Lord Darzi of Denham, the Health minister and a practising surgeon, has resigned from the Government after two years in the post.
His departure marks the almost total collapse of Gordon Brown's attempt to form a "Government of all the talents" (Goat) by hiring ministers from outside the Labour Party.
Lord Carter, the Communications minister, leaves this summer after completing his report into Digital Britain. Lord Malloch-Brown, the Africa minister, is following him, citing "family and personal reasons". Lord Jones, the former Trade minister, left his post last October.
Lord West, the Security minister, is the only remaining "Goat". Alan Sugar, the star of The Apprentice, has been recruited to advise the Government but he has not become a minister.
Friends of Lord Darzi said he was exhausted from holding two jobs and had done what he had set out to do and put the NHS on the path to reform. "He was trying to be a minister and an innovative surgeon at the same time – it's knackering," said one friend.
He was appointed in 2007 as the Government was within sight of conquering the NHS's waiting list problem by reducing maximum waits to 18 weeks. His brief was to switch the focus from increasing the quantity of treatment – a task that had preoccupied the NHS for 60 years – to improving its quality. His report High Quality Care for All, published in July 2008, set out plans to tie the income of NHS trusts to their record on safety and effectiveness of care, and on patient satisfaction
He published a one-year update last month that proposed awarding "gold standard" status to the best hospitals. His update showed GPs were offering longer surgery hours and more than 50 GP polyclinics had been set up.
Colleagues were puzzled over the timing of his decision to leave but the squeeze on public spending would have made implementing his agenda more difficult. A source said: "There was always an understanding he would do the [quality] report, do the one-year review and then see where things were going from there."
The shadow Health Secretary, Andrew Lansley, said: "Darzi's laudable focus on quality was increasingly at odds with the Brownite fixation with targets and command and control."
The Liberal Democrat health spokesman, Norman Lamb, said: "A short spell as a minister seems to be the new route into the House of Lords for New Labour supporters."
The Health Secretary, Andy Burnham, said Lord Darzi had set a "defining vision" for the NHS for years to come. Lord Darzi said: "The time has now come for me to return to care for my patients, lead my academic department, and continue my research full time."