The Alchemy and Biochemistry of OOL

[peter2...@gmail.com]

First off, let's give the alchemists of the middle ages their due: they
came up with a goodly number of useful things, including sulfuric acid,
which is essential to so many manufacturing processes.

It is in that spirit that I refer to the following as belonging to the "alchemy of OOL":
the Miller-Urey experiment of 1953 and research in the intervening 70 years
to produce amino acids, nucleotides, lipid vesicles, sugars, etc. under primitive earth conditions.

After seeing a testy comment by Athel Cornish-Bowden distinguishing sharply
between the biochemistry of life (about which Athel wrote a whole book)
and the biochemistry of OOL (the Origin of Life, a.k.a. abiogenesis),
I've decided to use the phrase "biochemistry of OOL" to refer to those
prebiotic phenomena that tend in the direction of ribozymes, and beyond.

Ribozymes are enzymes composed of RNA rather than the far better known
ones that are proteins. Enzymes are essential to OOL because they drive
reproduction of prebiotic molecules, including new ribozymes.

There are experiments that advance the biochemistry of OOL, and I plan to discuss
the ones I know about later today. In my next post I will enlarge upon that
phrase, "including new ribozymes," and make some comments on the concept of "RNA World."


Peter Nyikos
Professor, Dept. of Mathematics -- standard disclaimer--
University of South Carolina
http://people.math.sc.edu/nyikos

[Gary Hurd]

On Monday, September 4, 2023 at 1:55:25 PM UTC-7, peter2...@gmail.com wrote:
> First off, let's give the alchemists of the middle ages their due: they
> came up with a goodly number of useful things, including sulfuric acid,
> which is essential to so many manufacturing processes.
>
> It is in that spirit that I refer to the following as belonging to the "alchemy of OOL":
> the Miller-Urey experiment of 1953 and research in the intervening 70 years
> to produce amino acids, nucleotides, lipid vesicles, sugars, etc. under primitive earth conditions.
>

> Peter Nyikos

“Ignorance more frequently begets confidence than does knowledge: it is those who know little, and not those who know much, who so positively assert that this or that problem will never be solved by science.” – Charles Darwin “The Descent of Man, and Selection in Relation to Sex” (John Murray, London, 1871) vol. 1, p. 3.

My reading recommendations on the origin of life for people without college chemistry, are;

Hazen, RM 2005 "Gen-e-sis" Washington DC: Joseph Henry Press

Deamer, David W. 2011 “First Life: Discovering the Connections between Stars, Cells, and How Life Began” University of California Press.

They are a bit dated, but are readable for people without much background study.

If you have had a good background, First year college; Introduction to Chemistry, Second year; Organic Chemistry and at least one biochem or genetics course see;

Deamer, David W. 2019 "Assembling Life: How can life begin on Earth and other habitable planets?" Oxford University Press.

Hazen, RM 2019 "Symphony in C: Carbon and the Evolution of (Almost) Everything" Norton and Co.

Note: Bob Hazen thinks his 2019 book can be read by non-scientists. I doubt it.

Nick Lane 2015 "The Vital Question" W. W. Norton & Company

Nick Lane spent some pages on the differences between Archaea and Bacteria cell boundary chemistry, and mitochondria chemistry. That could hint at a single RNA/DNA life that diverged very early, and then hybridized. Very interesting idea!

Nick Lane
2022 "Transformer: The Deep Chemistry of Life and Death" W. W. Norton & Company

In this book Professor Lane is focused on the chemistry of the Krebs Cycle (and its’ reverse) for the existence of life, and its’ origin. I did need to read a few sections more than once.

[peter2...@gmail.com]

On Monday, September 4, 2023 at 4:55:25 PM UTC-4, peter2...@gmail.com wrote:

> I've decided to use the phrase "biochemistry of OOL" to refer to those
> prebiotic phenomena that tend in the direction of ribozymes, and beyond.
>
> Ribozymes are enzymes composed of RNA rather than the far better known
> ones that are proteins. Enzymes are essential to OOL because they drive
> reproduction of prebiotic molecules, including new ribozymes.
>
> There are experiments that advance the biochemistry of OOL, and I plan to discuss
> the ones I know about later today. In my next post I will enlarge upon that
> phrase, "including new ribozymes," and make some comments on the concept of "RNA World."

