Abiogenesis is mathematically impossible

Naturalism does not plausibly explain the origin of life. Creation by an intelligent powerful designer does.

https://reasonandscience.catsboard.com/t2895-syllogistic-arguments-of-gods-existence-based-on-positive-evidence#9106

1. Life requires four basic biomolecules ( RNA and DNA, amino acids, phospholipids, and carbohydrates), a genome  to store instructional information for assembly and operation of the cell, through the genetic code, with a minimal content of 1,3 Mio bits of information ( P.Ubique). The genetic code is a set of rules, where 64 nucleotide triplets called codons ( genetic words) are assigned to 20 amino acids. It directs the making of amino acid polypeptide chains, which are the basic components of proteins ( the molecular machines, the working horses of the cell ).  The proteome is a large team of enzymes, that catalyze the reactions to keep the cell alive, and in special, they produce the four basic building blocks of life in a cooperative manner. The metabolome is a network of integrated and carefully regulated metabolic pathways, where thousands of complex reactions catalyzed by globular proteins, enzymes, occur simultaneously to contribute to the sum of activities that a cell has to perform. The interactome defines all cellular interactions, amongst it, all protein-protein interactions of a cell.
2. To go from primordial goo to a fully free-living, autonomous, self-replicating living cell,  the four building blocks of life have to be readily available, and so the genome, metabolome, proteome, interactome, have to be fully set up. Wilhelm Huck chemist, wrote: A working cell is more than the sum of its parts. "A functioning cell must be entirely correct at once, in all its complexity. And Emily Singer, in the article: How Structure Arose in the Primordial Soup, wrote: The cell, the genetic code, and an energy system, ALL THREE of these are ESSENTIAL to life as we know it. And Lynn Margulis: To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium.
3. Origin of life hypotheses must face and address major hurdles:

a. There was no selection process to sort out the molecules of life from those that are not used in life.
b. There was no primordial process to purify the molecules.
c. Systems, given energy and left to themselves, DEVOLVE to give uselessly complex mixtures, “asphalts”.  the literature reports exactly  ZERO CONFIRMED OBSERVATIONS where “ living cells emerged spontaneously from a devolving chemical system.
d. Monomers can bond with each other in a large variety of ways and unwanted molecules can interfere with the required purity. Even in a very short DNA of just two nucleotides, there are dozens of incorrect possible arrangements of the components and only one correct arrangement.
e. Proteins are made of chains of amino acids, and nucleic acids are chains of nucleotides. If the chains are placed in water, it attacks the links and eventually breaks them. Robert Shapiro wrote: In carbon chemistry, “water is an enemy to be excluded as rigorously as possible”. RNA requires water to function, but RNA cannot emerge in water and does not persist in water without repair.
f. A minimal genome to start life would have been TOO LONG TO HAVE ARISEN SPONTANEOUSLY and not escaped asphaltic devolution in water.
g. The smallest genome of the simplest free-living bacteria, Pelagibacter unique, is 1,308,759 base pairs and codes for 1,354 proteins.  If a chain could link up, the probability that the code letters might by chance be in some order which would be a usable gene, to get the sequence randomly would be 10^722,000. There are 10^80 atoms in the universe.
h. The cell membrane had to emerge fully functional with " gates " that permit the right materials in, and the waste product out.
i. Once the data storage system (DNA) emerged, a language based on a code system had to be established, and the blueprint to store the information to make all parts of the cell had to be stored within it, and DNA replication errors had to be reduced 10.000.000.000 times.  It had to be able to check replication errors and minimize them, react to stimuli, and changing environments. That's is, the ability to adapt to the environment is a must right from the beginning.
j. If just ONE single protein or enzyme - of many - is missing, no life. If topoisomerase II or helicase are missing - no replication - no perpetuation of life.
k. Somehow, that envelope had to create a homeostatic environment, diminishing the calcium concentration in the cell 10000 times below the external environment, to permit signaling. At the same time, a signaling code would have had to be established, and immediately begin to function, with a common agreement between sender and receiver
l. Energy supply would have been a major problem since almost all life forms depend on the supply of glucose, which is a product of complex metabolic pathways, and not readily available on the prebiotic earth. Most proteins require active metal clusters in their reaction centers. These clusters are in most cases ultracomplex, each cluster had to have the right atoms interconnected in the right way, and get the correct 3-dimensional form. They require the complex uptake of the basic materials, like iron and sulfur, molybdenum, and complex biosynthesis processes, and after the correct assembling, the insertion in the right way and form inside the proteins.
m. All cellular processes require energy, in form of ATP, not readily available - since ATP is the product of complex proteins, like ATP synthase - which by themselves depend on a proton gradient.

4. There is simply no feasible viable prebiotic route to go from a random prebiotic soup to the first living self-replicating cell by unguided means. This is not a conclusion by ignorance & incredulity, but it is reasonable to be skeptical, that this irreducibly complex biological system, entire factory complexes composed of myriads of interconnected highly optimized production lines, full of computers and robots could emerge naturally defying known and reasonable principles of the limited range of random unguided events and physical necessity. Cells have a codified description of themselves in digital form stored in genes and have the machinery to transform that blueprint through information transfer into an identical representation in analog 3D form, the physical 'reality' of that description. Comparing the two competing hypotheses, unguided random chaotic stochastic lucky events on the prebiotic earth, versus intelligent design, the second is simply by far the more case-adequate, plausible, rational & reasonable explanation.

Abiogenesis is mathematically  impossible
https://reasonandscience.catsboard.com/t1279-abiogenesis-is-mathematically-impossible

The factory maker argument
https://reasonandscience.catsboard.com/t2245-abiogenesis-the-factory-maker-argument

The cell is irreducibly complex
https://reasonandscience.catsboard.com/t1299-abiogenesis-the-cell-is-irreducibly-complex

Essential elements and building blocks for the origin of life
http://reasonandscience.heavenforum.org/t2437-essential-elements-and-building-blocks-for-the-origin-of-life

What might be a Cell’s minimal requirement of parts ?  
https://reasonandscience.catsboard.com/t2110-what-might-be-a-protocells-minimal-requirement-of-parts

Major metabolic pathways and their inadequacy for origin of life proposals
https://reasonandscience.catsboard.com/t2004-major-metabolic-pathways-and-their-inadequacy-for-origin-of-life-proposals

Prevital unguided origin of the four basic building blocks of life: Impossible !!
https://reasonandscience.catsboard.com/t2894-prevital-unguided-origin-of-the-four-basic-building-blocks-of-life-impossible

The interdependent and irreducible structures required to make proteins
https://reasonandscience.catsboard.com/t2039-the-interdependent-and-irreducible-structures-required-to-make-proteins

Peptide bonding of amino acids to form proteins and its origins
https://reasonandscience.catsboard.com/t2130-peptide-bonding-of-amino-acids-to-form-proteins-and-its-origins

Forces Stabilizing Proteins - essential for their correct folding
https://reasonandscience.catsboard.com/t2692-forces-stabilizing-proteins-essential-for-their-correct-folding

Proteins: how they provide striking evidence of design
https://reasonandscience.catsboard.com/t2062-proteins-how-they-provide-striking-evidence-of-design

Biosynthesis of Iron-sulfur clusters, basic building blocks for life  
https://reasonandscience.catsboard.com/t2285-iron-sulfur-clusters-basic-building-blocks-for-life

What are the odds to have a functional interactome for the smallest known living cell?
https://reasonandscience.catsboard.com/t3120-what-are-the-odds-to-have-a-functional-interactome-for-the-smallest-known-living-cell

How  intracellular Calcium signaling,  gradient and its role as a universal intracellular regulator points to design
https://reasonandscience.catsboard.com/t2448-howintracellular-calcium-signaling-gradient-and-its-role-as-a-universal-intracellular-regulator-points-to-design

DNA and RNA error checking and  repair, amazing evidence of design
https://reasonandscience.catsboard.com/t2043-dna-and-rna-error-checking-and-repair-amazing-evidence-of-design

Error detection and repair during the biogenesis & maturation of the ribosome, tRNA's, Aminoacyl-tRNA synthetases, and translation: by chance, or design?
https://reasonandscience.catsboard.com/t2984-error-check-and-repair-during-messengerrna-translation-in-the-ribosome-by-chance-or-design

ATP: The  Energy  Currency for the Cell
https://reasonandscience.catsboard.com/t2137-atp-the-energy-currency-for-the-cell

Dr.Sara Walter, on Twitter: What is life? Does alien life exist? astrobiologist Dr.Sara Walker

Thinking about how you identify a molecule in atmosphere of exoplanet on another world as being alien or how would you know the context of analytes parent that you succeeded that you've evolved delay form from scratch. So in order to do that you have to be able to look at chemistry and say there's something in this chemistry tributed to the back life emerging of this stuff and so so leaves the actual experimentalist and he came up with this idea of trying to think of a molecule basically and the place you take molecule cut in half and cut it again. Cut in half again until your elementary building blocks and then you can think about trying to build up those building blocks to make the original molecule, and there's not a unique pathway there, right? 


There are actually lots and lots of pathways, and the larger that molecule is more complex it is. It's an exponentially growing number of pathways, but what we're interested in is the shortest amount of steps to produce that molecule. There would not be 'cause there's this combinatorial explosion of all the different kinds of molecules that could exist so much chemical space. I should qualify. This is so large it's almost unfathomable. In some sense, people think like the physical size of the universe is big, but if you think about the combinatorial space of chemistry, it's really, really, really really, really big and so. So when you start building up more complex molecules, the space is exponentially growing.

So if you're thinking about the shortest path as being a measure of a distance into that space, the idea was if that's that shortest path is sufficiently long, you actually need a system that has information about making that specific molecule.


There's kind of success that we specific molecule sometimes living system, basically to have made that molecule. So this introduces the idea that in an assembly space is there should be a threshold in complexity and assembly above which only living systems would be the things that could produce objects with that complexity. And so when you think about that in chemistry, it means that it should be certain molecules that are definitive biosignatures that an alien was present based on having a high assemb

Now this seems kind of. Yeah, some people might argue against that like there's some niche Geochemical environment that can produce that molecule somewhere. 


But like counter-argument to that is, would you expect a cell phone to spontaneously fluctuate into existence on Mars? 

And what I mean by that, is there a surefire complex objects that exist in our universe that require evolution to produce them? And what we're doing in assembly theory is basically quantifying that in terms of the causal st
Units the fundamental objects in your theory are now assembly. Space is everything. In reality is a causal graph. I'm one with a very long shortest path, but and maybe you know a simple molecule is a shorter shortest path lane, but you can. You can now think about all of these things basically being these objects that end in time, because all of these ways of assembling them have to be occur overtime.
I can give a simple analogy of what that looks like, but but I I should probably stop there and my well, I think I.
OK.
Yeah, so so I I mean, a lot of people like to now I make an analogy to like Lego blocks with assembly. So like I like to imagine that I have a stack of blue and yellow Legos, right? So imagine you know, you just have a stack of 10. Legos are blue and yellow and some arrangement so everybody and it has this in their mind now. And so to make the assembly space for that stack of letters basically take it apart to the individual building blocks. And then you follow all the pathways of being able to
Exist across time, they're actually physical things that exist across time, because when you assemble a pathway, you can only see the structure of that pathway. If you resolve it across what we call the passage of time and what we're saying in assembly through at least how I interpret it, is that's actually a physical attribute of that Lego stack, or that molecule, when it when you look at that that thing, it's actually all of those ways of assembling it across time.
So it has a very complex structure in time.
Yeah.

Wow.
Think about that.

So I think the the most promising tool we have right now for looking for alien life is to use assembly theory and the reason for that is I mentioned that we had conjectured that there was this threshold in assembly spaces above, which if you saw a molecule with a sufficiently high Assembly number, it had produced by life. These lab actually has empirically, you know, gone in the lab and they've confirmed that that's consistent with experimental data from nonliving and living systems. So this is
And so we have really concrete. It's not just that we have a theory in our mind that we think accounts for some features of life, it's that we're actually really working very hard to connect these deep theoretical ideas about this new physics that might be in life with what's done in the lab. And so now we have a number that had that number of step happening to be 15 from the sort of experimental data so Solis up here now, and he can explain some of that a bit more if you guys are interested in
or tight end or venus or places in the solar system with a mass spec and we can look for these high assembly molecules that would be the best indicator that we have right now of alien life so that the idea is to look for complex objects high assembly objects is bio signatures

The question is not only what life is, but how it came to be. 
Cells have a codified description of themselves stored in genes and have the machinery to transform that instructional assembly data through information transfer into an identical representation in analog 3D form, the physical 'reality' of that description. How do you explain such an interdependent system based on unguided events, if we have only seen intelligence instantiate such things?

Review of: 

https://reasonandscience.catsboard.com/t1279p25-abiogenesis-is-mathematically-impossible#9197

Jason P. Schrum The Origins of Cellular Life  2010 Sep; 2 1

Claim: Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of functional information.

Reply: The proposal is meaningless, if such a "protocell" cannot perform what is proposed that it should do. As such, it is an entirely theoretical construct, that bears no resemblance, nor relevance to the real world, but is just a hypothesis, result of fertile scientist minds. 

" Recent studies of vesicles composed of fatty-acid membranes have shed considerable light on pathways for protocell growth and division, as well as means by which protocells could take up nutrients from their environment. " 

In regards of "protocell" - membranes: 

The Interdependency of Lipid Membranes and Membrane Proteins 
https://reasonandscience.catsboard.com/t2397-the-interdependency-of-lipid-membranes-and-membrane-proteins

Cell membranes only come from cell membranes. A cell cannot produce the cell membrane de novo from scratch. It inherits it. Daughter cell membranes come only from mother cell membranes. Even in the simplest cells, the membrane is a biological device of a staggering complexity that carries diverse protein complexes mediating energy-dependent – and tightly regulated - import and export of metabolites and polymers 2

Remarkably, even the author of the book: Agents Under Fire: Materialism and the Rationality of Science, pgs. 104-105 (Rowman & Littlefield, 2004). HT: ENV. asks the readers: Hence a chicken and egg paradox: a lipid membrane would be useless without membrane proteins but how could membrane proteins have evolved in the absence of functional membranes?

Claim: " Additional work with genetic polymers has provided insight into the potential for chemical genome replication and compatibility with membrane encapsulation. The integration of a dynamic fatty-acid compartment with robust, generalized genetic polymer replication would yield a laboratory model of a protocell with the potential for classical Darwinian biological evolution, and may help to evaluate potential pathways for the emergence of life on the early Earth. Here we discuss efforts to devise such an integrated protocell model. " 

Reply: In regards of an informational polymer that allows for the replication:

There is a long way to get to such a polymer, and science is far from explaining how it could emerge prebiotically:

The origin of replication and translation and the RNA World
https://reasonandscience.catsboard.com/t2234-the-origin-of-replication-and-translation-and-the-rna-world

The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on how recent observations of the catalytic properties of various forms of RNA fit with this hypothesis.
https://en.wikipedia.org/wiki/RNA_world

Leslie Orgel: Prebiotic chemistry and the origin of the RNA world Mar-Apr 2004
It is possible that all of these, and many other difficulties, will one day be overcome and that a convincing prebiotic synthesis of RNA will become available. However, many researchers in the field, myself included, think that this is unlikely
https://pubmed.ncbi.nlm.nih.gov/15217990/

Christian de Duve: The Beginnings of Life on Earth   September-October 1995 issue of American Scientist.
Contrary to what is sometimes intimated, the idea of a few RNA molecules coming together by some chance combination of circumstances and henceforth being reproduced and amplified by replication simply is not tenable. There could be no replication without a robust chemical underpinning continuing to provide the necessary materials and energy.
https://www2.nau.edu/~gaud/bio372/class/readings/beglifeerth.htm

Claim: " Although recognizing the many gaps in our knowledge of prebiotic chemistry and the early planetary setting in which life emerged, we will assume for the purpose of this review that the requisite chemical building blocks were available ".

Reply: In order to provide a PLAUSIBLE naturalistic  origin of life scenario, the proponents need to start from scratch. That includes an explanation of how the basic building blocks were sorted out and selected. That is a major OOL problem:

Prevital unguided origin of the four basic building blocks of life: Impossible !!
https://reasonandscience.catsboard.com/t2894-prevital-unguided-origin-of-the-four-basic-building-blocks-of-life-impossible

Steve Benner, leading origin of life researcher, prior Harvard University professor. Paradoxes in the origin of life. 2015 Jan 22 

" We are now 60 years into the modern era of prebiotic chemistry. That era has produced tens of thousands of papers attempting to define processes by which “molecules that look like biology” might arise from “molecules that do not look like biology” …. For the most part, these papers report “success” in the sense that those papers define the term…. And yet, the problem remains unsolved "

MICHAEL MARSHALL 'Impossible' chemistry may reveal origins of life on Earth APRIL 4, 2022 1

https://reasonandscience.catsboard.com/t1279p25-abiogenesis-is-mathematically-impossible#9199

Markus Ralser never intended to study the origin of life. His research focused mainly on how cells feed themselves, and on how these processes can go wrong in organisms that are stressed or ill. But about a decade ago, by sheer accident, Ralser and his team made a shocking discovery.

The group, based at the University of Cambridge at the time, was studying glycolysis, a process that breaks down sugar in a series of chemical reactions, releasing energy that cells can use. When they used sensitive techniques to track the many steps in the process, they were surprised to find that some of the reactions seemed to be “happening spontaneously,” says Ralser, who is now based at the Francis Crick Institute in London. In control experiments that lacked some of the required molecules for the reactions, parts of glycolysis were happening anyway.

“It can’t be possibly true,” Ralser recalls other scientists telling him.

Every living cell has at its core a kind of chemical engine. This is true for a neuron in a human brain as well as for the simplest bacterium. These chemical engines drive metabolism, the processes that transform an energy source such as food into useful parts and build up the cell. By all accounts metabolic processes, including glycolysis, require a lot of sophisticated microscopic machinery to keep going. But Ralser’s team found that one of these engines could run by itself, without several of the complex molecules that scientists believed were required.

Since the serendipitous find, a wave of excitement has spread among researchers who study life’s origins. After all, if this could happen in a test tube, perhaps it could also have happened billions of years ago in a deep-sea volcanic vent, or on land in thermal pools, or somewhere else with lots of chemical activity and organic material. It may even be that metabolic reactions began the chain of events that led to the birth of life.

Some teams are now working to make these chemical engines from scratch. In addition to glycolysis, scientists have re-created parts of other fundamental cellular processes, including the reverse citric acid cycle, or the reverse Krebs cycle, which is believed to have first appeared in very ancient cells.

This exciting new area of research has scientists rethinking the steps that could have led to the first living organism, and it has forced them to once again confront a longstanding question: How do we define life in the first place?

Enigmatic origins
How life began is one of science’s greatest outstanding mysteries. We know it happened early in our planet’s history because there are fossil microorganisms in rocks laid down 3.5 billion years ago, a mere billion years after Earth formed. But how and where it happened remain uncertain.

A key problem is that living organisms are extraordinarily complicated. Even the simplest bacterial cell has hundreds of genes and thousands of different molecules. All of these building blocks work together in an intricate dance, shuttling food into the cell and passing waste out, repairing damage, copying genes, and much more.

The scale of this complexity is illustrated by research published in 2021 that compares the DNA of 1,089 bacteria, which are the simplest living organisms. The researchers, led by bioengineer Joana C. Xavier, who was at Heinrich Heine University Düsseldorf in Germany at the time, looked for protein families that were common across the species of bacteria, as these were likely to be truly ancient—dating back over three billion years to the last common ancestor of all bacteria. They found 146 such protein families, revealing that even the earliest bacteria were extraordinarily intricate and the product of a long period of evolution.


