Amino acids are common enough -- glycine has been found in comets and, controversially, even in the interstellar medium. Other amino acids have also been found in comets.
It's also presumed that cometary ice bombardment is the source of Earth's surface water, as ice or water present any earlier would have boiled off when the planet was young and hot.
It's not much of a stretch to imagine that comets brought amino acids, organic compounds, and minerals to Earth as they were bringing water ice. A lot of those aminos and organics would turn into tar, but some would be protected from UV radiation by that same tar. With a heat source, maybe some lightning strikes, a good location, and a lot of luck, you get RNA...
What we can't yet do is assign a probability or likelihood to this process. But the ingredients should be common enough.
About a half of the amino acids used in proteins, i.e. ten of them, can form easily in abiotic conditions and they are widespread in some celestial bodies.
They are easily distinguished from terrestrial contaminants, because they are a mixture of left-handed and right-handed isomers.
When analyzing the genetic code in order to determine which amino acids have already been used in the earlier versions of the genetic code and which have been added more recently, the same simpler amino acids that are easy to synthesize even in the absence of life are also those that appear to have been the only amino acids used earlier.
The article contains the phrase "Given the fact that the current scenario is that life on Earth started with RNA".
This is a fact that it is too often repeated like if it were true, when in reality one of the few things that can be said with certainty about the origin of life is that it has not started with RNA.
What must be true is only that RNA had existed a very long time before DNA and DNA has been an innovation that has been the result of a long evolution of already existing life forms, long before the last ancestor of all living beings that still exist now on Earth.
On the other hand, proteins, or more correctly said peptides, must have existed before any RNA. Moreover, ATP must have existed long before any RNA.
RNA has two main functions based on its information-storage property: the replication of RNA using a template of RNA (which was the single form of nucleic acid replication before the existence of DNA) and the synthesis of proteins using RNA as a template.
Both processes require complex molecular machines, so it is impossible for both of them to have appeared simultaneously. One process must have appeared before the other and there can be no doubt that the replication of RNA must have appeared before the synthesis of proteins.
Had synthesis of proteins appeared first, it would have been instantly lost at the death of the host living being, because the RNA able to be used as a template for proteins could not have been replicated, therefore it could not have been transmitted to descendants.
So in the beginning RNA must have been only a molecule with the ability of self replication. All its other functions have evolved in living beings where abundant RNA existed, being produced by self replication.
The RNA replication process requires energy and monomers, in the form of ATP together with the other 3 phosphorylated nucleotides. Therefore all 4 nucleotides and their phosphorylated forms like ATP must have existed before RNA.
ATP must have been used long before RNA, like today, as a means of extracting water from organic molecules, causing the condensations of monomers like amino acids into polymers like peptides.
The chemical reactions in the early living forms were certainly regulated much less well than in the present living beings, so many secondary undesirable reactions must have happened concurrently with the useful chemical reactions.
So the existence of abundant ATP and other phosphorylated nucleotides must have had as a consequence the initially undesirable polymerization and co-polymerization of the nucleotides, forming random RNA molecules, until by chance a self-replicating RNA molecule was produced.
Because the first self-replicating RNA molecule did not perform any useful function for the host life form, but it diverted useful nucleotides from its metabolism, this first self-replicating RNA molecule must be considered as the first virus. Only much later, after these early viruses have evolved the ability to synthesize proteins, some of them must have become integrated with their hosts, becoming their genome.
The catalytic functions that are now performed mostly by proteins, i.e. amino acid polymers that are synthesized using an RNA template, must have been performed earlier by peptides, i.e. typically shorter amino acid polymers that are synthesized without the use of RNA templates.
Even today, all living beings contain many non-ribosomal peptides, which are made without RNA, using processes that are much less understood than those that involve nucleic acids.
The difference between a living being that would be able to make only non-ribosomal peptides and one that makes proteins using RNA templates is pretty much the same difference as between a CPU with hard-wired control and a CPU with micro-programmed control, with the same advantages and disadvantages.
Life forms able to reproduce themselves must have existed before the appearance of the nucleic acids, but they must have been incapable of significant evolution, because any random change in the structure of the molecules that composed them would have been very likely to result in a defective organism that would have died without descendants. This is similar with a hard-wired control, where small random changes in the circuits are unlikely to result in a functional device.
On the other hand, once the structure of the enzymes was written in molecules of nucleic acids, the random copying errors could result in structures very different from the original structures, which could not have been obtained by gradual changes in the original structures without passing through non functional structures that could not have been inherited.
So the use of molecules that can store the structural information of a living being has enabled the evolution towards much more complex life forms, but it cannot have had any role in the apparition of the first life forms, because the replication of any such molecule requires energy that can be provided only by an already existing life form.
>On the other hand, proteins, or more correctly said peptides, must have existed before any RNA
How come? It seems you can have reproducing RNA without protein needed. Here's Gerald Joyce talking briefly about making those https://youtu.be/aBrYsFeeVzE?t=171
Reproducing RNA without proteins has nothing to do with the necessity of peptides/proteins existing before any RNA.
Polymerizing nucleotides into RNA requires energy and monomers that can be provided only by an already living being with a functional metabolism.
That requires enzymes for catalyzing the chemical reactions that compose the metabolism, which must have been non-ribosomal peptides, before the existence of nucleic acids.
The main source of energy for the first life forms must have been the conversion of free hydrogen (dihydrogen) and carbon monoxide and/or dioxide into acetic acid (acetogenesis). An auxiliary source of energy could have been the gradient of ions that exists in hydrothermal vents. Both sources of energy have their origin in the oxidation of volcanic rocks by water, and the energy comes ultimately from the internal heat of the planet (because the volcanic rocks formed at high temperatures, where they are in chemical equilibrium, are no longer in chemical equilibrium in the presence of water after they cool to lower temperatures). At least for now, there is no known mechanism for the appearance of life elsewhere than on a planet with water, internal heat and volcanism.