That phrase has to do with what I have called, in several threads,
"The First Holy Grail of OOL." By this I mean the production,
under simulated prebiotic conditions, of an RNA replicase.

An RNA replicase is an enzyme that can take ANY string of RNA in a medium
with an adequate quantity of the four RNA nucleotides, and catalyze
the production of the complementary string. This includes doing it with a speed
of a magnitude not far from the speed at which existing RNA replicases do it.

The catch here is that the existing RNA replicases are *protein* enzymes,
and there is no way to get them in OOL except by going through
*ribozyme* RNA replicases. And here is the big problem: we have
no clue as to what the chemical formula [meaning the sequence of its nucleotides]
of a ribozyme RNA replicase could possibly look like.

In fact, the only reason we know about *protein* RNA replicases is
that they are found in some kinds of viruses. Were it not for that,
we would be very much in the dark about what protein RNA replicases
could possibly look like.


Now, on to the messy topic of RNA World. The Wikipedia entry
on it, with all its uncertainties about the order in which stages (such as "RNP world")
came about, is not conducive to a coherent discussion.

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

Accordingly, I propose to discuss what I call "RNA-run World." This is a "super-stage"
that begins with the first ribozyme, has the First Holy Grail as one of its main benchmarks,
and ends only with the Final Holy Grail, where ribozymes are replaced by protein enzymes
in the final stage of what is commonly called "the protein takeover."

Peter Nyikos
Professor, Dept. of Mathematics -- standard disclaimer--

Univ. of South Carolina at Columbia
http://people.math.sc.edu/nyikos

[peter2...@gmail.com]

On Monday, September 4, 2023 at 5:30:25 PM UTC-4, Gary Hurd wrote:
> On Monday, September 4, 2023 at 1:55:25 PM UTC-7, peter2...@gmail.com wrote:
> > First off, let's give the alchemists of the middle ages their due: they
> > came up with a goodly number of useful things, including sulfuric acid,
> > which is essential to so many manufacturing processes.
> >
> > It is in that spirit that I refer to the following as belonging to the "alchemy of OOL":
> > the Miller-Urey experiment of 1953 and research in the intervening 70 years
> > to produce amino acids, nucleotides, lipid vesicles, sugars, etc. under primitive earth conditions.
> >
> > Peter Nyikos

> “Ignorance more frequently begets confidence than does knowledge: it is those who know little, and not those who know much, who so positively assert that this or that problem will never be solved by science.” – Charles Darwin “The Descent of Man, and Selection in Relation to Sex” (John Murray, London, 1871) vol. 1, p. 3.

Is this a clueless attempt to read my mind?

If so, stay posted. You may be in for a surprise as to how far I am
from pronouncing it impossible. But it will take some serious, intensive
research in what I call "the biochemistry of OOL", perhaps 70 additional
years, to get to what I call the First Holy Grail of OOL. See my second post to this thread
for what I mean by that.

>
> My reading recommendations on the origin of life for people without college chemistry, are;
>
> Hazen, RM 2005 "Gen-e-sis" Washington DC: Joseph Henry Press
>
> Deamer, David W. 2011 “First Life: Discovering the Connections between Stars, Cells, and How Life Began” University of California Press.

Without getting into biochemistry, these will be like the things I read in my
adolescence which made me think that, to closely paraphrase Gould,
"Life is as inevitable as quartz" on a planet that has the bare essentials for it.

And, thinking of cells as "bits of the jelly-like substance called protoplasm", I envisioned
a process of making them that is very much like the alchemy of the middle ages,
only with modern chemicals and equipment.

I got two rude shocks in 1996: _Vital Dust_, by Nobel Laureate biochemist Christian deDuve,
who got only a bit further along in his theory than what has been accomplished in the last 70 years,
and then skipped all the way over to the biochemistry of life, which Athel pronounced as
being utterly different than the biochemistry of OOL.

