I remember reading about what it’s actually like inside a cell - that it’s not the smooth and organised world you see in biology animations. It’s a mess of molecules moving around at hundreds of miles an hour.

That’s what life is inside all our cells. Just a bunch of molecules bashing around randomly but because it’s all the right ingredients in there, the right things find each other and fit together and somehow it still works.

Yes, cells are extremely crowded and fast-moving inside. Molecules are moving at 250 miles per hour inside cells due to thermal motion, and a particular molecule collides with other molecules billions of times per second.

When you see an animation of a cell, it's puzzling how the right molecule shows up in the right place. But in reality, a typical enzyme collides with something to react with 500,000 times per second just from random motion.

I wrote a blog post discussing this in more detail: http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...

>it's puzzling how the right molecule shows up in the right place.

Most chemistry is like that though isn't it? Everything is flying around randomly but the electron density distributions mean some "bonds" have better probability of being broken and made during reactions.

It is almost like life is possible just due to a biological fuzzer.

I'm trying to visualize that in my mind. But what is BETWEEN the molecules? Vacuum?

Imagine a glass of water and all the water molecules in it. They are all touching (kind of) and constantly moving around. There is a bit of space between the molecules, the inter-molecular space, which is a vacuum. Keep in mind that the molecules aren't really touching since they aren't built from rigid spheres but have electron clouds. The water molecules repel each other if they get too close, but also attract each other via hydrogen bonds, so they are about 0.3 nm apart. (Compare to 3 nm semiconductor process node.)

A cell is similar (since it is 60% water), but with many other types of molecules as well.

Thanks for the explanation. I guess the reason I find it hard to visualize is that we ordinarily think that 'vacuum sucks". If there is container which has been pumped empty of air and we make a hole in it it sucks in air. So it looks like empty/vacuum space "sucks" anything around in it.

But that is obviously a misconception. Vacuum is not attracting anything, it is the fast moving molecules around it that PUSH themselves into the vacuum if we make a whole in the container.

What makes it hard to visualize is that we don't see the fast-moving molecules ever, which are forcing themselves into the container through the pierced hole by the power of their own (tiny) momentum yet very fast speed. :-)

It is also counter-intuitive that tiny things could have fast speeds, perhaps because we think in terms of a person being able to walk much faster than say an ant.

There is also water between the molecules, but note that cells are generally quite crowded places. You can check out David Goodsell's images for getting a sense of how crowded a cell is.

https://www.google.com/search?q=David+Goodsell&tbm=isch

Isn’t it Cytoplasm? https://en.m.wikipedia.org/wiki/Cytoplasm

Interesting comment / blogpost! Thanks, learned some new things today :)

I was baffled in school how tRNA "moves" amino acid to ribosome. Asked and got no answer.

Found out much later — tag so many amino acids, that it would stumble on ribosome. Genius.

This chart shows the known biochemical pathways in the cell. http://biochemical-pathways.com/#/map/1

worst spaghetti code ever

Yes I remember one of the most interesting examples I saw of this was with how actin and myosin gain motion in cells, there's enough stuff bashing around everywhere that the right chemical reactions cause them to take each step.

It kinda makes it more amazing doesn't it? Before I read that i just had this totally false view of tiny-biology as this cold, organised place. But I really like the truth that it's chaotic and messy and powerful.

Silly question, but could that explain bad health? People who don’t enough sports don’t shake their cells enough, so they aren’t as functional? I know the usual explanation is blood circulation and organ maintenance, but did we think of looking intra-cell?

There may well be subcellular problems that cause all kinds of bad-health, but not being well-mixed is not one of them.

Movement at the level of sports won't cause well-mixed cells - their fundamental frequencies are too different.

That would make people who ride older rail trains (like Chicago's trains) regularly super healthy. People who ride horses would be super healthy, too. Train conductors. Anyone who does a lot of off-roading. Etc. Oh actually, people who have shaky legs would have disproportionately healthier legs than the rest of their body.

But actually moving around a lot wouldn't make a difference if the bits in your cells are moving around at hundreds of miles per hour.

> but did we think of looking intra-cell?

Yes, a lot of science has "thought of" at looking intra-cell. In fact, the explanation of "don't shake their cells enough" must be very fringe because I haven't heard it any one time before from any serious scientist or a health book etc. The human body is much more complicated, and the way we understand many of the functions of it, including healthy functions, are based on biochemistry, both intra-cell and throughout the body.

