Physical Sciences︱ The COOLscience Club Exploring the origins of life with autocatalytic sets How did we get here? ne of the most popular are still those in the fullerene family, This question has plagued theories about the beginnings which are strange, football-shaped philosophers, scientists and Oof our universe is the Big networks of carbon atoms, but even individuals alike for hundreds, Bang theory. This is the idea that the largest of these contains just the universe started as an infinitely 70 atoms. if not thousands of years. How did our complex chemistry evolve? The COOL Science Club explore questions around Evolved species, such as dense and warm point that suddenly the origin of life. humans, are incredibly complex violently expanded within just a few Fullerenes aren’t found everywhere. systems, even down to the fractions of a second. While the exact Many planets only have very simple microscopic cellular level, beginning of the universe, what molecules, composed of less than structures. Understanding how such in 1971. Later on, the theory was and understanding our own happened within the first trillionth of 10 atoms. So how did such simple sets work might not just give us a further developed by him and others, origins of life and how our Professor Stuart Kauffman and a trillionth of a second, still has many chemical building blocks come deeper understanding of the origins of with computational and experimental collaborators are working on the theory DNA came to be what we mysteries, scientists now have many together to create the complexity our life but pave the way to new living studies looking to investigate and of autocatalytic sets. know today is a challenging compelling models and evidence for and variety of chemical species technologies, that use such chemistry identify the chemical compounds question. The COOLscience what happened in the instants just we have on Earth, including the as part of their function and growth. necessary to form autocatalytic sets Club is an international after our universe was born. chemical compounds like DNA that for the creation of RNA, proteins RNA – NATURE’S DECODER collaboration investigating how are responsible for life? SELF-SUSTAINING CHEMISTRY or small organic molecules. Originally, the concept of autocatalytic the answer to this might lie in The beginnings of life as we know it, The concept of an autocatalytic set sets was a controversial one. One of self-replicating systems called however, are not so well established. Professor Stuart Kauffman, a retired but is a set of chemical reactions that form Now Professor Kauffman is working the dominant views in origin-of-life autocatalytic sets. Evolved life represents an incredibly still highly active biologist, is interested a self-sustaining network. As long as with a number of collaborators to research is the RNA world hypothesis. complex mixture of chemistry and in tackling exactly this question. There there is a basic food source, molecules take an interdisciplinary approach RNA is another type of nucleic acid like biology, with the whole human have been many competing theories DNA but, instead of storing all genetic genome containing an estimated on how complex life came to be, information as DNA does, RNA acts 204 billion atoms. For comparison, but he is interested in the role that Life is more than the sum of its more as a decoder, to read the genetic a water molecule contains just three. autocatalytic sets may have played information contained in the DNA and The largest molecules found in space in the formation of complex chemical constituent molecules. It depends convert it into actionable instructions on how these molecules interact for cells. with each other. In the RNA world hypothesis, RNA alone was initially responsible for within such a reaction network are to the problem of autocatalytic both the replication and expression of capable of mutually catalysing each sets. By combining methods from genetic information, meaning it would other’s formation. This means that chemistry, physics, mathematics, have to be capable of self-replication. individual molecules do not need biology and computer science, the Only recently has evidence of self- to be capable of catalysing their group aim to better understand replication in short RNA strands been own formation as this can be done the conditions necessary for an found, but there is no evidence (yet) by another molecule in the network. autocatalytic set to form and then how that RNA can catalyse its own template- The end result is a combined set of such sets can evolve and grow. Such directed replication so RNA could reactions that are fully self-sustaining. an explanation might not just hold the be replicated and express genetic answer for how primordial soup led information. Kauffman originally proposed the to RNA, DNA and complex cellular concept of autocatalytic sets and their life but could also inspire new self- If autocatalytic sets are instead potential role in complex evolution sustaining technologies. considered to