What Progress Can We Expect in Understanding the Origin of Life, Over the Next 10-20 Years?
Given the unprecedented progress in Origins research over the past decade, this is a good time to speculate on what we hope to achieve over the next decade or two. This essay accompanies the “Critical Questions” essay above that summarizes the seven big questions that we would like to answer to achieve a reasonable understanding of how life emerged on our planet and more generally how common or rare Life might be in our Universe. Here, we take a critical look at these large scale questions and our current level of understanding, and ask what progress we might expect over the next ten to twenty years in answering these questions. There are some questions that we can be very confident of answering over the next few years, while it is equally clear that there are larger questions, notably the prevalence of Life in the Universe, that may take many decades to answer. Our hope is that this essay will help to stimulate the conversations between people in different disciplines that are necessary for unexpected insights and advances to arise.
From Astrochemistry to Exoplanets
This is going to be an exciting decade of surprises from the new generation of space and land-based telescopes. JWST will provide both an expanded statistical picture of exoplanet distributions, as well as much more detailed characterizations of the closest and most interesting of these distant planets. At the same time, data from ALMA will continue to expand our understanding of the chemistry of protoplanetary disks and the physical processes that result in planet formation. As the next generation of telescopes and instruments come online, we can expect to gain a much more detailed understanding of the path from cold interstellar molecular clouds to protoplanetary disks to planets. Better models, constrained by much improved observations, will help us to understand the surprising diversity of planetary systems, as well as giving us insight into the frequency of planets with the potential to give rise to and maintain life.
Despite the flood of incoming data, unless we are very lucky we may still have to wait for some time to find and study truly Earth-like planets orbiting sun-like stars. While we can be confident that the coming decades will see the development of the improved technology required to detect life ‘out there’, the search for life on exoplanets is likely to continue for the foreseeable future. That said, one short-term goal – characterizing the redox state of exoplanet atmospheres of large rocky Earth-like planets (Super-Earths) is technically possible with JWST. This will be valuable for understanding the fundamental processes that drive the state of Earth’s and Mars’ surface conditions over their history. Such understanding is crucial to calculating model fluxes of UV penetration and other surface variables in synergy with lab experiments, as described in “Prebiotic Chemistry” below.
Prebiotic Chemistry
The past decade has seen a revolution in our understanding of prebiotic chemistry. Together the cyanosulfidic and carboxysulfidic photoredox reaction networks provide pathways from simple and plausible feedstocks such as cyanide and CO2 to the building blocks of biology including the nucleotides, amino acids and many key metabolic intermediates. However, we are only half way done: we still have only a marginal understanding of fatty acid and lipid synthesis, purine nucleotide synthesis remains unclear, and perhaps most important of all, activation chemistry remains a puzzle. These very specific questions are the focus of intense research, and it is highly likely that they will be answered over the coming decade if not sooner.
Beyond completing the basic reaction pathways needed to supply the building blocks of life, what’s next? It is clear that further progress will involve going beyond having a set of pathways that give high yields in the laboratory to developing an understanding of how this chemistry might work in the real world. Addressing the complexity and variability of the real world requires detailed modeling combined with experimental constraints to paint a picture of how prebiotic chemistry might play out on the surface of the early Earth. For example, the use of calculated fluxes of UV radiation at the surface, as a function of wavelength and atmospheric composition, helps to define the conditions under which postulated photochemical processes could actually take place. Similarly, we have demonstrated pathways leading to homochirality, and the next step is to show how this could occur in nature. This kind of work is still in its infancy, so we can expect that much will be learned in the coming years.
Protocells: First Life
Over the next five years, we can expect to see the development of an experimental system in which a population of protocells undergo indefinite cycles of genome replication along with compartment growth and division. While incomplete, our current understanding of both RNA copying chemistry and protocell growth and division is clearly adequate to enable laboratory studies of cycles of protocell reproduction. The use of a flow system will allow for the delivery of nutrients including activated nucleotides, membrane lipids and other small molecules, as well as facilitating the exploration of appropriate environmental fluctuations. Such a protocell model system will allow, for the first time, experimental studies of the evolutionary dynamics of replicating protocells. It may even be possible to observe the spontaneous evolution of novel ribozymes that provide a selective advantage to host protocells, although this may well require a longer time frame.
The first replicating protocell systems will be proof-of-principle models that are unrealistic from a prebiotic perspective. However, learning from the constraints required to achieve replication will inform efforts to model protocell reproduction in more realistic geochemical environments, and over the following five or more years, it should be possible to converge on a plausible scenario for the origin of the first cells on the early Earth. In the longer term, it may even be possible to identify more than one class of environments with the potential to give rise to life.