Also "shaking the cells" can't even be that important physically, when you compare the speeds at which the limbs move during running to the base speeds of molecules inside the cell due to basic heat-based brownian motion.

It looks random, but it's not. Were you to look at a car building company, you'd find some elements act randomly, when their actions are totally determined.

The insides of the simplest cell are far more complicated than any production line.

That's pretty much the premise of the RNA world. I assume your actual question is why we don't observe RNA based lifeforms anymore. And the most likely explanation is that this type of life form has a massive evolutionary disadvantage to currently existing life forms in terms of competing over resources and is extinct as the huge majority of all once existing species have gone extinct in the course of this planet's history.

In a sense we are RNA-based lifeforms. Our protein synthesis machinery is dependent entirely upon RNA. I think there’s a perspective here that the RNA world never disappeared, just became symbiotic with higher-order protein structures. On one hand, RNA viruses continue to replicate successfully (i.e. SARS-nCoV-2) and on the other we rely on rRNA, tRNA and mRNA to function as a highly-conserved part of cellular function across all organisms.

When I was in grad school my default assumption was that ribozymes (catalytic RNA) are far more abundant than we currently know. RNA just very difficult to work with so there’s a selection bias against our ability to measure its behavior in vivo.

> In a sense we are RNA-based lifeforms. Our protein synthesis machinery is dependent entirely upon RNA.

Yes, we are RNA organisms that have been incorporated into larger organisms, just as we are prokaryotes that have been incorporated into eukaryotes through endosymbiosis.

https://evolution.berkeley.edu/evolibrary/article/_0_0/endos...

Absolutely the comparison I was intending to convey! Biology is a messy and beautiful place filled with competition and cooperation. :)

As much as 8% of our DNA was laterally transferred from viruses! In a sense, some infections result in a symbiosis with a host.

https://en.m.wikipedia.org/wiki/Endogenous_retrovirus

Lateral DNA transfer is awesome. Check out this visualisation of the molecular apparatus assembled on the surface of a bacterium to inject a chunk of DNA into a neighbouring bacterium.

Type 4 secretion system: ii- Pilus biogenesis

https://www.youtube.com/watch?v=ihlFqOK5cZM

What parent commenter was wondering - if prokaryotes didn’t die off when eukaryotes appeared, a question is why non-cellular life disappeared when cellular life appeared.

Even if cellular life has a huge evolutionary advantage we should still find pockets of original life somewhere.

I think you're basing this on a false premise. There's no rule that states that every life form that ever existed must have any descendants. In fact the opposite is true, the vast majority of life forms were exctinct.

Famous case in point are the Ediacarean fossils in Newfoundland, the first known multicellular organisms. No descendants live today, they are completely extinct. Without these fossils we wouldn't even be aware of this branch of the evolutionary tree.

Maybe we can't find it because we don't know how it looks like? Maybe it's everywhere? If you dig up some dirt and sequence the genome, you find tons of DNA and RNA but for most we have no idea about what it does. Likely once we find the first pre-cellular life (if it exists), we'll figure out what to look for and then suddenly it'll appear everywhere.

Another thing is that the current world is more hostile to RNA. Anyone who has ever worked with RNA will tell you that you need to be very careful during the preparation to avoid contamination with ribonuclease enzymes that degrade RNA. We're covered in them.

This comment and its sibling is very interesting to me, because it's something I hadn't heard before.

Why are ribonuclease enzymes so omnipresent?

Is this the only reason why RNA is so difficult to work with, or are there other technical hurdles that are more difficult to overcome?

Are we missing a big piece of the biological puzzle because of this?

Any recent developments in this area?

RNA is a less stable molecule than DNA — it can be single-stranded, form double strands, self-pair (form loops), react readily with proteins... just difficult to deal with. On top of that, as mentioned, RNAses (enzymes that destroy RNA) are everywhere. Your skin secretes them as an anti-pathogen defense against viral RNA [0]. So do a plethora of other living organisms including single-celled bacteria ubiquitous in the atmosphere and on surfaces.

I haven’t heard of any recent developments — it’s been a decade since I was in grad school and now I build software — but I briefly studied a subcategory of ribozyme called self-splicing group I introns which is where my interest comes from.