Some people see that simple organic substances can form in any place in the cosmic space where there is not enough oxygen to oxidize them, so they assume that perhaps life could appear there. However that is wrong, because without a continuous source of energy all those organic substances will stay dead forever. The only suitable continuous source of energy is the internal heat of big enough planets, which will not cool quickly, because capturing the energy of stellar light requires very complex structures that cannot be generated spontaneously, but they can be only the result of a long evolution of already existing life forms.
>>>Some people see that simple organic substances can form in any place in the cosmic space where there is not enough oxygen to oxidize them, so they assume that perhaps life could appear there.
LUCA is considered anaerobic - any contact with oxygen would have killed it. However we do not know what were preRNA Life forms.
>>>However that is wrong, because without a continuous source of energy all those organic substances will stay dead forever.
Unless they are getting frozen and put on pause, like all the stable chemical ingredients can exist in your household.
>>>The only suitable continuous source of energy is the internal heat of big enough planets, which will not cool quickly, because capturing the energy of stellar light requires very complex structures that cannot be generated spontaneously, but they can be only the result of a long evolution of already existing life forms.
The only known life, that is known to me that can process stellar light are plants and animals, that have eaten plants and are getting sugar from their cells, that are integrated into their organism.
I am not sure what this text was compiled together from, but most of chemical processes that are happening on any planet does not require any stellar light. Initially all of matter was part of a Sun and when it went Supernova, it involved some stellar light, but after that, no need for that.
>>>The main source of energy for the first life forms must have been the conversion of free hydrogen (dihydrogen) and carbon monoxide and/or dioxide into acetic acid (acetogenesis). An auxiliary source of energy could have been the gradient of ions that exists in hydrothermal vents. Both sources of energy have their origin in the oxidation of volcanic rocks by water, and the energy comes ultimately from the internal heat of the planet (because the volcanic rocks formed at high temperatures, where they are in chemical equilibrium, are no longer in chemical equilibrium in the presence of water after they cool to lower temperatures). At least for now, there is no known mechanism for the appearance of life elsewhere than on a planet with water, internal heat and volcanism.
This also looks like something compiled from different thoughts. But, ok - in terms of Life originating on the planet, this is only more or less applicable to evolutionary stage of Life, that happened on our planet in thermal vents, and only when planet was stable enough for a Life to exist there as we have no idea if Life was on our planet already, before Theia merged into our planet and destroyed everything organic, which seems to have been the case.
But the issue here is not so much if Life originated on our planet, but where all the previous organic forms evolved, which are considered much older than our planet and primordal soup that is needed to create Life simply could not have happened in thermal vent like you are supposing.
From what I have read, comets are excellent places for primordal soup to happen as one of the prerequisites for a Life. Whenever they are approaching Sun, there is water boiling and all the processes that are similar to what thermal vents would have, but with light in addition and plentiful of resources for Life to spring. Like I mentioned earlier, freezing over would not reverse chemical processes that ere happening during that boiling and in next approach they would continue and there is basically indefinite time for those cycles to happen and disperse whatever end products that were happening on comets whenever they were passing plants - not to mention if they would land on them. There is life, that can exist in atmosphere, so there is actually no need for a comet to hit a planet to disperse product from their primordial soup. So, generally comets are one of the stages for prereq of Life, where explosion of Suns to disperse their thermonuclear product is previous stage. There seems to be impossible for Life not to appear the way how Universe functions.
PS I am not challenging RNA stuff, but Life also includes preRNA Life, so while your POV in regards to RNA based Life seems to be ok, everything outside of those boundaries are not ok.
Awesome post and thanks for writing this out - probably the most insightful piece I’ve read on plausible origin of life through pre-RNA autocatalytic peptides. Would you be willing to share a contact email / online profile? (could edit afterward to delete if you are worried about spam from crawlers)
sorry if I missed it, but it sounds like you've just pushed the mystery one step back but still ended up with the same mystery - where did the original Titan species come from? is there any evidence for their existence other than your belief that an RNA replicator would have needed a host cell? would this host cell have been built out of lipid bilayers? what would its inside mechanisms be made of - if not protein or RNA?
Ultimately science always terminates in so-called brute facts. I'm not sure it always makes sense to call these mysteries. In the end, some things appear to simply be without any sort of causal or even logical explanation. I try not to get too worked up about it.
On the other hand, one has to keep kicking over rocks to see what is underneath or life would get boring.
It is not certain that the first living beings consisted of cells. This is actually very unlikely.
The very first living being that was able to reproduce itself could not have had a closed cell membrane, because that cannot function without pores and pumps provided by peptides/proteins, which control the exchange of substances through the membrane.
The very first self-reproducing chemical system is likely to have been an open structure formed by organic substances attached to the surface of a mineral containing the catalysts for the metabolic reactions, e.g. an iron sulfide impurified with nickel and cobalt.
There is a hypothesis, which seems very plausible, that before the appearance of closed cells, the living beings consisted of discoidal fatty membranes with peptides attached to them, which obstructed pores in minerals located in hydrothermal vents, where the environment provided a flux of ions equivalent with the flux of ions that must be provided by ionic pumps in any closed living cell.
It is likely that only after the development of active trans-membrane ionic pumps, it became possible for living beings to take the form of free closed cells, unattached to minerals.
It is not clear which happened first, the transition to free closed cells or the apparition of self-replicating RNA.
The first membranes must have also been formed by molecules with hydrophobic and hydrophilic parts like the present lipid bilayers. However the molecules must have been different and simpler. Perhaps the first membranes were made just of free fatty acids, but with short chains. They certainly must have been much more permeable than today, to allow the passing of some molecules for which there were not yet adequate transporters. In any case, the phospholipids that are dominant today in membranes are likely to have appeared only some time later than the first life forms.
There is not much positive evidence about the early forms of life, but there is a lot of evidence about many things that are impossible, so we can say for sure that they could not have existed in the first forms of life.
