Metabolism happened First: The Origin of Life

This paper was written for Joe's Astrobiology class, and describes one hypothesis about how life might have started on Earth. Send us an email if you have further questions for Joe!
He also posted this essay on his personal site Forbland.com
============================================

     Self-sustaining chemical reactions are the hallmarks of life on planet earth. These reactions drive the processes that provide cells with energy, as well as allow them to grow and reproduce, also known as metabolism. In searching for life on other worlds, finding for evidence of the earliest metabolism would provide us with the first glimpse of a biotic world. Elements such as DNA and phospholipids found in the cell membrane would not be able to be constructed without metabolic reactions. For this reason, the “Metabolism First” world seems the most probable to create the first precursor to life, because the complexity of biomolecules would require an efficient, and preexisting, metabolic energy source for formation in a pre-biotic world. This paper will explore the various ways in which self-sustaining reactions could have formed in the pre-biotic ocean, focusing on pyrite formation found in hydrothermal vents. Descriptions of possible reactions that could have occurred, supported by computational modeling will provide evidence to the first step in the origin of life.
      Every ancient culture has a theory as to how life formed, principally because it is the fundamental question that drives the search of all knowledge. In earliest times, it was thought to be a divine being who willed life into existence. As humankind's understanding of the physical world grew, the theories as to how life formed adapted to the new information. With a general understanding of the basic elements of life, where genetic material encased in a protective membrane is capable of generating its own chemical reactions, researchers began to try and find how the creation of these building blocks of life might be used to find the origins of life. Some researchers speculated that the cellular casing might have been the first to form, and then the other elements of life either found their way inside it, or formed inside it. This “Cells First” or “Lipid World” idea is based around the way that oily organic molecules can interact with water (Segré et al. 2001),⁠ however it is difficult to see how a drop of oil in water can be confused for a precursor to life. Alternatively, the “Genes First” scenario is based on the concept of a “RNA World” (Gilbert 1986).⁠ In this world, proto-RNA molecules self-assembled, along with a ribosome, and managed to insert themselves into a membrane where they were able to catalyze their own reactions and self-replicate. This “RNA World” scenario for the origins of life is very well studied and is preferred by many researchers because of the ability of the RNA molecule to perform multiple tasks, as well being a system that is truly self-replicating system. However, problems with this system arise with the fact that so many things had to happen in order for it to work, especially that the RNA molecule had to self-assemble twice (as the RNA template and the Ribosome). The final idea for the origins of life is “Metabolism First” (Wächtershäuser 1988),⁠ where self-sustaining chemical reactions gave rise to the formation of organic molecules, and then into life. Central to “Metabolism First” is the idea of the Iron-Sulfur World, where many of these pre-biotic reactions ran on clusters of pyrite (FeS₂) that existed in the oceans. Pyrite clusters have been dated to as early as 4.31±0.06 Ga, which coincides well with time periods in which life was first thought to have formed (Smith et al. 2005).⁠ This “Metabolism First” scenario provides the most straightforward approach to discovering the origins of life because it provides a mechanism by which all the other elements of life can be constructed.
      As previously stated, crucial to the “Metabolism First” model is the presence of pyrite, or iron sulfide (FeS₂), in the oceans of early earth. German chemist Günter Wächtershäuser introduced the model in the 1980’s, and the model has been refined by researchers since then. Wächtershäuser’s model shows that pyrite can be formed by the following reaction:

FeS +H₂S–›FeS₂+H₂

which releases -87.0 kJ mol^-1 of free energy and hydrogen, and that would be enough to catalyze reactions with CO₂ to form organic molecules (Kundell 2011).⁠ Similar to the Krebs cycle, CO₂ can be reduced on the pyrite substrate, and producing CH₃COO⁻ (acetate) and water (Plaxco and Gross 2006).⁠ Over time, these biomolecules could increase in complexity, ultimately leading to complex organic molecules. While Wächtershäuser was only able to perform his experiment in the laboratory using CO instead of CO₂, later researchers successfully demonstrated this reaction with CO₂ (Zhang and Martin 2006).⁠ Wächtershäuser should be given credit though, as his ingenuity in recognizing that biomolecules could be built through self-sustaining metabolic processes. This model was a first step in showing that “Metabolism First” was the manner in which life first took hold.
      Wächtershäuser and others soon put forth many ideas in which life could have formed “Metabolism First.” In 2010, Frederick Kundell performed computational work on many of these ideas and that showed pyrite would be capable of doing far more than generating simple organic molecules, that it could create proto-nucleic acids. Many laboratory experiments that have tried to replicate “Metabolism First” have not fared well, however it is impossible to replicate in the lab what conditions were like in pre-biotic earth, and that is why computational models can be useful. Computer models can show whether a reaction is thermodynamically possible. If the reaction is possible, then over the course of a few hundred million years, provided the reagents are available, it becomes more likely to occur. Kundell systematically identified each of the reactions required to form ribose, a proto-nucleic acid, from iron(II)sulfide and hydrogen sulfide, and showed that these they were thermodynamically possible. As the backbone of RNA, the formation of ribose shows that the building blocks of genetic material can be formed using these self-sustaining metabolic processes. His computations showed that the formation of pyrite (using the above chemical equation) would not only generate free energy, but would also trap the hydrogen gas in the mineral’s disulfide bond, making it available for further reactions (Kundell 2011).⁠ Prior to this work, other researchers were able to show that phosphate ions could be absorbed into pyrite on damaged sections where disulfide bonds had occurred. Kundell was able to show that ribose would be able to from from that position through a series of intermediate steps. (Kundell 2011).⁠ This series of reactions shows that not only is “Metabolism First” the best way to explain the origins of life, but can actually happen faster than Wächtershäuser had initially anticipated.
      What the previous two points of evidence lacked was a means of tying all of the processes of life together. Both examples were able to illustrate that pyrite is able to create organic molecules, and in some cases complex organic molecules, however that does nothing in bringing the whole life system together. In 1996, researcher Matthew Edward was able to theoretically show how pyrite formations were able to create not only organic molecules and nucleic acids, but also lipids that could be used in the formation of a membrane. In this scenario CO, CO₂, or NO₂^- that have bonded to the surface of pyrite are photo-excited by photons (Edwards 1998)⁠ (Edwards 1996).⁠ This mechanism can create a range of molecules (depending on additional metals in the pyrite, Ni for example) including, glycine, acetyl group molecules, and thioacetyls. These primary building blocks can then combine to form longer more complex structures such as peptides and pyruvate. The pyruvate can then continue to combine with other products to ultimately create nucleic acids. What makes this mechanism so convincing is that because the reactions are driven by photoelectrons, with the pyrite only being used as a catalytic base, and therefore able to continue driving the metabolic process. By illustrating how it is possible that pyrite clusters can conceivably generate all the elements of life, this scenario shows that a preexisting metabolic source is indeed the most likely way that life originated.
      These examples showed that “Metabolism First” is the best way to explain life because it provides the mechanism required for building of complex molecules that life needs. As was stated in each case, pyrite, which consists of iron and sulfur, was critical for the reactions in each case. An interesting fact about iron-sulfur is that in all extant life, clusters of iron sulfide can be found in enzymes that are responsible for election-transfer, and conduct such functions as respiration and photosynthesis (Fontecave 2006).⁠ While the presence of iron-sulfur clusters in life does not prove that pyrite directed metabolism came first, it may provide insight into the mechanism of life that started 3.5 billion years ago.

