The Wellcome Trust will take a back seat in funding UK science for the foreseeable future, according to its former director, Mike Dexter, who left in March.
Dr Dexter told The THES that the UK biomedical research community was too dependent on the organisation, which spent almost £400 million last year on research in UK institutions - £40 million more than the government-funded Medical Research Council.
"The dependency is so strong that disentangling that or even reducing it is not going to be easy," he said.
He warned there would be no sacred cows in the trust's review of spending, which is taking place in the wake of global stock market falls that in the past three years have wiped more than £5 billion off the biomedical research charity's total worth.
"What I want to be sure of is that the schemes we fund are completely justifiable, high quality and something that is adding not simply to the community in the UK but also to the mission of the Wellcome Trust."
He denied there was a crisis, but said that the state of the markets would colour plans for the future.
During his five years as Wellcome director, Dr Dexter built a close relationship with the government. He persuaded the Treasury to contribute more than £1 billion to revamp university laboratories.
The trust gave £110 million to the Diamond synchrotron project, in Oxfordshire.
"It's clear that the trust cannot continue doing these major one-off initiatives," he said.
Last summer, the government announced an extra £1.25 billion for the science budget in the comprehensive spending review. By then, Wellcome's asset base had fallen dramatically.
"I was aware that there was no way the trust could come in with huge chunks of money for continuing replacement of decaying university infrastructure," he said.
But he said the outlook for British science was rosy. He was pleased with the new science budgets and expected the markets to pick up.
Dr Dexter said he had not decided what he would do next apart from take up an offer to sit on the North West Science Council. He left the trust after promising his youngest children that he would be there for them during their school examinations.
Mark Walport of Imperial College London will take up the reins at the Wellcome Trust in June.