We can say with absolute certainly that no other function of RNA could have existed before it acquired the ability of self-replication. More precisely, if any such function would have happened accidentally in any living being it would have been immediately lost forever, because it could not have been transmitted to descendants.
We can also say with absolute certainty that the self-replication of RNA could never appear otherwise than in an environment where a source of energy ensured a continuous production of the 4 monomers required for making RNA.
That environment must have been an already existing living being, not only because there is no other known environment that could produce phosphorylated nucleotides, but also because without such an already living host there would not have been a path of evolution for the self-replicating RNA, where it acquired extra abilities of catalyzing other chemical reactions, culminating in the ability of synthesizing proteins, such that eventually the mechanism of making proteins via RNA has substituted in most cases the mechanisms for making non-ribosomal peptides.
There are many other things that we know that they could not have existed in the first living beings. Most of the living beings that we know, including many anaerobic bacteria from places without light about which it is frequent to see in the popular but incompetent press claims that they live independently of the Sun, depend either directly or indirectly on the phototrophic living beings, which capture solar energy.
There are only two kinds of bacteria or archaea that are really independent of the solar energy, which do either acetogenesis or methanogenesis. We can rule out with certainty both phototrophy and methanogenesis as sources of energy for the first living beings, which leaves only acetogenesis, a process for which there is ample evidence that it already existed in the ancestor of all present living beings.
Besides the source of energy, we also have a pretty good knowledge about the chemical composition of the first living beings.
While a human needs around 20 chemical elements, much less are needed for the simplest self-reproducible life forms.
5 non-metals are certainly needed in any life form for the organic substances: H, C, N, O and S. These happen to also be the most abundant non-metals in the Universe (not counting noble gases). The minimal set of metabolic reactions for a self-reproducing chemical system powered by acetogenesis requires at least 3 catalytic metals, iron, nickel and cobalt. The consumption of carbon dioxide instead of the less abundant carbon monoxide and of dinitrogen instead of the less abundant ammonia requires an additional catalytic metal, either molybdenum or tungsten. This extra catalyst may be a later addition to the living beings, enabling them to also live in less reducing environments, where carbon monoxide and ammonia became scarce. Besides organic substances and catalysts, there is a necessity for the first living beings to have abundant potassium ions in their environment, in order to neutralize the excess of organic acids from living matter. While in the present oceans sodium is more abundant, forcing all living beings to have means to expel sodium from their cells, it is likely that in the early oceans potassium was more abundant because it is easier dissolved from the volcanic rocks than any other component, so it was the first to become abundant in sea water, until the concentration of other ions has caught up with it after the passing of time has brought them in solution too.
This brings the total to 9 chemical elements that are certain to have been used in the first self-replicating living beings. With the later increase in complexity, other chemical elements must have been added, the most important being the addition of phoshphorus (as phosphoric acid) and of magnesium, which have lead to the use of ATP as a dehydrating agent, presumably replacing the earlier use of thioesters, which had as a byproduct the appearance of RNA.
There are a lot of unknowns, but there are also a lot of restrictions to the space of possible solutions, so there are chances that eventually it would become possible to demonstrate a self-replicating system of chemical reactions that could be similar with the first forms of life, even if it is unlikely that the solution is unique, so we might never know the precise details how it happened.
> RNA has two main functions based on its information-storage property: the replication of RNA using a template of RNA (which was the single form of nucleic acid replication before the existence of DNA) and the synthesis of proteins using RNA as a template.
This heavily simplifies what RNA is capable of doing. When we talk about the ribosome templating rna to make protein, that is true, but the ribosome itself is made out of structural rRNA and some rna bound protein. RNAs have been found to have enzyme activity alone. When people talk about the RNA world hypothesis they mean that RNA is sufficient to be the information and catalytic unit of early life, as a sort of occams razor what is the most simple step with the fewest parts involved before taking more complicated steps with more separate pieces sort of way.
“ the majority of known ribozymes carry out mostly phosphoryl transfer reactions”
Now that sure seems like a potential smoking gun for an early phosphorylation based energy cycle.
Been a while since I interacted with this science, but I think the assumption about the magma ocean “boiling off” the water was an early idea that doesn’t hold up? The mantle holds an impressive amount of water dissolved inside it, as it turns out.
Not if it's hot enough that the water molecules reach escape velocity in the exosphere! (As happens with helium today, helium atoms being lighter move faster at a given temperature than water molecules)
It's not clear what the probability is over the ~hundreds of millions of years that it took on Earth. Could be that, under the conditions and on that timescale, we're an average or statistically unremarkable case.
Time may correlate with increase in entropy in general. But also consider assembly theory. Once certain assemblies dominate an environment, they constrain future possibilities. Environments and the life it supports evolve together.
A common belief, but manifestly false. Probabilities tend to combine exponentially, and that defeats our polynomial universe.
Or, to put it another way, it does not matter how many times you try to roll a million fair dice and get them to all come up six. It doesn't matter if the entire observable universe does nothing but that for the entire time from the start of the universe to the heat death end. It will still never happen.
Probabilities can easily be "larger" than our entire universe considered across both space and time. It isn't even a particularly remarkable thing to encounter such a probability.
Surely you realize that the universe could well be infinite -- and, to all appearances, is in any case not bounded in time. As such, every low probability thing will "at some point" occur. Thus the repugnant conclusion: Boltzmann Brains. But also Boltzmann planets, Boltzmann galaxies, and whatever else can occur will occur.
"Could well be" is just a "could well be". It is not actually an argument, because there is an infinite range of "could well be". It "could well be" that we exist because the Great Simulator simply put us here, but you can only distinguish between outcomes based on actual observations.
If you want to invoke "well, things just happen because there's so many rolls of the metaphorical dice", your logical number of rolls is determined by the observable universe. When you step into hypotheticals beyond that, you must step into all of them all at once, not just pick one, smoke some hash and goggle at the one possibility you picked out. That's the mistake people make. And there's so many "well, it could be..." that in effect they cancel each other out and you can't do any logic on them.