Works Cited:

Edwards MR (1996) Metabolite channeling in the origin of life. J Theor Biol 179:313–22. doi: 10.1006/jtbi.1996.0070
Edwards MR (1998) From a soup or a seed? Pyritic metabolic complexes in the origin of life. Trends Ecol. Evol. 13:178–181.
Fontecave M (2006) Iron-sulfur clusters: ever-expanding roles. Nat Chem Biol 2:171–174. doi: 10.1038/nchembio0406-171
Gilbert W (1986) Origin of life: The RNA world.
Kundell FA (2011) A Suggested Pioneer Organism for the Wachtershauser Origin of Life Hypothesis. Orig Life Evol Biosph 41:175–198. doi: 10.1007/s11084-010-9217-y
Plaxco KW, Gross M (2006) Astrobiology, 2nd edn. John Hopkins, Baltimore
Segré D, Ben-Eli D, Deamer DW, Lancet D (2001) The Lipid World. Orig Life Evol Biosph 31:119–145. doi: 10.1023/A:1006746807104
Smith PE, Evensen NM, York D, Moorbath S (2005) Oldest reliable terrestrial 40Ar-39Ar age from pyrite crystals at Isua west Greenland. Geophys Res Lett 32:1–4. doi: 10.1029/2005GL024066
Wächtershäuser G (1988) Pyrite Formation, the First Energy Source for Life: a Hypothesis. Syst Appl Microbiol 10:207–210.
Zhang X V., Martin ST (2006) Driving parts of Krebs cycle in reverse through mineral photochemistry. J Am Chem Soc 128:16032–16033. doi: 10.1021/ja066103k

Flagship Science on Main

We had our first-ever Science on Main in Downtown Mesa last Friday night.

To all small-business owners and entrepreneurs out there: I salute you. It's a scary thing to put together a network of people, organize an event, order a custom table runner and supplies, and have no idea if it is going to be worth the money and effort. Fortunately, the organizers at Second Friday make it easy and inexpensive to try out a pilot project like this. Thank you Second Friday, and thank you Arizona Museum of Natural History for loaning us some materials!

Here we go! It almost looks like we know what we're doing!

The anticipation is kind of making us flustered.

That said, we had a ton of folks come out and talk to us about some pretty cool topics! Some of our conversations ranged from stellar nucleosynthesis, to the origin of life, to shark rabies, to properties of ice and water. It was so much fun!

In addition to questions, we got some important feedback. One woman commented that she appreciated that we weren't on "a soapbox" with a lecture prepared. Some people were pretty surprised that we had nothing to sell or demonstrate, and that we're just giving away free knowledge. There were other scientists and engineers in the crowd on Friday that seemed inspired by the idea, so let's hope this project spreads! 

Other science people came to talk to us, too! It's always fun finding fellow science people running wild and out in the world (there are more out there than you think!).

Thank you Dr. Smith for taking pics! We were all too engrossed in discussions to think about documenting it ;-)

We had a great question later in the night that I wanted to re-iterate: "So what are you getting out of this? What's your agenda?"
We just think science is cool, and want people to know how cool (and understandable) it is. We want people to know that science experts are pretty regular people. We also want science experts to be more accessible, and be better communicators. That's it.

So, some of our lessons learned from our inaugural Science on Main:
1. People really seemed to like this idea.
     a) People have a lot of fun and interesting questions
     b) Sure, one can always Google an answer to a question, but talking to a real-live science person is more fun. Who knows where the conversation will go next?
     c) Chatting with people is way more engaging than a lecture or demo.
     d) Some people just want to hang and listen to us talk about stuff. By all means, do so!
2. We should probably bring in more experts
3. We should definitely do this again :-)

Most importantly, we want to thank all of the people that came by to see us on Friday. We hear you: this is worth it, and we'll keep bringing this back for you.

Fear not, we'll be out on January 12 in the same spot (in front of Pomeroy's).