Stem cell controversy highlights difficulty of judging contrarian research

The strangest and most gripping story in science over the past few weeks has been the Japanese and Boston stem-cell papers, in which researchers appeared to show that mature mouse blood cells could be transformed into powerful stem cells with a startlingly simple method.

As soon as they were published in Nature, the discovery was greeted with amazement, excitement, and also a heavy dose of skepticism. This week researchers seem to be backing away, with one calling for the papers to be retracted, and as I type this post, were awaiting an announcement from a Japanese research institution on Friday that will reveal the progress of an ongoing investigation into alleged problems with the research. But as of now, the papers stand, and nobody wants to dismiss a technique that really could be a breakthrough.

The difficulty of sorting out visionary ideas from crackpot onesor even outright fraudhas long been part of science, especially at the cutting edge.

Many weird ideas (weird, that is, after the acid test of time) have been advanced in the canonical form of true science. Yet there are many examples in history of people we now regard as outstanding scientists whose early writings look like those of a raving lunatic, Fred Gruenberger of the Rand Corporation wrote in A Measure for Crackpots, published in the journal Science in 1964.

Its a discussion that happens in the scientific community any time a profoundly unexpected, game-changing discovery is published: Is this real, or is it too good to be true?

Chris Miller, a professor of biochemistry at Brandeis Univeristy, has been mulling over this question for years, when he isnt doing his research on ion channels in cell membranes. He recently gave a talk at the Oxford University Museum of Natural History about the topic. Although he wasnt thinking of the unfolding story of the Japanese stem cell research, his review of the pantheon of scientific characters who push unpopular ideas helps illuminate how science works and also how difficult it can be to tell which character youre dealing with in real-time.

Miller said he began thinking about the question when he was a graduate student working for a scientist he would only slowly realize was a crackpot who was persistently and blindly pursuing a dogma-challenging idea.

Miller was working for Gilbert Ling, a professor at the University of Pennsylvania, whose exciting ideas about cellsthat they didnt actually have membraneshad entranced him.

I came into his lab as a convinced acolyte; I had read his book and didnt know any biology and I was a physicist and I said, Oh, hes got to be right, Miller recalled. He advised us, Dont read the literature, it will only confuse you. We had night-time subversive meetings where wed actually read the literature and wed come to realize this is just not tenable.

Miller spent five years in the laboratory and ultimately did experiments that showed his advisers predictions were not correct. Ling did not show up for Millers thesis defense, and his thesis committee had to draft a passerby at the last-minute so that they would have a quorum.

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Stem cell controversy highlights difficulty of judging contrarian research