My comment:  The author tries to smuggle in evolution into the explanatory toolbox, ignoring the fact that evolution depends on dna replication of living cells. So unless the first living cell was not self replicating, evolution could not kick in.

All hypotheses about the origin of life attempt to strip away this complexity and imagine something far simpler that could have arisen spontaneously. The difficulty is deciding what this proto-life would have been like. What parts of the living cells we see today were the first to form?

Many ideas have been put forward, including a molecule that can copy itself such as a strand of RNA, or a fatty “bubble” or “blob” that could have acted as the foundational structure of a cell. But a growing group of scientists believe that before genes or cell walls, the first thing life needed was an engine.

The first metabolism
Life is fundamentally active. Even in seemingly stationary organisms like trees, there is furious activity at the microscopic scale.

Xavier, who is now based at University College London, compares a living cell to a cup of water with a hole in the bottom and a faucet pouring in. If the two flows are equal, the volume of water in the cup stays the same, “but there is transformation going on.”

Similarly, every living thing takes in nutrients and uses them to build and repair its body. For humans, that means eating foods and then using our digestive systems to break them down into simple chemicals that our bodies can use.

Other organisms get their energy from sunlight, or from chemicals like methane, but the same principle applies. Thousands of reactions are constantly transforming one substance into another and shuttling things to where they are needed. All of these processes make up an organism’s metabolism. If metabolism stops, the organism dies.

The chemistry of metabolism is so central to life that many researchers believe it must have been at the core of the first living cells. Once a metabolic engine was up and running, the thinking goes, it could create the other chemicals that life needs, and gradually cells would self-assemble, says Joseph Moran of the University of Strasbourg in France.

However, all metabolism-first hypotheses for the origin of life face the same problem: Metabolism, like life itself, is remarkably complex. In Xavier’s study of the last bacterial common ancestor, she estimated that this ancient organism’s genes could produce 243 chemicals through metabolic processes, as well as transforming chemicals into one another.

Even the individual pathways in metabolism are intricate. Take the citric acid cycle, or Krebs cycle, which is one of the ways cells can extract energy from nutrients. As the name suggests, it starts with citric acid, the chemical that gives citrus fruits their sharp taste. This is converted into a second substance called cis-aconitate, and then into a further seven chemicals before the last step re-creates the citric acid. Along the way, a host of biological chemicals are produced and distributed to the rest of the cell.

It is hard to imagine how such an intricate process could have started by itself. Complicating things further, each step is controlled by a molecule called an enzyme, which speeds up the chemical reactions in question. For a process like the Krebs cycle to work, enzymes are required. But enzymes are complicated molecules that can only be made through metabolism, under the control of genes.

So scientists face a biochemical chicken-or-the-egg dilemma: Which came first, the chemical engine to build the cell, or the cellular mechanisms needed to build the engine?

Jump-starting the engines of life
After Ralser and his team made their initial discovery in the early 2010s, they decided to further investigate metabolic reactions that could run on their own. They dissolved 12 different chemicals that are used in glycolysis, each on their own, in pure water. Then they heated the samples to 70°C for five hours, mimicking conditions near an undersea volcano. Seventeen chemical reactions, either from glycolysis or from a related metabolic pathway, started occurring in the experiments.

Ralser then contacted Alexandra Turchyn, a geochemist at the University of Cambridge who gave him a list of chemicals that are thought to have been dissolved in the primordial ocean, including metals like iron and sodium. The team added these to their mixtures to see if they made the reactions work better.

“We got one hit, which was iron,” Ralser says. By 2014 they had 28 working reactions, including a complete metabolic cycle. The team built on their initial results, showing in 2017 that they could make a version of the citric acid cycle driven by sulphate, and that they could make sugars from simpler chemicals in a process called gluconeogenesis—although the latter had to be done in ice.

The idea of metabolic cycles without enzymes was then taken up by Moran at the University of Strasbourg, in collaboration with his former student Kamila Muchowska. They have made similar breakthroughs with other metabolic processes such as the acetyl-CoA pathway, which converts carbon dioxide into acetyl-CoA—one of the most important chemicals in metabolism.

But of life’s many mechanisms, scientists have returned again and again to the reverse citric acid cycle. This process, which is essentially the citric acid cycle running backward, is used by some bacteria to make complex carbon compounds out of carbon dioxide and water. And there is evidence that it is extremely ancient.

Like Ralser, Moran and Muchowska used metals such as iron to drive chemical reactions in the lab. In 2017 they were able to trigger six of the 11 reactions in the reverse citric acid cycle, and two years later they found additional reactions.

“We didn’t ever produce the entire cycle,” Moran says. But they are getting close.

Not quite biology
Despite the excitement, scientists are split on whether entire cellular cycles could really happen without enzymes to facilitate the process. For Ramanarayanan Krishnamurthy of the Scripps Research Institute in La Jolla, California, it is not convincing to reproduce only parts of a cycle.

“It’s like breaking a glass jar into pieces, and then saying: The pieces came from the jar, therefore I can put the jar together,” he says.

Krishnamurthy and his colleagues are trying a different approach. “We are disconnecting ourselves from biology,” he says, because what happens in cells today is an imperfect guide to what happened billions of years ago. “I’m just going to let the chemistry guide me.”

In 2018 Krishnamurthy’s team demonstrated a new metabolic engine that consists of two cycles and works without enzymes. “We bypass some of the most unstable molecules, some of the most difficult steps biology is able to do beautifully because of highly sophisticated evolved enzymes,” Krishnamurthy says. He suggests that the resulting process could have been an ancient precursor to the reverse Krebs cycle.

More recently, his team has experimented with adding cyanide, which is thought to have been abundant on primordial Earth. Previous research has shown that cyanide can produce many of the chemicals of life because it is so reactive—but it’s unclear if cyanide really played a role in the origin of life because it is poisonous to actual organisms. Nevertheless, Krishnamurthy’s team has shown that cyanide can trigger metabolic engines that resemble some of life’s functions.

Moran is skeptical of this approach because these alternative engines don’t make some of the key chemicals of life. “I don’t understand why you would want to do that,” he says.

It remains to be seen whether complete versions of all today’s metabolic cycles can be made to work without enzymes, or if the first life had to make do with alternative and simplified versions like those Krishnamurthy has made.

A living engine?
The ability to mimic life’s processes in simplified forms at all has led to a profound question: At what point would we call these chemical systems “life”? If a metabolic engine is humming away in a glass vial, is it alive?

Most scientists would say no. For something to be alive, “we need to have a system that is complex enough that it can metabolize and replicate,” Ralser says. A metabolic engine on its own isn’t doing that, but it is a step along the path to something that can.

“Nobody has really defined life,” Krishnamurthy says, and there are so many edge cases. For example, many definitions of life specify that an organism must be able to reproduce, but individual sexual animals cannot reproduce without a partner—so by these strict definitions, a lone rabbit isn’t alive.

“All there is between non-living and living is a gradient,” Muchowska says. Metabolic engines are not wholly inanimate the way that rocks are, nor are they fully living the way a bacterium is.

Life, in a sense, is a kind of chemical accident—a whirling dance that has not stopped in more than three and a half billion years. No matter how we define it, that dance keeps going, slowly honing the biological machinery that built Earth’s endless forms most beautiful and most wonderful.

https://www.nationalgeographic.com/science/article/impossible-chemistry-may-reveal-origins-of-life-on-earth#:~:text=Experiments%20suggest%20that%20metabolism%20could,rethink%20how%20we%20define%20life.

How Cellular Enzymatic and Metabolic networks point to design
https://reasonandscience.catsboard.com/t2371-how-cellular-enzymatic-and-metabolic-networks-point-to-design

1.Cells contain high information content that directs and controls integrated metabolic pathways which if alterated are inevitably damaged or destroys their function. They also require regulation and are structured in a cascade manner, similar to electronic circuit boards.
2. There is always an observable consequence if a circuit is interrupted. Since these consequences are always catastrophically bad, flexibility is minimal, and since the circuits are all interconnected, the whole network partakes of the quality that there is only one way for things to work.
3. Naturalistic mechanisms or undirected causes do not suffice to explain the origin and set up of information (instructional prescribing complex information), integrated complex circuits with little tolerance of change.
4. There is no way to write the code for all the enzymes unless one knows the 3D shapes of the substrates they act upon, and one can't know this unless one sees "the big picture" of the context within which and WHY they are needed for each life-essential product (or the final end products would not be produced), it becomes very clear that believing it could "evolve" without deliberate planning, foreknowledge, etc. stretches plausibility, reason, and logic, to say the least.Therefore, intelligent design constitutes the best explanation for the origin of these systems.

A response to : Astrophysicist Breaks Down The Origins Of Life | Edge Of Knowledge | Ars Technica

https://reasonandscience.catsboard.com/t1279p25-abiogenesis-is-mathematically-impossible#9218

https://www.youtube.com/watch?v=k92xoQJdifk

Claim: For example, there could be hydrothermal vents in the deep sea. This is a source of energy, it has the right chemical mix, and is a stable environment.
Reply: The hydrothermal-vent hypothesis , and why it fails

https://reasonandscience.catsboard.com/t1394-the-hydrothermal-vent-hypothesis-and-why-it-fails

Dr. Stanley L. Miller, University of California San Diego  14
What about submarine vents as a source of prebiotic compounds?
I have a very simple response to that . Submarine vents don't make organic compounds, they decompose them. Indeed, these vents are one of the limiting factors on what organic compounds you are going to have in the primitive oceans. At the present time, the entire ocean goes through those vents in 10 million years. So all of the organic compounds get zapped every ten million years. That places a constraint on how much organic material you can get. Furthermore, it gives you a time scale for the origin of life. If all the polymers and other goodies that you make get destroyed, it means life has to start early and rapidly. If you look at the process in detail, it seems that long periods of time are detrimental, rather than helpful.

Claim: Like maybe beaches that were struck by lightning, providing the right kind of chemical mix and the source of energy.
Reply: Lightning can fix nitrogen, which is an essential ingredient for all lifeforms on earth, but its far from settled that it could have been the source of nitrogen, before its fixation through a complex enzyme, called nitrogenase.

Availability of nitrogen and ammonia on early earth
https://reasonandscience.catsboard.com/t2689-availability-of-ammonia-in-a-prebiotic-earth

David P. SummersPrebiotic ammonia from reduction of nitrite by iron (II) on the early Earth  01 October 1993
THEORIES for the origin of life require the availability of reduced (or 'fixed') nitrogen-containing compounds, in particular ammonia. In reducing atmospheres, such compounds are readily formed by electrical discharges but geochemical evidence suggests that the early Earth had a non-reducing atmosphere in which discharges would have instead produced NO ( Nitrogen oxide may refer to a binary compound of oxygen and nitrogen, or a mixture of such compounds ). This would have been converted into nitric and nitrous acids and delivered to the early oceans as acid rain.

Claim: And perhaps the most useful one for this context is that life is a self-sustaining chemical reaction that is subject to Darwinian evolution.
Reply: What is life ? I think the best answer to that question was given by Paul Davies. He writes: 

https://reasonandscience.catsboard.com/t1435-paul-davies-what-is-life

Paul Davies:
http://www.nytimes.com/books/first/d/davies-miracle.html

Reproduction.
Metabolism. 
Homeostasis
Nutrition.
Complexity.
Organization. 
Growth and development.
Information content. 
Hardware/software entanglement. 
Permanence and change. 

All living organisms share several key characteristics or functions: order, sensitivity or response to the environment, reproduction, growth and development, regulation, homeostasis, and energy processing. When viewed together, these characteristics serve to define life.
https://courses.lumenlearning.com/wm-biology2/chapter/properties-of-life/

NASA’s current working definition of life
is “a self-sustaining chemical system capable of Darwinian evolution.”

Szent-Györgyi, who was awarded the 1937 Nobel Prize in Physiology or Medicine for his discovery of the action of ascorbic acid:
“In my hunt for the secret of life, I started research in histology. Unsatisfied by the information that cellular morphology could give me about life, I turned to physiology. Finding physiology too complex I took up pharmacology. Still finding the situation too complicated I turned to bacteriology. But bacteria were even too complex, so I descended to the molecular level, studying chemistry and physical chemistry. After twenty years' work, I was led to conclude that to understand life we have to descend to the electronic level, and to the world of wave mechanics. But electrons are just electrons, and have no life at all. Evidently, on the way I lost life; it had run out between my fingers.”


Claim: they need to perform three things. One, they need to store information. They need to keep some sort of memory about who they are and what they're capable of doing. Next, they need to catalyze reactions. This is AKA metabolism, and what makes life so much fun. And lastly, they need to be able to self-replicate. They need to be able make copies of themselves so that they can remember who they are and what they're capable of doing, and pass all that onto a new generation. Modern life uses a set of three macromolecules to get all those jobs done.
Reply:  How could they emerge individually, if, by their own, without the other parts, there would be no function ?

The cell is irreducibly complex
https://reasonandscience.catsboard.com/t1299-abiogenesis-the-cell-is-irreducibly-complex

Emily Singer How Structure Arose in the Primordial Soup May 19, 2015
About 4 billion years ago, molecules began to make copies of themselves, an event that marked the beginning of life on Earth. A few hundred million years later, primitive organisms began to split into the different branches that make up the tree of life. In between those two seminal events, some of the greatest innovations in existence emerged: the cell, the genetic code and an energy system to fuel it all. ALL THREE of these are ESSENTIAL to life as we know it, yet scientists know disappointingly little about how any of these remarkable biological innovations came about.
https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/

The Cell and Irreducible Complexity
1.  Up until this past Century, we had no idea just how complex and interactively dependent biological systems are…
2.  A cell is like a very complex factory. Many different ‘molecular machines’, like the golgi-apparatus, the endoplasmic reticulum, the mitochondria and many more, take care of various processes within the cell. The processes are all part of one system, which means that the one process cannot function without other processes. You could say there is a certain cooperation between the various organelles within the cell.
3.The cell is yet another example of something that is irreducibly complex
4. The point is the evolutionary processes would not produce such complexity by definition – biological processes according to evolution will weed out that which is useless or detrimental. Unless, you have each of the parts showing up at the exact same time in the same life form – the individual components would serve no purpose.
https://web.archive.org/web/20170522092740/http://christianevidences.org/scientific-evidence/hematology/the-cell-and-irreducible-complexity/

Claim:  The DNA creates RNA, which transcribes that information and then manufactures proteins. And the proteins are the ones who do the job of catalyzing reactions, including replicating DNA so it can make copies of itself. And this is an extraordinarily complex interaction that honestly we don't fully understand. And it's so complex and interconnected that it's obvious that early life must have been simpler.
Reply:   ..... Or the system had to be designed from scratch by an intelligent designer, with foresight, intelligence, and will, for his own purposes.

The problem of the origin of the hardware and software in the cell is far greater than commonly appreciated
https://reasonandscience.catsboard.com/t2997-the-problem-of-the-origin-of-the-hardware-and-software-in-the-cell-is-far-greater-than-commonly-appreciated

1. The cell coordinates its functions by virtue of a ‘genetic program’ encoded in the DNA that directs and controls the expression of a specific set of RNAs and proteins, which assemble deterministically into stable ‘molecular machines’ that reliably and efficiently execute predetermined operations according to the mechanisms of cell division, endocytosis, signal transduction, etc.
2. This is analogous to engineers, which produce blueprints, which prescribe and instruct the making and assembly of machines for specific purposes. 
3. Herschel 1830 1987, p. 148: “If the analogy of two phenomena be very close and striking, while, at the same time, the cause of one is very obvious, it becomes scarcely possible to refuse to admit the action of an analogous cause in the other, though not so obvious in itself.” A metaphor (“A biological cell is like a production system”) demonstrates that similar behaviors are driven by similar causal mechanisms.
4. Since there was no human mind present when life started, we can conclude that a nonhuman higher intelligent agency must have created life. 

Claim:  And it's possible that early life didn't even use proteins or DNA. It's possible that early life only used RNA.
Reply:    No life form is known that does not use DNA. And the RNA world has been debunked.

The origin of replication and translation and the RNA World
https://reasonandscience.catsboard.com/t2234-the-origin-of-replication-and-translation-and-the-rna-world

The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on how recent observations of the catalytic properties of various forms of RNA fit with this hypothesis.
https://en.wikipedia.org/wiki/RNA_world

Leslie Orgel: Prebiotic chemistry and the origin of the RNA world Mar-Apr 2004
It is possible that all of these, and many other difficulties, will one day be overcome and that a convincing prebiotic synthesis of RNA will become available. However, many researchers in the field, myself included, think that this is unlikely
https://pubmed.ncbi.nlm.nih.gov/15217990/

Christian de Duve: The Beginnings of Life on Earth   September-October 1995 issue of American Scientist.
Contrary to what is sometimes intimated, the idea of a few RNA molecules coming together by some chance combination of circumstances and henceforth being reproduced and amplified by replication simply is not tenable. There could be no replication without a robust chemical underpinning continuing to provide the necessary materials and energy.
https://www2.nau.edu/~gaud/bio372/class/readings/beglifeerth.htm


Claim: This is called the RNA world hypothesis, and it works because RNA is capable of self-replicating. It's capable of catalyzing reactions.
Reply: Evidence says otherwise. 

The difficult case of an RNA-only origin of life AUGUST 28 2019
Despite a large body of evidence supporting the idea that RNA is capable of kick-starting autocatalytic self-replication and thus initiating the emergence of life, seemingly insurmountable weaknesses in the theory have also been highlighted. Despite advances in prebiotic chemistry, it has not yet been possible to demonstrate robust and continuous RNA self-replication from a realistic feedstock. RNA in isolation may not be sufficient to catalyse its own replication and may require help from either other molecules or the environment.
https://portlandpress.com/emergtoplifesci/article/3/5/469/220563/The-difficult-case-of-an-RNA-only-origin-of-life

Eörs Szathmáry:  Toward major evolutionary transitions theory 2.0  April 2, 2015
Despite recent progress, we still have no general RNA-based replicase that could replicate a great variety of sequences, including copies of its own.
https://www.pnas.org/content/112/33/10104

Claim:  But eventually, short RNA strands appear. And then, these short RNA strands start participating in chemical reactions that get ever more complex. And then, slowly over time due to evolutionary pressure, eventually DNA and proteins emerge as more efficient versions of the same basic process.
Reply: It doesn't matter how confidently and enthusiastically, and convincingly the claim is made, this is pseudo-scientific gobbledygook.

