Stairway to Life by Change L. Tan and Rob Stadler

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41

Racemization in amino acids is known, that’s an example of the natural direction of isomer populations reaching a distribution consistent with the law of large numbers. I’m not the first to point out the relation!

The law of large numbers determines that, in the absence of any chiral polarization, the racemic composition will always be obtained.

Spontaneous mirror symmetry breaking and origin of biological homochirality - PMC

But in non-equilibrium systems, the law of large numbers can be over-ridden, that’s why plants can catabolize D-amino acids.

Amino acids may be made homochiral by a variety of mechanisms, but not so easy with nucleotides and the issue of homogenous linkage. These problems are described by the law of large numbers. Of course a machine can be built to overcome these problems – such as a man-made Sigma Aldrich DNA synthesis machine or a God-made cell, not a random chemical soup.

The point is, a route to a dissipative structure which will overcome problems posed by the law of large number needs to be solved by OOL research.

But that only scratches the beginning of problem since this is only a couple of steps in the Stairway to Life.

42

The law of large numbers says absolutely nothing about which direction amino acids should racemize. That is an empirical question. Once the rates have been empirically determined, the law of large numbers can be employed to calculate the overall trend over time.

Guess why the origin of life is thought to be a non-equilibrium process, taking place in an environment that can persist out of equilibrium for a long time(such as the interfaces between land and water, or between water and atmosphere), and not a “random chemical soup”!

I mean it’s ridiculous to keep pointing out as somehow debilitating flaws of the field, things which are taken as basically axiomatic, and understood even better and more comprehensively than you by everyone in the field.

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43

Racemize means 50% L, 50% D. There is only one direction, that is toward the mean of 50% of L (or equivalent 50% of D) – exactly as predicted by the Law of Large numbers and echoed by the paper I cited which said:

The law of large numbers determines that, in the absence of any chiral polarization, the racemic composition will always be obtained.

Chiral polarizaiton is achieved by living organisms, like a plant catabolizing a D-amino acid and then maybe re-assembling its parts into part of an L-amino acid.

44

One point of charitable interpretation for Rob’s video is in order. He mentioned ATP sythase making ATP. That is true. It might seem he’s saying that’s the only way to make ATP, it’s not – well not exactly. The citric acid cycle (plus a GTP conversion) can make ATP:

citric_acid_atp_gtp
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BUT, in the context of oxidative phosphorylation, the source of NAD+ and FAD come from the processes connected to ATP synthase in the electron transport chain:

oxidative_phosphorylation_electron_transport_chain
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There might be other paths to ATP synthesis, but well, the first problem is making an RNA precursor, and Adenine Monophospate or even Adenine nucleoside (Adenosine).

45

You seem to be forgetting simple glycolysis as a source of ATP.

46

Thanks!

BUT, the first step involves ATP converting to ADP via the catalytic action of hexokinase. Isn’t that a bit of a chicken and egg paradox?

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Anyway there might some other primitive ATP generators. Thanks to evograd for pointing that out. Anyone else can weigh in.

47

Not if the first step was circumvented. There’s also a whole bunch of non-enzymatic reactions leading to ATP, see table 3 in this paper:

48

Sure, which is why ATP is thought to have been preceded by another, simpler form of energy currency, such as acetyl phosphate, acetyl thioesters, or other similar molecules that either do not involve nucleotides, or even phosphate.

See for example: Goldford JE, Hartman H, Smith TF, Segrè D. Remnants of an Ancient Metabolism without Phosphate. Cell. 2017 Mar 9;168(6):1126-1134.e9. doi:
10.1016/j.cell.2017.02.001.

Whicher A, Camprubi E, Pinna S, Herschy B, Lane N. Acetyl Phosphate as a Primordial Energy Currency at the Origin of Life. Orig Life Evol Biosph. 2018 Jun;48(2):159-179. doi: 10.1007/s11084-018-9555-8.

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49

There has been no argument advanced so far that shows anything in origin of life research to have actually regressed.

Key challenges and questions that everyone would like answers to, have been pointed out, and then from this we’re fed a stream of “but how could?”-type questions, as if our current ignorance or lack of understanding means we should think no headway is possible on these questions. But that simply isn’t true, and in fact there is historical precedent for the diametrically opposite.
Challenges have been and still are being solved, such as the possibility active metabolite and ion transport across membranes without transport proteins, the nonenzymatic catalysis of the basal carbon fixation pathways, and the formation and stability of lipid bilayer vesicles in sea water and at higher temperatures.