>you try to roll a million fair dice and get them to all come up six.
That is not a low probability event; that is an impossibility.
I think the problem here is that you think I am a digital electronic computer. I am not.
I am a human being.
I do not now, have never, and will never care about the technically possible I only care about the actually possible.
As a human, I know that six to the power of one million is impossible. Not to mention that rolling one million dice is absurd.
But as a human I also know that the chemical reaction needed to spark life isn't a six to the power of one million proposition.
I don't know what it is but it ain't that because it's been done, at least once.
edit: It's not absurd, rolling one million dice.
The heaviest verifiable weight ever lifted by a human being is 2422.18kg.
A 4mm die is 0.4g. Conceivably a contraption could be built by which a human could "roll" several million dice using the strength of their entire body.
> As a human, I know that six to the power of one million is impossible.
This is plain wrong. If you roll a million dice, anything that comes up has the exact same probability. We think all 6 is special because it holds some meaning to us, but it is exactly as likely as any other result. So any result has a probability of 6^1M to happen. And yet, one of those 6^1M configurations will happen with probability 1.
I'm not saying that we'll see the all six combination if we actually threw a million dice. I'm saying that if we throw a million dice, we'll see some combination, and that should be just as amazing as the all six combination, because, whatever it is, it was monumentally unlucky to happen.
My only point is that there is no way to say "events with probability < X are impossible in real life", for X > 0. For any probability value, it's trivial to construct an experiment that will be guaranteed to have an outcome whose probability is that low.
This argument I think hints at something i regard as mysterious regarding probability as applied to the real world (as opposed to the platonic, pure math concept)
My own view is that there something deep about probability akin to the measurement problem. My view is that probability is not an objective fixed thing, but that it is something relative to the observer of experiments.
> My view is that probability is not an objective fixed thing, but that it is something relative to the observer of experiments.
This is basically the Bayesian view of probability - that probability is a measure of the knowledge of an agent, not a property of a system. There are even some interpretations of QM that try to find a way to apply this to the measurement problem.
However, for this particular case, I don't think there is anything all that mysterious. If a process is more or less equally likely to produce any of a huge number of outcomes, it stands to reason that you can't predict which outcome will happen, even while knowing some outcome is fully guaranteed.
The probability of life and all the steps that lead to it is obviously not more infinitesimal than all potential actions of all the molecules in the universe over time. It happened on Earth and it "only" took 150-650 million years after water formed on the planet. We just don't know how much more likely it is than "so rare we are lucky to be the only ones."
I never like the emphasis on genetics and information in a lot of origin of life stuff. IMO it is too extensional; what is needed is good intensional reasoning.
At the heart of chemical life is https://en.wikipedia.org/wiki/Autocatalysis, this is a great intensional definition of the reproductive side. That just leaves the evolutionary side.
What do "genetics" achieve for reproduction. From the autocatalysis point of view, they create a family of "nearby" autocatalytic sets: because different nucleic acid sequences reproduce in much the same way, the conditions needed to propagate one should also propogate another. This in turn makes safer mutations and....Lamarckian inheritance! If you, a microrganism get a good mutation which makes you fit, and then you split, you pass that mutation on.
Genetics are sufficient for the above properties, but are they necessary? Probably not! We can probably find other things which have such a "dense/smooth mutation space" with fewer local maxima traps. Perhaps it is fine to say such things definitionally encode information, but IMO information still comes second, philosophically.
The meanings of both life and intelligence have been obscured by human conceit. We simply cannot accept that we came from what is essentially a random process over eons (which makes it no less extraordinary, but imo far more understandable). The science and math of LLMs and GPTs has been around for a while, but it took time and effort (people putting stuff online plus GPUs) to finally make it usable.
I have a layman theory on protocell organization. It can't explain replication, but hear me out. So one of the most likely candidate locations for abiogenesis, purportedly, are hydrothermal vents. Now, consider Cymatics (https://en.wikipedia.org/wiki/Cymatics). Maybe you can draw the same conclusion I did.
Wave formations are a source of order amidst the chaos (pressure waves in this case). This may be testable, even. If it did hold any truth, then the popular, common mythos' of "the Word" or "speaking things into existence", or creation via music etc... maybe was more intuitive than we realized :)
Well, my comment is going to end up hidden. I guess this just isn't that interesting, and I assume the video I am linking here will be seen as meaningless with no possible historical bearing on physics or chemistry.
Is there a good reason this is not being considered? Like, these abiogensis articles never say anything new, and have no interesting propositions. They say it's a mystery, then propose a vague implausibility that can only be explained by another mystery. Like, I would appreciate at least some creative thinking here.
Hmm, is there anything you can think of, barring an individual's death or mutation etc.., that we'd consider alive but can't reproduce or evolve? I hadn't thought of it previously, but that does seem like a fundamental difference between being inert and alive.
Amino acids are common enough -- glycine has been found in comets and, controversially, even in the interstellar medium. Other amino acids have also been found in comets.
Comet organics, under pressure, can turn into amino acids in situ: https://www.llnl.gov/article/36016/amino-acids-could-be-prod...
It's also presumed that cometary ice bombardment is the source of Earth's surface water, as ice or water present any earlier would have boiled off when the planet was young and hot.
It's not much of a stretch to imagine that comets brought amino acids, organic compounds, and minerals to Earth as they were bringing water ice. A lot of those aminos and organics would turn into tar, but some would be protected from UV radiation by that same tar. With a heat source, maybe some lightning strikes, a good location, and a lot of luck, you get RNA...
What we can't yet do is assign a probability or likelihood to this process. But the ingredients should be common enough.
About a half of the amino acids used in proteins, i.e. ten of them, can form easily in abiotic conditions and they are widespread in some celestial bodies.
They are easily distinguished from terrestrial contaminants, because they are a mixture of left-handed and right-handed isomers.
