Scientists and academics in Scotland would lose access to billions of pounds in grants and the UK's world-leading research programmes if it became independent, the Westminster government has warned.
David Willetts, the UK science minister, said Scottish universities were "thriving" because of the UK's generous and highly integrated system for funding scientific research, winning far more funding per head than the UK average.
Unveiling a new UK government paper on the impact of independence on scientific research, Willetts said that despite its size the UK was second only to the United States for the quality of its research.
"We do great things as a single, integrated system and a single integrated brings with it great strengths," he said.
Overall spending on scientific research and development in Scottish universities from government, charitable and industry sources was more than £950m in 2011, giving a per capita spend of £180 compared to just £112 per head across the UK as a whole.
Scottish institutions also consistently won a far larger share of UK research council grants, attracting 13% of UK funding on research excluding infrastructure, compared to its 8% share of the UK's GDP, Willetts said.
Scotland's universities were also more reliant on UK grants too, studies from the Higher Education Statistics Agency suggested, providing 26% of their overall research funding compared 22% for the UK as a whole. That had peaked at £339m or 11.7% of total spending, in 2009.
Provoking accusations from Scottish ministers of "outright scaremongering", Willetts flatly rejected suggestions that Alex Salmond is expected to make in his independence white paper later this month that the UK and Scotland set up a new joint-funded research initiative.
While an independent Scotland would gain ownership of physical assets like research centres and equipment, and cross-border collaboration would continue, Willetts said "that flow of funding would cease".
Willetts said independence would require the Scottish government-run Scottish Funding Council (SFC) to make up any future funding shortfall from the loss of central UK research council funding, a figure the paper implied would mean the SFC would need to be more than double its current spend of £258m.
Apart from EU scientific research, which makes up only 7% of overall funding in Scotland, the only comparable international model for cross-border scientific funding came from a Nordic scheme. But that spent just £13m a year and had taken years to build, and in future Scottish universities would be treated in the same way that the Sorbonne in Paris or German universities would be.
"It all hangs together. It's a coherent system which works well for Scotland; we don't want to see it fragmented or split up," Willetts said.
The University of Edinburgh provided the most dramatic example of the significance of UK funding, the Department of Business, Innovation and Skills (Bis) said. It won a third of all its research funding from UK grants, some £83m, more than that from the SFC.
Edinburgh's globally significant Hector supercomputer project would be among the programmes to lose their UK government funding, Willetts said, which would switch to its competitors in England.
Alistair Carmichael, the Scottish secretary, implied that Scottish universities would face a brain drain of scientific talent after independence as funding declined. "There's going to be no falling off a cliff here, I don't think, but there's an enormous premium to be had for science and research, being part of the UK," Carmichael said.
Pressed on whether he was implying that meant talented researchers would leave Scotland if research quality suffered after independence, he said: "If people want to join up the dots for themselves they may do, but today is a positive message, which is the great opportunity given to Scottish academics by the UK."
Universities Scotland, the sector's umbrella body, indicated it was anxious about the implications of a yes vote in next September's referendum, urging Willett to consider the benefits of cross-border working regardless of the result.
Professor Pete Downes, Universities Scotland's convener, said the Bis paper recognised how important Scottish institutions were to the UK's research "eco-system." He added: "This collaborative eco-system transcends all borders and strengthens the quality of research and development. It is in everyone's interests that this important and vigorous cross-border collaboration is supported to continue, whatever the result of the constitutional referendum."
Michael Russell, the Scottish education secretary, said the Scottish parliament had a powerful track record defending higher education, protecting free tuition and directly funding research. "Scotland's universities are a case study in the benefits of decisions about Scotland being taken in Scotland – the central point of the Independence debate," he said.
"Indeed, helpfully, the no-camp's paper highlights the world-class research and standing of Scotland's universities. We have more world class universities per head of population than any other country and it is precisely because of that global excellence that in an independent Scotland will continue to attract valuable investment, research funding and students from around the globe."