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Anti-war demonstrators are marching on an RAF airbase on Saturday, after the first unmanned drone missions were carried out against the Taliban from British soil.
Members of the Stop The War Coalition, CND, The Drone Campaign Network and War on Want will march from Lincoln to nearby RAF Waddington in the first national demonstartion against the use of drones in the UK.
The RAF confirmed it had begun operating its Reaper unmanned aerial vehicles in the skies over Afghanistan from the base earlier this week, with a series of raids flown by 13 Squadron.
The drones were previously operated from a US Air Force base in Nevada, in missions to support coalition ground forces in Afghanistan.
An MoD spokesman said they had been carrying out missions involving intelligence, surveillance and reconnaissance, but refused to be drawn further.
The drones carry 500lb bombs and Hellfire missiles for use in air strikes against insurgents. They are piloted remotely, but launched and landed with human help at Kandahar airbase.
Protesters are urging the government to abandon its use of drones, claiming the high civilian death toll makes their use unacceptable.
War on Want senior campaigns officer Rafeef Ziadah told the Daily Mail: "Drones, controlled far away from conflict zones, ease politicians' decisions to launch military strikes and order extrajudicial assassinations, without democratic oversight or accountability to the public. Now is the time to ban killer drones, before it is too late."
Chris Nineham, vice-chairman of the Stop the War Coalition, claimed drones were being used to continue the "deeply unpopular War on Terror" with no public scrutiny.
He called for armed drones to be banned, saying: "They're using them to fight wars behind our backs."
The relocation of the drone command-and-control centre to UK soil marks an expansion in Britain's drones programme, say activists.
The move coincides with MoD plans to increase the number of remote-operated Reaper aircraft from five to ten.
An MoD spokesman said: "UK Reaper aircraft are piloted by highly trained professional military pilots who adhere strictly to the same laws of armed conflict and are bound by the same clearly defined rules of engagement which apply to traditionally manned RAF aircraft."
Roads will be closed along the route of the march, which will proceed from South Common along the A15 to a camp site opposite RAF Waddington. Protesters had consulted police on the plans to stage the rally, Lincolnshire police said.
The MoD spokesman said: "We fully respect people's right to protest peacefully and within the law and would do nothing to prevent members of the public exercising their right to peaceful protest. Nevertheless, we have a duty to protect public property, and to ensure that we meet our operational needs.
"The MoD has a duty to maintain security at all defence installations and uses all lawful means to do so, including the right to seek injunctions against any person who persists in trespassing on MoD property."
The use of drones has caused nationwide fury across the border in Pakistan, where the US has pursued a policy of "targeted assassinations" of suspected militants included on the Obama administration's "kill lists" of terror suspects.
US drone attacks in Pakistan killed up to 3,533 people between 2004 and 2013, many of them civilians.
The MoD has denied British drones have been used against militants in Pakistan's tribal areas.
The UN began an inquiry into the impact on civilians of drone strikes and other targeted killings earlier this year.