be responsible for life, www.researchoutreach.org www.researchoutreach.org Some current and former members of the COOLscience Club. From left to right: of which other molecules – and a ‘food- Flamm, Kauffman, Hordijk, Szathmary, generated’ subset – which molecules Behind the Research Lehman, and Villani. can be created from the food source. This mathematical description paved XxDr WimXxxxxx Hordijk xxxxxx the way for more detailed theoretical and computational work and revealed E: [email protected] W: WorldWideWanderings.net two key things: how these sets could form spontaneously from a given food source, and how they could potentially evolve and diversify. These sets are Research Objectives References not just restricted to the reactions involved in the origins of life either. The Cooperative Origin Of Life (“COOL”) science Hordijk, W. (2019). A History of Autocatalytic Sets. Biological Groups have looked at the set of club investigates the origin of life, particularly with Theory. https://doi.org/10.1007/s13752-019-00330-w reactions involved in the metabolic autocatalytic sets. processes of particular archaea Hordijk, W., & Steel, M. (2017). Chasing the tail: The and bacteria, and examples of lab- emergence of autocatalytic networks. BioSystems, 152, 1–10. generated sets have been successfully https://doi.org/10.1016/j.biosystems.2016.12.002 constructed since the mid-90s. Detail Hordijk, W. (2019). How did life begin? Orbiter. https:// SUM OF PARTS Bio orbitermag.com/how-did-life-begin-part-1/ The origin of life is a complex An autocatalytic set is something where The COOLscience Club is an international and the system is truly greater than the sum interdisciplinary collaboration of scientists studying problem, requiring a highly of its parts. Even if you put all the cellular the origin and early evolution of life in terms of Personal Response components of bacteria in a solution, chemical reaction networks involving several different interdisciplinary approach. they will never spontaneously assemble types of molecules that cooperatively and collectively to have the capabilities of a bacterial are self-reproducing, rather than focusing on the What areas of autocatalytic sets will you be RNA does not need to be capable One of the key developments in helping cell. However, when all the components properties and synthesis of single molecule types. focusing on in your future work? of both regulation and self-expression. to establish the potential and power work together as part of this complex To have autocatalytic sets emerge and evolve However, some critics of the hypothesis of autocatalytic sets was the work network, a series of genetic information, Funding spontaneously in a controlled laboratory setting. This have argued that it is difficult to see how of Prof Mike Steel and Dr Wim Hordijk cell walls and so on suddenly become ATTRACT could be a prebiotically relevant setting to study the origin of life, or any other setting that results in the highly complex networks of reactions on a formal mathematical framework something highly sophisticated, https://attract-eu.com/ spontaneous synthesis of chemically or biologically could arise themselves spontaneously, to describe autocatalytic sets, known complex and living. “useful” products and reaction networks. or how the set could evolve and adapt as Reflexively Autocatalytic and Food- Collaborators without disrupting the fine balance of generated (RAF) theory. This helped to While the individual reactions in a COOLscience Club reactions needed for the set as a whole capture in a more mathematically formal set may not be particularly useful https://coolscience.club/ to function. Many agree, though, that way the potential ways autocatalytic in isolation or make the desired final even if such sets aren’t responsible for all sets could form by explicitly defining products of a reaction, combining of the origin of life, they are a plausible a ‘reflexively autocatalytic’ subset – their joint power with other chemistry explanation for initial RNA synthesis. which molecules catalyse the formation is key to unlocking their potential to synthesise complex life. As the underlying theory of autocatalytic sets laid out by Prof Kauffman and colleagues is fully extendable to larger networks, and is highly flexible and can be applied to any related problems, then it is possible to think of using this methodology to deliberately target the creation of certain molecular species. As part of an EU joint project, Prof Kauffman and colleagues are hoping to harness this theory, in collaboration with industrial partners, to identify potential reactions, sequence molecules and A small example of a (hypothetical) autocatalytic detect products. This research could set. Green dots are food molecules, black dots be used to not just identify the origins are reaction products, and white boxes represent chemical reactions. Dashed arrows indicate of life but also as a technological tool which molecules catalyse which reactions. for new types of automated synthesis.