The Transition From Protocells to More Complex Cells
We are currently in the very early stages of understanding the evolutionary transitions that led from prebiotic chemistry and simple replicating protocells to much more complex cells, with their subsystems of metabolism, coded protein synthesis and electrochemically controlled membrane transport and energy generation. We can already see the first hints of progress in understanding the puzzle of translation, and it is likely that a more complete understanding of the origin of ribosomal protein synthesis will develop over the coming decade. In contrast, our understanding of the origins of cellular metabolism is negligible. However, by building on our growing knowledge of prebiotic chemistry and protocell reproduction, it will soon become possible to think about a step by step accumulation of genetically encoded catalysts, with each new ribozyme or peptide contributing to cellular fitness. We already know that ribozymes are good at catalyzing phosphoryl and acyl transfer reactions, so exploring how sets of ribozymes could enhance nucleotide, peptide and lipid synthesis may provide an entrée into understanding the gradual evolution of intracellular metabolism. The evolution of acyl-transferases that generate more robust membranes will both allow for intracellular metabolism and require the evolution of simple membrane transporters, presumably peptide based. Experimental exploration of the origins of membrane transport will be possible in the coming decade, but whether this will shed light on how trans-membrane proton gradients were first harnessed for ATP synthesis is impossible to predict at this point.
The Planetary Context
To really understand how both prebiotic chemistry and protocell propagation could occur on the early Earth we need to know the geological environments that would have been available and the corresponding geochemical and geophysical constraints. Earth’s earliest geological record has been largely erased by plate tectonics, but recent exploration missions to Mars have provided important constraints on how surface environments on young rocky planetary bodies like the early Earth would have behaved. Additional progress on this front continues to be driven by the feedback between laboratory experiments and modeling of environments. For example, if a critical reaction requires UV light, or formamide as a solvent, or if RNA replication requires a flow of fluctuating composition, we have to think about how these constraints could be met in a realistic environment. Conversely, if certain environmental scenarios can be shown to be plausible while others can be ruled out, we must look for chemistry that works under realistic conditions. As our understanding of realistic constraints sharpens, this feedback mechanism points us to surprising solutions to seeming insoluble problems. This is why we are optimistic that a set of geochemical scenarios that will drive the sequential stages of prebiotic chemistry and protocell assembly and propagation will be worked out in the coming years. Indeed, progress has been accelerating, as seen by recent solutions to problems such as the accumulation of cyanide and the availability of phosphate. We expect that geochemical solutions to fatty acid synthesis, activation chemistry and other apparent bottlenecks will emerge in the coming years.
An important higher order question is how many distinct environments are required in order to go through the series of steps on the path from cyanide to life, and under which geological scenarios could these have been linked together? For example, the thermal processing of ferrocyanide salts is clearly incompatible with the accumulation of a reservoir of crystalline RAO, which must also occur in a distinct environment from the fluctuating fluid flows required for protocell propagation. We can expect significant progress in defining the requisite environments and time scales for individual steps on the pathway to life. However, linking these individual steps together in a realistic series of events occurring in different locations and at different times may be much more challenging, but is precisely what is required to give insight into the origin of life.
Evolution of Life in the Universe
We are at a crucial transition in terms of understanding whether life may or may not exist outside our Earth. Over the coming decades the number of exoplanets with resolved atmospheric spectra will mean that we may be able to start moving beyond our n = 1 of life, and onto populations of (bio)spheres. Exoplanets may therefore provide opportunities to understand biological evolution that can never be possible with a single history of life. The drivers of the major biological evolutionary transitions and the inevitability of their sequence remains uncertain. Yet, because each transition phase has different biosignatures, by comparing predictions with exoplanetary atmospheres, we may be able to assess the frequency with which complex biospheres emerge on other planets. These comparisons have the potential to constrain the universality of the timing and nature of major evolutionary transitions, shedding light on key aspects of Earth’s own evolution, and our understanding of the fundamental nature of biology.
Closer to home there are multiple ongoing or planned missions to other planetary bodies with either present or past conditions potentially suitable for life. These offer exciting opportunities to consider origins of life chemistry in environments either quite similar to the early Earth (Mars), or quite distinct (Europa, Enceladus and other outer Solar System objects). Several of these bodies will be searched for signs of present or extant life in the coming decades. If life is discovered, this will provide invaluable clues to how chemistry is transformed into organisms, and if it is not, we will obtain new constraints on the prebiotic chemical evolution.
Conclusion
Based on the arguments presented above, it is likely that over the next 10-20 years the outlines of a continuous pathway for the origin of life will emerge, beginning with planet formation, and proceeding through prebiotic chemistry to the emergence and early evolution of life. Although the challenges involved are still great, the field is poised for almost explosive development: questions that have puzzled humanity for millennia will in fact be answered in the next two decades. Of course, this can only happen if there is support for the diverse community of scientists who are dedicated to tackling the puzzles of the Origin of Life. Philanthropic support is especially important for young scientists who want to become or remain active in this field. Most modern techniques also require expensive instrumentation and computational resources, which are often difficult to access. However, with enough long term support from Foundations to maintain continuity of effort, there is no doubt that this is the unique time in history in which we will finally understand our own Origins and our place in the Universe.