By Ben Hirschler and Kate Kelland

LONDON (Reuters) - They no longer fear the Spanish Inquisition.

But four centuries after Galileo, charges of heresy from their peers and dread of being cast into a wilderness of ridicule and shame still haunt those pioneers who strike out beyond the frontiers of established science to win Nobel prizes.

Dan Shechtman's chemistry Nobel this week for discovering quasicrystals was sweet vindication after years being branded a "quasi-scientist" by one of the greatest names in his field. New laureates in physics and medicine also told of fear after making revolutionary discoveries or of good ideas left long overlooked.

"In the forefront of science there is not much difference between religion and science," Shechtman said earlier this year. "People harbor beliefs. That's what happens when people believe something religiously."

Galileo was grilled by the Inquisition in Rome in the 17th century and branded a heretic by the church for promoting Copernicus's idea that the Earth moved round the Sun.

Today it is loss of grants and public humiliation that gives sleepless nights to those whose studies force a rewrite of accepted laws of nature, like the astronomers who found the universe's expansion was speeding up, not slowing down.

"It seemed too crazy to be right, and I think we were a little scared," said Brian Schmidt after winning the 2011 Nobel physics prize for a discovery which also revealed the likely existence of mysterious dark energy, or anti-gravity -- an idea Einstein once had and later dismissed as his "biggest blunder."

The researchers who said last month that they appeared to have fired sub-atomic particles from the CERN center at Geneva to Italy's Gran Sasso laboratory at faster than the speed of light -- in seeming defiance of Einstein -- have similar anxiety about embarrassment as they ask others to check their findings.

While scientists generally defend and applaud a system of skeptical peer review, the neglect of apparently promising new discoveries -- such as the potential germ- and cancer-killing dendritic cells discovered in the 1970s by 2011 medicine Nobel winner Ralph Steinman -- can surprise the public at large.

So too will Shechtman's recollections of the humiliation he suffered on identifying what turned out to be an entirely new class of solid material, between amorphous matter like glass and regular, repeating patterned crystals. Speaking to Israel's Haaretz newspaper in April, he remembered the leader of his research team in the United States approaching his desk in 1982.

"He gave a sheepish smile, placed a textbook on my desk and said, 'Please read what's written here'," Shechtman said. A day later, the unrepentant Israeli was asked to leave the team for "bringing disgrace" on his fellow researchers.

WILDERNESS YEARS

"The wilderness years are common in the history of science, especially when there's a paradigm shift in the offing," said Carole Reeves, a historian of medicine at University College London (UCL).

Copernicus, Newton, Lavoisier, Einstein, Darwin -- all later hailed as revolutionaries -- created new models that required the scientific community to reject an existing one. Reeves picks out Copernicus who, like Darwin with evolution, was loathe to publish his new theory because of the expected controversy, particularly in theological terms.

Martin Rees, Britain's Astronomer Royal and professor of cosmology and astrophysics at the University of Cambridge, says things have got a little better recently, but there is still "a minority who are underappreciated and have a tough time."

Tragically, Ralph Steinman died three days before learning of his Nobel award, after a long period early on when his work on a new type of immune system cell was largely ignored. "He really had to pursue this ... discovery in the face of a lot of skepticism," his son Adam told Reuters.

While scientific advances don't always involve disruptive and counter-intuitive ideas, very often the biggest ones do -- and the task of the scientific community is to stress test these ideas to breaking-point.

Bassam Shakhashiri, president-elect of the American Chemical Society (ACS), says that's the nature of the game.

"That's how we do science," he told Reuters. "We scrutinize, we contemplate, we look at evidence, we debate with each other about the consistency of the evidence and how it makes sense."

The ACS lauded Shechtman's "a great work of discovery" this week, when his Nobel prize was announced.

Yet in the 1980s and early 1990s it was a one-time president of the ACS, the double Nobel laureate Linus Pauling, who was the fiercest critic of Shechtman's research, saying: "There is no such thing as quasicrystals, only quasi-scientists."

For those researchers whose work is at odds with the established dogma, life is not easy.

"Of course scientists, being people, need to be convinced about revolutionary advances more than incremental advances," Alan Leshner, chief executive of the American Association for the Advancement of Science, told Reuters. "That's how science proceeds: Prove it to me. If you can't prove it, it remains a bad idea."

Shechtman said he was all too aware of the high stakes in the years before the world's crystallography textbooks were rewritten in his favor: "I knew that if it turned out to be a flop, it would be a major flop," he said.

John Forrester, professor of history and philosophy of the sciences at the University of Cambridge, finds many echoes of past controversies in the 2011 Nobel science prizes.

He points to the late Thomas Kuhn, who set out the idea that science undergoes periodic upheavals in his 1962 book "The Structure of Scientific Revolutions." It was Kuhn who first used the term "paradigm shift" for such cutting-edge research.

"It's a dangerous place to be because careers can be put on the line. But that is the Kuhnian story -- you are going to have conflicts between groups," Forrester said in an interview.

EINSTEIN'S "SPOOKY ACTION"

Pauling, who died in 1994, was not alone among science's big guns in questioning a new idea that turned out to be a winner.

An exasperated Einstein famously dismissed quantum entanglement -- the theory that particles can be connected in such a way that changing the state of one instantly affects the other, even when they're miles apart -- as "spooky action at a distance."

Einstein may have been dissatisfied with the concept, but research in the 1970s, 1980s and 1990s confirmed the effect. Scientists behind this work were actually tipped this year as potential winners of the Nobel prize in physics by analysts at Thomson Reuters.

So why does it have to be so lonely out there?

Experts say the nature of scientific revolution is that new models are incompatible with the old, and they force the professional community to re-evaluate long familiar concepts which they may not be too eager to let go of.

Reeves and Rees point to the discovery by Barry Marshall and Robin Warren -- who won the 2005 Nobel for medicine -- of Helicobacter pylori as the bacteria responsible for around 80 percent of peptic ulcers as another illustration of scientists having to stand alone for many years.

"A whole industry had been built on seeing peptic ulcer disease simply as one of over-secretion of gastric acid," Reeves explains, adding that in the 1980s this theory also supported GlaxoSmithKline's then biggest selling drug Zantac, which reduced stomach acid.

"It was literally a billion-dollar product so you can see why powerful pharmaceutical companies, scientists funded by them who were working on gastric acid secretion, surgeons who had developed umpteen surgical procedures to resect the stomach and duodenum, might have challenged the findings," she said.

In the end, going down in history as a revolutionary scientist may come down to strength of character as much as strength of conviction.

Perhaps recalling the mortification of that day when his research team leader brought him the crystallography textbook to read, Shechtman took to Twitter after his Nobel vindication to record succinctly: "A good scientist is a scientist that is not sure 100 percent in what he read in the textbooks."

(Additional reporting by Julie Steenhuysen in Chicago and Michelle Nichols in New York)