Let us first postulate the problem of abiogenesis, what is it exactly? If one reads popular science articles such as this one https://www.sciencefriday.com/segments/spontaneous-generation/ one might get confused by a sentence such as this one:
>>“Spontaneous generation” was the idea that living organisms can spring into existence from non-living matter.<<
Being written by superficial evangelists of science of today, it is no wonder that it poses a question, at least to a reader who is not a native English speaker, how come was abiogenesis possible then, if that idea is wrong, and what does that sentence mean at all? To convey anything meaningful, it obviously relies heavily on the distinct meaning of the phrase "spring into existence", vs "come into existence", or "arise". The difference is that it means "arise suddenly", but the precise meaning of the word "suddenly", in that context was not given.
Wikipedia article https://en.wikipedia.org/wiki/Spontaneous_generation however gives another qualification of that distinction between abiogenesis and spontaneous generation:
"Spontaneous generation is a superseded scientific theory that held that living creatures could arise from nonliving matter and that such processes were commonplace and regular."
So, it is not just a question of dynamics of the process, how sudden one was not, the one that happened (abiogenesis), as opposed to the other one, that we know is impossible (spontaneous generation), it is a question of its spontaneity, regularity, reproducibility and repeatability. It is a statement similar to this: "nuclear fusion is a process that cannot happen spontaneously on the Earth, it can only be produced by human activity, as opposed to the Sun, where it happens regularly and spontaneously, due to its greater mass in comparison with the Earth".
So, once abiogenesis happened naturally in a primordial soup, the computation it performed, which consisted of navigating through a vast chemical space, in search of reactions to assemble nucleotides into nucleic acids and amino acids into proteins, via mutually dependent processes, that computation stopped in a phase transition like event, and these nutrients ("generic resources") became involved in processes that are regular in living organisms, such as reproduction and metabolism, using mechanisms derived during abiogenesis. The whole biomass of today is now assembled into material that is either built into living organisms, or once was built into those who died, and will imminently be built again into those who are alive, and thus not available to perform the previously mentioned computation. Which highly reduces the massive parallel computational power which primordial soup once had, and if you furthermore separate some tiny piece of that remaining free biomass into a laboratory experiment setup, and expect that it will spontaneously yield life, if you just wait a couple of years, this is probably not going to happen, as it is basically the equivalent of spontaneous generation, lacking resources such as time and computational power. But, the hypothesis is that if human explorers search more actively through that chemical space, they will be able to reproduce that process, just as they managed to produce nuclear fusion on Earth, bringing into action their intelligent agency, like no other animal can do. At least that is a hope of Lee Cronin, the inventor of the chemical Turing machine, intended to automate that search, and that is a core of the problem of abiogenesis as I understand it. I think that search problem is very, very hard, just as Lex Fridman thought when he asked here: https://www.youtube.com/watch?v=ZecQ64l-gKM&t=1144s
LF: "How hard is that?
LC: "I think it's really really easy"
LF: "OK, I did not expect that"
HDJ: ":-)"
James Tour must be thinking the same when he says the origin of life researchers should be held accountable for their claim that the solution of that riddle is imminent. I do not think I am creationist if I say that I believe in the hypothesis of abiogenesis, as a search problem in a chemical space, but that I would also rather know the exact answer instead of having to believe in any hypothesis. So, I share some opinions with both James Tour and Lee Cronin (for example, John von Neumann is my hero too). Besides that, if human race manages to deploy its intelligent agency to find the chemical path to abiogenesis, that is a weak proof that some kind of intelligent agency as we know it, in a narrower sense, was not involved in the original process, because although we ascribe computational power to the primordial soup, we still do not ascribe intelligence to it, that is cognitive capabilities of collective or centralized intelligence, and we still have to believe that primordial soup was able to do the same complicated chemical process by itself without any help, or maybe there already is a strong and strict proof for that, even before there is a weak proof produced in a laboratory?