[0] https://en.m.wikipedia.org/wiki/Ribonuclease

[1] https://en.m.wikipedia.org/wiki/Group_I_catalytic_intron

> In addition, active RNA degradation systems are a first defense against RNA viruses, and provide the underlying machinery for more advanced cellular immune strategies such as RNAi.

Huh... today I learned. I didn't realise we have such "low-level" immune defences, I always just assumed that the simplest defence we had were antibodies.

Is that an antiviral defense or something else?

It might just be that DNA has a better sweet-spot in terms of mutation probability, useful for evolution, and robustness, important for survival and transmission of useful genetic information.

To add on to that (sorry, I think it's a very exciting topic): it's hypothesized that virions (a virus-like 'thing' that infects plants) are descendants of such RNA life that evolved to be parasitic.

Interesting. That still doesn't give us any nonparasitic or non-symbiotic survivors. Merge with it, feed on it or go extinct.

A problem with RNA world is that RNA, and even ribose, is not very stable. It's not very plausible that the components of RNA could be present in pure forms that could allow faithful RNA replication, even ignoring energy needed for that.

RNA viruses do exist. After a certain length, the instability issues you point out cause problems, so usually they have a shorter genome. But I'd say that earliest life forms had shorter genomes anyways. Also, not every copy has to work out. You can see that with viruses, there are viruses where errors in manufacturing render most created viruses inactive.

RNA viruses exist. They exploit the highly "artificial" conditions inside living cells, where these unstable components are constantly being constructed and undesirable chemicals excluded.

A primordial soup, without the precision enzymes and constant energy expenditure of this synthetic machinery, will be a grab bag of random glop. In Miller-Urey experiments the concentrations of any particular chemical decline exponentially with the number of atoms in that chemical. I believe ribose has never been seen in any such experiment (and certainly not in any but extremely low concentration), never mind the triphosphorylated nucleotides that provide the energy to drive RNA synthesis.

A part of the hypothesis about the RNA world is correct, but all of it seems very unlikely. It is almost certain that DNA appeared later than RNA, probably in some kind of virus.

Also, it is a logical necessity that the transcription of RNA into proteins, including the ribosomes and the transfer RNAs appeared only later than the replication of RNA.

The part of the RNA world hypothesis that seems unlikely because it has very few supporting data is that the original biocatalysts a.k.a. enzymes were RNA molecules unlike anything that exists today.

In my opinion, it is far more likely that the first enzymes were non-ribosomal peptides, somewhat resembling to parts of the proteins that constitute the enzymes of recent life forms.

ATP and other nucleotides must have existed before RNA as a means to perform condensation (i.e. dehydration) reactions and the copolymerization of the nucleotides must have appeared as some undesirable side reaction, which somehow at some point generated some sort of self-replicating RNA, which was in fact the first virus, because its synthesis could not have any beneficial effects for the hosting life form.

Only after the appearance of the transcription of RNA to proteins, the RNA could evolve into a source of components for the hosting life form so that RNA could change from a parasitic entity to an essential part.

Life forms with RNA (and later with DNA) are analog with microprogrammable processors, because the nucleic acid molecules are memories which direct the synthesis of other components, so you can change the components by writing a different information in the memories, without changing the synthesis machinery. This kind of flexibility was certainly necessary for further evolution.

Life forms before RNA are analog to hard-coded processors. Supposing that they were made with non-ribosomal peptides, there must have been a mechanism by which a complete life form was replicated, by a cycle of reactions were some kinds of peptides were assembled by other kinds of peptides.

Non-ribosomal peptides exist even today in all living beings and they are assembled in the correct sequence from amino-acids without depending directly on the information stored in nucleic acids, like the proteins.

Memories, like nucleic acids, are certainly not necessary for designing an ensemble of molecules able of self-replication, exactly like a memory is not necessary for implementing the control automaton of a processor.

Nevertheless, it is likely that the further evolution of such a primordial life form was almost impossible, because all accidental changes in the structure of the component molecules would have resulted in a replication failure.

After the separation of functions between a memory (nucleic acid) and a generic synthesis machine, evolution by changing the memory content became much more likely to be successful.

You seem to be basing your opinion on two main assumptions, of which one is unknown and one is untrue:

> the original biocatalysts a.k.a. enzymes were RNA molecules unlike anything that exists today.

Why “unlike anything that exists today”? Catalytically active RNA is still ubiquitous and well preserved across kingdoms (they’re some of the most ancient mechanisms for which we have phylogenetic evidence).