The origin of life is still an unsolved problem to be sure, and a difficult one. But it is simply a falsehood to say it is “regressing”. That is a vacuous talking point.

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50

IIRC the way Stadler frames the “regression” in his conversation with Perry is that because we’ve learned so much about the complexity of life since the 60s, while much less has been learned about how a natural origin of life is possible, the “goal” is now further away than it was in the 60s. In that sense he says there’s more unanswered questions than there was in the 60s, hence “regression”.

51

Someone gave a pretty good analogy in the chat section of the video linked earlier. That’s like saying walking into a dark maze you don’t know the size of, wielding only a flashlight, you later find a lightswitch that allows you to see the total size of the maze. That doesn’t mean you went from a small to a much bigger problem, that means you went from a state of ignorance ignorance of, to appreciation of the scope of the problem. The size of the problem was always the same.

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52

Thanks a million!

53

Cards lying flat on the ground or some flat surface is a highly probable configuration from random orientations and positions and velocities over time for the cards, etc.

cards_random_flat

In contrast, the following is not a highly probable configuration from random orientations and positions and velocities over time for the cards:

cards_pyramid
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The house of cards is improbable in the statistical sense of the space of trajectories that can construct it.

It’s not an artifact of our imagination that the house of cards is improbable. The house of cards is improbable in a way that resists both the Texas Sharpshooter Fallacy

texas_sharpshooter_fallacy
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and the Single Target Fallacy when there are multiple targets available:

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The structure of the house of cards is improbable as a matter of principle, and so are things like DNA in the sense of the requisite orientation and positioning and connection of the monomers that form it. Vague appeals to some other chemical replicating machinery that doesn’t use DNA doesn’t make the emergence of DNA more probable!

Vague appeals to something not directly testable, not provable, not repeatable, not observable – that’s faith, not empiricism. Faith is fine as far as faith goes, but call a spade a spade, please, don’t call it empirical proof, call it FAITH.

Perry referred to RNA replicators as “life”. That’s the equivocation I was talking about – OOL researchers have redefined the problem so as to claim victory, when the problems isn’t making replicators subject to some sort of adaptive evolution. The problem is trying to show the improbable structure of cellular replicators isn’t really improbable – somewhat like trying to show the improbable structure of the house of cards above isn’t really improbable, that some mindless mechanism that obeys random distributions can put it together.

How improbable does something have to be before one accepts a miracle? Jon Perry said he would abandon OOL if there were another scientific research program. That’s reasonable, but if miracles aren’t repeatable, then how how will he, via a research program that searches for repeatable mechanisms ever reasonably infer that a miracle happened IF indeed a miracle was the cause of life? Miracles by definition aren’t repeatable on demand like laboratory chemistry. So Perry won’t get the “proof” of a miracle he is searching for. It is, on some level akin to the problem I posed to Tracie Harris regarding the blind individuals healed by prayer…

Whether life was a miracle is probably an undecidable proposition either way, and it’s something of a faith statement for each side of the argument. Same for the miracles that people may experience in their personal life. This raises the issue of the hiddeness of God and His selective distribution of miracles to some people and not others, (Prov 25:2, Matt 11:23, Matt 11:25, 1 Cor 1:26-29 etc.).

But, what Tan and Stadler’s book has done is shown, it’s premature at best to say OOL has progressed as a discipline in making naturalistic OOL of cellular life look solvable. Asphalt looks like the probable trajectory of biotic precursors, not life.

54

Modern enzymes are not needed to produce oligonucleotides (at the very least) in prebiotic conditions. Rather, a heterogeneous collection of protein-like molecules can do the trick:

Jungck JR, Fox SW. Synthesis of oligonucleotides by proteinoid microspheres
acting on ATP. Naturwissenschaften. 1973 Sep;60(9):425-7. PubMed PMID: 4772133.

55

One of the steps in the stairway of life is the Water Paradox. The paradox was in Steve Benner’s legendary essay on the paradoxes of life.

Water, or some solvent, is needed for transport of molecules, but water is also bad on some levels for life emerging naturally in a water environment.

Spontaneous hydrolysis or at best the inability to effect a condensation reaction in water without an energy source and requisite machinery is a problem for forming various biological chemicals such as biopolymers of RNA, DNA and proteins.

In life, to overcome the problem of the water paradox we have things like polymerases and ribosomes to form biopolymers.