When analyzing the genetic code in order to determine which amino acids have already been used in the earlier versions of the genetic code and which have been added more recently, the same simpler amino acids that are easy to synthesize even in the absence of life are also those that appear to have been the only amino acids used earlier.
The article contains the phrase "Given the fact that the current scenario is that life on Earth started with RNA".
This is a fact that it is too often repeated like if it were true, when in reality one of the few things that can be said with certainty about the origin of life is that it has not started with RNA.
What must be true is only that RNA had existed a very long time before DNA and DNA has been an innovation that has been the result of a long evolution of already existing life forms, long before the last ancestor of all living beings that still exist now on Earth.
On the other hand, proteins, or more correctly said peptides, must have existed before any RNA. Moreover, ATP must have existed long before any RNA.
RNA has two main functions based on its information-storage property: the replication of RNA using a template of RNA (which was the single form of nucleic acid replication before the existence of DNA) and the synthesis of proteins using RNA as a template.
Both processes require complex molecular machines, so it is impossible for both of them to have appeared simultaneously. One process must have appeared before the other and there can be no doubt that the replication of RNA must have appeared before the synthesis of proteins.
Had synthesis of proteins appeared first, it would have been instantly lost at the death of the host living being, because the RNA able to be used as a template for proteins could not have been replicated, therefore it could not have been transmitted to descendants.
So in the beginning RNA must have been only a molecule with the ability of self replication. All its other functions have evolved in living beings where abundant RNA existed, being produced by self replication.
The RNA replication process requires energy and monomers, in the form of ATP together with the other 3 phosphorylated nucleotides. Therefore all 4 nucleotides and their phosphorylated forms like ATP must have existed before RNA.
ATP must have been used long before RNA, like today, as a means of extracting water from organic molecules, causing the condensations of monomers like amino acids into polymers like peptides.
The chemical reactions in the early living forms were certainly regulated much less well than in the present living beings, so many secondary undesirable reactions must have happened concurrently with the useful chemical reactions.
So the existence of abundant ATP and other phosphorylated nucleotides must have had as a consequence the initially undesirable polymerization and co-polymerization of the nucleotides, forming random RNA molecules, until by chance a self-replicating RNA molecule was produced.
Because the first self-replicating RNA molecule did not perform any useful function for the host life form, but it diverted useful nucleotides from its metabolism, this first self-replicating RNA molecule must be considered as the first virus. Only much later, after these early viruses have evolved the ability to synthesize proteins, some of them must have become integrated with their hosts, becoming their genome.
The catalytic functions that are now performed mostly by proteins, i.e. amino acid polymers that are synthesized using an RNA template, must have been performed earlier by peptides, i.e. typically shorter amino acid polymers that are synthesized without the use of RNA templates.
Even today, all living beings contain many non-ribosomal peptides, which are made without RNA, using processes that are much less understood than those that involve nucleic acids.
The difference between a living being that would be able to make only non-ribosomal peptides and one that makes proteins using RNA templates is pretty much the same difference as between a CPU with hard-wired control and a CPU with micro-programmed control, with the same advantages and disadvantages.
Life forms able to reproduce themselves must have existed before the appearance of the nucleic acids, but they must have been incapable of significant evolution, because any random change in the structure of the molecules that composed them would have been very likely to result in a defective organism that would have died without descendants. This is similar with a hard-wired control, where small random changes in the circuits are unlikely to result in a functional device.
On the other hand, once the structure of the enzymes was written in molecules of nucleic acids, the random copying errors could result in structures very different from the original structures, which could not have been obtained by gradual changes in the original structures without passing through non functional structures that could not have been inherited.
So the use of molecules that can store the structural information of a living being has enabled the evolution towards much more complex life forms, but it cannot have had any role in the apparition of the first life forms, because the replication of any such molecule requires energy that can be provided only by an already existing life form.
>On the other hand, proteins, or more correctly said peptides, must have existed before any RNA
How come? It seems you can have reproducing RNA without protein needed. Here's Gerald Joyce talking briefly about making those https://youtu.be/aBrYsFeeVzE?t=171
Reproducing RNA without proteins has nothing to do with the necessity of peptides/proteins existing before any RNA.
Polymerizing nucleotides into RNA requires energy and monomers that can be provided only by an already living being with a functional metabolism.
That requires enzymes for catalyzing the chemical reactions that compose the metabolism, which must have been non-ribosomal peptides, before the existence of nucleic acids.
The main source of energy for the first life forms must have been the conversion of free hydrogen (dihydrogen) and carbon monoxide and/or dioxide into acetic acid (acetogenesis). An auxiliary source of energy could have been the gradient of ions that exists in hydrothermal vents. Both sources of energy have their origin in the oxidation of volcanic rocks by water, and the energy comes ultimately from the internal heat of the planet (because the volcanic rocks formed at high temperatures, where they are in chemical equilibrium, are no longer in chemical equilibrium in the presence of water after they cool to lower temperatures). At least for now, there is no known mechanism for the appearance of life elsewhere than on a planet with water, internal heat and volcanism.
Some people see that simple organic substances can form in any place in the cosmic space where there is not enough oxygen to oxidize them, so they assume that perhaps life could appear there. However that is wrong, because without a continuous source of energy all those organic substances will stay dead forever. The only suitable continuous source of energy is the internal heat of big enough planets, which will not cool quickly, because capturing the energy of stellar light requires very complex structures that cannot be generated spontaneously, but they can be only the result of a long evolution of already existing life forms.
>>>Some people see that simple organic substances can form in any place in the cosmic space where there is not enough oxygen to oxidize them, so they assume that perhaps life could appear there.
LUCA is considered anaerobic - any contact with oxygen would have killed it. However we do not know what were preRNA Life forms.
>>>However that is wrong, because without a continuous source of energy all those organic substances will stay dead forever.
Unless they are getting frozen and put on pause, like all the stable chemical ingredients can exist in your household.
>>>The only suitable continuous source of energy is the internal heat of big enough planets, which will not cool quickly, because capturing the energy of stellar light requires very complex structures that cannot be generated spontaneously, but they can be only the result of a long evolution of already existing life forms.