> it is far more likely that the first enzymes were non-ribosomal peptides

Peptides are good catalysts but they lack a high-fidelity copying mechanism so they’re not good raw material for evolution.

Taken together, your hypothesis seems to be based on a disbelief that RNAs lost their catalytic capability (which isn’t actually the case), but conversely you readily accept (without any evidence) that peptides used to have replication capabilities that were lost without a trace.

> Non-ribosomal peptides exist even today in all living beings and they are assembled in the correct sequence from amino-acids without depending directly on the information stored in nucleic acids, like the proteins.

Can you give an example of a catalytically active polypeptide which is assembled without any RNA template? I can’t think of any.

> Memories, like nucleic acids, are certainly not necessary for designing an ensemble of molecules able of self-replication

No, but what’s necessary is some kind of structure that records bits of information in some kind of order, and a mechanism for reading and writing this. Individual oligopeptides are fundamentally insufficient, you need structures capable of larger assemblies, and the information of these assemblies needs to be recorded. RNA elegantly solves both these requirements. DNA solves the storage requirement but is a very bad catalyst. Peptides solve the catalytic part of the requirement but are bad information store (prions can store specific configurations but they don’t seem to generalise).

It’s hard to overstate how important this information storage requirement is for evolution — arguably much more important than even marginally efficient catalysis. To the extent that some (admittedly far-fetched) hypotheses for early life even posit carriers such as clay minerals [1] which have, to a close approximation, zero catalytic capability — simply because they’re such an attractive medium for storing information (in the form of crystal lattice surfaces), high fidelity replication (through deposition of a new layer of minerals), and mutation (through structural modifications of the surface which are carried over through generations).

[1]: https://en.wikipedia.org/wiki/Graham_Cairns-Smith

You are right that are examples of RNA that functions as a catalyst, e.g. inside the ribosomes and in the spliceosome.

While the known functions of catalytic RNA are indeed, as you say, ubiquitous, very important and they certainly were already present in the last common ancestor of all present cellular living beings, none of those functions are likely to be so ancient as to have existed in the first life forms.

The nucleotides that compose a RNA molecule do not have chemical properties that are different enough to allow RNA to have a versatility comparable with the peptides/proteins, which can be used to make catalysts for a much wider range of chemical reactions and which can be attached to membranes for some of the most important functions, e.g. for ionic pumps.

While the number of amino-acids must have been much smaller in the beginning, it is likely that about 6 were already in use, i.e. alanine, a hydrophobic (valine), an acid (aspartic), an alcohol (serine) and 2 with unusual forms (glycine and proline) that can determine how the peptide will coil and fold.

The variety of amino-acid properties, even in the minimal set, allows the implementation of much more functions than can be imagined for RNA.

I am not aware of an example of a catalytically active polypeptide which is assembled without any RNA template, but that is not very relevant, because there is no doubt that, after the appearance of the transcription of RNA into proteins, most non-ribosomal peptides must have been replaced by more complex proteins, which were able to perform a more specific and faster catalysis.

I do not agree that "what’s necessary is some kind of structure that records bits of information in some kind of order".

On the contrary, this is what is impossible to have existed and it is the main reason why RNA must have been a later invention, after self-replicating life forms already existed for a long time.

What I say here about RNA, is valid for any other kind of molecular memory, so it is unlikely that any other polymer was used before RNA, as in some hypotheses.

Any other function of RNA besides the self replication of the RNA molecule must have appeared only much later, after a long evolution of RNA.

The reason is that even if any kind of useful RNA molecule, e.g. a catalytic ribozyme, ever appeared earlier, it disappeared without descendents, because it was not replicated.

So, if the RNA replication was the first function, that requires both the presence of ATP and of the other nucleotides and of some macromolecule that will catch the nucleotides and link them into the RNA molecule, using as a template the RNA that is replicated.

Even if we assume that the actual catalyst of the RNA replication was also a RNA molecule, that leaves open the source of the component nucleotides.

There must have already existed a catalytic system that transformed the simple precursors from the environment into ATP and other nucleotides through a long chain of reactions.

There exists no other better hypothesis for the nature of those catalysts than that they were non-ribosomal peptides resembling the active segments of the present-day enzymes that are used for those reactions.

Like I have already said, it is a logical impossibility for any kind of information-recording molecular memory to have existed since the beginning.