For DNA in life, the reaction to append a monomer such as a dAMP (deoxy Adenosine Monophosphate), dCMP, dGMP, dTMP to a pre-existing DNA requires the corresponding nucleoside triphosphates (dATP, dCMP, dGMP, dTMP). But these nucleoside triphospahtes don’t form spontaneously, nor the corresponding polymerases that catalyzes the reaction. Neither of these components is freely available in a pre-biotic context. Of course one can imagine based on faith some mechanism made it feasible, but it’s has not been demonstrated to be a highly probable scenario.

Similar issues for formation of RNAs from ATP, CTP, GTP, UTP.

Of course, polymerases and (deoxy) nucleoside triphosphates aren’t the ONLY route to making DNA/RNA polymers – one could use man-made intelligently designed Sigma Aldrich/Blue Heron synthesis processes to make them, but these aren’t available in pre-biotic synthesis either!

Then we have proteins. UGH! A ribosome can make them, but well, that’s not available in a pre-biotic environment either. Not to mention, unless one has a way of repeating a recipe (like genes as a blueprint for the protein), it’s not very feasible to randomly assemble proteins and expect the outcome to be life – asphalt is it’s destiny.

And that is a sketch of the water paradox.

The water paradox and the asphalt paradox are not creationist concoctions, those are the probabilities imposed by basic chemistry. And these are only the first steps in the Stairway to Life.

56

Thanks for the reference, I’ll look at it.

57

You’re welcome, but this is the sort of thing I’d expect to be in the book. If they didn’t discuss some of those papers, which I was able to find with 2 minutes of googling, then I have to ask how comprehensive the book actually is, and whether it surveys the entire literature or just a subset chosen to present a particular biased conclusion.

58

The fact that Steve Benner and others in their review papers point out the general problem of Asphalt Paradox, Single Biopolymer Paradox, Water Paradox, etc. is consistent with the Tan and Stadler’s general theme. To argue OOL is highly probable based on some of the papers your google search found would be a biased representation of the state of affairs.

Stairway to Life is not comprehensive, it is for modestly chemistry literate audiences, not OOL researchers.

If they didn’t discuss some of those papers,

That’s partly why I started this thread so we can discuss such papers in more detail. The first issue, as James Tour pointed out, is re-examining the actual feasibility of some of these lab experiments in a realistic pre-biotic scenario. Tour got tired of seeing the same old template where researchers represented lab experiments under unrealistic pre-biotic conditions and representing it as progress toward solving OOL.

Many times the fine print isn’t explored like what happened with Urey-Miller and Sidney Fox and so many other experiments. They were just dead ends and showed more problems for OOL than they actually solved, not to mention in Urey-Miller’s case the assumption of an ammonia atmosphere was unjustified. The Haber Process of making ammonia shows just how hard it can be to even make a simple pre-biotic molecule, not to mention an ammonia atmosphere might not last more than a few hundred thousand years.

Another example is the Formamide hypothesis proposed to solve the water paradox. Does it really solve the paradox, since the formamide hypothesis creates a whole other set of problems, not the least of which is why formamide should be sufficiently abundant on the Earth billions of years ago, why it disappeared, and how life that lived in a formamide environment transitioned to a water environment. That illustrates what I mean about studying the fine print vs. the hype on some of these papers.

We can explore papers here as I want to write some supplements to Tan and Stadler’s book and make it available on the web. It is a good exercise for me to get re-acquainted with chemistry I studied and to also learn new chemistry.

but this is the sort of thing I’d expect to be in the book.

Do you have the book? I’ve combed through their bibliography and it is extensive. Dr. Tan, having to teach molecular biology, was very interested in the issue. The book is only a fraction of her knowledge base (as she is also a physical organic chemist) and I would like to share some of that in this thread that wasn’t in the final version of the book (i.e. some of passages from the first draft that Dr. Tan gave me permission to share, like the 5 forms of deoxyribose in solution that I posted above).

59

Uhh no, you don’t get asphalt from random protein assembly. I think you should take a break from the asphalt argument, it’s starting to come out of the wrong orifice.

60

In other words, rather than consider how, if, and why a host of experimental results undermine Stadler’s conclusion about the putative unfeasibility of the origin of life, and his claim that it is “regressing”, you want to try to come up with just more fancy technical-sounding ways to dismiss all the work done in the field.

Here’s a suggestion for something to write on your website:
I, Salvador Cordova, and by extension all Creationists who have made similar insinuations based on similar such arguments, was wrong to suggest that the field of origin of life studies is in some sense regressing or appears hopeless, on the basis of an argument I made that you need complex transport proteins to get metabolites, ions, and waste products in and out of lipid vesicles, because such a mechanism operating on simple physical principles entirely without transport proteins is actually known and has been experimentally verified.

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