The other, which confirmed my worst suspicions of deDuve's rhapsodic book of the genre
(though not on the lowly level) of those two books, was _LIfe_Itself_ by another Nobel Laureate
biochemist, Francis Crick. The book teaches basic biochemistry in a highly readable way
(unlike deDuve's) and then makes good on the words,

"An honest man, armed with all the knowledge available
to us now, could only state that in some sense, the
origin of life seems at the moment to be almost a miracle,
so many are the conditions which would have had to have
been satisfied to get it going."
--_Life Itself_, Simon and Schuster, 1981, p. 88.

There are trolls whose knee-jerk reaction is to look at the date and then,
without a clue as to how little progress there has been since then,
will claim that those words are obsolete. They aren't.

> They are a bit dated, but are readable for people without much background study.
>
> If you have had a good background, First year college; Introduction to Chemistry, Second year; Organic Chemistry and at least one biochem or genetics course see;
>
> Deamer, David W. 2019 "Assembling Life: How can life begin on Earth and other habitable planets?" Oxford University Press.

Can you give me one reason why this does NOT belong to the Alchemy of OOL?
The description on Amazon.com strongly hints that it belongs squarely there,
except for the following highly anomalous bit:

"For instance, how did nonliving organic compounds assemble into the first forms of primitive cellular life?"

Short answer: they didn't. Life is the endpoint of vast detours in what I call
"the biochemistry of OOL." Small wonder you deleted everything I wrote about that in my OP.

I was originally planning to give readers some insight into research on "the biochemistry of OOL"
today, but it's getting late and I have some pressing commitments to my students
and my family, but it will have to wait until tomorrow, perhaps already the morning.


The titles of the other books you tout below sound at least as suspiciously irrelevant
as the one of Deamer.

>
> Hazen, RM 2019 "Symphony in C: Carbon and the Evolution of (Almost) Everything" Norton and Co.

The reckless optimism reminds me of that of Cairn's-Smith on the magic of clays. See:
https://en.wikipedia.org/wiki/Graham_Cairns-Smith

With the hindsight of decades, he comes across as a bit of a crank. The RNA nucleotides his clays
polymerized are almost surely evolutionary dead ends, like the proteinoids of Fox are known to be.

>
> Note: Bob Hazen thinks his 2019 book can be read by non-scientists. I doubt it.

> Nick Lane 2015 "The Vital Question" W. W. Norton & Company

Title reminiscent of _Vital Dust_, see above. How good is his understanding of the biochemistry of OOL?

> Nick Lane spent some pages on the differences between Archaea and Bacteria cell boundary chemistry, and mitochondria chemistry. That could hint at a single RNA/DNA life that diverged very early, and then hybridized. Very interesting idea!

I think Athel Cornish-Bowden would just call it naive, were he interested in discussing OOL.
But the smart money says he isn't interested, because he could burst the bubble of many here,
including yourself, on how much y'all think we understand of OOL.
And that's the last thing he wants to do.

>
> Nick Lane
> 2022 "Transformer: The Deep Chemistry of Life and Death" W. W. Norton & Company
>
> In this book Professor Lane is focused on the chemistry of the Krebs Cycle (and its’ reverse) for the existence of life, and its’ origin. I did need to read a few sections more than once.

The Krebs cycle belongs to the biochemistry of life, not OOL, and you need to make a case
for the reverse cycle being relevant to that of OOL. Do you feel up to it?

Peter Nyikos
Professor, Dept. of Mathematics -- standard disclaimer--

Univ. of South Carolina in Columbia
http://people.math.sc.edu/nyikos

[peter2...@gmail.com]

Problems with my laptop kept me from posting at all to talk.origins yesterday,
but now I am ready to post on recent experiments in the biochemistry of OOL.

> I've decided to use the phrase "biochemistry of OOL" to refer to those
> prebiotic phenomena that tend in the direction of ribozymes, and beyond.
>
> Ribozymes are enzymes composed of RNA rather than the far better known
> ones that are proteins. Enzymes are essential to OOL because they drive
> reproduction of prebiotic molecules, including new ribozymes.
>
> There are experiments that advance the biochemistry of OOL, and I plan to discuss
> the ones I know about later today.

That's been postponed, but here it is now.