The way how the still existing non-ribosomal peptides are assembled in the correct sequence in the present-day organisms is not known well. Also the way how membranes are assembled is not known well. We have much less information about these than about nucleic acid replication and protein synthesis, for which a large number of investigative tools have been developed.

In any case, it is possible to imagine (and I believe that the attempt to design such a system would be a worthy research subject) a self-replicating system without any molecular memory, where some kind of peptides directed the assembling of another kind of peptides, which directed the assembling of another kind of peptides and so on for several steps, until the cycle was closed and the last kind of peptides directed the assembling of the first kind.

Of course, that must not have been just a simple cycle but a network of reactions, to generate all the components of the life form, but the network of reactions must have included all the cycles required to ensure that the complete replication of the life form is done.

In conclusion, you are right about "how important this information storage requirement is for evolution" and I have already written in a previous post that the evolution of the complex living beings of today could not have happened without the invention of a molecular memory.

Nevertheless, it is impossible for any such information storage mechanism to have already existed since the origin of life.

Good point. See my reply to paulryanrogers

Conway's game of life shows how small building blocks randomly create giant crazy complicated formations that have the capability to do astonishing things, like replicate themselves in an organized way. Kind of implying that logically functional structures arise from randomness given enough time. The rules in Conway's game of life are simpler than real world physics, but it is enough to convince me that in a reasonable time frame (Earth's timeline), given enough building blocks and iterations, there's not really any reason to not assume the chemical building blocks of life happened to create all sorts of complicated structures that constantly failed to replicate or survive.

On Earth, there was a lot of primordial soup, and there were a lot of chemical reactions. On a span of millions of years, complex data structures (such as RNA) may have occurred constantly somewhere on the planet. Every now and then, a cell randomly formed. Sometimes prokaryotes with RNA formed, like weird things in Conway's game of life. And then maybe once upon a time, a cell with just the right RNA to make it be able to reproduce in the ooze formed.

That or life on Earth is panspermic and we have skipped the pre-prokaryotic evolution altogether

> The rules in Conway's game of life are simpler than real world physics

This is tricky. Conway's rules are "simpler" but far more rigid (e.g. tractable/computable). In real life, we deal with not just plain ol' turbulence (Navier–Stokes three-dimensional existence is yet to be proved), but also quantum effects (some of which might also not be computable, such as entropy in a Hamiltonian system).

I'd say it's ultimately hard to argue if these more random constraints (compared to Conway's game of life) are more _helpful_ or _harmful_ towards the ability to produce life or life-like structures.

> ...more random constraints

Want to point out that this is much more than simply "random" constraints (the universe isn't merely a probabilistic machine). These are not (or at least might not be) computable constraints; any comparison with Conway's Game of Life stops right there.

Perhaps not Conway's version, but a 3 dimensional cellular automaton with 50-100+ states for each cell could very likely result in intelligent life over a large timeframe.

Greg Egan discusses a similar idea with his concept of the "Autoverse"

> The big question isn't how simple molecules (building blocks) come about. [...] but there is nothing in between the primordial chemical soup and the simplest life forms.

There's a view that the early evolution of "life" involved metabolic cycles that were not yet bounded in cells, but perhaps in increasingly constrained geological boundaries. So for example, early precursors to the Krebs Cycle may have started within oceans, or perhaps some arrangement of pools and geysers or other geological features. So in essence, early life was bounded not in membranes, but within the flows of rock and air and heat of the atmosphere itself.

For more citable references to this stuff, this podcast episode from the Santa Fe Institute touches on it: https://complexity.simplecast.com/episodes/40

There's a lot of vague handwaving like that. But that's really all it is.

It's possible there was once an abundance of such life and they were too simple to be preserved in the fossil record. And now that life has leveled up and conditions have changed such forms are rare or non-existent today.

Something like that yea. But what could have changed so radically that it would kill every trace of those simpler life forms? Anaerobic bacteria thrive despite the oxygen rich atmosphere. One would expect at least a trace of these simpler life form if not an abundance. What environment existed 4 billion years ago that is totally gone today? Thats the more interesting question to me.

A pet theory of mine is that they simply were out-competed. If these processes require chemical concentration 100X over timespan 100X to form de-novo, but a basic prokaryotic structure may only require concentration 1X over timespan 1X, that could make de-novo synthesis entirely unfavorable. Once those prokaryotic structures propagate enough, it could be reasonable that the conditions for de-novo genesis would no longer be routine enough that it would play an observable role today. This also helps make sense of why more complex organisms would form de-novo - they would be entropically more stable ("Filling a niche").

