcutta Cup game with Scotland at Twickenham Stadium on Saturday 4 February (4.45pm KO) means Bath centre Ollie Lawrence's stock is on the rise having been brought into the squad initially as an injury replacement for Saracens' Elliot Daly who will miss the entire tournament due to a hamstring injury.
Lawrence is now just one of four out-and-out centres in the squad along with Sale's Manu Tuilagi, Harlequins' Joe Marchant and Leicester's Dan Kelly - although the idea of playing England captain Owen Farrell at inside centre instead of at fly-half is a well-tested experiment.
Saracens hooker Jamie George has been named in the squad and will continue to work through his Graduated Return to Play protocols following a concussion, however Bath's Tom Dunn remains in the squad to compete for the number two jersey with Newcastle's Jamie Blamire returning to his club.
Former Bath man turned Leicester Tiger Anthony Watson has also been recalled following injury by his former club boss Steve Borthwick.
Borthwick said: “This is a very important week for us as we prepare for our first game against Scotland.
“We know that Scotland are an excellent side with a great coaching team led by Gregor Townsend. They’re a settled squad who have been together a long time and have dominated this fixture in recent seasons.
“They will be coming to Twickenham full of confidence.
“We know we have a lot of work to do. The team trained very hard last week and are ready to go again this week. We can’t wait to run out at Twickenham again in front of our incredible supporters.”
Slade and Courtney Lawes will also be in camp this week to continue rehab work.
England v Scotland is live on ITV 1 and BBC Radio 5 Live.
Ollie Chessum (Leicester Tigers, 5 caps)
Dan Cole (Leicester Tigers, 95 caps)
Ben Curry (Sale Sharks,1 cap)
Alex Dombrandt (Harlequins, 9 caps)
Tom Dunn (Bath Rugby, 3 caps)
Ben Earl (Saracens, 13 caps)
Ellis Genge (Bristol Bears, 43 caps)
Jamie George (Saracens, 72 caps)
Joe Heyes (Leicester Tigers, 7 caps)
Jonny Hill (Sale Sharks, 19 caps)
Nick Isiekwe (Saracens, 8 caps)
Maro Itoje (Saracens, 62 caps)
Lewis Ludlam (Northampton Saints, 14 caps)
David Ribbans (Northampton Saints, 3 caps)
Bevan Rodd (Sale Sharks, 2 caps)
Sam Simmonds (Exeter Chiefs, 18 caps)
Kyle Sinckler (Bristol Bears, 56 caps)
Mako Vunipola (Saracens, 74 caps)
Jack Walker (Harlequins, uncapped)
Jack Willis (Toulouse, 6 caps)
Owen Farrell (Saracens, 101 caps)
Tommy Freeman (Northampton Saints, 3 caps)
Ollie Hassell-Collins (London Irish, uncapped)
Dan Kelly (Leicester Tigers, 1 cap)
Ollie Lawrence (Bath Rugby, 7 caps)
Max Malins (Saracens, 14 caps)
Joe Marchant (Harlequins, 13 caps)
Alex Mitchell (Northampton Saints, 1 cap)
Cadan Murley (Harlequins, uncapped)
Fin Smith (Northampton Saints, uncapped)
Marcus Smith (Harlequins, 17 caps)
Freddie Steward (Leicester Tigers, 17 caps)
Manu Tuilagi (Sale Sharks, 50 caps)
Jack van Poortvliet (Leicester Tigers, 7 caps)
Anthony Watson (Leicester Tigers, 51 caps)
Ben Youngs (Leicester Tigers, 121 caps)