Jack Szostak is one of the top researchers in OOL. Recently he gave a fascinating lecture,
available on YouTube in two different sites, on recent research in the subject:

https://www.youtube.com/watch?v=ZLzyco3Q_Rg
The Origin of Life: Not as Hard as it Looks? Jack Szosta[k], Spring 2023 Eyring Lecturer

https://www.youtube.com/watch?v=U841Zrd4C5g
Scientist Stories: Jack Szostak, The Origin of Life Not as Hard as it Looks


A MUCH better title would have been, "A Few Isolated Steps in the Origin of Life Are Not as Hard as they Look." This is especially evident in the 35 minute Q&A session in the end, after the 55 minute lecture itself.
In that session, Szostak confesses to much current ignorance about some key steps in OOL.

In one answer, he just talked about the current way in which proteins are produced
rather taking the opportunity to talk about how that complicated,
yet beautifully interactive mechanism could possibly have arisen.
This is one of the hardest and latest series of steps on the way to life as we know it.
[The questioner starts at about 1:06 and the answer ends about 1:06:40.]


However, he did describe several experiments which do shed a bit of light on the early steps.
I had a hard time seeing the point of one of them, at first, and made the following comment
on the webpage for the second video listed above:

"At one point in the film, between the ca. 13:00 minute point and the ca. 13:50 point, Szostak completely abandons the project of trying to re-create prebiotic conditions or simulating something like natural selection. Instead, he talks about an unspecified number of "generations" of RNA molecules in the laboratory, in which the human experimenters carefully select the mutants that are in the direction of "molecules that do uh what we want okay."

[RNA molecules are strings of the four RNA nucleotides in a specific order; the order is
their chemical formula.]

The "what we want" is to bind an ATP molecule; at this Szostak & co. succeeded, but at the price
of looking like they were researching Intelligent Design, even to the "what we want"
simulating teleology (purposiveness), which was kicked out of empirical science a century ago
where all but the higher animals are concerned.


However, appearances are deceiving. This procedure is the best way we currently have
of learning what ribozymes are possible, and what their chemical formula [see above]
could possibly be. More about this in my next post to this thread.

Peter Nyikos
Professor, Dept. of Mathematics

Univ. of South Carolina -- standard disclaimer--
http://people.math.sc.edu/nyikos

[Lawyer Daggett]

I have been waiting to respond but so little has been said.

I have a guilty pleasure of caring about the mystery of Oak Island.
Since my preteen years a few friends and I indulged in conspiracy
thinking about the mysterious hole that might contain pirate treasure
and the mystique surrounding it, even if I gave up on the ideas way back
in my past, but it was fun for me and some preteen friends for a while.

There's a very bad TV series called the Curse of Oak Island that sucks
at that old conspiracy theory. It's really bad. It is a series of teasing
suggestions of things that might be suggested to be potentially implied
to be possibly hinted at about implying things that might be revealed
in subsequent episodes that could implicate aspects of things that could
perhaps be ... you get the idea.

That seems to match to Nyikos posts about abiogenisis.

Say something dammit. What's with the extended tease that does little
more than pretend to understand the field? I am almost tempted to extract
the few claims you've actually made to dispute them but they are so sparse.
They are dubious, but it's crazy how diluted they are with ramblings.
Say something of significance.

[peter2...@gmail.com]

"so little" ABOUT WHAT? I gave you information about what's in Szostak's
lecture, complete with times in the YouTube film where he said it.

You've given us nothing here but caviling -- but only after some bilge about a much-publicized
"mystery" that is on the level of tales of the Bermuda Triangle.

> I have a guilty pleasure of caring about the mystery of Oak Island.
> Since my preteen years a few friends and I indulged in conspiracy
> thinking about the mysterious hole that might contain pirate treasure
> and the mystique surrounding it, even if I gave up on the ideas way back
> in my past, but it was fun for me and some preteen friends for a while.
>
> There's a very bad TV series called the Curse of Oak Island that sucks
> at that old conspiracy theory. It's really bad. It is a series of teasing
> suggestions of things that might be suggested to be potentially implied
> to be possibly hinted at about implying things that might be revealed
> in subsequent episodes that could implicate aspects of things that could
> perhaps be ... you get the idea.
>
> That seems to match to Nyikos posts about abiogenisis.

