A Labour MP representing a seat with a majority of just 2,564 over the Conservatives is to quit.
Jamie Reed’s resignation in Copeland, Cumbria, hands Theresa May a gilt-edged opportunity to advance into Labour’s heartlands.
Mr Reed has been one of Jeremy Corbyn’s most vocal critics and was among the first of the Labour leader’s frontbenchers to resign last year.
He insists that he is quitting to take a job in the nuclear industry, however, and his resignation is not intended to trigger another leadership challenge.
In a letter to Mr Corbyn announcing his decision, Mr Reed said that leaving parliament was “the hardest decision of my life”.
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“We desperately need a Labour government so that communities like mine can build the future they deserve,” he said.
Addressing the party leader, he said: “I wish you every success in your endeavours to become our next Labour prime minister.”
A Labour frontbencher said: “We don’t think that this is the start of a wave of suicide bombers. It’s more of a reflection of how Jamie saw his future — or the lack of it — in the Commons.”
Mr Reed, who worked as a press officer at Sellafield before entering parliament, said his decision to stand down was motivated in part by a desire to spend more time with his family, saying it was “very difficult being a long-distance dad”. Friends said that family ill-health was likely to have played a part in the decision.
Labour sources acknowledged that holding the seat, represented by Jack Cunningham before Mr Reed took over in 2005, will be far from straightforward.
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Mr Corbyn’s opposition to nuclear power and nuclear weapons will be sure to come under the spotlight during the by-election campaign in a constituency dominated by the Sellafield plant.
Neighbouring Barrow is the location for construction work on the submarines that will replace Trident.
Mr Reed has described Mr Corbyn’s position on nuclear weapons as juvenile and narcissistic.
Just minutes before the MP’s decision was made public, Ed Balls was asked on BBC Radio 2 whether he ever wanted to be back in the House of Commons.
He replied: “I never say never, because who knows? It’s such a wild time in politics at the moment and I miss the purpose of being in politics.”
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However, he added: “It’s not my plan and it’s not what I am expecting to do.”
Paul Nuttall, the Ukip leader, has pledged to target Labour’s northern heartlands but the largely rural Copeland is a far from an ideal battleground. In the 2015 election Mr Reed polled 16,750 votes, the Conservatives 14,186 and Ukip 6,148.
Given Sellafield’s dominance, Labour’s ability to hold Copeland could become a test of the GMB union’s willingness to help the party mount a defence. Tim Roche, the union’s general secretary, has been openly critical of Mr Corbyn in recent months.
Sir Patrick McLoughlin, the Conservative Party chairman, said: “We are sorry to see Jamie Reed leaving parliament, but congratulate him on his new job, and what must have been a very difficult decision for him and his family.
“It is a sorry state of affairs when talented members of parliament like him no longer feel comfortable representing Jeremy Corbyn’s Labour Party.
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“We look forward to the by-election, and the opportunity to set out how the Conservatives are building a country that works for everyone, not just the privileged few.”