> A pet theory of mine is that they simply were out-competed.

This is the (by far!) most prevalent expert opinion.

> What environment existed 4 billion years ago that is totally gone today?

One with no complex lifeforms but sufficient resources to support life seems like the obvious answer.

Also, you can't really ignore the transformative effect that life has had on all environments (underwater and on land) in terms of chemical composition. Less water, less oxygen, etc.

Presumably the evolution of cellular life was synergistic with the evolution of the environments on the planet?

If those simpler life forms existed it's almost certain we've loads of traces, it's just we can't distinguish them from noise because they've degenerated so far. It's like looking for fossil structures in crude oil - crude oil is remnants of life but is mainly long carbon chains. Very little if any structure remains.

Analogy #2: your great-great-...-great grandparents of 10,000 years ago unquestionably existed, but show me any direct evidence they did. You can't. All signal is gone.

Very nice question. Perhaps this could hint towards primordial life structure to be from outside our planet?

not simple, just not fossilized. complex things would not have been fossilized if they were not in an area conducive to fossilization. natural selection assumes rapid iteration, so for every evolution tree, you have to imagine thousands of more variants at each step, not shown and not fossilized.

Yeah I was thinking I should've written 'fragile'. And many environments aren't suited to preserving evidence for billions of years.

RNA life forms do still exist: they're inside more complex cells. These simpler life forms just came together into cells in a stable arrangement that was able to replicate itself, and evolution took care of spreading them over.

>I would expect a huge mass of simple RNA based life forms simpler than prokaryotes.

There is such a mass: viruses. As such, we know that cellular life has evolved multiple mechanisms to efficiently kill external RNA.

If cellular life can efficiently outcompete non-cellular life for resources (and perhaps for RNA itself), then this outcome is not unreasonable at all.

Counter-example: There are (far) more Homo sapiens on the planet than other primates in total.

Isn’t the big question how matter exists at all?

My outlook is that things just exist in some higher dimension but because we perceive things in 3D we wrongfully assume there needs to be a start/end.

Look inside a box of mirrors at the infinitely repeating pattern and ask yourself where it begins/ends?

Curious to hear how other people rationalize the irrational.

This has been bugging me quite a bit recently. The model I keep coming back to is some giant cellular automata embedded in a some sort of higher dimensional compute structure —- perhaps what we call the “big bang” was the randomly initialized start state, and everything since has been its update algorithm ticking along with an encoding of what we call “physics”. This plays interestingly with things like quantum mechanics - perhaps they’re the underlying implementation of “Math.random()” and things like entanglement are implementation details leaking through. Similarly, perhaps wave/particle duality is the result of some sort of legacy code built to deal with light as particles that got shoehorned into the current implementation’s wave-based approach (easer to simulate at-scale), and it only gets activated when the results are under observation!

It, like every proposed answer to the existential question, is both unverifiable and unrefutable, making pondering it somewhat pointless. Though it is good to know even our proposed higher-dimensional overlords haven’t solved the problem of leaky abstractions!

I had a pet theory that Plank Time is the clock-step (or mantissa precission) of our simulation. :)

A global clock can't exist.

https://en.wikipedia.org/wiki/Relativity_of_simultaneity

Who said anything about global? Each “cell” (elementary particle? string?) in the automata could be responsible for its own update function, based on its own clock ticking along at its own plank time.

Plank Time would be the smallest size of a grid in that Wikipedia animation.

There's an idea I really like that if we ever reach "the end" of pi then that's strong evidence that we're in a programmed world.

You cannot reach the end of pi:

https://en.wikipedia.org/wiki/Proof_that_%CF%80_is_irrationa...

Yes, that's the whole idea. Pi is infinite, so if we ever get to the end of pi or it starts repeating, it means whatever is simulating our universe has finite resources. There are a lot of issues with this idea, but I like it. I doubt we'll ever find the end of pi, though.

>My outlook is that things just exist in some higher dimension but because we perceive things in 3D we wrongfully assume there needs to be a start/end.