The only known life, that is known to me that can process stellar light are plants and animals, that have eaten plants and are getting sugar from their cells, that are integrated into their organism.
I am not sure what this text was compiled together from, but most of chemical processes that are happening on any planet does not require any stellar light. Initially all of matter was part of a Sun and when it went Supernova, it involved some stellar light, but after that, no need for that.
>>>The main source of energy for the first life forms must have been the conversion of free hydrogen (dihydrogen) and carbon monoxide and/or dioxide into acetic acid (acetogenesis). An auxiliary source of energy could have been the gradient of ions that exists in hydrothermal vents. Both sources of energy have their origin in the oxidation of volcanic rocks by water, and the energy comes ultimately from the internal heat of the planet (because the volcanic rocks formed at high temperatures, where they are in chemical equilibrium, are no longer in chemical equilibrium in the presence of water after they cool to lower temperatures). At least for now, there is no known mechanism for the appearance of life elsewhere than on a planet with water, internal heat and volcanism.
This also looks like something compiled from different thoughts. But, ok - in terms of Life originating on the planet, this is only more or less applicable to evolutionary stage of Life, that happened on our planet in thermal vents, and only when planet was stable enough for a Life to exist there as we have no idea if Life was on our planet already, before Theia merged into our planet and destroyed everything organic, which seems to have been the case. But the issue here is not so much if Life originated on our planet, but where all the previous organic forms evolved, which are considered much older than our planet and primordal soup that is needed to create Life simply could not have happened in thermal vent like you are supposing.
From what I have read, comets are excellent places for primordal soup to happen as one of the prerequisites for a Life. Whenever they are approaching Sun, there is water boiling and all the processes that are similar to what thermal vents would have, but with light in addition and plentiful of resources for Life to spring. Like I mentioned earlier, freezing over would not reverse chemical processes that ere happening during that boiling and in next approach they would continue and there is basically indefinite time for those cycles to happen and disperse whatever end products that were happening on comets whenever they were passing plants - not to mention if they would land on them. There is life, that can exist in atmosphere, so there is actually no need for a comet to hit a planet to disperse product from their primordial soup. So, generally comets are one of the stages for prereq of Life, where explosion of Suns to disperse their thermonuclear product is previous stage. There seems to be impossible for Life not to appear the way how Universe functions.
PS I am not challenging RNA stuff, but Life also includes preRNA Life, so while your POV in regards to RNA based Life seems to be ok, everything outside of those boundaries are not ok.
Awesome post and thanks for writing this out - probably the most insightful piece I’ve read on plausible origin of life through pre-RNA autocatalytic peptides. Would you be willing to share a contact email / online profile? (could edit afterward to delete if you are worried about spam from crawlers)
a dot bocaniciu at computer dot org
Beautiful work! Do you have any thoughts on the relative size of complexity spaces explored by different forms of mutation?
sorry if I missed it, but it sounds like you've just pushed the mystery one step back but still ended up with the same mystery - where did the original Titan species come from? is there any evidence for their existence other than your belief that an RNA replicator would have needed a host cell? would this host cell have been built out of lipid bilayers? what would its inside mechanisms be made of - if not protein or RNA?
Ultimately science always terminates in so-called brute facts. I'm not sure it always makes sense to call these mysteries. In the end, some things appear to simply be without any sort of causal or even logical explanation. I try not to get too worked up about it.
On the other hand, one has to keep kicking over rocks to see what is underneath or life would get boring.
It is not certain that the first living beings consisted of cells. This is actually very unlikely.
The very first living being that was able to reproduce itself could not have had a closed cell membrane, because that cannot function without pores and pumps provided by peptides/proteins, which control the exchange of substances through the membrane.
The very first self-reproducing chemical system is likely to have been an open structure formed by organic substances attached to the surface of a mineral containing the catalysts for the metabolic reactions, e.g. an iron sulfide impurified with nickel and cobalt.
There is a hypothesis, which seems very plausible, that before the appearance of closed cells, the living beings consisted of discoidal fatty membranes with peptides attached to them, which obstructed pores in minerals located in hydrothermal vents, where the environment provided a flux of ions equivalent with the flux of ions that must be provided by ionic pumps in any closed living cell.
It is likely that only after the development of active trans-membrane ionic pumps, it became possible for living beings to take the form of free closed cells, unattached to minerals.
It is not clear which happened first, the transition to free closed cells or the apparition of self-replicating RNA.
The first membranes must have also been formed by molecules with hydrophobic and hydrophilic parts like the present lipid bilayers. However the molecules must have been different and simpler. Perhaps the first membranes were made just of free fatty acids, but with short chains. They certainly must have been much more permeable than today, to allow the passing of some molecules for which there were not yet adequate transporters. In any case, the phospholipids that are dominant today in membranes are likely to have appeared only some time later than the first life forms.
There is not much positive evidence about the early forms of life, but there is a lot of evidence about many things that are impossible, so we can say for sure that they could not have existed in the first forms of life.
We can say with absolute certainly that no other function of RNA could have existed before it acquired the ability of self-replication. More precisely, if any such function would have happened accidentally in any living being it would have been immediately lost forever, because it could not have been transmitted to descendants.
We can also say with absolute certainty that the self-replication of RNA could never appear otherwise than in an environment where a source of energy ensured a continuous production of the 4 monomers required for making RNA.
That environment must have been an already existing living being, not only because there is no other known environment that could produce phosphorylated nucleotides, but also because without such an already living host there would not have been a path of evolution for the self-replicating RNA, where it acquired extra abilities of catalyzing other chemical reactions, culminating in the ability of synthesizing proteins, such that eventually the mechanism of making proteins via RNA has substituted in most cases the mechanisms for making non-ribosomal peptides.
