Gordon Brown yesterday faced an unprecedented challenge to his authority as he came under new pressure to cave in over controversial embryo research legislation.

Stephen Byers, the former cabinet minister, intervened in the row by attacking Downing Street’s plans to deny Labour MPs a free vote on the bill. Byers is the most senior Labour figure yet to criticise Brown’s uncompromising approach, which could lead to several cabinet resignations.

For the first time usually loyal MPs are openly questioning the prime minister’s political judgment, amid growing concerns that Labour is heading for general election defeat.

Charles Clarke, another former cabinet minister, has been circulating a so-called “doomsday list” of Labour MPs at risk of losing their seats, which high-lights how vulnerable the party’s grip on power has become.

The Human Fertilisation and Embryology Bill will allow scientists researching treatments for diseases such as multiple sclerosis to create human-animal hybrid embryos. Opponents, led by the Catholic church, argue that such experiments interfere with the sanctity of life.

Byers, a former transport secretary, called for a compromise. “The public would 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 ministers and MPs how to vote,” he said.

He urged Brown to relent and allow free votes on selected amendments so that potential rebel ministers and backbench MPs would no longer face a moral dilemma.

Byers, who describes himself as nonpractising Methodist, said: “I believe it is important that while Labour MPs should support the government at the second reading of the bill, we should be given a free vote on a limited number of amendments when they are put forward at a later date.” Backbenchers opposed to the bill warn that they will not settle for anything less than free votes on the most controversial issues. One Labour MP, who is a Catholic, said: “The iron fist approach just won’t work on this. This is much more important than politics. It is about morality and ethics.”

Researchers are seeking permission to use animal eggs because of the shortage of human eggs. They would remove the nucleus of the animal cell and replace it with a nucleus taken from a human cell. It can then grow and divide like a normal embryo, generating stem cells that can be harvested by scientists.

The stem cells have the potential to become almost any type of cell within the body and it might be possible to use them to create a “repair kit” for humans.

A number of Catholic ministers are believed to have told the whips that they would consider their future if forced to vote with the government. These include Paul Murphy, the Welsh secretary, who is a papal knight of St Gregory, Ruth Kelly, the transport secretary, who is a member of Opus Dei, the Catholic sect, and Des Browne, the defence secretary.

Labour is alone in insisting on whipping its MPs, with both the Conservative and Liberal Democrat leaderships granting their MPs a free vote on the bill.

There were signs last night that No 10 was preparing a compromise, where ministers and MPs might be allowed to vote against certain clauses, provided the overall bill was not wrecked.

Stephen Pound, another Catholic and the Labour MP for Ealing North, said: “There are six major clauses in this bill. Half are perfectly acceptable. But three are nonnegotiable. Hiding behind the bike sheds while the bell goes is not an option.”

Geraldine Smith, MP for Morecambe, said: “I find it incredible that they did not declare right at the start there would free votes.”

Brown’s baby son James Fraser suffers from cystic fibrosis, a condition for which stem cell research offers new hope.

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