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In this De-Natured segment of Nature League, Brit breaks down a recent scientific journal article about the beginnings of life on Earth.

Article citation:

G. Springsteen, J.R. Yerabolu, J. Nelson, C.J. Rhea, R. Krishnamurthy.
Linked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle
Nature Communications, 9 (2018), p. 91

Article link:

https://www.nature.com/articles/s41467-017-02591-0

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Scientific, peer-reviewed journal articles are the currency of scientific discovery.

But if you’ve ever read one of these articles, you know that they read more like jargon than information. While journal articles /are/ the critical information connections between scientists, the language used and the writing density is a major turn off for...well...almost everyone else.

And this is a problem. How can we be excited about a discovery if we can’t understand what was discovered? Can we actually care deeply about something if terminology gets in the way?

On Nature League, we’ll spend the third week of each month exploring a current and trending article from the peer-reviewed literature. This segment will be called “De-Natured”, because much like when a protein becomes denatured and breaks down, I’ll be breaking down an article each month so that it’s digestible by everyone. [CHEERY MUSIC INTRO]. For our first De-Natured segment, we’re going to look at an article published at the start of 2018 in the prestigious journal Nature Communications.

The title of the paper is “Linked cycles of oxidative decarboxylation of glyoxylate as proto-metabolic analogs of the citric acid cycle”. Soooo yeah. Remember when I mentioned jargon?

Perfect example…. Don’t be daunted by the title. This study is actually really cool, and is centered around investigating the beginnings of life on Earth.

First, some background information. Aerobic organisms are ones that require oxygen to grow and develop, and all aerobic organisms on Earth release and use cellular energy by relying on something called the citric acid cycle. This cycle is also called the Krebs cycle or TCA cycle, but for this, we’ll stick to citric acid cycle.

So, we know most life on Earth requires oxygen, and life that requires oxygen uses the citric acid cycle to release and use energy. Fair enough. But what does this have to do with the /origins/ of life on Earth?

The thing is, we’re still trying to figure out what the first metabolic, or energy, cycles on Earth looked like. Keep in mind that this is an Earth /before/ life as we know it, so a lot of this field of research tries to figure out what these old school pieces and cycles were. It’s crazy to think about how life actually started.

I mean...was there something “metabolic” before actual metabolisms existed? How could these cycles operate without things like enzymes and DNA? Those players weren’t even /there/ yet!

Currently, most life on Earth uses the citric acid cycle, so this cycle and its reverse are currently the most investigated modern metabolic cycles when it comes to figuring out early life. Most studies have tried to use the citric acid cycle as a template for reactions on a prebiotic, or before life, Earth. Basically, they’ve assumed that this early Earth citric acid cycle would use the same molecular ingredients as the current one.

However, these studies have yet to yield sustainable cycles, and the authors of the new study believe this is because those ingredients simply didn’t /exist/ yet on early Earth. In this new study, the researchers went in the opposite direction. Instead of trying to replicate modern biochemistry using the citric acid cycle, they instead used a bottom-up approach and started with several very simple abiotic, or non-living, molecules.

In other words, they kept the same end goal of a functioning cycle, but asked themselves which ingredients present on early Earth would get them there. And now the exciting part - what did they find? Overall, the study found two linked abiotic cycles that not only produce carbon dioxide, but that generate stepping stone molecules that appear in the modern citric acid cycle.

These intermediate molecules can even serve as a source of amino acids, which are the building blocks of proteins. Voila- life! What’s more, the cycles proceeded at mild temperatures and pH, meaning that there weren’t any crazy, artificial conditions being forced in the lab.

In summary, the scientists found potential non-living starter cycles that may have paved the way for the citric acid cycle, and hence, most life on Earth. See, I /told/ you it was cooler than what the title hinted at... Whenever I see a new edition of a scientific journal come out, I always like to question why the one cover article was chosen over all of the other submissions.

Is it groundbreaking? Maybe it’s relevant? Something cultural?

It’s fun to think of the potential significance. The same goes for articles published in highly prestigious journals, much like Nature Communications, the journal where this article ended up. So, here are my thoughts on why this made the cut for one of the top journals in the natural sciences.

First off, originality. Not just in the way they approached the subject, but in the results they found. For example, while other studies haven’t been able to sustain a reaction that keeps cycling, /this/ team found abiotic cycles that have sustained turnover.

And there’s nothing like being first when it comes to getting published. While this study /does/ exhibit some excellent creativity and novel results, I think there’s something else going on in regards to its popularity and prowess. And that, I believe, is the general subject matter.

We’re obsessed with knowing where we came from. And by “we”, I mean almost everyone… /including/ scientific journal editors and publishers. So when a study like this comes along to propose a possible route from non-living to living things on Earth - well, it’s easy to want that in your journal.

You’ve probably heard that the Devil’s in the details, but in scientific articles he’s definitely in the methods section. Whenever I read papers in high profile journals, I like to look out for potential pitfalls in the methodology and conclusions. Articles with promising information that might relate to the origins of life on Earth are really sexy to journal editors.

But with excitement comes occasional overlooking of issues. In this last section, I’d like to offer some balanced criticism of the study. Overall, this kind of study doesn’t lend itself to being easily biased, or misinterpreting results.

Either you got a sustained cycle with turnover or you didn’t, and it’s easy to document the exact processes along the way without bias. Like...we added 15 mg of this one chemical, and it didn’t have to do with what the expected or wanted to see. So at least in this aspect, the study is well-done.

While there is very little bias in this study, there are some definite question marks surrounding the applicability. After all, we’re talking about prebiotic Earth! Like, /billions/ of years ago!

And with billions of years comes a lot of uncertainty. Yes, the team was able to produce amino acids from starting molecules that we have evidence of existing on early Earth. But things like temperature and pH?

Well...we just can’t really be /sure/ about what that environment was like on early Earth. Plus, just because the team found cycles that could be precursors to the citric acid cycle /doesn’t/ mean that these two cycles were absolutely the things that became what we know today. The results are just one /possibility/ of pre-life energy cycles that /could have/ led to living energy cycles.

Luckily, the authors point this out themselves, saying that “similarities between the proto-metabolic cycles and the evolved biochemical pathways do not imply that there must be a historical link between them.” In other words, they caution that just because their results are similar to today’s citric acid cycle, it doesn’t mean the cycles they found /became/ the citric acid cycle over time. There’s simply no way to know at this stage, and responsibly so, the authors state this alongside their exciting results. Thanks for watching our first episode of De-Natured!

Here on Nature League, we believe that breaking scientific news and articles aren’t /just/ for scientists- they’re for everyone! And we’ll be here to serve as the translator.