Like hell it does. It matches YOURS.

Abiogenesis has many aspects to it, and like any serious
subject, it cannot be even outlined in a few posts.
You have done NOTHING to contribute to a serious look at the subject.

> Say something dammit. What's with the extended tease that does little
> more than pretend to understand the field?

What's with your piece of free association that dares not try
to address anything I actually wrote on the subject in the post
to which you are bottom-posting?

> I am almost tempted to extract
> the few claims you've actually made to dispute them but they are so sparse.
> They are dubious, but it's crazy how diluted they are with ramblings.
> Say something of significance.

...glass houses...stones.


Are you following in the footsteps of Erik Simpson, who kept accusing
me of being unclear and wanting to know what my point was?

Erik finally gave the game away by claiming he couldn't follow something I wrote,
and I rewrote it with new explanations BUT THEN he adamantly refused
to give me any feedback on it. That set off an accusation about Erik that
resulted in a big stink, with Erik disappearing as three regulars of talk.origins
[two of whom are still very active] got egg on their faces by the clueless
way they "defended" him. But until I called them on it, they seemed
quite persuasive.

If that is your game, keep writing the way you do here; if not,
you need to contribute some on-topic information about OOL
of your own.

But the smart money says you aren't going to do it, lest you
give away either

(1) your cluelessness about what is relevant and what is not

or

(2) how OOL is still in its early embryonic form, and destined
to stay that way for decades.


Peter Nyikos

[peter2...@gmail.com]

Undaunted by a counterproductive post by someone who makes Gary Hurd
look good in comparison, I continue my treatment of Szostak's experiments.

On Wednesday, September 6, 2023 at 5:35:27 PM UTC-4, peter2...@gmail.com wrote:

In my OP to this thread, I wrote:

> > I've decided to use the phrase "biochemistry of OOL" to refer to those
> > prebiotic phenomena that tend in the direction of ribozymes, and beyond.
> >
> > Ribozymes are enzymes composed of RNA rather than the far better known
> > ones that are proteins. Enzymes are essential to OOL because they drive
> > reproduction of prebiotic molecules, including new ribozymes.

>

> Jack Szostak is one of the top researchers in OOL. Recently he gave a fascinating lecture,
> available on YouTube in two different sites, on recent research in the subject:
>
> https://www.youtube.com/watch?v=ZLzyco3Q_Rg
> The Origin of Life: Not as Hard as it Looks? Jack Szosta[k], Spring 2023 Eyring Lecturer
>
> https://www.youtube.com/watch?v=U841Zrd4C5g
> Scientist Stories: Jack Szostak, The Origin of Life Not as Hard as it Looks
>

Here, in the transcript of his lecture, is a description of an experiment that resulted in
a ribozyme. It is very different from any experiment in what I call "the Alchemy of OOL".
I've not tried to edit what I downloaded from the transcript besides some cosmetic changes.
Numbers in the margins tell how far along in the video we are:

"so the experiments that we started doing were, to begin with, completely a library
11:52 of completely random sequences, okay, very large
11:58 sequences and what we wanted to know is: "How likely is it that a given random
12:06 sequence can actually do something interesting?" and as an experimenter of course you can
12:12 you can define the task that will be binding to a target molecule could be
12:17 catalyzing a reaction. I want to know how much information does it take to
12:23 specify a functional molecule
[...]
so what we were able to do pretty easily was build libraries of on the order of
13:09 10 to the 15th different random sequences made in DNA transcribed into
13:15 RNA and then take that set of sequences and subject it
13:21 to a selection; so enriching for the ones that do what we want and throwing away the ones
13:28 that don't and then amplifying those survivors with or without adding a little bit more variation and going
13:35 around and around this cycle,
13:41going around and around that cycle, until the population is taken over by
13:46 molecules that do what we want.
13:52 Okay, and so the answer was that we could actually -- this actually worked and
13:59 we could get molecules like the one shown here so this is
14:04 a sort of surface view of the three-dimensional structure of a short bit of RNA that folds up and it makes
14:10 this beautiful three-dimensional shape that has a little cleft on the surface
14:16 that's complementary in shape and electrostatics to ATP, so the combined
14:21 ATP at a concentration that's biologically relevant; and this was at
14:27 about one in ten to the minus 10 of the random sequences that we started with so
14:33 actually not that hard to get functional sequences out of, out of nothing.
[...]
but if you select for tighter and
16:05 tighter and ighter binding then you end up getting more complicated structures. So these are a little bit more
16:11 complicated and if you keep going you get these ones which bind a hundred
16:16 times tighter and they're much more complicated in their secondary structures than in the number of bases
16:23 that have to be what they are and so you can actually -- you can do the same kind of
16:29 experiment selecting for catalysis so this came out of an experiment that
16:34 was done by Dave Bartel when he was a graduate student in the lab selected for
16:39 ribozymes -- RNA enzymes that could catalyze a ligation reaction; and again he got more than one answer to that
16:47 problem and I'm showing you here one ribozyme that's fairly small and simple that does
16:53 this reaction with a certain rate and this much more complicated reaction that does a much better job.
It's a better
17:00 catalyst and it's more complicated you can see it takes more information to
17:05 specify the sequence that does something better.

At this point, there was a transition away from experimentation to theory and the talk
became more and more speculative and vague.

But what IS accomplished by such careful, intelligently selective and intelligently goal-oriented
experiments is to get some inkling of what ribozymes are possible and which ones to shoot for.

But at some point this fun ends, and the really hard work begins.
Some researchers have to revert to the Alchemy of trying to find primitive earth conditions
that push the RNA strings in the direction of the ribozymes you found.

Success is far from guaranteed: in fact, at some point they might get fed up
with lack of progress towards ANY of the strings in the batch
that "gave the Biochemists of OOL what they wanted."

This would call for re-running the experiment to find quite different
ribozymes that offer a better chance of success for the Alchemists of OOL.


But even if the successes so far could be validated by the Alchemists,
they would still be a far cry from The First Holy Grail of OOL,
described in an earlier post to this thread. Next week I will write about
other Holy Grails on the way to "life as we know it."


Peter Nyikos

Professor, Dept. of Mathematics -- standard disclaimer--

University of So. Carolina at Columbia
http://people.math.sc.edu/nyikos

[Lawyer Daggett]

First "claim" regarding template directed protein synthesis.

> > > This is one of the hardest and latest series of steps on the way to life as we know it.

Claim 1 contains two parts regards "hardest" and "latest".

> > > However, he did describe several experiments which do shed a bit of light on the early steps.
> > > I had a hard time seeing the point of one of them, at first, and made the following comment
> > > on the webpage for the second video listed above:
> > >
> > > "At one point in the film, between the ca. 13:00 minute point and the ca. 13:50 point, Szostak completely abandons the project of trying to re-create prebiotic conditions or simulating something like natural selection. Instead, he talks about an unspecified number of "generations" of RNA molecules in the laboratory, in which the human experimenters carefully select the mutants that are in the direction of "molecules that do uh what we want okay."
> > >
> > > [RNA molecules are strings of the four RNA nucleotides in a specific order; the order is
> > > their chemical formula.]
> > >
> > > The "what we want" is to bind an ATP molecule; at this Szostak & co. succeeded, but at the price
> > > of looking like they were researching Intelligent Design, even to the "what we want"
> > > simulating teleology (purposiveness), which was kicked out of empirical science a century ago
> > > where all but the higher animals are concerned.
> > >
> > >
> > > However, appearances are deceiving. This procedure is the best way we currently have
> > > of learning what ribozymes are possible, and what their chemical formula [see above]
> > > could possibly be. More about this in my next post to this thread.

There's too much meta. Who cares if experiments "look like ID"? I have objections to
that meta-claim about OoL but it's a tangent.

Claim2
> > > ... This procedure is the best way we currently have

> > > of learning what ribozymes are possible, and what their chemical formula [see above]

This claim is about "best way" and "we".