The RNA world, and the origins of life
https://reasonandscience.catsboard.com/t2024-the-rna-world-and-the-origins-of-life

Robert P. Bywater On dating stages in prebiotic chemical evolution 15 February 2012
Despite the wide repertoire of chemical and biological properties of RNA, which make it such an appealing contender for being the first type of molecular species to usher in life onto this planet, there is no explanation for how such a complex chemical species could have arisen in the absence of sophisticated chemical machinery. The generation of complex chemicals require many millions of cycles of synthesis, partial degradation, concentration, selection and reannealing in combinatorially new ways such that sufficiently diverse species could be produced and reproduced, from which particularly suitable entities survived 34

Formation of Deoxyribonucleotides
https://reasonandscience.catsboard.com/t2028-the-dna-double-helix-evidence-of-design#3432

From RNA to DNA impossible
https://reasonandscience.catsboard.com/t1784-from-rna-to-dna-impossible

Claim:  We can look at all the bacteria, and there are a lot of bacteria, to see what few genes we have in common. And this kinds of sequencing has revealed about 330 genes that all life on Earth shares.
Reply: What might be a Cell’s minimal requirement of parts ?  [url=file:///E:/Desktop/apdf files/FirstGeneCh10.pdf]1[/url]
https://reasonandscience.catsboard.com/t2110-what-might-be-a-protocells-minimal-requirement-of-parts

Let's suppose, we have a fully operational raw material, and the genetic language upon which to store genetic information. Only now, we can ask: Where did the information come from to make the first living organism? Various attempts have been made to lower the minimal information content to produce a fully working operational cell. Often, Mycoplasma is mentioned as a reference to the threshold of the living from the non-living. Mycoplasma genitalium is held as the smallest possible living self-replicating cell. It is, however, a pathogen, an endosymbiont that only lives and survives within the body or cells of another organism ( humans ).  As such, it IMPORTS many nutrients from the host organism. The host provides most of the nutrients such bacteria require, hence the bacteria do not need the genes for producing such compounds themselves. As such, it does not require the same complexity of biosynthesis pathways to manufacturing all nutrients as a free-living bacterium. 

The simplest free-living bacteria is Pelagibacter ubique. It is known to be one of the smallest and simplest, self-replicating, and free-living cells.  It has complete biosynthetic pathways for all 20 amino acids.  These organisms get by with about 1,300 genes and 1,308,759 base pairs and code for 1,354 proteins. They survive without any dependence on other life forms. Incidentally, these are also the most “successful” organisms on Earth. They make up about 25% of all microbial cells.   If a chain could link up, what is the probability that the code letters might by chance be in some order which would be a usable gene, usable somewhere—anywhere—in some potentially living thing? If we take a model size of 1,200,000 base pairs, the chance to get the sequence randomly would be 4^1,200,000 or 10^722,000. 2

Claim:   - Are you aware of these debates when it comes to the origin of life between replication-first scenarios and metabolism-first scenarios?
Reply: Replicator first, and metabolism first scenarios
http://reasonandscience.heavenforum.org/t1428-replicator-first-and-metabolism-first-scenarios

Beyond the controversy opposing "replication first" to metabolismfirst", the predictive arguments of theories on "catalytic closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors having emerged as complex, self-replicating entities from which a genetic code arose under natural selection.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478661/

The whole is more than the sum of the parts. Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. Why would natural selection select an intermediate biosynthesis product, which has by its own no use for the organism, unless that product keeps going through all necessary steps, up to the point to be ready to be assembled in a larger system? Never do we see blind, unguided processes leading to complex functional systems with integrated parts contributing to the overarching design goal.
A minimal amount of instructional complex information is required for a gene to produce useful proteins. A minimal size of a protein is necessary for it to be functional. Thus, before a region of DNA contains the requisite information to make useful proteins, natural selection would not select for a positive trait and play no role in guiding its evolution.

Claim:   The potential to produce the raw materials is huge. It's not one little test tube in a lab. - Right, it's billions of test tubes over the course of potentially hundreds of millions of years.
Reply: There was no prebiotic selection to get life originating

https://reasonandscience.catsboard.com/t3121-there-was-no-prebiotic-selection-to-get-life-originating

1. Life requires the use of a limited set of complex biomolecules, a universal convention, and unity which is composed of the four basic building blocks of life ( RNA and DNA's, amino acids, phospholipids, and carbohydrates). They are of a very specific complex functional composition and made by cells in extremely sophisticated orchestrated metabolic pathways, which were not extant on the early earth. If abiogenesis were true, these biomolecules had to be prebiotically available and naturally occurring ( in non-enzyme-catalyzed ways by natural means ) and then somehow join in an organized way and form the first living cells. They had to be available in big quantities and concentrated at one specific building site.
2. Making things for a specific purpose, for a distant goal, requires goal-directedness. And that's a big problem for naturalistic explanations of the origin of life. There was a potentially unlimited variety of molecules on the prebiotic earth. Competition and selection among them would never have occurred at all, to promote a separation of those molecules that are used in life, from those that are useless. Selection is a scope and powerless mechanism to explain all of the living order, and even the ability to maintain order in the short term and to explain the emergence, overall organization, and long-term persistence of life from non-living precursors. It is an error of false conceptual reduction to suppose that competition and selection will thereby be the source of explanation for all relevant forms of the living order.
3. We know that a) unguided random purposeless events are unlikely to the extreme to make specific purposeful elementary components to build large integrated macromolecular systems, and b) intelligence has goal-directedness. Bricks do not form from clay by themselves, and then line up to make walls. Someone made them. Phospholipids do not form from glycerol, a phosphate group, and two fatty acid chains by themselves, and line up to make cell membranes. Someone made them. That is God.

Time makes everything become possible. Really?
https://reasonandscience.catsboard.com/t2025-time-makes-everything-become-possible-really

Time is not the atheist's friend. Time does not complexify molecules. It disintegrates them. Long periods of time do not make life inevitable; they only make randomization more complete.

Ilya Prigogine, Nobel Prize-winning chemist
The probability that at ordinary temperatures a macroscopic number of molecules is assembled to give rise to the highly ordered structures and to the coordinated functions characterizing living organisms is vanishingly small. The idea of spontaneous genesis of life in its present form is therefore highly improbable, even on the scale of the billions of years during which prebiotic evolution occurred

Paradoxes in the Origin of Life Steven A. Benner
https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/25608919

The Asphalt Paradox
An enormous amount of empirical data have established, as a rule, that organic systems, given energy and left to themselves, devolve to give uselessly complex mixtures, “asphalts”. The theory that enumerates small molecule space, as well as Structure Theory in chemistry, can be construed to regard this devolution a necessary consequence of theory. Conversely, the literature reports (to our knowledge) exactly zero confirmed observations where “replication involving replicable imperfections” (RIRI) evolution emerged spontaneously from a devolving chemical system. Further, chemical theories, including the second law of thermodynamics, bonding theory that describes the “space” accessible to sets of atoms, and structure theory requiring that replication systems occupy only tiny fractions of that space, suggest that it is impossible for any non-living chemical system to escape devolution to enter into the Darwinian world of the “living”. Such statements of impossibility apply even to macromolecules not assumed to be necessary for RIRI evolution. Again richly supported by empirical observation, material escapes from known metabolic cycles that might be viewed as models for a “metabolism first” origin of life, making such cycles short-lived. Lipids that provide tidy compartments under the close supervision of a graduate student (supporting a protocell first model for origins) are quite non-robust with respect to small environmental perturbations, such as a change in the salt concentration, the introduction of organic solvents, or a change in temperature.

Claim: When did DNA happen? - DNA chemically is only one atom different from RNA. Since DNA is more stable, there would be an evolutionary selection towards having a more stable repository for genetic material.
Reply:  Now, this is pure pseudo-scientific nonsense. The transistion from RNA to DNA is extremely complex, and requires some of the most sophisticated complex enzymes, like Ribonucleotide reductase enzymes.

https://reasonandscience.catsboard.com/t2028-the-dna-double-helix-evidence-of-design#3432

The science paper:  Ribonucleotide reductases: the link between an RNA and a DNA world? 59  make a remarkable claim:
RNRs evolved and provide an essential link between the RNA and DNA world. These enzymes are essential for both DNA replication and repair.

Question: How could evolution be a driving force prior to the emergence of DNA, upon which evolution depends?

Assuming that a ribozyme will not be capable of catalyzing such complex radical chemistry, then proteins must have preceded DNA in the transition from an RNA to a DNA world.

This is a paradox. Proteins are encoded in DNA, and could not precede it.

From Prelife to Life: How Chemical Kinetics Become Evolutionary Dynamics
https://sci-hub.ee/10.1021/ar2002683

Wilhelm T. S. Huck Robustness, Entrainment, and Hybridization in Dissipative Molecular Networks, and the Origin of Life May 30, 2019
How simple chemical reactions self-assembled into complex, robust networks at the origin of life is unknown. This general problem of self-assembly of dissipative molecular networks (  out of, and often far from, thermodynamic equilibrium ) is also important in understanding the growth of complexity from simplicity in molecular and biomolecular systems.  
https://robobees.seas.harvard.edu/files/gmwgroup/files/1320.pdf

Bridging the trajectory from non-life to life, the gap is far, far too wide. It's difficult to describe. Analogies do not do justice to illustrate and clarify the hopeless situation. 

People that have no clue, that have heard about the Miller-Urey experiment, often cite it, and claim, that it gave a successful result, demonstrating that abiogenesis is possible in principle. Others point to the various hypotheses, claiming that they warrant the belief that it could theoretically occur.   

Imagine a cause that needs to create an interlinked factory complex containing 1300 complex machines that are installed in specialized compartments, ordered based on the specific task that they perform, and interlinked in a functional way to be part of automated and carefully regulated production lines, that make specific intermediate parts, that permit the higher-order construction and assembly and subsequently self-replication of that factory. From scratch. Performing 1500 reactions in parallel. Unfortunately, that cause has a problem. It is not an intelligent engineer. And another problem: There is no directed energy source available to construct that factory. Only unspecific thermic energy from volcanoes, thermal vents, earthquakes, thunderstorms, the sun, and lightning. 

Let's suppose the number of all atoms in the universe ( 10^80) would be small molecules. Getting the right specified sequence of amino acids to get just one-third of the size of an average-sized protein of 300 amino acids,  one of the 1300 proteins used in that factory, is like painting one of all these molecules in the universe ( roughly 10^80) in red, then throwing a dart randomly, and by luck, hitting the red molecule, with the first attempt. The odds to have all the 1300 proteins assembled by chance, and then interlinked in the right way, is one in 10^725000 !! 

Whatever organism one wants to suggest as a minimal possible life form - no matter if we remove some metabolic pathways and imagine that it got its amino acids alphabet externally, as suggested by Madeline C. Weiss and colleagues in their well-known article: The physiology and habitat of the last universal common ancestor from 2016, the gulf to be bridged, the hurdles to be overcome, to go from lifeless early earth to the first self-replicating cell are hardly commensurable, and difficult to imagine. 

Following gives us an idea: The ability to transfer just ONE SINGLE CARBON atom is absolutely essential for the metabolism of the amino acids glycine, serine, methionine, and histidine, and the biosynthesis of purines and pyrimidines - which constitute DNA molecules, the information carriers of cells.

And in order for biological cells to achieve this transfer, they require tetrahydrofolate cofactors, consisting of three moieties. Folates are among the most complex pterin coenzymes. The folate pathway is central to any study related to DNA methylation, dTMP synthesis, or purine synthesis, and as such, to the origin of life itself, since without amino acids, and DNA - no life.

At this link you can see the Folate biosynthesis pathway: https://www.genome.jp/pathway/map00790 - at each branch point, there is a ramification of a web of complex enzymes which work in a coordinated, orchestrated, and interconnected way together to produce just this Tetrahydrofolate cofactor. To make things even more complex, the two essential precursors of folate biosynthesis are 4-aminobenzoate (a product of the shikimate biosynthesis pathway: https://www.genome.jp/kegg-bin/show_pathway?map01063 ) and  Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate.  

Abiogenesis proponents need to explain at least the origin of a minimal genome, the epigenome, the glycome, the lipidome, the mobilome, the transcriptome, the metabolome, the proteome, and the interactome, the signalosome, and the metallome of our minimal cell. A set of metabolic pathways ( the metabolome) consisting of at least 400 reactions performed by hundreds of enzymes and proteins, the molecular robots, producing all relevant molecules. The synthesis of the four building blocks of life, and salvage and recycling pathways ( That includes uptake and processing of the big, major, and trace elements  [ nitrogen and carbon fixation]. Furthermore, the genome, that directs the making of hundreds of proteins ( the proteome) - complex molecular machines made through transcription ( the transcriptome) and translation, the proteins interconnection ( the interactome), using the genetic code, the machinery of DNA replication, error-check and repair mechanisms starting with DNA, all the way through to the ribosome ( 13 check and repair mechanisms alone). An epigenome, that controls DNA–protein interactions ( DNA methylation that performs transcriptional activation and repressions, and the formation of phenotypic variants) timing of DNA replication, partitioning nascent chromosomes to daughter cells, repair of DNA, and timing of transposition and conjugal transfer of plasmids. The chromosome segregation machinery ( topoisomerase II).  

The ribosome is especially noteworthy. The Universal Gene Set of Life (UGSL) consists of less than 100 genes and is dominated by translation-related genes. These ribosomal RNAs (rRNAs), transfer RNAs (tRNAs and the machinery to synthesize and modify tRNAs, a full set of aminoacyl tRNA synthetases) small RNAs, and ribosomal proteins make up the most abundant macromolecular species in all living organisms ( Bernstein 2019). Ribosome biogenesis: It would require all proteins that assemble ribosomes, including proteins, that make proteins, that make the subunits of the ribosome, and the entire error check and repair, and recycle machinery.  It would require chaperones, proteins that help proteins that come out from the ribosome, and are being misfolded, to get their right fold. That includes chaperones, that help chaperones to be folded properly. ( In other words, machines, that help machines, that help other machines) Furthermore, the membrane includes millions of complex membrane-embedded protein channels, ion pumps, ion exchangers, transporters, importers, translocons, translocases, symporters, and antiporters that control what is imported, what leaves the cell, and the intracellular levels of all life-essential elements. Then the enzymes that are involved in cell division, and it's regulation. A way to fix carbon to produce carbohydrates, that are digested through catabolism to feed ATP synthase, electron transport, and a proton gradient to generate ATP, the energy currency in the cell. It would also require at least 8 co-factors, and vitamins.  

Thioesters were almost certainly involved in the prebiotic formation of many molecules that are important in contemporary biology. Their formation depends on Coenzyme A (CoA). Coenzyme A synthesis depends on five enzymes used in the five-step universal pathway of coenzyme A (CoA) biosynthesis.  Numerous machines uptake iron ( Non-ribosomal peptide synthetase to make siderophores) and chelate it ( making it available in soluble form for uptake), sulfur, and the machinery to create Iron-sulfur (Fe/S) clusters, essential in many vital proteins in their reaction centers. Life essential proteins, replete with FeS clusters and radical reaction mechanisms, depend upon transition metals, flavins, S-adenosyl methionine, ferredoxin, molybdopterin, corrins, and selenium. It had to create a homeostatic environment, in one of many other cases, diminishing the calcium concentration in the cell 10000 times below the external environment, to permit signaling. It requires osmoregulation to maintain the fluid balance and the concentration of electrolytes, preventing the cytosol to be too diluted or concentrated. Furthermore, it would - from the get-go, have to be able to adapt to the variegated environmental conditions, able to get and interpret signals from the environment the outside and react accordingly ( like thermal conditions).

Consider that you cannot resort to evolution, and long periods of time: 

Wilhelm T. S. Huck Robustness, Entrainment, and Hybridization in Dissipative Molecular Networks, and the Origin of Life May 30, 2019
Life emerged spontaneously from the selfassembly, or spontaneous organization, of the organic products of reactions, occurring in complex mixtures of molecules formed abiotically from simple precursors and sequences of reactions.
https://robobees.seas.harvard.edu/files/gmwgroup/files/1320.pdf

I have not enough faith to believe that life can come from non-life, by unguided mechanisms.

Some Prebiotic Chemical Problems Remaining To Be Solved 
1. Primitive Earth's Environment. More detailed studies of the chemical reactions following the acquisition of comets and asteroids during the first 600 million years, 
2. ~bose Formation, Possible prebiotic reactions for more selective synthesis of ribose, 3. Homochirality and Polymerization. Study of polymerization reactions (nucleotides, peptides) leading to the selective or preferential incorporation of either D or L isomers. The actual differentiation process was probably based on the stabilization of homochiral polymers by processes of molecular natural selection, lower energy states or catalytic activity. Because of the relatively high racemization rates, it does not appear that the genesis of homochirality can be a physical or chemical problem related to the individual synthesis of monomeric enantiomers. Homochirality probably appeared in the transition from pre-life to life, during the process of macromolecular self-organization, and subsequent "survival" of the fittest macromolecules according to their selective function. 
4. ~. Additional studies on the synthesis of fatty acids and amphiphilic lipids capable of forming semipermeable membranes are required. 
5. ~elf Organizati~, SeLf-assembly of catalytic ribonucleotides, nucleotide substrates, and high energy compounds (pyrophosphate, ATP, GTP, etc.) within a semipermeable membrane. 
6. ]~ner~¢ Sources. Continuous synthesis, through a semipermeable membrane, of ATP or other high-energy phosphates by means of a proton gradient, or by photochemical activation. 7. Translation and Aut0eatalvtic Feedback. Prebiotic molecular translation of coding RNA polymers into catalytic peptides that are capable of synthesizing RNA.

https://sci-hub.ee/10.1007/bf00700430

ADDY PROSS: What is Life? How Chemistry becomes Biology

Life’s evident design, in particular, stands out, as a source of endless speculation. The creativity and precision so evident in that design is nothing less than spectacular.  Due to the remarkable advances in molecular biology over the past six decades we have discovered that nature’s design capabilities can be immeasurably greater. Take the ribosome, for example. The ribosome is a tiny organelle present in all living cells in thousands of copies that manufactures the protein molecules on which all life is based. It effectively operates as a highly organized and intricate miniature factory, churning out those proteins—long chain-like molecules—by stitching together a hundred or more amino acid molecules in just the right order, and all within a few seconds. And this exquisitely efficient entity is contained within a complex chemical structure that is just some 20–30 nanometres in diameter— that’s just 2–3 millionths of a centimeter! Think about that—an entire factory, with all the elements you’d expect to find in any regular factory, but within a structure so tiny it is completely invisible to the naked eye. Indeed, for elucidating the structure and function of this remarkable organelle, Ada Yonath from the Weizmann Institute, Israel, Venkatraman Ramakrishnan from the Laboratory of Molecular Biology at Cambridge, and Thomas Steitz from Yale University were awarded the 2009 Nobel Prize in Chemistry.

 No less impressive than life’s extraordinary design capabilities is its breathtaking diversity, a perpetual source of inspiration. Red roses, giraffes, butterflies, snakes, towering redwoods, whales, fungi, crocodiles, cockroaches, mosquitoes, coral reefs—the mind boggles at nature’s spectacular and unmitigated creativity. Literally millions of species, and that’s before we have even touched upon the hidden kingdom, the bacterial one. That invisible kingdom is itself a source of overwhelming, almost incomprehensible diversity, one that is just beginning to come to light. But life’s design and diversity are just two characteristics out of a wider set that serves to compound the mystery and uniqueness of the life phenomenon. Some of life’s characteristics are so striking you don’t have to be too observant to notice them. Take life’s independent and purposeful character, for example. 

We have an intriguing phenomenon—biologists, the scientists who devote themselves to the study of living systems, and who possess a deep appreciation of life’s complexity, having successfully probed many of its key components, remain mystified by what life is, and physicists, with their deep understanding of nature’s most fundamental laws, are no less confused. Both continue to struggle with the nature of life question and we can only conclude that the 3,000-year ‘what is life’ riddle remains that—a riddle. 

Organized complexity and one of the most fundamental laws of the universe—the Second Law of Thermodynamics—are inherently adversarial. Nature prefers chaos to order, so disorganization is the natural order. Within living systems, however, the highly organized state that is absolutely essential for viable biological function is somehow maintained with remarkable precision. : The living cell is able to maintain its structural integrity and its organization through the continual utilization of energy, which is in fact part of the cell’s modus operandi. . So there is no thermodynamic contradiction in life’s organized high-energy state, just as there is no contradiction in a car being able to drive uphill in opposition to the Earth’s gravitational pull, or a refrigerator in maintaining a cool interior despite the constant flow of heat into that interior from the warmer exterior. Both the car driving uphill and the refrigerator with its cold interior can maintain their energetically unstable state through the continual utilization of energy. In the car’s case the burning of gasoline in the car’s engine is the energy source, while in the case of the refrigerator, the energy source is the electricity supply that operates the refrigerator’s compressor. In an analogous manner, energetically speaking, the body can maintain its highly organized state through the continual utilization of energy from some external source—the chemical energy inherent within the foods we eat, or, in the case of plants, the solar energy that is captured by the chlorophyll pigment found in all plants. 

But how the initial organization associated with the simplest living system came about originally is a much tougher question.

There is even a biological term for the phenomenon whereby that organized state is maintained—homeostasis, from the Greek meaning ‘standing still’.

The living cell is a highly organized entity. We can compare it to a familiar mechanical entity, a clock. Both are organized in the sense that all of the component parts contribute to the operation of the holistic entity. The parts of the clock enable it to fulfill its function of telling the time, and the parts of the cell enable it to fulfill its function and become two cells. Of course the clock is an organized entity that has been constructed to fulfil its particular function—it is man-made, then how can the bacterial cell have somehow come about on its own accord? Nevertheless, the machine metaphor for understanding living systems has been useful and allowed us to continue to probe cell function, to discover in ever greater detail the precise workings of this remarkable ‘machine’. Closer examination of the two ‘machines’, however, reveals an extraordinary distinction between the machine-like characteristics of the clock and the cell. Within the clock the components remain in place and continue to operate until one or other of them wears out and the system ceases to function. But within the living cell the situation is spectacularly different. Whereas a clock is a static system, whose parts are permanent and unchanged, every living system is dynamic. Its parts are continually being turned over. Let me explain. 

You meet an old friend that you haven’t seen in a few years and you greet him with the comment: ‘Hi Bill, great to see you again, you haven’t changed a bit!’ You make that comment because Bill looks very much as you remember him from your last encounter. But here is an extraordinary fact. The person standing in front of you, who looks like Bill, talks like Bill, and is called Bill, is, materially speaking, effectively a totally different person from the Bill you saw some time back. Just about every molecule in Bill’s body has been replaced since you last saw him. Almost all the stuff of which Bill (and you and me) is made has been turned over. For some parts of us, our hair and fingernails, for example, that turnover is obvious. But for the rest of what makes you, you, the turnover is hidden from view. It takes place surreptitiously. Like all human beings you are primarily composed of the some 10 thousand billion (10,000,000,000,000) cells that make up your body. (We actually also contain within our bodies some 100 thousand billion foreign cells, bacteria. And each of those cells is itself composed of an array of biomolecules—lipids, proteins, nucleic acids, and so on.

ADDY PROSS: What is Life?: How Chemistry Becomes Biology  2012

Origin-of-Life Expert Jokes about Becoming a Creationist   11/05/2004


https://web.archive.org/web/20121130144326/http://creationsafaris.com/crev200411.htm


Exclusive  At the Jet Propulsion Laboratory Nov. 5, a world-renowned origin-of-life researcher spoke to a packed auditorium on the status of his field, chemical evolution and the origin of life.  Dr. Steven Benner (U. of Florida) trains graduate students in the subject, knows all the big names in the field personally, and has published and worked on this subject for over 20 years.  His outline dealt with 4 approaches to probing the black box of life’s origin: (1) working forward in time from stars and planets, (2) working backward in time from existing life to its ancestors, (3) experimenting with synthetic life, and (4) searching suitable habitats in space.
    More interesting, though, were his candid admissions about the problems facing anyone in this field, and his joking references a couple of times that if these problems remain unsolveable, he might have to become a creationist.  He didn’t mean it, of course.  These were chuckle-garnering hyperboles to express the frustration he has felt for decades over problems that are still far from a solution.  For instance:

1. DNA: as good as it gets?  Benner spent some time discussing how perfect DNA and RNA are for information storage.  The upshot: don’t expect to find non-DNA-based life elsewhere.  Alien life might have more than 4 base pairs in its genetic code, but the physical chemistry of DNA and RNA are hard to beat.  Part of the reason is that the electrochemical charges on the backbone keep the molecule rigid so it doesn’t fold up on itself, and keep the base pairs facing each other.  The entire molecule maximizes the potential for hydrogen bonding, which is counter-intuitive, since it would seem to a chemist that the worst environment to exploit hydrogen bonding would be in water.  Yet DNA twists into its double helix in water just fine, keeping its base pairs optimized for hydrogen bonds, because of the particular structures of its sugars, phosphates and nucleotides.  The oft-touted substitute named PNA falls apart with more than 20 bases.  Other proposed alternatives have their own serious failings.
   
   
2. Sugar substitute:  Ribose sugar is the molecule of choice for nucleic acids, yet because it is difficult to imagine forming under plausible prebiotic conditions and has a short lifetime, origin-of-life researchers have searched diligently for alternatives, like glycerol, that might have served as scaffolding for prebiotic chemicals prior to the emergence of DNA.  Unfortunately, they don’t work.  He was emphatic: over 280 alternative molecules have been tested, and they just do not work at all; those that might be better than ribose are implausible under prebiotic conditions.  “Ribose is actually quite good – uniquely good,” he said.  Deal with it: one’s chemical evolution model is going to have to include ribose.  That means figuring out how it can form, how it can avoid destruction in water, and how it can avoid clumping into useless globs of tar.  (RNA, the main player in the leading “RNA World” scenario for the origin of life, uses ribose; DNA uses a closely-related sugar, deoxyribose.)
   
   
3. Genetic takeovers:  Benner chided those whose models invoke genetic takeovers: i.e., starting with another sugar then switching to ribose, starting with another informational macromolecule then switching to DNA, etc.  For instance, some flippantly suggest to get DNA’s sugar, “just add an OH to ribose....”  The professor got animated.  That adds a charge to the molecule, he exclaimed, and what is more important to the behavior of a molecule than its electrostatic charge?  You can’t just add a charge to a molecule and expect it to keep behaving like it did before.
   
   
4. Adding Ad Hoc:  When a researcher keeps having to multiply ad hoc scenarios to keep his model together, it quickly becomes a target of criticism.  The professor spoke of Robert Shapiro, a long time critic of this bad habit among his colleagues.  He said one of his requirements for graduate students is to endure Shapiro’s critique.  He spoke as if this is a common, well-known fault in the origin of life community – invoking a meteor strike here, a clay mineral there, a volcano over yonder, a deep sea vent somewhere else – all needing to be present at the right time and place to get the scheme to work.  He also spoke as if his own model was not immune from that criticism.
   
   

The ribose problem appeared so severe to him early in his studies, he felt certain at the time that researchers simply had to find an alternate sugar for chemical evolution.  Stanley Miller was similarly emphatic in his writings, stating that ribose sugars were not components of the earliest life.  His colleagues (researchers in this field tend to be a sociological society, he quipped) have gone back and forth on this issue for years, but the 280 molecules they have tested are worse than ribose; they don’t work.
    This intractable problem has led him to a novel solution: life didn’t form in the water, but in a desert.  Serendipitously, he found that a mineral – borate – can stabilize ribose long enough to make it a contender (see 01/09/2004 headline).  Like ribose, borate also decomposes in water and needs a dry environment.  If borate is found on Mars, he speculated, maybe ribose will also be found there, he announced to the planetary scientists and engineers in the room.  But then, how can the other necessary molecules associate with ribose if it is in a desert?  And how would it be shielded from ultraviolet radiation, as a questioner asked about Mars (to which he answered that much more research needs to be done on the effect of sunlight on ribose).  And how could ribose on a desert continent survive the impact record on the early earth?  Worse, the fact that borate and ribose seem made for each other raises the old specter of the Anthropic Principle: why should two independent substances that are not common in the universe be found together in the same place and time?  He admitted this gave him a shrinking feeling; “it was almost a creationist argument,” he confessed half seriously.
    This reporter had the opportunity to ask follow-up questions to the professor during the Q&A; period, and in person after the meeting was adjourned:
Besides the problems, another thing stood out from his presentation: the exquisite perfection of DNA, RNA and ribose for the jobs they have to do.  Maybe this would be a good time to follow the path of former chemical evolution researcher, Dean Kenyon: become a creationist.

Several important and valuable lessons came out of this interchange.  One was the observation that in a packed room of intelligent people, I was the only one to ask really challenging questions.  The others, many of them college graduates with advanced degrees, seemed to just accept what was being said, and appeared hopeful that science was making real progress in finding out how life evolved.  Few, if any, seemed to notice that most of what he discussed was either irrelevant to the question, or too speculative to be considered scientific.

Consider his four approaches: (1) Working forward in time from the earliest stars and planets to the origin of life.  This assumes evolution without offering a shred of evidence.  Irrelevant.  (2) Working backward in time from existing life to ancestral life.  This assumes evolution with only circumstantial evidence from comparative genomics, but has the additional problem that no evidence for life earlier than 2.5 billion years has been found (assuming evolutionary dating).  Speculation without evidence.  (3) Synthetic biology: tweaking proteins and DNA to explore the limits of life.  This is intelligent design (see 01/09/2003 headline).  Irrelevant.  (4) Exploring new habitats in space on other planets.  This is banking on hope, and even if life were found, it would not prove it evolved.  Irrelevant.

He provided no evidence to demonstrate chemical evolution is a viable scientific theory.  He shared some interesting organic chemistry, which is fine, but none of it was applicable to explaining the origin of life by natural means.  He himself once wrote, “It is difficult to believe that larger pools of random RNA emerged spontaneously without the gentle coaxing of a graduate student desiring a completed dissertation.”  That’s intelligent design, not evolution.
    Few in the audience, also, seemed to care that the problems he described were so serious as to falsify chemical evolution.  Each problem was a show stopper, yet his show went on.  Then there were the problems he didn’t even talk about.  Everything in evolution he accepted as true has problems of its own: common ancestry of all life, the RNA World hypothesis (see 07/11/2002 headline), Darwinian natural selection, the long ages of the geologists and the phylogenetic tree-building methods of the biologists.  Each of these things he merely assumed were true, but each has monstrous problems of its own.  Yet in spite of his faith in the cause to which he has devoted his professional life, he intimated a shrinking feeling that maybe the creationists might be right.
    This episode underscores the fact that, on this subject, creationists have the Darwinists in a hammerlock with their faces to the floor wincing in pain.  Darwinism has fouled out on the origin of life, and one cannot continue competing if he has fouled out in the first round.  If a designing intelligence is needed to get life going, then all the questions and answers change.  The fluff about finch beaks and peppered moths and Lucy is irrelevant, because a totally new approach to looking at the world is needed: an approach that recognizes that information from an intelligent cause is a fundamental property of life.  If that happens to have profound religious or metaphysical implications, so be it.  Meanwhile, keep the hammerlock on until they repent of their storytelling and cry UNCLE: Uniformitarian Naturalism Cannot Life Explain.
Next headline on:   Origin of Life

At least 14 major hurdles of abiogenesis 

https://reasonandscience.catsboard.com/t1279p25-abiogenesis-is-mathematically-impossible#9362

Demonstrating that life from non-life by unguided means is possible would entail researchers to build a nano-scaled self-replicating factory in their laboratory by leaving an impure mix of raw materials ( some used in life, but the majority not), and waiting for unguided processes to take their course...Never has a team of researchers ever tried, much less, succeeded.

Memory-stored controls transform symbols into physical states. Von Neumann felt, "That they should occur in the world at all is a miracle of the first magnitude."
Paul Davies: How did stupid atoms spontaneously write their own software … ? Nobody knows … … there is no known law of physics able to create information from nothing.

Cells have a codified description of themselves in digital form stored in genes and have the machinery to transform that blueprint through information transfer from genotype to phenotype, into an identical representation in analog 3D form, the physical 'reality' of that description.

G. F. Joyce, L. E. Orgel: Prospects for Understanding the Origin of the RNA World 1993
A blueprint cannot produce a car all by itself without a factory and workers to assemble the parts according to the instructions contained in the blueprint; in the same way, the blueprint contained in RNA cannot produce proteins by itself without the cooperation of other cellular components which follow the instructions contained in the RNA.

The cause leading to a machine’s and factory's functionality is found in the mind of the engineer and nowhere else.

Jack W. Szostak: It is virtually impossible to imagine how a cell’s machines, which are mostly protein-based catalysts called enzymes, could have formed spontaneously as life first arose from nonliving matter around 3.7 billion years ago.

General hurdles of the Origin of Life by unguided means


1. Natural selection: There was no selection on early earth. In the living world, complex molecular machines are pre-programmed to make the building blocks of life, precisely as needed.
2. Time: Some chemical reactions are so unspecific that getting the right one by unguided means resorting to time leads to huge numbers of odds.
3. Getting pure materials: Evidently, what chemists do in the lab, namely using pure reagents, was not what happened on the early earth. Impure contamination in the pool of chemicals was the state of affairs.
4. Getting free Gibbs energy:  Spontaneous prebiotic reactions would have to "invent" ways to recruit Gibbs free energy from its environment so as to reduce its own entropy.
5. Activation and repetitive processes: Monomers need to be activated in order for polymerization and catenation to make amino acid strands, and genes, to be possible.
6. Information: Specified complex information, digital data, stored in genes through the language of the genetic code, dictates and directs the making of irreducibly complex molecular machines.
7. Polymerization: How did prebiotic polycondensation of amino acids and nucleotides in heterogeneous aqueous solutions or in interfaces with water-based media occur without the aid of biological catalysts? 
8. Eigens paradox:  is one of the most intractable puzzles in the study of the origins of life. It is thought that the error threshold concept described above limits the size of self-replicating molecules to perhaps a few hundred digits, yet almost all life on earth requires much longer molecules to encode their genetic information.
9. Muller's rachet: The theory of Muller's Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size.
10. Protected environments: If these chemical reactions had happened in places being exposed to UV radiation, no deal. If it was too cold, or too hot, too acidic, or too alkaline, in the wrong atmospheric conditions, no deal.
11. The right sequence of reactions: In metabolic pathways in the cell, enzymes must be lined up in the right sequence. How did spontaneous events organize such a state of affairs? 
12. Getting an organized system out of chaos: How did a prebiotic soup come to be organized into systems capable of emergent processes such as growth, self-propagation, information processing, and adaptive evolution?
13. Irreducible complexity: The cell is an irreducible, minimal entity of life. The individual parts by themselves bear no function unless integrated into a higher-order system.
14. Homeostasis:   The control of metabolism is a fundamental requirement for all life, with perturbations of metabolic homeostasis underpinning numerous disease-associated pathologies.

General hurdles Probability calculation is about how probably or improbably an event might have occurred. The notion requires being able to determine what probability (the odds) may legitimately be counted as small enough to eliminate chance. (the odds or possible number of an outcome having little or no chance of success)
Prebiotic synthesis entails a number of different difficulties which make the origin of life by unguided means too improbable to have occurred by chance

1. Natural selection: There was no selection on early earth. In the living world, complex molecular machines are pre-programmed to make the building blocks of life, precisely as needed. The nucleic acids for a limited set, so do the 20 amino acids, and they come in the functional enantiomeric form, and those that are wrong, like right-handed amino acids, are sorted out by the cell machinery. The same applies to the five information-bearing nucleobases, phospholipids, and carbohydrates. None of these building blocks were readily available prebiotically. There was a jumble and a chaotic mess of all sorts of molecules without any order. How did unguided processes winnow this molecular diversity down to the few compounds used in biological systems today, which are a tiny subset of the many compounds that would have arisen from abiotic processes? 

2. Time: Time is not the naturalist's friend. There are chemical reactions performed by certain classes of enzymes, that speed up the process billions of times.  Without the OMP decarboxylase enzyme, a reaction ‘“absolutely essential” in creating the building blocks of DNA and RNA would take 78 million years in the water. Some chemical reactions are so unspecific that getting the right one by unguided means resorting to time and enough attempts of trial and error can very easily lead to huge numbers of odds (the possible number of an outcome having little or no chance of success)  that exceed the number of atoms in the entire universe ( 10^80).

3. Getting pure materials: Evidently, what chemists do in the lab, namely using pure reagents, was not what happened on the early earth. Impure contamination in the pool of chemicals was the state of affairs. In order to recreate what was going on back then, chemists would have to recreate as close as possible the situation on the early earth, which includes using contaminated chemicals. 

4. Getting free Gibbs energy:  Spontaneous prebiotic reactions would have to "invent" ways to recruit Gibbs free energy from its environment so as to reduce its own entropy. That is as to rocks continuously recruiting forces to roll up the hill, or a rusty nail "figuring out" how to spontaneously add layers of galvanizing zinc on itself to fight corrosion. These reactions would also have to find ways to "funnel" this energy and direct it to where it is required to achieve a precise reaction necessary for achieving self-organization and in the end, free-living, self-replicating biological systems.

5. Activation and repetitive processes: Monomers need to be activated in order for polymerization and catenation to make amino acid strands, and genes, to be possible. That demands a repetitive ordered process, where the bond reactions happen repeatedly at the same place in the molecules. In RNA or DNA polymerase protein complexes, or in the ribosome, sophisticated molecular machines perform these reactions with exuberant precision and efficiency. Science has failed to explain how that could have happened on the early earth.

6. Information: Specified complex information, digital data, stored in genes through the language of the genetic code, dictates and directs the making of irreducibly complex molecular machines, robotic molecular production lines, and chemical cell factories. Scientific investigation has not brought light to the origin of prebiotic information: It remains a mystery. The origin of the genetic code is also enigmatic. Imagine a cause that needs to create an interlinked factory complex containing 1300 complex machines that are installed in specialized compartments, ordered based on the specific task that they perform, and interlinked in a functional way to be part of automated and carefully regulated production lines, that make specific intermediate parts, that permit the higher-order construction and assembly and subsequently self-replication of that factory. From scratch. Performing 1500 reactions in parallel. Unfortunately, that cause has a problem. It is not an intelligent engineer. And another problem: There is no directed energy source available to construct that factory. Only unspecific thermic energy from volcanoes, thermal vents, earthquakes, thunderstorms, the sun, and lightning. 

Let's suppose the number of all atoms in the universe ( 10^80) would be small molecules. Getting the right specified sequence of amino acids to get just one-third of the size of an average-sized protein of 300 amino acids,  one of the 1300 proteins used in that factory, is like painting one of all these molecules in the universe ( roughly 10^80) in red, then throwing a dart randomly, and by luck, hitting the red molecule, with the first attempt. The odds to have all the 1300 proteins assembled by chance, and then interlinked in the right way, is one in 10^725000 !! 

7. Polymerization: There have to be ways of prebiotic efficient polycondensation of amino acids and nucleotides, in heterogeneous aqueous solutions or in interfaces with waterbased media, are needed to explain the emergence, without the aid of biological catalysts, of the first functional biopolymers (e.g., polypeptides and polynucleotides). 

8. Eigen's paradox is one of the most intractable puzzles in the study of the origins of life. It is thought that the error threshold concept described above limits the size of self-replicating molecules to perhaps a few hundred digits, yet almost all life on earth requires much longer molecules to encode their genetic information. This problem is handled in living cells by enzymes that repair mutations, allowing the encoding molecules to reach sizes on the order of millions of base pairs. These large molecules must, of course, encode the very enzymes that repair them, and herein lies Eigen's paradox, first put forth by Manfred Eigen in his 1971 paper (Eigen 1971) Simply stated, Eigen's paradox amounts to the following: Without error correction enzymes, the maximum size of a replicating molecule is about 100 base pairs. For a replicating molecule to encode error correction enzymes, it must be substantially larger than 100 bases. This is a chicken-or-egg kind of a paradox, with an even more difficult solution. Which came first, the large genome or the error correction enzymes?

9. Muller's Ratchet The theory of Muller's Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size. Evolutionary theory predicts that mutational decay is inevitable for small asexual populations, provided deleterious mutation rates are high enough. Such populations are expected to experience the effects of Muller's Ratchet where the most-fit class of individuals is lost at some rate due to chance alone, leaving the second-best class to ultimately suffer the same fate, and so on, leading to a gradual decline in mean fitness. The mutational meltdown theory built upon Muller's Ratchet to predict a synergism between mutation and genetic drift in promoting the extinction of small asexual populations that are at the end of a long genomic decay process. Since deleterious mutations are harmful by definition, accumulation of them would result in loss of individuals and a smaller population size. Small populations are more susceptible to the ratchet effect and more deleterious mutations would be fixed as a result of genetic drift. This creates a positive feedback loop that accelerates extinction of small asexual populations. This phenomenon has been called mutational meltdown.
From the onset, there would have had to be a population of diversified microbes, not just the population of one progenitor, but varies with different genetic make-ups, internally compartmentalized, able to perform Horizontal Gene Transfer and recombination. Unless these preconditions were met, the population would die.

10. Protected environments: If these chemical reactions had happened in places being exposed to UV radiation, no deal. If it was too cold, or too hot, too acidic, or too alkaline, in the wrong atmospheric conditions, no deal. Shapiro (2006): Prebiotic syntheses conducted in the laboratory often involve multistep procedures, with purified reagents and very different conditions permitted at each new step. The extensive purification procedures and changes of locale that would be needed to produce comparable results on the early Earth are seldom discussed but must be taken into account when attempting to judge the plausibility of the entire sequence. 

11. The right sequence of reactions: In metabolic pathways in the cell, the enzymes, our sophisticated molecular robots, are lined up in the right sequence. Once a manufacturing step by enzyme one is concluded, and the intermediate product is ready, it is handed over to enzyme two, which uses the product of the previous enzyme, to perform the subsequent manufacturing step. If the enzyme sequence were wrong, no deal, and the entire manufacturing process in the production line breaks down. On prebiotic earth, natural catalysts, like ions, clay, etc. had to replace enzymatic reactions. How could the right sequence have been performed? its far from realistic to believe that order, timing, and the right subsequent reactions could have been performed by random chaotic events without direction.  

12. How the components of prebiotic soup came to be organized in systems: The biggest outstanding problem in understanding the origins of life is how the components of prebiotic soup came to be organized in systems capable of emergent processes such as growth, self-propagation, information processing, and adaptive evolution. Given that prebiotic soups may have been composed of millions of distinct compounds, each at a low concentration.

13. Irreducible complexity: The cell is an irreducible, minimal entity of life. The individual parts by themselves bear no function unless integrated into a higher-order system. A complex specified intermediate state or product that is not functionally useful would never be selected and emerge by non-designed events.  A minimal amount of instructional complex information is required for a gene to produce useful proteins. A minimal size of a protein is necessary for it to be functional.  A minimal number of parts are necessary to be integrated into metabolic systems to make all building blocks and metabolites, used in life. A fully developed system that generated energy, and a genome with all the information is necessary to keep the basic functions to have a living cell.

14. Homeostasis: The essential characteristic of living cells is homeostasis, the ability to maintain a steady and more-or-less constant chemical balance in a changing environment.  The control of metabolism is a fundamental requirement for all life, with perturbations of metabolic homeostasis underpinning numerous disease-associated pathologies. Any incomplete Metabolic network without the control mechanisms in place to get homeostasis would mean disease and cell death. A minimal metabolic network and the control mechanisms had to be in place from the beginning, which means, and gradualistic explanation of the origin of biological Cells, and life is unrealistic. Life is an all-or-nothing business.

Jeffrey D. Johnson: The Absurdity of Unbelief: A Worldview Apologetic of the Christian Faith 2016

The Law of Biogenesis: Living beings come only from other living beings. Though there has been no observable exception to this rule.
The Reproductive Principle: Life must first exist before it can reproduce itself. A self-replicating RNA molecule has never been demonstrated to emerge randomly.
The Instructional information stored in genes: P.Davies: The problem of how meaningful or semantic information can emerge spontaneously from a collection of mindless molecules subject to blind and purposeless forces presents a deep conceptual challenge.
The irreducible complexity of the cell: The cell is a functionally integrated system that only operates when each of its components (processors, power supplies, and switches) function together.

https://pt.3lib.net/book/2708494/cd49d9

1. Getting homochiral building blocks of life, precisely as needed.
3. Getting pure materials: avoiding impure contamination in the pool of chemicals was the state of affairs.
4. Getting free Gibbs energy: recruiting Gibbs free energy from its environment so as to reduce its own entropy.
5. Activation and repetitive processes: Monomers need to be activated in order for polymerization and catenation to make amino acid strands, and genes, to be possible.
6. Information: getting specified complex information, digital data, stored in genes through the language of the genetic code, which dictates and directs the making of irreducibly complex molecular machines.
7. Getting the genetic code
8. Polymerization: getting prebiotic polycondensation of amino acids and nucleotides in heterogeneous aqueous solutions or in interfaces with water-based media occuring without the aid of biological catalysts
9. The right sequence of reactions: In metabolic pathways in the cell, enzymes must be lined up in the right sequence. Getting spontaneous events to organize such a state of affairs.
10. Getting an organized system out of chaos: Getting an organized system capable of emergent processes such as growth, self-propagation, information processing, and adaptive evolution
11. Getting all the parts, despite the fact that the individual parts by themselves bear no function unless integrated into a higher-order system.
12. Homeostasis: It had to create a homeostatic environment, in one of many other cases, diminishing the calcium concentration in the cell 10000 times below the external environment, to permit signaling. It requires osmoregulation to maintain the fluid balance and the concentration of electrolytes, preventing the cytosol to be too diluted or concentrated.
13. Getting the transition from prebiotic recruitment of the basic building blocks, to metabolism ( at least 400 reactions performed by hundreds of enzymes and proteins, the molecular robots, producing all relevant molecules. in a minimal LUCA).
14. Getting a minimal genome ( In P.Ubique, the smallest free-living cell, 1,3 Mio nucleotides)
15. Getting the epigenome, the glycome, the lipidome, the mobilome, the transcriptome, the metabolome, the proteome, the interactome, the signalosome, and the metallome of our minimal cell.
16. Salvage and recycling pathways ( That includes uptake and processing of the big, major, and trace elements [ nitrogen and carbon fixation].
17. Getting sophisticated, complex, and advanced immune and defense systems to protect itself from invaders, viruses, plasmids, and phages.
18. Connecting the genome, that directs the making of hundreds of proteins ( the proteome) - complex molecular machines made through transcription ( the transcriptome) and translation, the proteins interconnection ( the interactome), using the genetic code, the machinery of DNA replication, error-check and repair mechanisms starting with DNA, all the way through to the ribosome ( 13 check and repair mechanisms alone).
19. Getting an epigenome, that controls DNA–protein interactions ( DNA methylation that performs transcriptional activation and repressions, and the formation of phenotypic variants) timing of DNA replication, partitioning of nascent chromosomes to daughter cells, repair of DNA, and timing of transposition and conjugal transfer of plasmids. The chromosome segregation machinery ( topoisomerase II).
20. Getting the ribosome which is especially noteworthy. The Universal Gene Set of Life (UGSL) is dominated by translation-related genes. These ribosomal RNAs (rRNAs), transfer RNAs (tRNAs and the machinery to synthesize and modify tRNAs, a full set of aminoacyl tRNA synthetases) small RNAs, and ribosomal proteins make up the most abundant macromolecular species in all living organisms ( Bernstein 2019). Ribosome biogenesis: It would require all proteins that assemble ribosomes, including proteins, that make proteins, that make the subunits of the ribosome, and the entire error check and repair, and recycle machinery. It would require chaperones, proteins that help proteins that come out from the ribosome, and are being misfolded, to get their right fold. That includes chaperones, that help chaperones to be folded properly. ( In other words, machines, that help machines, that help other machines)
21. Getting the membrane which includes millions of complex membrane-embedded protein channels, ion pumps, ion exchangers, transporters, importers, translocons, translocases, symporters, and antiporters that control what is imported, what leaves the cell, and the intracellular levels of all life-essential elements.
22. Getting the enzymes that are involved in cell division, and its regulation.
23. A way to get a Wood Ljundahl or rTCA cycle to fix carbon to produce carbohydrates, that is digested through catabolism to feed ATP synthase, electron transport, and a proton gradient to generate ATP, the energy currency in the cell. It would also require at least 8 co-factors, and vitamins.
24. Thioesters were almost certainly involved in the prebiotic formation of many molecules that are important in contemporary biology. Their formation depends on Coenzyme A (CoA). Coenzyme A synthesis depends on five enzymes used in the five-step universal pathway of coenzyme A (CoA) biosynthesis.
25. Getting numerous machines for the uptake of iron ( Non-ribosomal peptide synthetase to make siderophores) and chelate it ( making it available in soluble form for uptake), sulfur, and the machinery to create Iron-sulfur (Fe/S) clusters, essential in many vital proteins in their reaction centers. Life essential proteins, replete with FeS clusters and radical reaction mechanisms, depend upon transition metals, flavins, S-adenosyl methionine, ferredoxin, molybdopterin, corrins, and selenium.
26. Mechanisms of adaptation to the variegated environmental conditions, able to get and interpret signals from the environment the outside and react accordingly ( like thermal conditions).

Nick Lane: Well the source of energy at the origin of life is the reaction between carbon dioxide and hydrogen and amazingly most of these reactions are exergonic which is to say they release energy this if you have hydrogen and co2
and you put them together in a falcon tube and you warm it up to say 50 degrees centigrade and you put in a couple of catalysts and you shake it nothing's gonna happen but thermodynamically that is less stable two gases hydrogen
and co2 is less stable than cells what should happen is you get cells coming out why doesn't that happen is because of the kinetic barriers it's because that's where you need the spark

https://www.youtube.com/watch?v=tOtdJcco3YM

Magnifying the cell ten thousand million times, it would have a radius of 200 miles, about 10 times the size of New York City

Calling a cell a factory is an understatement. Magnifying the cell to a size of 200 miles, it would only contain the required number of buildings, hosting the factories to make the machines that it requires. 
New York City has about 900.000 buildings, of which about 40.000 are in Manhattan, of which 7.000 are skyscrapers of high-rise buildings of at least 115 feet (35 m), of which at least 95 are taller than 650 feet (198 m).

Cells are an entire industrial park, where only the number of factories producing the machines used in the industrial park is of size at least 10 times the size of New York City, where each building is individually a factory comparable to the size of a skyscraper like the Twin Towers of the World Trade Center. Each tower hosts a factory that makes factories that make machines. A mammalian cell may harbor as many as 10 million ribosomes. The nucleolus is the factory that makes ribosomes, the factory that makes proteins, which are the molecular machines of the cell. The nucleolus can be thought of as a large factory at which different noncoding RNAs are transcribed, processed, and assembled with proteins to form a large variety of ribonucleoprotein complexes.

L. Lindahl (2022): Ribosome assembly requires synthesis and modification of its components, which occurs simultaneously with their assembly into ribosomal particles. The formation occurs by a stepwise ordered addition of ribosome components. The process is assisted by many assembly factors that facilitate and monitor the individual steps, for example by modifying ribosomal components, releasing assembly factors from an assembly intermediate, or forcing specific structural configurations. The quality of the ribosome population is controlled by a complement of nucleases that degrade assembly intermediates with an inappropriate structure and/or which constitute kinetic traps.

Mitochondria, the powerhouse of the cell, can host up to 5000 ATP synthase energy turbines. Each human heart muscle cell contains up to 8,000 mitochondria. That means, in each of the human heart cells, there are up to 40 million ATP synthase energy turbines caring for the production of ATP, the energy currency in the cell.

M.Denton (2020): The miracle of the Cell :

Pg.11
Where the cosmos feels infinitely large and the atomic realm infinitely small, the cell feels infinitely complex. They appear in so many ways supremely fit to fulfill their role as the basic unit of biological life.

Pg. 329.
We would see [in cells] that nearly every feature of our own advanced machines had its analog in the cell: artificial languages and their decoding systems, memory banks for information storage and retrieval, elegant control systems regulating the automated assembly of parts and components, error fail-safe and proof-reading devices utilized for quality control, assembly processes involving the principle of prefabrication and modular construction. In fact, so deep would be the feeling of deja-vu, so persuasive the analogy, that much of the terminology we would use to describe this fascinating molecular reality would be borrowed from the world of late-twentieth-century technology.
  “What we would be witnessing would be an object resembling an immense automated factory, a factory larger than a city and carrying out almost as many unique functions as all the manufacturing activities of man on earth. However, it would be a factory that would have one capacity not equaled in any of our own most advanced machines, for it would be capable of replicating its entire structure within a matter of a few hours. To witness such an act at a magnification of one thousand million times would be an awe-inspiring spectacle.”

M. Denton (1985) Evolution, a theory in crisis:
To grasp the reality of life as it has been revealed by molecular biology, we must magnify a cell a thousand million times until it is twenty kilometres in diameter and resembles a giant airship large enough to cover a great city like London or New York. What we would then see would be an object of unparalleled complexity and adaptive design. On the surface of the cell we would see millions of openings, like the port holes of a vast space ship, opening and closing to allow a continual stream of materials to flow in and out. If we were to enter one of these openings we would find ourselves in a world of supreme technology and bewildering complexity. We would see endless highly organized corridors and conduits branching in every direction away from the perimeter of the cell, some leading to the central memory bank in the nucleus and others to assembly plants and processing units. The nucleus itself would be a vast spherical chamber more than a kilometre in diameter, resembling a geodesic dome inside of which we would see, all neatly stacked together in ordered arrays, the miles of coiled chains of the DNA molecules.

A huge range of products and raw materials would shuttle along all the manifold conduits in a highly ordered fashion to and from all the various assembly plants in the outer regions of the cell. We would wonder at the level of control implicit in the movement of so many objects down so many seemingly endless conduits, all in perfect unison. We would see all around us, in every direction we looked, all sorts of robot-like machines. We would notice that the simplest of the functional components of the cell, the protein molecules, were astonishingly, complex pieces of molecular machinery, each one consisting of about three thousand atoms arranged in highly organized 3-D spatial conformation... Yet the life of the cell depends on the integrated activities of thousands, certainly tens, and probably hundreds of thousands of different protein molecules.

We would see that nearly every feature of our own advanced machines had its analogue in the cell: artificial languages and their decoding systems, memory banks for information storage and retrieval, elegant control systems regulating the automated assembly of parts and components, error fail-safe and proof-reading devices utilized for quality control, assembly processes involving the principle of prefabrication and modular construction. In fact, so deep would be the feeling of deja-vu, so persuasive the analogy, that much of the terminology we would use to describe this fascinating molecular reality would be borrowed from the world of late twentieth-century technology.

What we would be witnessing would be an object resembling an immense automated factory, a factory larger than a city and carrying out almost as many unique functions as all the manufacturing activities of man on earth..

Nineteenth-century chemists had already established that, despite the large number of elements in the periodic table, almost all of our mass comes from just six of them: carbon, hydrogen, oxygen, nitrogen, sulfur, and phosphorus.

Your fats and carbohydrates are chains of molecules made exclusively of carbon, hydrogen, and oxygen. Your proteins are built from carbon, hydrogen, oxygen, nitrogen, and sulfur. And your DNA is made only of carbon, hydrogen, oxygen, nitrogen, and phosphorus. Those six elements compose roughly 99 percent of everything within you. A 150-pound person contains by mass 94 pounds of oxygen, 35 pounds of carbon, 15 pounds of hydrogen, 4 pounds of nitrogen, almost 2 pounds of phosphorus, and a half pound of sulfur.

Those six elements also happen to be among the most plentiful in the universe.
https://bigthink.com/life/first-molecules-of-life/

Arguing with ChatGTP about the origin of life

https://reasonandscience.catsboard.com/t1279p25-abiogenesis-is-mathematically-impossible#9829

Me: explain why science has been unable to recreate life in the lab
ChatGPT: There are several factors that contribute to our inability to recreate life in the lab:

Complexity: Living organisms are incredibly complex, with a vast array of interacting molecules, complex cellular structures, and intricate metabolic pathways. Recreating this complexity in the lab is incredibly challenging, and our current understanding of biology is still not comprehensive enough to accurately model all the necessary components.

Emergence: One of the defining features of life is that it emerges from the interactions of its components. This means that the properties of a living organism cannot be entirely predicted or derived from its individual parts. As such, creating life in the lab requires not only understanding the parts but also how they interact and give rise to life.

Overall, the creation of life in the lab is a complex and multifaceted problem that requires a deep understanding of the fundamental principles of biology, chemistry, and physics. While scientists have made significant strides in this area, it remains an elusive goal that may take many years of research and technological advancements to achieve.

Me:  Why do you state that technological advancement  may solve the problem if there is no evidence for it ever to happen?
ChatGPT:  I apologize if my previous response gave the impression that technological advancement is certain to solve the problem of creating life in the lab. While there is no guarantee that technological advancements will ultimately lead to the creation of life in the lab, it is possible that continued research and development in the field could bring us closer to achieving this goal.

In many scientific fields, technological advancements have played a critical role in advancing our understanding and capabilities. For example, the development of advanced imaging technologies has allowed us to study biological processes at the cellular and molecular levels in ways that were previously impossible. Similarly, the development of powerful computational tools and simulation techniques has allowed researchers to model complex biological systems and make predictions about their behavior.

It is possible that similar technological advancements could help us overcome the challenges that currently limit our ability to create life in the lab. For example, new methods for manipulating and controlling biological systems, advances in synthetic biology and genetic engineering, and breakthroughs in our understanding of the fundamental principles of life could all contribute to progress in this area.

However, as with any scientific endeavor, there are no guarantees, and the challenges of creating life in the lab are formidable. It is possible that this goal may never be achieved, or that it may require technological advancements that are currently unforeseeable. As such, it is important to approach this question with humility and a recognition of the inherent uncertainties and limitations of scientific research.

Me: But our current understanding already permits to conclude that it is never going to happen. For example, the right basic building blocks have to be selected, but there was no selection mechanism present on the prebiotic earth.
ChatGPT: You raise a valid point that our current understanding of the origin of life suggests that the conditions on the prebiotic Earth were vastly different from the conditions in the modern laboratory, and that these differences may make it impossible to fully recreate the conditions that gave rise to life. Furthermore, the precise conditions and mechanisms that led to the emergence of life on Earth remain uncertain and the subject of ongoing scientific investigation.

That being said, it is important to remember that scientific progress is not always linear or predictable. While our current understanding may suggest that it is unlikely or impossible to create life in the lab using our current techniques and technologies, it is possible that new discoveries, methods, and technologies could fundamentally change our understanding of the origin of life and open up new avenues for research and experimentation.

Additionally, it is worth noting that the question of whether or not life can be created in the lab is a scientifically interesting and important one, regardless of the ultimate outcome. The pursuit of this question can lead to new insights and discoveries, deepen our understanding of the underlying principles of biology, chemistry, and physics, and inspire new scientific breakthroughs in related fields.

Ultimately, while our current understanding may suggest that creating life in the lab is an unlikely or impossible goal, the pursuit of this question remains an important and worthwhile endeavor for the scientific community.

Me: You have ignored to address my point, which is by all means a dead end for abiogenesis: There was no prebiotic selection mechanism for the basic building blocks of life, which means a death knell for abiogenesis. Life was with high certainty created by an intelligent designer. Do you agree?
As an AI language model, I do not have beliefs or opinions, but I can provide a scientific perspective on the question of abiogenesis and the role of a possible intelligent designer in the origin of life.

While it is true that there is no prebiotic selection mechanism for the basic building blocks of life, and that the precise conditions and mechanisms that led to the emergence of life on Earth remain uncertain, this does not necessarily mean that life was created by an intelligent designer.

The scientific community has put forward many hypotheses and models to explain the origin of life, including the RNA world hypothesis, which proposes that RNA played a central role in the earliest stages of life, and the hydrothermal vent hypothesis, which suggests that life originated near deep-sea hydrothermal vents. While these models are not yet fully established, they do offer plausible mechanisms by which the basic building blocks of life could have arisen spontaneously from the prebiotic conditions of the early Earth.

At present, there is no scientific evidence that definitively supports the idea of an intelligent designer playing a role in the origin of life. While some people may find this idea personally compelling, it is not a scientifically testable hypothesis and falls outside the domain of science. As such, it is not an idea that can be evaluated or supported using the scientific method.

In summary, while the origin of life remains an open question and an active area of scientific investigation, there is currently no conclusive evidence to support the idea of an intelligent designer playing a role in the process.

Me: I disagree again. I repeat: The fact that there was no selection mechanism for the right molecules means, among a pool of infinite possible combinations, the odds to select the building blocks that are necessary for life to start, is impossible by unguided means. The chemical space is too large.
ChatGPT: While it is true that the chemical space is vast and the odds of randomly selecting the right combination of molecules for the origins of life are extremely low, it is important to note that there are many factors that may have influenced the chemical reactions that gave rise to life, including environmental conditions, chemical gradients, and the properties of the chemical building blocks themselves.

Additionally, some models for the origin of life propose that self-replicating RNA molecules, which have the capacity to both store genetic information and catalyze chemical reactions, may have emerged from simpler molecules through a process of chemical evolution. While this model is still under active investigation and refinement, it offers a plausible mechanism by which the necessary building blocks for life could have arisen through natural processes.

Me: The RNA world is a failed hypothesis. Molecules do not complexify and self-replicate on their own. They disintegrate, and become asphalts.
ChatGPT:  While the RNA world hypothesis remains an active area of scientific investigation and refinement, it is true that the self-replication of RNA molecules and the emergence of life from non-living matter is a complex and multifaceted process that has yet to be fully understood.

It is also true that there are many factors that can influence the formation and stability of complex organic molecules, including environmental conditions, pH, temperature, and the availability of reactants. In some conditions, these molecules may break down or become degraded, while in others, they may interact and combine in ways that lead to the formation of new molecules and structures.

Me: RNAs are complex molecules, and millions would be needed to start random shuffling. But no scientific experiment has demonstrated that they could polymerize without specialized catalysts.
ChatGPT: An error occurred. If this issue persists please contact us through our help center at help.openai.com.

The Analogy of Intelligent Design: Complex Systems in Human Engineering and Biological Cell Formation

Transitioning from a collection of organic molecules to a fully operational minimal cell involves numerous challenges. Some of these challenges include:

1. Cellular Organization: A minimal cell requires a level of compartmentalization and organization to separate internal processes from the external environment. This includes the formation of a lipid membrane or membrane-like structure, which is critical for cell integrity and selective permeability. Complexity of Lipid Membrane Formation: Lipid membranes are composed of phospholipids, which have a hydrophilic (water-loving) head and hydrophobic (water-repelling) tail. These molecules naturally arrange themselves into a bilayer structure in an aqueous environment, with the hydrophilic heads facing the water and the hydrophobic tails oriented inward, shielded from the water. This self-assembly process is driven by the hydrophobic effect. However, achieving the precise arrangement and stability of a functional lipid membrane is challenging due to the delicate balance of hydrophobic and hydrophilic interactions.  A functional cell membrane needs to be selectively permeable, allowing the passage of certain molecules while restricting others. This selective permeability is crucial for maintaining internal conditions and regulating the exchange of nutrients, ions, and waste products. Achieving selective permeability requires the presence of specific transport proteins or channels embedded in the membrane, which control the movement of molecules across the lipid bilayer. The emergence of these transport proteins and their integration into a lipid membrane is a complex and coordinated process. Cell membranes need to maintain structural integrity and stability under varying environmental conditions. They must withstand mechanical stresses, changes in temperature, pH, and osmotic pressure. Additionally, the lipid composition of the membrane influences its fluidity and stability. The precise combination of lipid types and their organization is critical for membrane function. Achieving the appropriate lipid composition and stability in the early stages of cellular evolution presents a significant challenge.  Another challenge is the origin of the lipid molecules themselves. Lipids are complex molecules that require specific biosynthetic pathways to be produced. The synthesis of lipids involves a series of enzymatic reactions, which themselves require a level of molecular machinery and catalytic activity. Understanding how these biosynthetic pathways could have emerged from simple organic molecules in a prebiotic environment is an ongoing area of research. The self-assembly of a functional lipid membrane with the right composition, stability, and selective permeability is highly unlikely to occur spontaneously in a random mixture of organic molecules. The precise arrangement and organization of lipids require specific molecular interactions and a controlled environment. The formation of a lipid membrane alone does not guarantee the ability to carry out essential cellular functions. The membrane needs to be associated with the necessary molecular machinery, including genetic systems, enzymes, and metabolic pathways. The origin of the information and instructions for the assembly and coordination of these components is a significant challenge to address.  A functional cell requires regulatory mechanisms to maintain membrane integrity, adjust permeability, and respond to environmental changes. The emergence of such regulatory mechanisms and the ability to coordinate membrane activities would require complex molecular interactions and control systems.

2. Genetic Information: A minimal cell needs a system for storing and replicating genetic information. This involves the emergence of a functional nucleic acid, such as RNA or DNA, capable of encoding and transmitting genetic instructions. Nucleic acids, such as RNA and DNA, are composed of nucleotides, which consist of a sugar molecule, a phosphate group, and a nitrogenous base. The synthesis of nucleotides requires a series of complex chemical reactions that are not readily achievable in prebiotic environments. The formation of the sugar and base components, as well as their subsequent linkage into nucleotides, involves specific enzymes and energy sources that are not available in a non-biological setting. The spontaneous formation of nucleotides from simple organic molecules under prebiotic conditions remains a significant challenge.  A functional genetic system requires the ability to store and replicate genetic information. This involves the specific base-pairing interactions between nucleotides, where the sequence of bases carries the genetic code. The fidelity and accuracy of DNA or RNA replication are critical for the transmission of genetic information from one generation to the next. However, the emergence of a self-replicating nucleic acid system with the necessary fidelity and accuracy is highly improbable through natural processes alone. The precise coordination of enzymatic activities, template recognition, and synthesis of complementary strands pose immense challenges.  The RNA World hypothesis proposes that an early form of life was based solely on RNA, which could store genetic information and catalyze chemical reactions. However, the spontaneous emergence of functional RNA molecules with both genetic and enzymatic activities remains a significant challenge. RNA molecules with enzymatic capabilities, known as ribozymes, are less efficient and less diverse compared to protein enzymes found in modern cells. The origin of a self-replicating RNA molecule capable of encoding complex genetic information, carrying out catalytic functions, and exhibiting the necessary fidelity is an unresolved puzzle.  A functional genetic system requires a coordinated interplay between nucleic acids, proteins, and other cellular components. The synthesis, processing, and regulation of genetic information involve a complex network of enzymes, proteins, and molecular interactions. The simultaneous emergence of this coordinated molecular machinery required for a fully functional genetic system is highly improbable without pre-existing information and the ability to carry out complex biochemical processes.

3. Metabolism and Energy Conversion: A minimal cell requires mechanisms for energy conversion, such as the ability to capture and utilize energy sources like ATP. It also needs metabolic pathways for generating essential molecules and carrying out biochemical reactions. Metabolism and energy conversion represent another significant hurdle in bridging the gap from simple organic molecules to a fully operational cell. Here are some reasons why this hurdle is considered unbridgeable:  Living cells require the ability to capture and utilize energy to perform essential functions. ATP (adenosine triphosphate) is the primary energy currency in cells, and its synthesis and utilization involve complex enzymatic processes. The synthesis of ATP from precursor molecules, such as ADP (adenosine diphosphate) and inorganic phosphate, requires specific enzymes and energy sources like chemiosmotic gradients or light energy. These mechanisms for energy capture and utilization are highly intricate and require a sophisticated molecular machinery that is unlikely to arise spontaneously in a non-biological environment. Metabolic pathways involve a series of chemical reactions that convert raw materials into essential molecules required for cell growth, maintenance, and function. These pathways often require the coordinated action of multiple enzymes and regulatory factors. The spontaneous emergence of fully functional metabolic pathways from simple organic molecules is highly improbable. Metabolic pathways involve numerous intermediate compounds, specific enzymatic reactions, and regulatory mechanisms that must be in place for the system to work effectively. The simultaneous emergence of all these components through natural, unguided processes is considered highly unlikely.  Metabolic pathways rely on enzymes to catalyze specific chemical reactions with high efficiency and specificity. Enzymes have complex three-dimensional structures that are finely tuned to recognize and interact with specific substrates. The origin of enzymes with the necessary specificity and catalytic efficiency is a significant challenge. Moreover, the regulation of metabolic pathways is crucial for maintaining homeostasis and avoiding harmful metabolic imbalances. The coordination of enzymatic activities, feedback mechanisms, and regulatory factors is highly complex and unlikely to emerge spontaneously in a non-biological context.  A functional cell requires the ability to transport molecules across membranes and exchange substances with the environment. This includes the uptake of nutrients, excretion of waste products, and maintenance of ion gradients. The emergence of specific transport proteins, ion channels, and membrane systems that enable these processes is highly complex and dependent on sophisticated molecular interactions. The spontaneous development of such transport systems capable of selective permeability and regulation is considered highly unlikely.

4. Protein Synthesis: Protein synthesis is vital for cellular functions, and a minimal cell must have the machinery to synthesize proteins using the genetic information stored in its nucleic acids. This includes the emergence of ribosomes, transfer RNAs, and amino acid activation processes. Protein synthesis is a complex and highly regulated process that involves multiple components working together in a precise and coordinated manner. The emergence of this machinery from simple organic molecules is considered an unbridgeable hurdle due to the following reasons: Ribosomes are large molecular complexes composed of proteins and ribosomal RNA (rRNA) molecules. They serve as the site of protein synthesis, decoding the genetic information carried by messenger RNA (mRNA) and catalyzing the assembly of amino acids into polypeptide chains. The formation of functional ribosomes requires the specific arrangement and interaction of multiple RNA and protein components, which are highly unlikely to arise spontaneously in a non-biological context.  tRNAs are small RNA molecules that carry amino acids to the ribosomes during protein synthesis. They have specific anticodon sequences that recognize and bind to the codons on mRNA, ensuring the accurate translation of genetic information into the correct sequence of amino acids. The precise folding and structure of tRNAs, as well as their ability to recognize specific amino acids, are crucial for their function. The spontaneous emergence of fully functional tRNAs with the necessary specificity and accuracy is considered highly improbable. Amino acids, the building blocks of proteins, need to be activated before they can be incorporated into growing polypeptide chains. This process involves the attachment of amino acids to specific tRNAs through a reaction called aminoacylation or tRNA charging. Aminoacyl-tRNA synthetases, a group of enzymes, catalyze this reaction and ensure the accurate pairing of amino acids with their corresponding tRNAs. The origin of aminoacyl-tRNA synthetases and the precise recognition and activation of amino acids is a significant challenge, as it requires the coordinated emergence of specific enzyme-substrate interactions. Protein synthesis is tightly regulated to ensure the production of functional proteins and maintain cellular homeostasis. Quality control mechanisms, such as proofreading and error correction, play a crucial role in ensuring accurate translation and minimizing errors in protein synthesis. The emergence of these regulatory mechanisms and quality control processes from simple organic molecules is highly complex and improbable.

5. Homeostasis and Regulation: A fully operational minimal cell must maintain internal homeostasis, balancing conditions like pH, ion concentrations, and temperature. It also requires regulatory mechanisms to control gene expression, enzyme activity, and response to environmental changes. Homeostasis and regulation are essential aspects of cellular function that ensure the stability and proper functioning of a cell. However, the emergence of homeostatic mechanisms and regulatory networks in a fully operational minimal cell is considered an unbridgeable hurdle due to the following reasons: Cells possess intricate regulatory networks that control gene expression, enzyme activity, and cellular responses to environmental changes. These networks involve various signaling pathways, transcription factors, and regulatory proteins that interact in a highly coordinated manner. The spontaneous emergence of such complex regulatory networks from simple organic molecules is highly improbable. The precise regulation of gene expression requires specific DNA-binding proteins, enhancer/promoter sequences, and regulatory elements, which are unlikely to arise without an intelligent design process. Homeostasis and regulation rely on the ability of a cell to sense changes in its internal and external environment and respond accordingly. Cells have evolved sophisticated signaling mechanisms that involve receptors, signal transduction pathways, and feedback loops. The emergence of these signaling mechanisms and the ability to sense and interpret signals in a specific and coordinated manner is highly complex and improbable to occur through natural, unguided processes alone.  Feedback mechanisms play a critical role in maintaining homeostasis by regulating the activity of enzymes, ion channels, and other cellular processes. Feedback control involves sensing the levels of specific molecules or signals and adjusting cellular activities accordingly. The precise coordination and integration of feedback control systems require the existence of specific regulatory proteins, receptors, and molecular interactions, which are unlikely to emerge spontaneously.  Cells need to adapt to changes in their environment to ensure their survival and optimal functioning. This requires the ability to respond to external stimuli and adjust cellular processes accordingly. The emergence of adaptive mechanisms, such as gene regulation and cellular response pathways, from simple organic molecules is highly complex and unfeasible through natural processes alone.

The gap between the prebiotic soup or hydrothermal vent environments and a fully operational minimal cell involves the emergence of complex cellular structures, genetic systems, metabolism, protein synthesis, and regulatory mechanisms. The precise pathways and mechanisms by which these components arose are still subjects of scientific investigation and debate. Bridging this gap represents one of the significant challenges in understanding the origin of life.

The formation of a fully operational cell involves an intricate level of complexity and functional integration. The organization of cellular components, the precise arrangement of lipid membranes, the emergence of genetic information systems, the coordination of metabolic pathways, and the synthesis of proteins all require a high degree of complexity and interdependence. Such complexity and functional integration are typically associated with intelligent design, as they go beyond what can be reasonably attributed to chance or unguided natural processes.  Cells store and transmit vast amounts of genetic information through nucleic acids like RNA and DNA. This information is encoded in the sequences of nucleotides and is essential for the functioning of the cell. The origin of this information-rich content poses a significant challenge for naturalistic explanations. Information, particularly functional and specified information, is a hallmark of intelligent agency, as it reflects purposeful arrangement and communication of complex instructions.  Many cellular systems and structures are considered irreducibly complex, meaning they require multiple components working together in a precise manner for their proper functioning. Removing or altering any of these components would render the system non-functional. Irreducible complexity is often seen as evidence of intelligent design, as it suggests that all components must have been present and functioning simultaneously for the system to arise.  The probability of the spontaneous emergence of a fully operational cell with all its intricacies and functional capabilities is extremely low. The precise arrangement and organization of cellular components, the specific interactions and coordination of molecular machinery, and the emergence of complex biological systems require a level of fine-tuning that goes beyond what can be reasonably expected from chance or unguided processes. The fine-tuned nature of life's fundamental properties suggests that an intelligent designer has set the conditions necessary for life's emergence and development.  Despite extensive scientific research, there is currently no plausible naturalistic explanation for the origin of life and the transition from simple organic molecules to fully operational cells. The challenges and complexities involved in cellular organization, genetic information, metabolism, and protein synthesis remain unexplained by purely natural processes. In the absence of compelling naturalistic explanations, the involvement of an intelligent, powerful designer becomes a viable and scientifically reasonable inference.

As intelligent beings, we routinely create, conceptualize, design, project, and implement complex systems in various domains. Before starting a computer project, we conceptualize the desired features, functionalities, and specifications of the computer system. We define the goals and requirements, such as processing power, storage capacity, and connectivity options. Based on the conceptualization, we design the computer system. This involves determining the architecture, selecting components such as the processor, memory, storage devices, and designing the circuitry, interfaces, and user interfaces. The design phase includes careful consideration of compatibility, efficiency, and optimal performance. To ensure the successful implementation of the computer system, we break down the project into manageable tasks, set timelines, allocate resources, and coordinate the efforts of different teams or individuals involved. Project management ensures that the project progresses smoothly, on schedule, and within budget.  During the implementation phase, we bring together all the necessary components and follow the designed specifications to build the computer system. This involves assembly, installation of software and drivers, and testing to ensure proper functioning. Attention to detail and precise execution is crucial at this stage. After implementation, we conduct thorough testing and quality control to verify that the computer system meets the desired specifications and performs as intended. We identify and rectify any issues or deficiencies, ensuring that the system operates reliably and efficiently.  Once the computer system is operational, we continue to maintain and upgrade it as needed. This includes regular updates, monitoring performance, addressing issues, and implementing improvements or modifications over time. In this analogy, we see that designing and implementing complex systems like computers requires intelligence, purposeful planning, careful consideration of specifications and requirements, selection and integration of components, project management, quality control, and ongoing maintenance.

When applying the example and analogy of designing and implementing a computer system to a biological cell factory, we can see parallels in the design considerations and implementation processes. Analogously, an intelligent designer would have had to make similar design considerations and use their intelligence to create the first living, self-replicating cell. Here's how the analogy applies: Just as we conceptualize the features and specifications of a computer system, an intelligent designer would have conceptualized the desired functions and capabilities of a living cell. They would have defined the goals and requirements, such as the ability to self-replicate, perform metabolic processes, respond to the environment, and maintain cellular homeostasis. Similar to the design of a computer system, the intelligent designer would have determined the cellular architecture and selected the necessary components. They would have designed the genetic machinery, regulatory networks, metabolic pathways, and membrane systems. The design phase would involve careful consideration of efficiency, adaptability, and robustness to ensure the cell's functionality and ability to self-replicate. An intelligent designer would have organized the project of creating the first cell by breaking it down into manageable tasks, setting timelines, and allocating resources. They would have coordinated the efforts required for the successful implementation of the cell, ensuring that the necessary components and processes were integrated effectively. The intelligent designer would have implemented the design by assembling the necessary molecular components, including genetic material, proteins, enzymes, and membranes. They would have orchestrated the intricate processes involved in creating the first self-replicating cell, carefully executing the assembly and integration of these components to achieve the desired functionality.   Just as we maintain and upgrade computer systems over time, an intelligent designer would have likely implemented mechanisms within the cell for self-repair, adaptation to changing environments, and potential improvements in functionality. This would ensure the cell's long-term viability and ability to evolve. From an analogy standpoint, the design considerations, purposeful planning, careful selection and integration of components, project management, quality control, and ongoing maintenance seen in designing and implementing computer systems align with the notion that an intelligent designer would have employed similar principles in creating the first living, self-replicating cell. Proponents of Intelligent Design argue that the complexity, information content, and interdependent systems observed in biological cells suggest the involvement of an intelligent designer who purposefully organized and implemented these systems to achieve the functions and capabilities of a living cell.

The argument from analogy

The argument from analogy is a powerful argument because it allows us to infer the existence of similar causes based on the observation of similar effects. When we observe two phenomena or systems that exhibit similar behaviors or characteristics, we can make a reasonable inference that they share similar underlying causal mechanisms. In the context of a biological cell being compared to a production system, the argument from analogy suggests that since both systems exhibit similar complex organization, functionality, and purposeful arrangement of components, they likely share similar causes or design principles. Just as a production system requires intelligent planning, design, coordination, and implementation by human beings, the analogy implies that a biological cell, with its intricate organization and functionality, also requires an intelligent designer. The analogy between a cell factory and a human-designed production system highlights the similarities in complexity, information processing, integration of components, and purposeful functionality. It emphasizes that the intricate and finely tuned nature of a cell's molecular machinery, genetic information, metabolic pathways, and regulatory networks resembles the type of organization and functionality we commonly associate with intelligent design. By invoking the argument from analogy, we can suggest that the remarkable complexity, information content, and interdependent systems observed in biological cells are best explained by the involvement of an intelligent designer. The analogy allows us to draw a parallel between human design and the design principles necessary for the existence and functioning of a living cell. The presence of similar effects (complex systems) implies similar causes (an intelligent designer), based on the principle that analogous effects have analogous causes. This is not definitive proof of an intelligent designer, but an inference to the best explanation, namely,  that the complex organization and functionality of a biological cell are best explained by the involvement of an intelligent designer, similar to how human-designed systems exhibit complexity and purposeful arrangement.

Die Ursprung des Lebens ist eines der großen, noch ungelösten Rätsel in der Wissenschaft. Seit Jahrhunderten beschäftigen sich Forscher und Wissenschaftler mit dieser faszinierenden Frage. Wie ist das Leben auf der Erde entstanden? Wie hat sich aus anorganischer Materie lebende Organismen entwickelt? Trotz intensiver Forschung und zahlreicher Theorien gibt es bisher keine endgültige Antwort.

The Challenges of Relay Synthesis and Time in Prebiotic Origin of Life Research

In the context of prebiotic origin of life research, relay synthesis refers to a proposed chemical process that might have played a role in the formation of complex molecules necessary for life to emerge from simple precursor compounds on early Earth. The formation of complex molecules from simple precursors.The term "relay synthesis" suggests that the formation of certain molecules involved multiple steps or stages, with intermediate compounds acting as relays to facilitate the overall reaction. In other words, it is a stepwise process where simpler molecules are progressively transformed into more complex ones through a series of chemical reactions. The idea behind relay synthesis is that life's building blocks, such as amino acids, nucleotides (the building blocks of RNA and DNA), and other essential organic molecules, would have been formed through a combination of various chemical reactions in a sequential manner. These reactions would have taken place under the specific conditions of the early Earth, which were likely different from the present-day environment. Researchers studying the origin of life seek to understand the plausibility of relay synthesis as a potential mechanism for generating the molecular complexity needed for life to arise. They investigate how simple molecules, such as methane, ammonia, water, and carbon dioxide, could have reacted under various conditions, such as high temperatures, volcanic activity, or lightning strikes, to produce more complex organic compounds.

The idea is that scientists combine two or more molecules (A and B) in a reaction, hoping to produce a specific compound (AB). However, this process often leads to multiple products, including unwanted compounds. To isolate the desired AB compound, chemists use various complex tools and techniques to purify and extract it from the mixture. The problem arises when researchers claim they have identified the compound in the reaction mixture, but they cannot isolate it due to the complexity and messiness of the mixture. In such cases, they might resort to purchasing the pure AB compound to proceed with their experiments. This approach is a form of cheating because, in a real synthesis, scientists cannot skip the purification and isolation steps. Researchers in the field of prebiotic chemistry sometimes use this tactic to produce the desired compounds, even though such processes wouldn't have occurred naturally on an early Earth without intelligent intervention. Prebiotic researchers like Steve Benner and Lee Cronin, generate useless compounds and make bold claims about their research. The experiments conducted in these labs involve complex setups with external inputs, which are not reflective of natural conditions. The problem applies for example to the different parts of the sugar molecules. Once these monomers are synthesized, it is not enough to simply mix them together and expect the desired compounds to form spontaneously. The process is much more complex and challenging. Lee Cronin claims to achieve self-purification in his experiments. When Cronin adds more pure material during the reaction, he argues that it does not self-purify as claimed. Instead, what happens is that Cronin selectively removes certain components from the reaction mixture at each cycle, leading to the appearance of purification. However, the reality is that purification is not occurring through a natural process; it is being manipulated by the researcher at each step.

Moreover, Cronin's experiments using the foremost reaction, a process that generates billions of compounds in seconds to hours, do not lead to meaningful products relevant to prebiotic chemistry. The products obtained are considered junk and not conducive to the formation of life's essential building blocks. This lack of discernment and critical thinking in regard to these problems leads to the promotion of false scientific claims and hype in the field of prebiotic origin of life research. The scientific community needs to approach these experiments with rigor and intellectual honesty. The dissemination of misleading information to the public leads to a distorted perception of the state of research in the field of origin of life studies. The importance of non-covalent interactions in the context of origin-of-life research has to be outlined. These interactions are distinct from covalent bonds and play a crucial role in shaping the arrangement of molecules. While covalent bonds involve the sharing of electrons between atoms to form stable compounds, non-covalent interactions occur when molecules come into close proximity to each other without forming chemical bonds. These interactions are weaker than covalent bonds but are essential in various biological processes. In the context of the origin of life, non-covalent interactions are especially significant because they are involved in the proper arrangement of biomolecules, such as proteins, DNA, and RNA. These arrangements are critical for information transfer and biological function. For instance, in DNA, the sequence of nucleotide bases  contains instructions for building proteins and other cellular components. This sequence specificity is crucial for the functioning of living systems.

The number of possible ways molecules can interact through non-covalent interactions is astronomically high. This vast combinatorial space poses not only a significant challenge for prebiotic chemistry, but means de facto game over for undirected origin of life proposals. Achieving the correct arrangement of molecules that would lead to life's essential processes is highly improbable, its safe to say, impossible. It requires precise conditions and factors,  which were not present on early Earth or in prebiotic settings. However, Origin-of-Life researchers often overlook or downplay the complexities and challenges associated with non-covalent interactions. These researchers turn a blind eye, overlook and ignore the magnitude of the problem and its implications for their proposed scenarios of prebiotic chemistry. The origin of life research needs to address multiple levels of problems in understanding the characteristics of a cell and how life could have emerged from non-living matter. The first level is building the monomers, which are the small constituents and building blocks of molecules like amino acids in proteins or sugars, phosphates, and bases in DNA. These monomers are crucial components for the formation of larger biomolecules. The second level of complexity involves the sequence specificity of the constituent parts, particularly in DNA and proteins. This sequence specificity is analogous to written language or digital code, where the arrangement of nucleotide bases in DNA  contains information or instructions for building proteins or other molecules or carrying out specific cellular functions. This is the "information content" of DNA. Even if researchers manage to obtain the correct information-rich DNA with the specific arrangements required, there is an additional challenge related to the immense combinatorial complexity of interactions, especially in protein-protein interactions. These interactions are non-covalent in nature, meaning they don't involve the formation of chemical bonds. Instead, molecules come into close proximity and interact through electrostatic potentials and other non-covalent forces. The number of possible ways molecules can align in non-covalent interactions is extraordinarily large, with an immense number of potential combinations. Among these combinations, only a small fraction will lead to proper arrangements and functional outcomes. Achieving the correct arrangement of molecules, especially in complex interactions like protein-protein interactions, poses a significant challenge. Origin-of-Life researchers often neglect or avoid discussing these challenges associated with non-covalent interactions and the vast combinatorial space involved. Understanding and achieving the correct arrangements required for the emergence of life from non-living matter is a formidable task that requires considering multiple levels of complexity and the limitations of prebiotic environments.

There is a crucial misconception in the field of origin-of-life research regarding the role of time in the formation of complex biomolecules. It has been commonly believed that given enough time, random chemical interactions could lead to the formation of complex molecules and eventually life. This idea is often summarized as "chance is the hero of the plot," implying that with sufficient time, even highly improbable events can become inevitable. However, this perspective neglects an essential aspect of chemical reactions, especially in the context of prebiotic Earth conditions. Organic molecules, which are the building blocks of life, tend to decompose rapidly under the same conditions in which they are formed. This decomposition poses a significant problem for the spontaneous assembly of complex biomolecules over extended periods. The time taken for these complex molecules to form by chance is much longer than their tendency to decompose under the prevailing environmental conditions. Hence, time becomes an enemy rather than a friend when it comes to the spontaneous generation of complex biomolecules. In real chemical reactions, chemists have to carefully control the reaction conditions and intervene at the right moment to prevent decomposition and obtain the desired products. Leaving reactions to run for long periods, as some might assume for the origin of life, would lead to poor yields due to decomposition. The statement "time is on our side" is a colloquial expression used by some authors in research papers to refer to obtaining thermodynamically favored products rather than a kinetic product.  The idea that time alone can account for the origin of life is a misconception that fails to consider the significant obstacles posed by decomposition and the need for controlled intervention in chemical reactions. Understanding the complexity and challenges involved in the origin of life requires a more realistic and detailed examination of the chemical processes that occurred in prebiotic environments.

In the biosynthesis pathway of pyrimidine nucleobases, precursor molecules of RNA and DNA, there is one of the fastest enzymes known in the biological world. If OMP decarboxylase would take 1 second to perform its reaction, without the enzyme, the catalytic reaction would take 200 billion years (!!). In the real world, the catalytic reaction performed by the enzyme unfolds in a blink of an eye, a mere 18 milliseconds. Uncatalyzed, the reaction would take 78 million years. the decarboxylation of OMP (Orotidine 5'-monophosphate) to form UMP (Uridine 5'-monophosphate) is an essential step in the biosynthesis of functional RNA and DNA. Let me give you a hint. Ribose, the backbone of RNA and DNA, would not wait 78 million years, for the uncatalyzed reaction to unfold. The average time it takes for ribose to decompose at a temperature of around 20 degrees Celsius or 68 degrees Fahrenheit, is weeks, maximum, months.

In the biosynthesis pathway of pyrimidine nucleobases, precursor molecules of RNA and DNA, there is one of the fastest enzymes known in the biological world in action. If OMP decarboxylase would take 1 second to perform its reaction, without the enzyme, the catalytic reaction would take 200 billion years (!!). In the real world, the catalytic reaction performed by the enzyme unfolds in a blink of an eye, a mere 18 milliseconds. Uncatalyzed, the reaction would take 78 million years. the decarboxylation of OMP (Orotidine 5'-monophosphate) to form UMP (Uridine 5'-monophosphate) is an essential step in the biosynthesis of functional RNA and DNA. Let me give you a hint. Ribose, the backbone of RNA and DNA, would not wait 78 million years, for the uncatalyzed reaction to unfold. The average time it takes for ribose to decompose at a temperature of around 20 degrees Celsius or 68 degrees Fahrenheit, is weeks, maximum, months.

The prowess of catalysis astounds scientists and captivates the imagination. Dr. Richard Wolfenden, a distinguished enzyme expert from the University of North Carolina, unveiled the astonishing efficiency of these biological catalysts. In a groundbreaking 1998 study, he demonstrated that a crucial reaction in the creation of DNA and RNA, the very essence of life's genetic code, would languish in water for a staggering 78 million years. Yet, through the magical touch of an enzyme, this sluggish process was accelerated by an unimaginable factor of 10^18, transforming it into a swift ballet of molecular transformation. The enigmatic enzyme responsible for this feat was orotidine 5'-monophosphate decarboxylase, a key player in the synthesis of uridine 5'-phosphate—a vital precursor for the creation of RNA and DNA. By deftly decarboxylating orotidine 5'-monophosphate (OMP), this enzyme ensured the swift production of the building blocks of life. However, the tale of enzymatic marvels did not stop there. In 2003, Dr. Wolfenden unraveled another revelation, unearthing an enzyme that surpassed even the grand rate enhancement witnessed before. This time, it was a phosphatase—an enzyme that orchestrates the hydrolysis of phosphate dianions. This seemingly humble catalyst exhibited a mind-boggling rate enhancement of 10^21, surpassing all expectations. With its remarkable abilities, the phosphatase bestowed upon vital cellular reactions, crucial for signaling and regulation, the power to transpire in the blink of an eye. In the absence of this extraordinary enzyme, these essential reactions would languish for an inconceivable trillion years—an era that far surpasses the supposed age of our universe, estimated at around 15 billion years. Such revelations leave us in awe of the wonders of enzymatic ingenuity. Contemplating the implications of these astonishing discoveries, Dr. Wolfenden mused on the profound role of catalysts in the existence of life, from the humblest microbes to the complexity of humans. These catalysts, these enzymatic maestros, became the foundation upon which life itself was built. Enzymes emerge as the master conductors, orchestrating the symphony of biochemical processes that sustain life. Their unparalleled ability to transform the excruciatingly slow into the expeditious offers a glimpse into the fascinating realm where biology dances with precision. Through their catalytic artistry, enzymes have shaped the very essence of life on our planet, propelling it forward with breathtaking efficiency.

LUCA’s Complexity Challenges Evolutionary Origin of Life
https://reasons.org/explore/blogs/the-cells-design/lucas-complexity-challenges-evolutionary-origin-of-life

A. G. CAIRNS-SMITH genetic takeover,  page54 
The impurity problem:
First of all there is a problem which is seldom discussed. The starting monomers would have been grossly impure. On the basis of Simulation experiments they would have been present in complex mixtures that contained a great variety of variously reactive molecules. N0 sensible organic chemist would hope to get much out of a reaction from starting materials that were tars containing the reactants as minor constituents.

To bake the cake:
In organic chemistry it is often the work-up rather than the reaction that causes most of the trouble. Think about the techniques that are used: pH adjustments, solvent extractions, chromatography, evaporation to dryness, recrystallization, filtration and so on. Now you can say that such things might have taken place fortuitously under primitive geological conditions. Each individual operation can be imagined — a transfer of a solution, a washing of a precipitate, an evaporation, and so on. But very many such operations would have had to take place consistently and in the right order. In a typical work-up procedure there are subtle things that can make the difference between success and mess — how long to wait, say, after the pH adjustment before filtering. Practical organic chemistry is not easy. Very much has to be engineered. It is not sensible to suppose that an uninformed geochemistry would fortuitously be an expert in such things.

The concentration problem:
Next there is the problem of the concentrations of the monomers in primordial waters. It has been emphasized repeatedly that the idea of an oceanic primordial soup is difficult to sustain on thermodynamic and kinetic grounds. For example Hull (1960) says: ‘First, thermodynamic calculations predict vanishingly small concentrations of even the smallest organic compounds. Second, the reactions invoked to synthesize such compounds are seen to be much more effective in decomposition.’ Hull was discussing particularly the effects of ultraviolet radiation which he calculated would have destroyed 97 3/", of amino acids produced in the atmosphere before they reached the oceans.

The condensation problem: 
There is a third difficulty in prevital synthesis of biopolymers, and this is the most generally recognized: all the major biopolymers are metastable in aqueous solution in relation to their (deactivated) monomers. Left to itself in water, a polypeptide will hydrolyze to its constituent amino acids. 

Perhaps there is some other way of making peptides with more or less specified amino acid sequences; and perhaps this way does not need detailed control. Perhaps it could then have operated before there was life
on Earth, before that engineer, natural selection, appeared on the scene. But it is difficult to see how this could have been so. I think we would know by now if there was some much easier way. It is similarly difficult to imagine anything like polysaccharide being accumulated in primordial waters. As we saw, the monosaccharides could only have been made easily from formaldehyde, as far as anyone knows, and there is doubt if there could have been sufficient concentrations of that. In any case, as we saw, the product of the formose reaction is a very complex mixture that easily leads to higher polymers and to caramel.

page 66:
Now you may say that there are alternative ways of building up nucleotides, and perhaps there was some geochemical way on the early Earth. But what we know of the experimental difficulties in nucleotide synthesis speaks strongly against any such supposition. However it is to be put together, a nucleotide is too complex and metastable a molecule for there to be any reason to expect an easy synthesis. If you were to consider in more detail a process such as the purification of an intermediate ( to form amide bonds between amino acids and nucleotides ) you would find many subsidiary operations — washings, pH changes and so on. (Remember Merrifield’s machine: for one overall reaction, making one peptide bond, there were about 90 distinct operations required.)

page 70
Suppose that by chance some particular coacervate droplet in a primordial ocean happened to have a set of catalysts, etc. that could convert carbon dioxide into D-glucose. Would this have been a major step forward towards life? Probably not. Sooner or later the droplet would have sunk to the bottom of the ocean and never have been heard of again. It would not have mattered how ingenious or life-like some early system was; if it lacked the ability to pass on to offspring the secret of its success then it might as well never have existed. So I do not see life as emerging as a matter of course from the general evolution of the cosmos, via chemical evolution, in one grand gradual process of complexification. Instead, following Muller (1929) and others, I would take a genetic View and see the origin of life as hinging on a rather precise technical puzzle. What would have been the easiest way that hereditary machinery could have formed on the primitive Earth?

Commentary to Forrest Valkai & John Gleason's responses to caller Robert 04.14.24
https://reasonandscience.catsboard.com/t1279p25-abiogenesis-is-mathematically-impossible#11714

Got God Proof? Call Forrest Valkai & John Gleason | Sunday Show AFTER DARK 04.14.24
https://www.youtube.com/watch?v=VXB-h2l8oqE&t=1113s

00:18:31.600 - 00:23:42.559

Commentary: oxygen is required in biomolecules, but too much oxygen disrupts their formation. Definitively resolving this paradox is still an active area of origins of life research. Scientists have proposed various hypotheses to account for how oxygen could have been incorporated into biomolecules prebiotically, but many of these explanations fall short in resolving the paradox fully. One idea is that the early Earth's atmosphere had essentially no oxygen, allowing biomolecules to form without oxidation. However, this fails to explain how oxygen then got integrated into the molecular structures once an oxygen-rich atmosphere developed. Another hypothesis suggests biomolecules formed near deep-sea hydrothermal vents, where no oxygen was present. But it remains unclear how these molecules could have then dispersed and concentrated elsewhere to kick-start metabolism and replication. Some scientists speculate that oxidized minerals like iron oxides could have provided a source of bound oxygen to be incorporated without free oxygen. Yet the chemistry involved seems quite complex and improbable to yield all the required oxygen arrangements. The chemistry involved in achieving the precise incorporation of oxygen atoms into biomolecules like RNA, DNA, proteins and ATP through abiotic prebiotic processes appears extremely implausible and improbable.  Many biomolecules exhibit very specific arrangements of oxygen atoms that relate to their functional 3D structure. For example, the ribose sugar in RNA has several asymmetric carbon centers and the oxygen must be incorporated at exactly the right locations. Abiotic chemical synthesis typically yields mixtures of stereoisomers and regioisomers that are non-functional. In modern organic synthesis, complex molecules are built up systematically using protection/deprotection strategies to control reactivity. Without such regioselectivity, side reactions lead to scrambled, useless products. There are no known prebiotic mechanisms to achieve this selectivity. Many of the reaction types involved in building biomolecules are incompatible with water as a solvent due to hydrolysis and scrambling. Yet dry, non-aqueous conditions make incorporation of oxygen nearly impossible prebiotically. Forming cyclic structures like the ribose and deoxyribose sugars in a regiospecific manner is a formidable challenge under prebiotic conditions due to competing reactions, equilibria and entropy factors. Beyond just monomers, activated prebiotic routes to preferentially generate the precise sequences found in functional biopolymers like RNA and proteins appear powerfully implausible through chance chemistry alone. In each case, achieving the selective discriminative chemistry to methodically construct the oxygen arrangements seen in biomolecules requires a degree of control, design and regiospecificity that unguided prebiotic chemistry appears incapable of. Some intelligent direction seems fundamentally necessary. There are also propositions about oxidation being counterbalanced by reducing conditions driven by volcanic or atmospheric processes. But finely controlling those redox conditions to allow incorporation without disruption appears highly implausible by chance alone. While these ideas are scientifically explored, they rely on concatenating multiple low-probability events and extremely specific environmental conditions acting in precise coordination. At each stage, reactive oxygen poses potential disruptive pitfalls. For biomolecules like RNA, DNA, amino acids and ATP to emerge with their precise oxygen configurations seems to require tremendous serendipity in the selection and ordering of oxygen provisions from environmental sources. An intelligent directing process becomes a more straightforward explanation when faced with the intricacy and sensitivity involved in orchestrating these oxygen integration steps prebiotically.