This is a thought I've often had as well. Like we exist on an X-Y coordinate plane, but there's a Z axis we just can't access. Particles popping into and out of existence? Just moving along the Z axis (our entire existence is on a single scalar value on that axis). GR and the "warping of spacetime"? Well, the bowling ball on a trampoline analogy obviously requires an extra dimension beyond the 2D trampoline surface to warp into. EPR and Bell's Theorem, viz no local hidden variables? Well, there's the non-locality. I'm not a physicist and this is all obviously a vast oversimplification, but it just seems that so many fundamental questions are confounding because they all seem to point to a missing degree of freedom.

the way I deal with it.....

Don't come up with weird ass theories and posit them as true or even "possible". Things we don't have good evidence for, at best, can be said to be "an intriguing idea". They are fun to ponder, and help us consider what possibilities could lead to better descriptions of the cosmos, but they don't lead to any actual understanding of what is real

So the best thing for a lot of these questions is to get good at going "I don't know" and instead trying to understand what we do know. We have a bunch of problems to solve about the universe (dark matter / quantum gravity) that may change the nature how we might even ask this kind of question. So I mainly focus on what's the most we can know with reasonable certainty at the moment.

> Isn’t the big question how matter exists at all?

I think the big question is why we experience the existence of matter.

Matter exists because we observe it to collapse it into existence. Without humans there would be no universe ;)

Greg Egan's Quarantaine explores this idea.

There is also too many unknowns and assumptions about the goal.

From what I can tell, the best science right now is that if you simply put enough neurons in the same place, they'll start questioning the universe.

Why do these building blocks in some circumstances do anything? Why do they make life, or sentience, or even something to reproduce when the building blocks don't need to reproduce at all - nothing new is created or destroyed just the same building blocks being recycled in different configurations. Why would the building blocks go beyond the mere reproducing-life to something that thinks unnecessarily? All an accident that we can appreciate?

From one point of view, nothing is necessary. Life is not necessary, planets are not necessary, matter is not necessary.

From another, thinking is as necessary as anything can be. We observe thinking, therefore it exists. Anthropic principle.

One interpretation is entropy increases at the maximum rate although such an assumption cant be derived.

More complex life is more anthropic than simple life and is then an eventuality.

> There are more prokaryotes than eucaryotes, more singe celled than multi celled etc. but there is nothing in between the primordial chemical soup and the simplest life forms. I would expect a huge mass of simple RNA based life forms simpler than prokaryotes.

This is an interesting perspective.

Following this line of reasoning, prokaryotes must be close to the simplest unit that can self-replicate and grow to fill the planet. The simpler “proto-life” forms before that built up complex molecules by chance but could never quite achieve a replicative cycle.

Perhaps the closest to a huge mass of simple RNA based life forms that still exist today are viruses.

They must have achieved many replication cycles, but presumably proto-prokaryotes were much more efficient replicators and outcompeted their ancestors.

Viruses depend on the existence of complex structures (the machinery in cells) to replicate themselves, so I don't think it's valid to point to one as an organism in the same sense as a prokaryote.

Prokaryotes depend on the existence of complex structures (the world outside) to replicate themselves. Yours is not a good example.

That aside, people have argued that the viral particle is like a gamete, which is also an incomplete stage of life unable to replicate itself. It would be like calling a sperm a human and saying humans are therefore parasitic and not living. A virus's primary life stage is lived within the environment of the cell which it commandeers, and from where it sends its progeny. The whole commandeered cell is the viral organism, and very much living.

Invalid argument. Bacteria exist that can grow in very simple media with low structure. Viruses canmot. They absolutely depend on the existence of a very complex replication machinery.

Which evolved first cellular metabolism or replication ? Without replication you can't have evolution. Without metabolism you don't have a system to support replication. (What Is Life? by Erwin Schrödinger 1944)

Interesting read around that question: Stuart Kauffman’s At Home in the Universe: The Search for the Laws of Self-Organization and Complexity

Could someone point out a good eli5, recent book about this topic? From building blocks and their physics to membrane/rna/dna and so on?

Thank you.

The Vital Question, by Nick Lane is a pretty good book that takes a thermodynamics first approach to this question.

This is a very good recommendation.

There are several other publications on this subject by Nick Lane, which can be easily googled, and all of them are good.

They are somewhat incomplete, because there are parts that are not covered, especially about what is known on the metallic catalysts that were required for the emergence of life, but overall, the Nick Lane publications are the best from what I have seen.

Thank you!

You're right but the thing you're talking about isn't life. It's a precursor to life. Life would stick around but the precursor wouldn't. It's like a hot flash in a pan starting a more sustainable housefire. The flash is gone by the time the fire is raging.