Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

It’s probably not surprising, but you would be hard pressed to find an area that’s full of more intractable arguments than origin-of-life studies. There are so many theories, because it’s relatively easy to add new ones, and it’s difficult to impossible to put many of them to the real test. Meanwhile, the scientific stakes are potentially quite high, not to mention the philosophical ones. The universe (or large parts of it) appears to be swimming in water and simple organic building blocks. Under what conditions can these become self-replicating, complexity-amplifying systems like us, or an amoeba? How many such conditions are there, and how many outcomes are possible? And how likely are any of them? All open questions.

The “RNA world” hypothesis has many adherents, a scheme in which DNA evolved later than RNA and where catalytically functional RNA molecules came before proteins. This requires all of those earlier forms to have died out since then – no extant RNA-based life has been discovered – but there are some reasonable arguments about how this could have been an intermediate stage. But where and how did this happen? Fossil evidence shows that life got going rather early in our planet’s history – one recent paper may have pushed that back to almost 4.3 billion years ago, and the planet itself is only 4.6 billion years old. For that matter, the oceans are probably only about 4.4 billion years old themselves, and it seems likely that there were many more warm-to-hot aqueous environments than otherwise. The relative abundance of Archaea species and others around deep-sea hydrothermal vents have led many to speculate that these high-energy high-mineral-flux environments, or something like them, might be origin-of-life locations – indeed, those latest contenders for the oldest fossils may well have come from ancient hydrothermal vent sediments. It does seem plausible that iron sulfides could have come in useful for redox chemistry, and there’s plenty of that around some of these vents as well.

Chemical stability is a problem, though. Folded DNA and RNA species don’t last that long under hot aqueous conditions, and at an even more fundamental level, the nucleosides and nucleotides themselves aren’t so stable, either. Cytosine can be deaminated to uracil, and (similarly) cytidine to uridine, and this has been suggested as a problem for the various hot-water hypotheses. But one thing that hasn’t been investigated is the effect of pressure. Many chemical reactions can be sped up or slowed down if their transition states have a different volume than the starting materials and products, so it’s possible that stability studies of biomolecules are giving the wrong answers if this isn’t taken into account – in fact, this has been invoked as a way to rescue the whole RNA-around-deep-vents hypothesis.

Unfortunately, this new paper shows that pressure makes things even worse. The authors, a team from New Zealand, find (by using a specialized NMR rig) that high pressure actually accelerates cytidine’s decomposition. As the authors put it, this provides “scant support” for the hydrothermal proposals: