1 Research Paper 2 A Natural Origin-of-Life: Every Hypothetical Step 3 Appears Thwarted by Abiogenetic Randomization 4 by Timothy R. Stout, George Matzko https://osf.io/p5nw3 5 [email protected] [email protected] Copyright by the authors 6 This is a preprint and has not been peer reviewed. Open Access under CC0 1.0 7 Keywords : abiogenesis; natural selection; systems chemistry; discontinuity; Virchow; entropy; abiogenetic 8 disconnects; dynamic self organization 9 Abstract 10 Prebiotic processes naturally randomize their feedstock. This has resulted in the failure 11 of every experimentally tested hypothetical step in abiogenesis beginning with the 1953 12 Miller-Urey Experiment and continuing to the present. Not a single step has been 13 demonstrated which starts with appropriate supply chemicals, operates on the chemicals with 14 a prebiotic process, and yields new chemicals that represent progress towards life and which 15 can also be used in a subsequent step as produced. By contrast emergence of life requires this 16 from every step. Instead, the products of thousands of experiments over more than six 17 decades consistently exhibit either increased randomization over their initial composition or 18 no change. We propose the following hypothesis of Abiogenetic Randomization as the root 19 cause for most if not all of the failures: 1) prebiotic processes naturally form many different 20 kinds of products; life requires a few very specific kinds. 2) The needs of abiogenesis 21 spatially and temporally are not connected to and do not change the natural output of 22 prebiotic processes. 3) Prebiotic processes naturally randomize feedstock. A lengthy passage 23 of time only results in more complete randomization of the feedstock, not eventual provision 24 of chemicals suitable for life. The Murchison meteorite provides a clear example of this. 4) 25 At each hypothetical step of abiogenesis, the ratio of randomized to required products proves 26 fatal for that step. 5. The statistical law of large numbers applies, causing incidental 27 appearances of potentially useful products eventually to be overwhelmed by the overall, 28 normal product distribution. 6) The principle of emergence magnifies the problems: the 29 components used in the later steps of abiogenesis become so intertwined that single-step first 30 appearance of the entire set is required. Small molecules are not the answer. Dynamic 31 self-organization requires from the beginning large proteins for replication, metabolism and 32 active transport. Many steps across the entire spectrum of abiogenesis are examined, 33 showing how the hypothesis appears to predict the observed problems qualitatively. There is 34 broad experimental support for the hypothesis at each observed step with no currently known 35 exceptions. 36 Keywords: abiogenetic disconnects; emergence; abiogenesis; natural selection; systems 37 chemistry; discontinuity; Virchow; entropy; randomization; dynamic self-organization 38 1. Introduction 39 1.1 Overview 40 In 1953 Stanley Miller and Harold Urey reported an experiment that successfully 41 converted certain simple, naturally occurring compounds—methane, ammonia, hydrogen, 42 and water—into various amino acids [1]. Amino acids are the building blocks of life. It 43 appeared that natural processes were sufficient in themselves to provide the chemicals 44 needed for a natural, spontaneous origin of life. The ensuing excitement was so great that it 45 set off a new field of scientific study, initially called chemical evolution and now more 46 frequently called abiogenesis. Sara J. Walker et al , in the British Royal Society’s publication 47 Philosophical Transactions A , commented on the reactions to the experiment, “There was 48 some optimism that, had the experiment been left running, living creatures would soon be 49 crawling out of the laboratory [2].” 50 It has been over sixty years since Miller and Urey reported their results. However, the 51 results have not come close to living up to these early expectations. Not a single experiment 52 representing a hypothetical step in abiogenesis has successfully yielded product suitable for 53 use in its successor. 54 Steve Benner is the founder and president of the Westheimer Corporation, a private 55 research organization, and a prior Harvard University professor. He is one of the world’s 56 leading authorities on abiogenesis. This is his evaluation of what he has observed: 57 We are now 60 years into the modern era of prebiotic chemistry. That era has produced 58 tens of thousands of papers attempting to define processes by which “molecules that look 59 like biology” might arise from “molecules that do not look like biology” …. For the most 60 part, these papers report “success” in the sense that those papers define the term…. And 61 yet, the problem remains unsolved [3]. 