Chat GPT thinks this:
Anyway, as I understood that I did not pay sufficient attention to the article I already linked to in my first essay, this one: Subcellular Life Forms , by John Baez, I studied it a bit more, and there I found information about this interesting experiment conducted by Sol Spiegelman who first described it in 1965. It was mentioned in that article that Paul Davies said that Spiegelman's results were spectacular at that time, but from his description I did not see why exactly. I learned it here: RNA Replicase and Spiegelman's "Little Monster" 1961-1969 that it was the first time that a piece of nucleic acid made in the test tube worked as well as the stuff made in nature. Plus, the RNA replicases that he managed to isolate in order to produce the RNA of two bacteriophages were template specific, so called RNA-dependent RNA polymerases, which was unknown concept at that time, when the mechanism of replication of RNA viruses was poorely understood, actually, at that time the sole existence of RNA virus itself was a new fact, and the first problem it posed was to find a mechanism of replication of RNA within the host cell. First idea was to investigate the possible reverse transcription of virus RNA code into bacterial DNA, but there was no evidence of that in that concrete case. However, direct RNA replicase hypothesis posed to Spiegelman another interesting problem, and for me personally hard to understand at a glance. Namely, if such enzyme exists (after being created using translational machinery of the cell), how does it find within the cell the molecule it is supposed to act upon, the one which coded for its synthesis? The bacterial cell is more than 100 times bigger than the virus, and its cytoplasm contains of the order of 10000 free RNA molecules of various sorts. If the RNA replicase was not selective, how would it do its job without disrupting the cell by random copying and making the search problem even worse? First question that appeared to me was how the same problem does not appear to DNA replication enzymes? How many DNA molecules are there in a human cell, could it be just one? Well, I soon found out it is not just one, in a nucleus of a human somatic cell there are exactly 46 molecules, and they can be found in specific places, so called chromosomes, so I guess this helps avoiding similar search problem. Plus, there is exactly one molecule in mitochondria, one type, but multiple copies of it may exist, and the number of copies may vary, according to David Thaler. Putting aside my digression, elucidating these points regarding RNA viruses adds to the significance of Spiegelman's work related to that experiment. After isolating the mentioned RNA replicases and presenting them with the original viral RNA and giving sufficient supply of nutrients, RNA of two phages (he first worked with MS2 and later with QBeta) were replicated in the test tube, then a small amount of the resulting RNA was taken and the experiment was repeated fifteen times, making sure that the original viral RNA is diluted out by transfers and practically non existent in the fifteenth tube. Then such artificially produced RNA was inserted into bacteria protoplasts and it produced viruses there just as good as natural RNA. Which does not surprise me now, when I read about it in 2021., however in 1965. that was great scientific news. Even more important than this, in further experiments, Spiegelman demonstrated that although template specific (in a sense that they do not copy just any template presented, they recognize only some, notably the natural original which coded for their synthesis in the cell using cell's translational machinery, plus its successors) replicases were not affected by shortening of the original natural RNA template (in their ability to copy its shortened successors), which happened (the mentioned shortening) due to a suppresion of copying error correction mechanisms in the artificial environment. If such shortened RNA was introduced into the bacterium cell, it would not be able to produce viruses there, as it is missing some important parts such as those that code for the protein coat, for the replicase itself, and for its error correction enzymes. However, that does not prevent it from being replicated in the artificial environment, and actually outnumber the original functional RNA. Why shortened templates were favoured by the replicase was intriguing to Manfred Eigen who continued to work on this problem (Eigen’s paradox, shortly stated: without error correction enzymes, the maximum size of a replicating molecule is about 100 base pairs, for a replicating molecule to encode error correction enzymes, it must be substantially larger than 100 bases) formulated within his theory of quasispecies, and proposed a solution in the form of hypercycles. The fact that it inspired Eigen to do that, adds to the significance of Spiegelman’s experiment. Now that I mentioned Eigen's theory, I should also mention Cronin’s too, here is a wikipedia article on his assembly theory. It is somewhat related, but not entirely, this is about complexity of molecules, while Eigen's is about their autocatalytic capabilities.
