A graduate student who took a shortcut during a quality control procedure at the University of Cambridge accidentally discovered the first evidence of metabolism occurring outside a cell. The unexpected result may help to lift another veil on the mystery that is the origin of life.

How life began is a contentious debate among biologists—some believe that RNA was the first step to life on Earth because of the many roles it plays, from the creation of critical enzymes and proteins to its role in information storage and transfer. Others think that metabolism came first, generating the molecules necessary to produce RNA along the way. The student, who was working in Markus Ralser’s lab, detected pyruvate in a cell culture medium that hadn’t been used yet. It shouldn’t have been there. Pyruvate is a product of glycolysis, the metabolic pathway that breaks down the sugar glucose in one of the many steps that lead to the production of ATP, the energy storing molecule that makes our cells tick.

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Here’s Linda Geddes writing for New Scientist:

To test whether the same processes could have helped spark life on Earth, they approached colleagues in the Earth sciences department who had been working on reconstructing the chemistry of the Archean Ocean, which covered the planet almost 4 billion years ago. This was an oxygen-free world, predating photosynthesis, when the waters were rich in iron, as well as other metals and phosphate. All these substances could potentially facilitate chemical reactions like the ones seen in modern cells.

The team looked at solutions imitating early-ocean conditions and added substances known to be the starting points of modern metabolic pathways. Then they heated the solutions at temperatures roughly near that of hydrothermal vents. By looking at the resulting compounds, they could infer which chemical reactions were taking place and if any of them resembled metabolic pathways.

The pathways they detected were glycolysis and the pentose phosphate pathway, “reactions that form the core metabolic backbone of every living cell,” Ralser adds. Together these pathways produce some of the most important materials in modern cells, including ATP – the molecule cells use to drive their machinery, the sugars that form DNA and RNA, and the molecules needed to make fats and proteins. In all, 29 metabolism-like chemical reactions were spotted, seemingly catalyzed by iron and other metals that would have been found in early ocean sediments. The metabolic pathways aren’t identical to modern ones; some of the chemicals made by intermediate steps weren’t detected. However, “if you compare them side by side it is the same structure and many of the same molecules are formed,” Ralser says. These pathways could have been refined and improved once enzymes evolved within cells.

Perhaps even more astounding is their detection of ribose 5-phosphate, a precursor to RNA. RNA is DNA’s single-stranded cousin—it encodes information, can replicate, and helps jumpstart chemical reactions. This finding suggests that oceanic metabolic processes could have, over time, engendered the conditions necessary for RNA precursors to appear. The reactions observed so far only go in one direction—from complex sugars to the simpler, end-product molecules they’ve seen like pyruvate. Researcher’s still haven’t seen it go the other way, where reverse reactions create, rather than break down, complex sugars. Without evidence of those, some biologists are skeptical that these circumstances gave rise to today’s pathways. But, other scientists argue, chemical reactions are reversible. So maybe it’s just a matter of time. Learn what RNA is and how you can discover its secrets with NOVA's RNA Lab.

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