There are many other things that we know that they could not have existed in the first living beings. Most of the living beings that we know, including many anaerobic bacteria from places without light about which it is frequent to see in the popular but incompetent press claims that they live independently of the Sun, depend either directly or indirectly on the phototrophic living beings, which capture solar energy.
There are only two kinds of bacteria or archaea that are really independent of the solar energy, which do either acetogenesis or methanogenesis. We can rule out with certainty both phototrophy and methanogenesis as sources of energy for the first living beings, which leaves only acetogenesis, a process for which there is ample evidence that it already existed in the ancestor of all present living beings.
Besides the source of energy, we also have a pretty good knowledge about the chemical composition of the first living beings.
While a human needs around 20 chemical elements, much less are needed for the simplest self-reproducible life forms.
5 non-metals are certainly needed in any life form for the organic substances: H, C, N, O and S. These happen to also be the most abundant non-metals in the Universe (not counting noble gases). The minimal set of metabolic reactions for a self-reproducing chemical system powered by acetogenesis requires at least 3 catalytic metals, iron, nickel and cobalt. The consumption of carbon dioxide instead of the less abundant carbon monoxide and of dinitrogen instead of the less abundant ammonia requires an additional catalytic metal, either molybdenum or tungsten. This extra catalyst may be a later addition to the living beings, enabling them to also live in less reducing environments, where carbon monoxide and ammonia became scarce. Besides organic substances and catalysts, there is a necessity for the first living beings to have abundant potassium ions in their environment, in order to neutralize the excess of organic acids from living matter. While in the present oceans sodium is more abundant, forcing all living beings to have means to expel sodium from their cells, it is likely that in the early oceans potassium was more abundant because it is easier dissolved from the volcanic rocks than any other component, so it was the first to become abundant in sea water, until the concentration of other ions has caught up with it after the passing of time has brought them in solution too.
This brings the total to 9 chemical elements that are certain to have been used in the first self-replicating living beings. With the later increase in complexity, other chemical elements must have been added, the most important being the addition of phoshphorus (as phosphoric acid) and of magnesium, which have lead to the use of ATP as a dehydrating agent, presumably replacing the earlier use of thioesters, which had as a byproduct the appearance of RNA.
There are a lot of unknowns, but there are also a lot of restrictions to the space of possible solutions, so there are chances that eventually it would become possible to demonstrate a self-replicating system of chemical reactions that could be similar with the first forms of life, even if it is unlikely that the solution is unique, so we might never know the precise details how it happened.
What about sulfur-reducing bacteria? The process also requires iron, but seems to be possible without cobalt (desulfovibrio africanus).
> RNA has two main functions based on its information-storage property: the replication of RNA using a template of RNA (which was the single form of nucleic acid replication before the existence of DNA) and the synthesis of proteins using RNA as a template.
This heavily simplifies what RNA is capable of doing. When we talk about the ribosome templating rna to make protein, that is true, but the ribosome itself is made out of structural rRNA and some rna bound protein. RNAs have been found to have enzyme activity alone. When people talk about the RNA world hypothesis they mean that RNA is sufficient to be the information and catalytic unit of early life, as a sort of occams razor what is the most simple step with the fewest parts involved before taking more complicated steps with more separate pieces sort of way.
“ the majority of known ribozymes carry out mostly phosphoryl transfer reactions”
Now that sure seems like a potential smoking gun for an early phosphorylation based energy cycle.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10583251/
Thank you so much. Awesome post.
Thanks. People like you make HN an enjoyable place.
Been a while since I interacted with this science, but I think the assumption about the magma ocean “boiling off” the water was an early idea that doesn’t hold up? The mantle holds an impressive amount of water dissolved inside it, as it turns out.
But boiling off would have still kept that water in the atmosphere right?
Not if it's hot enough that the water molecules reach escape velocity in the exosphere! (As happens with helium today, helium atoms being lighter move faster at a given temperature than water molecules)
You don't need that much luck when you have billions of years.
Probability is believed to be quite low based on nobody having reproduced the process in the lab.
It's not clear what the probability is over the ~hundreds of millions of years that it took on Earth. Could be that, under the conditions and on that timescale, we're an average or statistically unremarkable case.
Time means more entropy, so I would think that makes the calculation much more problematic, no?
Time may correlate with increase in entropy in general. But also consider assembly theory. Once certain assemblies dominate an environment, they constrain future possibilities. Environments and the life it supports evolve together.
Low probabilities become certainties with billions of tests per year over hundreds of millions of years.
A common belief, but manifestly false. Probabilities tend to combine exponentially, and that defeats our polynomial universe.
Or, to put it another way, it does not matter how many times you try to roll a million fair dice and get them to all come up six. It doesn't matter if the entire observable universe does nothing but that for the entire time from the start of the universe to the heat death end. It will still never happen.
Probabilities can easily be "larger" than our entire universe considered across both space and time. It isn't even a particularly remarkable thing to encounter such a probability.
> polynomial universe
That's the mistake, right there.
Surely you realize that the universe could well be infinite -- and, to all appearances, is in any case not bounded in time. As such, every low probability thing will "at some point" occur. Thus the repugnant conclusion: Boltzmann Brains. But also Boltzmann planets, Boltzmann galaxies, and whatever else can occur will occur.
"Could well be" is just a "could well be". It is not actually an argument, because there is an infinite range of "could well be". It "could well be" that we exist because the Great Simulator simply put us here, but you can only distinguish between outcomes based on actual observations.
If you want to invoke "well, things just happen because there's so many rolls of the metaphorical dice", your logical number of rolls is determined by the observable universe. When you step into hypotheticals beyond that, you must step into all of them all at once, not just pick one, smoke some hash and goggle at the one possibility you picked out. That's the mistake people make. And there's so many "well, it could be..." that in effect they cancel each other out and you can't do any logic on them.
> every low probability thing will "at some point"
This is the "ergodic hypothesis" and is not necessarily true.
Then "God creating things" will also inevitably occur, right?
It depends on the definition of God.
>you try to roll a million fair dice and get them to all come up six.