The thread split so there was another claim about an RNA based RNA polymerase.
To my taste, it rambled, and became compound.
Ultimately Claim 3:

" . In fact, the only reason we know about *protein* RNA replicases is

. that they are found in some kinds of viruses. Were it not for that,
. we would be very much in the dark about what protein RNA replicases
. could possibly look like. "

It's rather unclear what it is you think we do or don't know.

Entangled with Claim 3 was poetic license about Holy Grails but also
an assertion that they key is a completely generic RNA polymerase that
can replicate any RNA template, presumably by first creating a complementary
sequence and then making the original by repeating the process by making
a subsequent complement of the first complement.
Call this added constraint Claim 4. For convienence, I'm repeating them
at the bottom.

First "claim" regarding template directed protein synthesis.

> > > This is one of the hardest and latest series of steps on the way to life as we know it.

Claim 1 contains two parts regards "hardest" and "latest".

Claim2
> > > ... This procedure is the best way we currently have

> > > of learning what ribozymes are possible, and what their chemical formula [see above]

This claim is about "best way" and "we".

The thread split so there was another claim about an RNA based RNA polymerase.
To my taste, it rambled, and became compound.
Ultimately Claim 3:

" . In fact, the only reason we know about *protein* RNA replicases is

. that they are found in some kinds of viruses. Were it not for that,
. we would be very much in the dark about what protein RNA replicases
. could possibly look like. "

It's rather unclear what it is you think we do or don't know.

Entangled with Claim 3 was poetic license about Holy Grails but also
an assertion that they key is a completely generic RNA polymerase that
can replicate any RNA template, presumably by first creating a complementary
sequence and then making the original by repeating the process by making
a subsequent complement of the first complement.

Call this added constraint Claim 4. For convenience, I'm repeating them
at the bottom.

I shall cut out everything else and address these claims.
I have no problem with rewordings of these extracted claims if
they don't actually match what it is you're attempting to claim.

[Lawyer Daggett]

On Friday, September 8, 2023 at 10:15:30 PM UTC-4, Lawyer Daggett wrote:
> On Friday, September 8, 2023 at 7:25:30 PM UTC-4, peter2...@gmail.com wrote:
> > On Thursday, September 7, 2023 at 7:25:29 AM UTC-4, Lawyer Daggett wrote:
> > > On Wednesday, September 6, 2023 at 5:35:27 PM UTC-4, peter2...@gmail.com wrote:

Apologies for replying to myself. It's generally obnoxious to do so.

> First "claim" regarding template directed protein synthesis.
> > > > This is one of the hardest and latest series of steps on the way to life as we know it.
> Claim 1 contains two parts regards "hardest" and "latest".

> Claim2
> > > > ... This procedure is the best way we currently have
> > > > of learning what ribozymes are possible, and what their chemical formula [see above]
> This claim is about "best way" and "we".

> The thread split so there was another claim about an RNA based RNA polymerase.
> To my taste, it rambled, and became compound.
> Ultimately Claim 3:
> " . In fact, the only reason we know about *protein* RNA replicases is
> . that they are found in some kinds of viruses. Were it not for that,
> . we would be very much in the dark about what protein RNA replicases
> . could possibly look like. "
>
> It's rather unclear what it is you think we do or don't know.
>
> Entangled with Claim 3 was poetic license about Holy Grails but also
> an assertion that they key is a completely generic RNA polymerase that
> can replicate any RNA template, presumably by first creating a complementary
> sequence and then making the original by repeating the process by making
> a subsequent complement of the first complement.

> Call this added constraint Claim 4. For convenience, I'm repeating them
> at the bottom.

I was awaiting some "correction" to my distillation of the claims.
Certainly, refinements are appropriate. But the above represents what seems
to be what is being claimed. Refinements remain welcome.

Problem the first: the whole scheme of complaints presumes too much
knowledge of the sequence of events involved in the Origin of Life.
Fundamental to this is the presumption of some sequence of events
that led to an entity that is hypothesized to be the primordial cell.

It isn't that the underlying scheme is completely implausible, but it isn't
at all required. Further, it contains aspects that defy intuitions that arise
from an education in biochemistry and enzymology. And yes, that does
tug back at the issue of being completely implausible.

Why would one suppose a strict RNA-only world? It makes no sense.
The purpose seems to be to avoid the chicken and egg question of
catalytic systems that require polypeptides of specific sequence.

