Gordon Brown last night faced a direct challenge from the leader of the Roman Catholic Church in England and Wales over his refusal to let Labour MPs vote with their conscience over laws on genetic research.
Cardinal Cormac Murphy-O'Connor said Catholic MPs must be granted a free vote on the Human Fertilisation and Embryology Bill.
Former cabinet minister Stephen Byers also warned that the public would "look on in disbelief" if MPs could not follow their convictions.
Downing Street and the whips' office maintained that they would not allow Catholic MPs to vote against the legislation when it returns to the House of Commons next month.
At least one cabinet minister is believed to be preparing to quit rather than support the Bill, or take the compromise option of abstaining offered by the Chief Whip, Geoff Hoon. The Bill would allow the creation of hybrid human-animal embryos for research into diseases such as Parkinson's and Alzheimer's.
In his Easter Sunday sermon, Cardinal Keith O'Brien, the head of Scottish Catholics, will describe the plans as "monstrous" and urge Mr Brown to allow a free vote.
Catholic Labour MP Joe Benton increased the pressure on the Prime Minister yesterday with a claim that a "substantial number" of his colleagues were ready to defy the Government.
Secretary of State for Wales, Paul Murphy, Secretary of State for Transport, Ruth Kelly, and Secretary of State for Defence, Des Browne, were also rumoured to be considering their positions.
Mr Byers said: "The public will look on in disbelief if a matter as sensitive as the creation of human-animal embryos is made a matter of party policy with the Government instructing its MPs how to vote."
Government officials maintained that Mr Brown had already made an "extraordinary" concession in allowing MPs to abstain. They insisted that a further relaxation in party orders would undermine commitment to a Bill that was set out in the Queen's Speech.
The Bill would allow scientists to transfer nuclei from human cells, such as skin cells, into animal egg cells that have had almost all of their genetic information removed.
The resulting "hybrid" embryos, which would be more than 99 per cent human, would be grown for a maximum of 14 days, then harvested for stem cells – immature cells than can become many types of tissue.Reuse content