That is not a low probability event; that is an impossibility.
I think the problem here is that you think I am a digital electronic computer. I am not.
I am a human being.
I do not now, have never, and will never care about the technically possible I only care about the actually possible.
As a human, I know that six to the power of one million is impossible. Not to mention that rolling one million dice is absurd.
But as a human I also know that the chemical reaction needed to spark life isn't a six to the power of one million proposition.
I don't know what it is but it ain't that because it's been done, at least once.
edit: It's not absurd, rolling one million dice.
The heaviest verifiable weight ever lifted by a human being is 2422.18kg.
A 4mm die is 0.4g. Conceivably a contraption could be built by which a human could "roll" several million dice using the strength of their entire body.
Now I kinda want that to happen.
> As a human, I know that six to the power of one million is impossible.
This is plain wrong. If you roll a million dice, anything that comes up has the exact same probability. We think all 6 is special because it holds some meaning to us, but it is exactly as likely as any other result. So any result has a probability of 6^1M to happen. And yet, one of those 6^1M configurations will happen with probability 1.
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I'm not saying that we'll see the all six combination if we actually threw a million dice. I'm saying that if we throw a million dice, we'll see some combination, and that should be just as amazing as the all six combination, because, whatever it is, it was monumentally unlucky to happen.
My only point is that there is no way to say "events with probability < X are impossible in real life", for X > 0. For any probability value, it's trivial to construct an experiment that will be guaranteed to have an outcome whose probability is that low.
This argument I think hints at something i regard as mysterious regarding probability as applied to the real world (as opposed to the platonic, pure math concept)
My own view is that there something deep about probability akin to the measurement problem. My view is that probability is not an objective fixed thing, but that it is something relative to the observer of experiments.
> My view is that probability is not an objective fixed thing, but that it is something relative to the observer of experiments.
This is basically the Bayesian view of probability - that probability is a measure of the knowledge of an agent, not a property of a system. There are even some interpretations of QM that try to find a way to apply this to the measurement problem.
However, for this particular case, I don't think there is anything all that mysterious. If a process is more or less equally likely to produce any of a huge number of outcomes, it stands to reason that you can't predict which outcome will happen, even while knowing some outcome is fully guaranteed.
The probability of life and all the steps that lead to it is obviously not more infinitesimal than all potential actions of all the molecules in the universe over time. It happened on Earth and it "only" took 150-650 million years after water formed on the planet. We just don't know how much more likely it is than "so rare we are lucky to be the only ones."
For a gambler, yes, but for a biological system? Stuff falls apart, it's like any progress continually gets wiped.
I never like the emphasis on genetics and information in a lot of origin of life stuff. IMO it is too extensional; what is needed is good intensional reasoning.
At the heart of chemical life is https://en.wikipedia.org/wiki/Autocatalysis, this is a great intensional definition of the reproductive side. That just leaves the evolutionary side.
What do "genetics" achieve for reproduction. From the autocatalysis point of view, they create a family of "nearby" autocatalytic sets: because different nucleic acid sequences reproduce in much the same way, the conditions needed to propagate one should also propogate another. This in turn makes safer mutations and....Lamarckian inheritance! If you, a microrganism get a good mutation which makes you fit, and then you split, you pass that mutation on.
Genetics are sufficient for the above properties, but are they necessary? Probably not! We can probably find other things which have such a "dense/smooth mutation space" with fewer local maxima traps. Perhaps it is fine to say such things definitionally encode information, but IMO information still comes second, philosophically.
The meanings of both life and intelligence have been obscured by human conceit. We simply cannot accept that we came from what is essentially a random process over eons (which makes it no less extraordinary, but imo far more understandable). The science and math of LLMs and GPTs has been around for a while, but it took time and effort (people putting stuff online plus GPUs) to finally make it usable.
My book dives into the timeline of life's origins as well as summarizing how we know what we know about roughly when life started:
https://impacts.to/downloads/lowres/impacts.pdf#page=10
The little orange dot represents where the events happened along the timeline between the start of the universe and recent times.
https://archive.ph/585kK
I have a layman theory on protocell organization. It can't explain replication, but hear me out. So one of the most likely candidate locations for abiogenesis, purportedly, are hydrothermal vents. Now, consider Cymatics (https://en.wikipedia.org/wiki/Cymatics). Maybe you can draw the same conclusion I did.
Wave formations are a source of order amidst the chaos (pressure waves in this case). This may be testable, even. If it did hold any truth, then the popular, common mythos' of "the Word" or "speaking things into existence", or creation via music etc... maybe was more intuitive than we realized :)
https://www.youtube.com/watch?v=OWLtTP07FCw
Well, my comment is going to end up hidden. I guess this just isn't that interesting, and I assume the video I am linking here will be seen as meaningless with no possible historical bearing on physics or chemistry.
Is there a good reason this is not being considered? Like, these abiogensis articles never say anything new, and have no interesting propositions. They say it's a mystery, then propose a vague implausibility that can only be explained by another mystery. Like, I would appreciate at least some creative thinking here.
>it has to be able to reproduce and evolve by natural selection
Not sure why something has to be able to evolve by natural selection in order to be considered alive.
Hmm, is there anything you can think of, barring an individual's death or mutation etc.., that we'd consider alive but can't reproduce or evolve? I hadn't thought of it previously, but that does seem like a fundamental difference between being inert and alive.
Just think about it, a conscious being deciding what a life should be. There is certainly a bias towards how we were made.
I mean. It was God (whatever that means to you).
Well, you had a chance to have a Programmer joke here, as it was RANDOM.
However, the issue with Life is that God is only human made concept and not all human societies have that concept as well.
Oh, you mean "Programmer #1" using the original assembly language?
But where did Ready Programmer #1 come from? and we're back to square one :)
He didn't come from any other thing, because he always existed. It's like asking where time came from.
Programmer #0 obviously.
It's programmers all the way down.
or up
what is up or down in a n dimensional space...