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What might have been

If you like interviews—and I usually can’t get enough of them—you can only applaud the launch of the interview series in PLoS Genetics, off to a good start with one-on-ones with Nicholas Wade and Tom Cech. The chat between PLoS interviewer Jane Gitschier and Wade is a wide-ranging one with a journalist who has worked for Nature, Science, and The New York Times (as an editorial writer and a news writer). I imagine there aren’t many people who can make that claim. Tom Cech’s personal and scientific history is of course interesting as well, and I took note of this comment in particular, at the tail end of a discussion of changes in RNA science:

But look back at Jacob and Monod’s early thinking that the lac repressor might be an RNA molecule. Once the lac repressor was proven to be a protein, people got all focused on gene expression being regulated by proteins. But if they had been looking in bacillus, rather than in E. coli, they would have found riboswitches built into transcripts that bind small-molecule metabolites and control transcriptional termination or translation. So the old Jacob/Monod model was actually right, but for a different branch of bacteria.

I had heard precisely the same observation when visiting the labs of Ron Breaker and Saeed Tavazoie, as part of a discussion I’m sure many people are having as to how regulatory RNAs could remain a secret for so long. Sydney Brenner has made an analogous point when he refers to ‘Morgan’s deviation’—Thomas Hunt Morgan’s fateful decision to turn from embryology to genetics, and all of the scientists he took with him. The dominance of the protein-regulatory paradigm as the consequence of a choice made by two scientists some 50 years ago is no doubt an oversimplification, but these kinds of counterfactuals are interesting and fun to think about. The conversation is currently on low simmer (see here and here), but perhaps we’ll hear more about it this in June at the Cold Spring Harbor symposium on regulatory RNAs.

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