But it makes more sense to consider pathways that produce sequence
specific polypeptide prior to modern ribosomal protein synthesis. It
isn't hard to do so.

The enumerated claims have other refutations of different character.
I'll happily respond once they are owned or refined.

[peter2...@gmail.com]

This has been an absolutely hectic week, and this is my first (and, hopefully, not the last)
post that I have done to Usenet all week. The latest complication was the removal of a
skin cancer on my right ear lobe that took a fair amount of digging; the surgeon estimated
that it had been growing for about a year. It seems, though, that it all got removed.

On Monday, September 4, 2023 at 6:55:25 PM UTC-4, peter2...@gmail.com wrote:
> On Monday, September 4, 2023 at 4:55:25 PM UTC-4, peter2...@gmail.com wrote:

I will be amplifying earlier comments and using them as springboards.
Unlike another participant to this thread, I see nothing wrong with doing
this if the main objective is the search for understanding of the main
hurdles on the way to OOL.

> > I've decided to use the phrase "biochemistry of OOL" to refer to those
> > prebiotic phenomena that tend in the direction of ribozymes, and beyond.
> >
> > Ribozymes are enzymes composed of RNA rather than the far better known
> > ones that are proteins. Enzymes are essential to OOL because they drive
> > reproduction of prebiotic molecules, including new ribozymes.

There are weighty reasons for the first enzymes being strings of nucleotides,
and they were probably RNA nucleotides; see below.

> > There are experiments that advance the biochemistry of OOL, and I plan to discuss
> > the ones I know about later today. In my next post I will enlarge upon that
> > phrase, "including new ribozymes," and make some comments on the concept of "RNA World."

> That phrase has to do with what I have called, in several threads,

> "The First Holy Grail of OOL." By this I mean the production,
> under simulated prebiotic conditions, of an RNA replicase.
>
> An RNA replicase is an enzyme that can take ANY string of RNA in a medium
> with an adequate quantity of the four RNA nucleotides, and catalyze
> the production of the complementary string. This includes doing it with a speed
> of a magnitude not far from the speed at which existing RNA replicases do it.

>
> The catch here is that the existing RNA replicases are *protein* enzymes,
> and there is no way to get them in OOL except by going through
> *ribozyme* RNA replicases.

Some people define "life" very loosely, with reproduction being both necessary
and sufficient for it. But to be a precursor of "life as we know it," the reproduction
has to be at a high rate of speed. And it's a two-step process even at this early level:
the first step is to produce the complementary strand, and then reproduction is
the production of the complement of the complement, hence a copy of the original.

Of course, there can be errors in this process, but that is necessary for evolution.
So the replicase itself could evolve into something else.

That "something else" includes three vital ingredients for "life as we know it":
a DNA replicase, a DNA-to-RNA transcriptase, and an RNA-to-DNA "reverse transcriptase".[1]
It remains to be seen whether these deserve to be called "Holy Grails" themselves.
Perhaps each will turn out to be a fairly routine modification of one of the others,
or it could be that to get a new one of high enough fidelity [2] could take a lot
of modification.

[1] All three would likely be RNA ribozymes. DNA has much inferior catalytic activity,
but is far more valuable as far as stability of a genome goes.

[2] The opposite extreme would be a ribozyme which is indifferent to as to whether
the next nucleotide is more like RNA or more like DNA, especially as to choosing
between uracil and thymine nucleobases.

> And here is the big problem: we have
> no clue as to what the chemical formula [meaning the sequence of its nucleotides]
> of a ribozyme RNA replicase could possibly look like.

The same goes for the other three "Holy Grail" candidates talked about above.


One thing is certain: we also need a completely different role for RNA,
namely to function as coded messages for the production of proteins.
The evolution of these messages would often be at odds to the evolution of
RNA strands functioning as enzymes. To have such a message system in place
is truly another Holy Grail in addition to the first, one that almost
perforce has to come after the First Holy Grail.

Peter Nyikos
Professor, Dept. of Mathematics -- standard disclaimer--

University of So. Carolina in Columbia
http://people.math.sc.edu/nyikos