Let us analyze now precisely how the replication exhibited by the Spiegelman artificial system does not resemble the one which exists in living systems, which is described by von Neumann replicator vehicle model. In living systems, DNA codes for all enzymes (which are mainly proteins, except for ribozymes, which are RNA), some enzymes (let’s call them C) catalyze copying of DNA, others (let’s call them B) catalyze synthesis of everything else, including B, C, and the rest of the cell (which is also coded for by DNA). Such a mutual support of DNA and enzymes provides self reproductive autocatalytic capability that is the essence of life and that does not exist in Spiegelman’s case. There is an enzyme produced in a cell and isolated from there, so that RNA coding for that enzyme becomes irrelevant in the artificial environment, as enzyme is not produced there, the only relevant feature of the system is that enzyme catalyzes copying of RNA. As Spiegelman pointed out himself, quickly dismissing newspaper stories about his experiment, this class of experiments that takes substrates from a living object, and shows their funcionality in vitro that is limited in comparison with functioning of living organism, can not solve directly the problem of abiogenesis, which can be formulated as discovering the chemical pathway/route (network or sequence of chemical reactions) from nutrients alone to the system that exhibits von Neuman accurate self reproducing capability. Regardless of all its merits, this experiment does not reveal how did that happen, we still don’t know exactly how RNA world appeared and worked, and how it was transformed into DNA world, which means that the problem of abiogenesis remains unsolved. In fact, the requirement in such a formulation of the problem is already heavily loosened if one does not take seriously into account the implicit requirement that the replicator is supposed to code for “the rest of a functioning cell”, which encompasses all other essential life functions, other than self replication. It is expected that the constructed self replicating system eventually evolves to that state, otherwise abiogenesis as we know it is not actually reproduced. How complex task that is, can be illustrated by a minute detail related to the self replication, the mentioned replicator is actually not a single object located at one place in the cell, as already mentioned, DNA exists in nucleus and in mitochondria, and in the cells of extant organisms, the vast majority of the proteins present in the mitochondria (numbering approximately 1500 different types in mammals) are coded for by nuclear DNA, but the genes for some, if not most of them are thought to have originally been of bacterial origin, having since been transferred to the eukaryotic nucleus during evolution, while mitochondrial DNA (the other part of replicator) altogether encodes for two rRNAs, 22 tRNAs, and 13 protein subunits, all of which are involved in the oxidative phosphorylation process. Furthermore, mitochondrial mRNA (encoded in mitochondrial DNA) is translated in mitochondrial ribosomes (a ribosome is made out of RNA and proteins), and while mitochondrial rRNAs are encoded in the mitochondrial genome, the proteins that make up mitoribosomes are encoded in the nucleus and assembled by cytoplasmic ribosomes before being implanted into the mitochondria. So there are not only two distinct and separate replicators, but also two different types of translation machines, mitochondrial and cytoplasmic ribosomes, and all of this from the engineering point of view looks far from optimal, but it works, and is necessary to be reproduced in order to produce such complex organisms as eukaryotic are. And it is a result of symbiosis of archaeal and bacterial cells in RNA-based entity (member of extinct perhaps pre-cellular lineage) to create the first eukaryote, as is widely believed.
Another class of experiments that has somewhat different purpose in the field of the origin of life are those that show the chemical pathway to some important classes of organic compounds in prebiotic conditions, that is from inorganic compounds and from those organic compounds for which such pathway is already found, without strict focus on their functioning, ie do they achieve von Neuman self reproducing capability or not. The classic in this area is Miller-Urey experiment from 1952., which showed synthesis of amino acids from simple precursors such as water, methane, ammonia and hydrogen. This experiment inspired multiple further ones, for example (quote from https://en.wikipedia.org/wiki/Miller–Urey_experiment):
>>There is abundant evidence of major volcanic eruptions 4 billion years ago, which would have released carbon dioxide, nitrogen, hydrogen sulfide (H2S), and sulfur dioxide (SO2) into the atmosphere. Experiments using these gases in addition to the ones in the original Miller–Urey experiment have produced more diverse molecules.<<
Another experiment in this class, by Stolar, Grubešić, Cindro, Meštrović, Užarević and Hernández, described here: Mechanochemical Prebiotic Peptide Bond Formation builds on the premise of a presence of amino acids on the prebiotic Earth, and investigates prebiotically plausible mechanochemical pathways to achieve peptides from unactivated amino acids, in the absence of bulk water (or solvents) and at ambient temperature or at increased temperature.
Being a layman in this area, it is hard for me to judge on how hard is the problem addressed by a second class of experiments, being able to make such a classification on my own is already an achievement for me (if that classification is sensible at all in the first place), so I will just list a few more papers I have studied in preparation for this essay, in no particular order:
and get back to comment that the first problem obviously looks particularly hard. If that was not the case, the tree of life would have multiple roots, new ones appearing every now and then, but the empirical fact is that this does not happen. Not only abiogenesis cannot be “skipped” by spontaneous generation, it also cannot be easily reproduced, neither in nature nor in laboratory, without gaining much more knowledge than people currently have. As for why it does not happen naturally again, it may be that certain conditions are not favourable any more, presence of existing living organisms may be one of them, but precise explanation is still unknown. And the mentioned knowledge is both practical, such as the exact laboratory procedure for reproducing the same process of abiogenesis as it happened once in the past, as well as theoretical, for example answering the question is it the only form of life possible, or can it be developed on a different chemical basis?
Anyway, common sense tells me that any chemical pathway that is not sufficiently hard to find and reproduce is not a good candidate solution for the problem of abiogenesis.
Comments
Post a Comment