The government's chief medical officer Sir Liam Donaldson will step down in May after nearly 12 years in the role.
Sir Liam (pictured), who led the government's battle against the swine flu pandemic and vigorously supported its plans to combat the virus, had originally intended to leave the position midway through this year.
But he told ministers that if the pandemic should take a surprise turn for the worse, he would stay in the role until May.
Earlier this year, Sir Liam clashed with the government over plans to introduce a minimum price on a unit of alcohol.
He said he was in favour of setting a price of 50p, but this received a lukewarm response from Prime Minister Gordon Brown, who said he did not want to penalise the majority of sensible drinkers.
Since 1998, Sir Liam has overseen the creation of the Health Protection Agency, making England smoke-free and creating new laws on the use of stem cells, organs and tissue.
In his resignation letter to the Cabinet Secretary and head of the civil service, Sir Gus O'Donnell, Sir Liam said: "I have been immensely privileged to serve in this post over the past nearly 12 years.
"I have been pleased to see many of my policy recommendations – stem cell research, smoke-free public places, reforms to the General Medical Council, changes to consent for organ and tissue retention and the creation of the Health Protection Agency – carried forward into legislation.
"I have been pleased too, that reforms I proposed to improve quality and safety of NHS care – clinical governance, a patient safety programme, procedures to identify, and prevent harm from, poor clinical practice – are fully embedded in the service and have been also adopted in many other parts of the world."
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