62 As we study the various stages of abiogenesis and hear about all of the optimism, it is well to 63 keep Benner’s comments in mind. There is still not a plausible scientific explanation for the 64 origin of life. 65 We suggest the following hypothesis explains the root cause of most if not all of the 66 observed failures in abiogenesis over the entire 60 plus years of its modern research activity. 67 2. We hypothesize: 68 1. Product Possibilities. At each hypothetical step of abiogenesis prebiotic processes at 69 work in that step will be capable of forming a significantly larger number of products 70 than are suitable for an advance towards the appearance of living cells. 71 2. Abiogenetic Disconnects. There is no connection between the natural products of 72 prebiotic processes at a given step and the principles of biology and biochemistry that 73 determine which products need to be provided for use spatially and temporally. 74 3. Randomization. Prebiotic processes are inherent randomizers. They tend to provide a 75 random assortment of possible products according to a natural statistical distribution. 76 Products suitable for life may appear on an incidental basis, but not systematically at 77 higher yield than the natural distribution. Lengthy, extended spans of time for 78 abiogenesis result in greater randomization of initial feedstock, not biochemicals. 79 4. Fatal Ratios. Because of randomization the ratio of wrong products provided at each 80 step to those that are required for an advance towards life will be large enough to prevent 81 any given step from successfully providing usable feedstock to its successor. This is the 82 ultimate cause of the consistently failed steps and experiments in abiogenesis. 83 5. Law of Large Numbers. The statistical law of large numbers applies to prebiotic 84 processes. A single mole of a given compound contains 6 x 10 23 instances of the 85 compound. This is a large number. In abiogenesis there will be a natural distribution of 86 possible products for the outcome of a given set of conditions and processes. 87 Fluctuations within the distribution are normal, but the larger the total number of 88 instances worked on, the closer the average distribution yielded comes to the natural 89 distribution. This effectively neutralizes the significance of incidental deviations. 90 6. Emergence. The principle of emergence can exponentially compound the difficulties 91 of the above assertions, particularly in later hypothetical steps towards the appearance of 92 living cells. 93 These assertions are not difficult to understand. Neither is their application. Yet, they 94 lead to conclusions with far reaching implications. Their simplicity and their ease of 95 application to a given scenario make the hypothesis a powerful tool. 96 Two generations of consistent failures without a single success should tell us that 97 something is fundamentally wrong with current foundational premises. We suggest that the 98 above hypothesis explains the problem. The assertions represent fundamental properties of 99 nature and any and every hypothetical step appears to be affected by them. In the Analysis 100 section to follow, we will look at a number of the major proposed steps to see if the 101 hypothesis provides a qualitative prediction/explanation of the outcome of experiments 102 associated with the steps. Over the past sixty years, there have been reputedly thousands of 103 experiments performed representing various postulated steps. None have been able to 104 provide product usable as feedstock for its successor, which is the standard defining success 105 within this analysis. The vast number of already performed experiments provides a 106 substantial base for evaluating the validity of the hypothesis. 107 3. Discussion on the hypothesis 108 3.1 Product possibilities 109 Carbon, nitrogen, oxygen, hydrogen, sulfur, and phosphorous are the primary elements 110 used in living cells. There are virtually an unlimited number of compounds that can be made 111 using all or some of the possible combinations of these elements. The Beilstein Database lists 112 over seven million organic compounds by their names and characteristics. Isomers are treated 113 as separate entries. Polymers are not included. Along the same lines the Murchison meteorite 114 contains over a million different organic compounds when isomers are included in the count 115 [4]. Isomers are properly treated as separate chemicals because they are not interchangeable 116 among themselves within proteins and nucleic acids. 117 The Murchison meteorite provides a true-life instance of prebiotic processes at work on 118 initial compounds without any kind of interference or guidance. An initial feedstock 119 plausibly consisting of only a handful of simple compounds was converted into over a 120 million variants. By contrast, most of cellular chemistry is based on proteins and nucleic 121 acids, which are built from a feedstock of twenty-eight kinds of building block 122 molecules—twenty canonical amino acids (coded for in DNA), four kinds of RNA 123 nucleotides, and four kinds of DNA nucleotides. Abiogenesis requires large, pure quantities 124 of these 28 molecules to the exclusion of most others.