Eurosceptic Conservative backbenchers have hit back at Ken Clarke's claim that they risk wrecking the prospect of the UK benefiting from a proposed trade deal with the United States.
David Cameron has hailed the possibility of the "biggest bilateral trade deal in history" as the US and European Union launched negotiations on a comprehensive transatlantic agreement.
Clarke, one of the most pro-European Conservatives, warned that it would be "curtains" for the UK's ability to play a leading role if the country left the EU.
The cabinet minister wrote in the Daily Telegraph that it was the UK's membership of the EU that made it a key player in negotiations with Barack Obama's administration in Washington and cautioned against demands for "Brexit" - a British exit from the organisation.
He said: "It is of course the EU that is making deals with America and Canada possible. It should come as no surprise that president Obama's officials have commented that they would have 'very little appetite' for a deal with the British alone.
"Quite simply, the political commitment and dedication that the creation of a free market encompassing over 800 million people, 47% of world GDP, and boosting the combined economies of the EU and the US by nearly £180 billion, could only ever be made by the leaders of evenly matched economic blocs."
Clarke said despite the "romantic" notion of the UK leaving the EU and joining the North American Free Trade Agreement, Britons were "a practical race".
He said: "That 'Brexit' would mean curtains for our ability to have any leadership role in world-defining plays like these free-trade agreements would greatly disturb us.
"Accepting a diminished situation in which the UK is forced to trade by EU rules which it has had no say in setting is simply not in our nature."
But Peterborough MP Stewart Jackson accused Clarke of repeating the same mistakes he made in the past.
"Wasn't Ken Clarke saying the same sort of dated Europhile propaganda stuff about our need to join the single currency in 1999?," he tweeted.
Brigg & Goole Tory Andrew Percy dismissed the former chancellor's warning as the "usual pro-EU tosh". He added: "Utter tripe."
And Clacton MP Douglas Carswell dismissed the notion membership of the EU was needed to secure trade deals.
Writing in the Daily Telegraph he said: "Genuine free trade agreements, as a rule of thumb, require little negotiation – just the removal of restrictions on trade."
"And you don’t really need diplomatic clout or a large negotiating block to do the deal making. Trade agreements involving the EU, by contrast, tend to drag on for years."
In his article Clarke said the trade deals being championed by Mr Cameron were "positively Thatcherite" and praised his efforts to reform the EU to make it "an ever greater asset".
"That is why there was such admiration for the European role that Mrs Thatcher played as PM: handbag swinging, never giving in, never giving up, she alternately charmed and cajoled Europe into the reforms which she saw were so clearly needed," he said.
"Because an asset it undoubtedly is," Clarke said. "The European Union amplifies our influence in the world, renders us safer, more secure, and more in control of our own destiny.
"As Germany shows, the EU can indeed be the home of powerhouse exporters who dominate global trade. The place for a powerful nation state in the world of today and tomorrow is within it, not outside it - even more so than in the 90s, when the economic giants of the East were still emerging.
"There remains an undoubted need for serious further European reform. The doom-mongers who say this will never be achieved should remember that a European-North Atlantic Free Trade Area was talked of as an unachievable dream for at least two decades.
"British leadership and lobbying means it really now could be a reality. There is plenty more that we can achieve in Europe. We must stay the course."