00:23:44.960- 00:24:20.120

Commentary: Gleason's statement actually supports the argument for intelligent design or a creator. The form and order in which chemicals combine is absolutely crucial. Even the smallest change in molecular structure can completely alter the properties and function of a compound. For life to emerge from non-living matter, not only would the correct basic elements need to come together, but they would need to bind in an extremely specific sequence and orientation to form the complex biomolecules like proteins, enzymes, and nucleic acids that are essential for even the most basic life processes. The chances of these molecules self-assembling into precisely the right structural configuration by random chance alone are astronomically low. It would be like expecting a tornado to rip through a junkyard and perfectly assemble a fully functional jet airplane. This actually highlights just how improbable it is that the materials and molecular machinery for life could have risen by unguided natural processes. The specificity we see in biochemical systems points profoundly to the work of an intelligent creator, carefully arranging the molecular building blocks of life into their functionally specified arrangements and sequences. The order and complexity we observe cries out for an orderer, rather than being the product of blind chance.

00:24:22.840- 00:26:23.320

Commentary:The ease with which RNA can undergo hydrolysis and oxidative cleavage presents a formidable challenge for any naturalistic scenario trying to explain its prebiotic formation. RNA is often cited as a prime candidate for the first self-replicating molecule that could have kicked off biological processes. However, its intrinsic instability seems to invalidate many of the hypothetical prebiotic pathways proposed for its abiotic synthesis. The extra 2' hydroxyl group on the ribose sugar makes RNA highly susceptible to hydrolytic cleavage, even in the mere presence of water. This suggests any prebiotically formed RNA would rapidly degrade back into its component nucleotides before it could participate in catalysis or replication cycles. Furthermore, the oxidative pathways, like oxidative ribose ring opening, provide another kinetic sink leading to fragmentation of RNA strands. The prebiotic environment, which lacked the protective biochemical machinery of modern cells, would have exposed any abiotically produced RNA to rampant degradation from hydrolysis, oxidation and more. So not only do origin of life theories need to overcome the astronomical improbability of spontaneously assembling functional RNA sequences from prebiotically available molecular building blocks, they also have to postulate conditions where that RNA could remain stable and intact long enough to undergo self-replication before disintegrating. The inherent instability of RNA seems to erect an incredibly high kinetic barrier that unguided prebiotic chemistry appears profoundly unable to circumvent. This serves to amplify the intellectual challenge abiogenesis hypotheses face - circumventing both the formidable thermodynamic AND kinetic hurdles to abiotic RNA formation through sheer chance and luck appears inordinately strained, pointing to the need for an intelligent governing force. The instability of RNA stands as a major hurdle for naturalistic origins theories.

00:26:26.200 - 00:28:22.960

Response: The claim that RNA's greater instability compared to DNA is irrelevant to the problem of abiogenesis is simply nonsensical from a scientific perspective. This dismissive handwaving completely ignores the enormous hurdle that RNA's inherent lability poses for any naturalistic origin of life scenario. First, you cannot simply bypass the challenge by asserting that RNA later evolved diverse roles in modern biochemistry. The key question is how RNA itself first emerged from abiotic chemistry to kick-start biological processes in the first place. Its facile degradation via hydrolysis and oxidation represents a kinetic death trap that any hypothetical prebiotic synthesis pathways must overcome. Secondly,  to imply that because DNA is more stable, the transition from an RNA world to DNA partly solves the instability issue. However, this is putting the cart before the horse. The transition from RNA to DNA represents an enormously complex  process involving the development of sophisticated enzymes, proof-reading mechanisms, and the entire molecular machinery of DNA replication, transcription and translation. Proposing this transition as a hand-waving solution simply punts the core abiogenesis question of how such intricate integrated systems could arise in the first place. The argument effectively assumes the primary hurdle of abiogenesis has already been solved by proposing something even more complex - an advanced DNA/protein molecular biology system - as the deus ex machina. This represents a form of circular reasoning that explains nothing. The fact remains that RNA, being a prime candidate for the first self-replicating molecule, faces the catch-22 of having to be abiotically generated while also remaining stable enough to persist and catalyze further reactions amidst the degrading forces omnipresent in plausible prebiotic environments. Handwaving away this fundamental hurdle does nothing to resolve the formidable challenge RNA's instability presents to naturalistic origin of life theories. A substantive, empirically grounded solution showing detailed prenabiotically plausible pathways overcoming this kinetic barrier is required, which you have not provided.

00:28:25.720 - 00:29:36.640

Response: Finding individual nucleobases like adenine, guanine, cytosine and uracil on meteors or in space is profoundly insufficient to claim we have observed abiotic RNA formation. This represents a glaring conflation of vastly different chemical scales and completely neglects the overwhelming hurdles involved. Simply having a motley assortment of scattered nucleobases present does not remotely constitute the self-assembly of functional RNA. RNA requires the precise regio- and stereospecific synthesis of ribose, followed by the regioselective glycosidic coupling of each base to the ribose in the exact required sequence, catalyzed formation of the phosphodiester backbone, and more - an enormously complex series of steps. Meteorites are awash in a heterogeneous mixture of millions of different organic compounds. The nucleobases found are invariably present in minuscule, unusable traces amidst this molecular jumble. There are no known plausible prebiotic mechanisms to selectively extract, purify, concentrate and order these nucleobases into functionalRNA sequences. This reality represents a chemical gulf of astronomical dimensions compared to the highly optimized, controlled enzymatic machinery modern cells use to synthesize RNA from activated, purified nucleotide building blocks. Claiming this unbridgeable chasm has been overcome based on meteors containing useless spatters of mixed nucleobases represents unsubstantiated overreach of the highest order. Without the sophisticated enzymes and catalystsRNA synthesis requires, any abiotically formed nucleobases would inevitably become hopelessly scrambled, randomized and consumed by myriad side reactions. The exact sequence specificity RNA requires would be erased in an instant amidst the deracinating chemical melée. So while meteors may demonstrate some primordial molecular building blocks were scattered abundantly, the intellectual gap between this and producing functionally sequenced RNA under plausible prebiotic conditions remains vast and unbridged. Unguided prebiotic chemistry falls inevitably short in circumventing this intractable combinatorial hurdle without underlying directing intelligence.

00:29:33.399- 00:30:46.039 

Commentary:
The claim that a study last year showed RNA polymerizing by itself in the presence of mundane minerals is not supported by evidence. While there have been some experiments attempting to demonstrate steps towards abiogenesis of RNA, there is no conclusive study showing the full spontaneous polymerization and self-replication of RNA from simple precursor molecules under plausible prebiotic conditions. The assertion that "all of the building blocks of RNA can self-assemble and phosphodiester bonds can form and RNA can polymerize to form oligoribonucleotides by themselves" is not true.  The claim that "we've seen it (RNA) self-replicate in the lab" is not accurate. No study has demonstrated the full self-replication of RNA without the involvement of protein enzymes or other biological molecules derived from extant life. Some RNA enzymes (ribozymes) can catalyze their own synthesis to a limited degree, but not true self-replication. The claims about finding RNA self-replicating in nature and coding for things to enhance self-replication are unfounded. All known examples of RNA replication require the presence of an entire cellular machinery.

00:30:48.240 - 00:39:36.280  

Commentary:
The assertion that finding ribonucleotides in asteroids or comets definitively proves an abiotic pathway for their formation is premature. Their mere presence does not reveal the full mechanistic details of how they arose. The implication that our current inability to fully explain the origin of biological homochirality (existence of only left-handed amino acids) means an undiscovered natural process must exist is an argument from ignorance. Lack of a known naturalistic explanation does not automatically validate an unknown natural process. The hypothetical scenarios proposed, such as life arising across the entire universe or existing in a simulation, are speculative and lack substantive evidence. Introducing unsubstantiated conjectures does not strengthen the naturalistic argument. 

Eliminative inductions argue for the truth of a proposition by arguing that competitors to that proposition are false. Persistent lack of progress on a scientific problem is exactly what one should expect when a causal puzzle has been fundamentally misconceived, or when the toolkit employed in causal explanation is too limited. ( Contrast this with Popperian falsification, where propositions are corroborated to the degree that they successfully withstand attempts to falsify them ) When the available option forms a dichotomy, just to option, A, or not A, they form a mutually exclusive and exhaustive class, eliminating all the competitors entails that the proposition is true. As Sherlock Holmes's famous dictum says: when you have eliminated the impossible, whatever remains, however improbable, must be the truth. In this case, eliminative inductions, in fact, become deductions.

00:39:38.720 - 00:45:13.160

Response: The claims made regarding the spontaneous origin of life from nonliving matter are unsubstantiated and premature. Despite ongoing research efforts, science has yet to provide a comprehensive, demonstrated pathway for the abiotic formation of even the simplest living systems from basic chemical precursors under plausible prebiotic conditions. Merely finding individual biomolecules like ribonucleotides in asteroids or comets does not constitute evidence for a fully naturalistic origin of life. Their mere presence does not reveal how they could have organized and assembled into a self-replicating system capable of darwinian evolution - the hallmark of life. The hypothetical scenarios proposed, such as life emerging across the entire universe or existing within a simulation, are unfounded speculations lacking empirical grounding. Introducing fanciful conjectures does not substantiate a natural explanation for life's origin. The assertion that an inability to yet explain biological homochirality implies an undiscovered natural process is a flawed argument from ignorance. Lack of a currently known naturalistic cause does not automatically validate one. This represents an unjustified assumption. Furthermore, the claim that even if abiogenesis could be reproduced experimentally, it would merely represent one potential natural pathway, fails to recognize the fundamental challenge faced. The fact that even one instance of non-trivial biological complexity could self-assemble by natural means would demand a comprehensive and satisfying explanation, which current theories cannot provide. While uncertainties and knowledge gaps undoubtedly remain in origins research, the naturalist's insistence that a fully naturalistic explanation must exist, and will eventually be found, appears rooted more in philosophical presuppositions than empirical evidence. An open-minded evaluation of the available data suggests that intelligent design, involving the intervention of a creator, provides a credible and causally adequate explanation worthy of serious consideration.

00:45:15.880 - 00:54:59.200 

Response: The naturalist claims experimental evidence exists for generating ATP abiotically and through simple proton gradients. However, these putative demonstrations still rely on pre-existing chemical complexities that beg the deeper question of their own origins. For ATP to arise from basic constituents would require the orchestrated integration of nucleotides arranged in precisely specific sequences - an astronomical improbability if left solely to random undirected processes. Analogies highlighting inconceivable odds, like a tornado assembling a jet engine from a junkyard, underscore the inherent challenge that unguided chance processes face. Even relatively simpler biomolecules like proteins require staggeringly improbable arrangements of amino acids to achieve minimum viability and function. Valkai and Gleason dismiss such probabilistic hurdles, but cannot adequately explain how such astronomical longshot events could self-actualize under any realistically pre-biotic conditions we know of. Moreover, the invocation of perpetually deferred "unknown natural processes" suspected to someday solve these conundrums is an argument from ignorance - a fallacious dedactic placeholder devoid of substantive explanatory power. Merely hypothesizing vaguely about as-yet-undiscovered chemical pathways does little to displace the challenge of biological complexity that screams intelligent design. While uncertainties remain in our understanding, the insistence that natural processes fully sufficient for abiogenesis will eventually be validated appears rooted more in philosophical bias against a creator than a reasoned evaluation of the empirical evidence we currently possess. An open-minded assessment suggests intelligent design is an explanatorily viable and cause-adequate framework worthy of serious consideration.

00:55:02.83 - 01:05:08.11

Commentary: The discovery of ribose and other bio-essential sugars in meteorites does not substantively advance a fully naturalistic explanation for the origin of life. While intriguing, these findings merely demonstrate that individual molecular building blocks can be dispersed throughout the cosmos. However, they do not reveal how such components could self-organize and integrate into self-replicating systems displaying the complexity inherent in even the simplest known life forms. Valkai & Gleason appeal to unknown future discoveries of undescribed chemical pathways and processes as a way to circumvent our current limitations. Yet this argumentative approach stems from the philosophical assumption that a comprehensively naturalistic explanation must exist, rather than following the evidence towards the most causally adequate and explanatorily powerful conclusions.

Invoking hypothetical scenarios like panspermia (life spreading from elsewhere) simply defers and relocates the very same problem it seeks to solve - how did such life initially arise from non-living matter? It does not provide a true naturalistic explanation for the ultimate origin of biological complexity and information-rich systems. Valkai & Gleason rightly acknowledge our inability to generate key molecules like ribose or reconstruct the biochemical systems of extant life in prebiotic conditions. However, rather than conceding an intelligent design inference from such evidence of choreographed complexity, they speculate about unknown exceptions or caveats that could still accommodate a naturalistic model. This regressive approach reflects an argument from ignorance - insisting that what we do not yet understand must be fully explainable by currently unknown natural causes.

In contrast, the evidence we do possess points towards mind-bending improbabilities and coherence of purpose that transcend what we understand of undirected, stochastic processes. From the astronomical luck required for minimally functional biomolecular sequences, to the molecular machinery enabling replication and metabolism, life exhibits an intricacy of organization that demands an adequate explanation. While uncertainties remain, dismissing intelligent design a priori for philosophical reasons risks committing a genetic fallacy - rejecting conclusions due to perceived ideological implications rather than assessing the empirical evidence objectively. An impartial evaluation suggests intelligent design is an causally adequate and evidentially supported explanation that warrants equal consideration with naturalistic models that remain incomplete and confronted by formidable conceptual challenges.

01:05:10.240 -  01:25:43.679

Commentary: While the arguments about requiring objective, reproducible evidence according to the scientific method have some merit,The materialistic worldview that demands all truth claims be verified through controlled experiments has significant philosophical limitations. If millions or billions of people across cultures and time periods independently attest to experiencing some higher power or consciousness, that is not something that can be easily hand-waved away, regardless of whether it fits current scientific models. At the very least, it demands further rigorous investigation from an impartial perspective, not knee-jerk dismissal. Moreover, you seem to place a lot of faith in the current scientific consensus, but the history of science is riddled with examples of paradigm shifts overturning what was once accepted as unassailable truth. To act as if today's scientific theories represent total objective knowledge is simply intellectual arrogance. Many of the greatest scientific minds like Newton were actually led to their breakthroughs by first intuiting the existence of a rational, intelligent framework underlying the natural world. So while I respect the scientific method as a powerful tool for understanding the material world, I don't accept the materialistic philosophy that nothing exists except what can be detected and measured by contemporary scientific instruments and methods. There are realms of inquiry and understanding that transcend those limited capacities. To remain completely closed off to evidence and experiences from other domains is not true open-mindedness, but rather a Tennessee of its own. We must follow the evidence wherever it leads, even if it points towards unconventional or currently inexplicable phenomena and forces us to question long-held assumptions.

The hurdles to Getting Amino Acids and Functional Peptides for the First Life Prebiotically
 
Title: Challenges in Prebiotic Amino Acid and Protein Formation: A Comprehensive Review

Abstract

This paper reviews the numerous challenges associated with the prebiotic formation of amino acids and functional proteins through naturalistic means. We examine the hurdles in obtaining amino acids prebiotically and the subsequent difficulties in polymerizing these into functional peptides. The review categorizes these challenges into several key areas, including thermodynamic and kinetic barriers, chirality issues, and the improbability of forming functional sequences. We conclude that the formation of a minimal functional proteome through purely naturalistic processes faces significant obstacles that current origin of life models struggle to overcome.

1. Introduction

The origin of life remains one of the most challenging questions in science. A critical aspect of this problem is understanding how the first functional proteins could have emerged from prebiotic chemistry. This review aims to systematically outline the major hurdles that must be overcome for amino acids to form and subsequently polymerize into functional proteins under prebiotic conditions.

2. Challenges in Prebiotic Amino Acid Formation

2.1  Challenges in the Availability of Precursors for Prebiotic Amino Acid Synthesis

The synthesis of amino acids under prebiotic conditions is a critical step in the hypothesized naturalistic emergence of life. However, several significant challenges arise when considering the availability of necessary chemical precursors. 

Availability of Precursors

The challenges in the availability of precursors for prebiotic amino acid synthesis encompass the scarcity of fixed nitrogen and carbon sources, the reactivity of organosulfur compounds, and the instability of ammonia ^{[1] [2] [3]}. Abiotic nitrogen fixation processes, reliant on sporadic events like lightning strikes, limit consistent nitrogen availability, while the reduction of sulfur compounds into reactive forms remains complex ^[1]. The rapid photochemical dissociation of ammonia under early Earth's conditions adds to the hurdles in sustaining a crucial nitrogen source for amino acid synthesis ^[1]. Meeting the specific requirements for amino acid synthesis proves challenging due to contradictions in necessary settings for precursor stability and reactivity ^[1]. Addressing these obstacles necessitates a comprehensive understanding of early Earth chemistry to devise plausible scenarios for precursor accumulation and reaction, guiding future research in prebiotic chemistry ^[1].

1. Fixed Nitrogen and Carbon
Nitrogen: The availability of nitrogen in a fixed, bioavailable form is crucial for amino acid synthesis. Nitrogen fixation processes, which convert atmospheric N₂ into ammonia (NH₃) or other reactive nitrogen species, are typically biological and require complex enzymatic machinery. Prebiotically, non-biological nitrogen fixation would rely on abiotic processes such as lightning strikes or volcanic activity, which are sporadic and inefficient. This results in limited and inconsistent availability of fixed nitrogen.
Carbon: Carbon must also be available in a form that can readily participate in organic synthesis. In prebiotic environments, carbon sources such as carbon dioxide (CO₂) or methane (CH₄) need to be converted into more reactive organic molecules, a process requiring specific conditions and catalysts. The efficiency of these processes under early Earth conditions is questionable, leading to potential shortages in the necessary carbon precursors.

2. Organosulfur Compounds
Presence and Reactivity: Certain amino acids, such as cysteine and methionine, require sulfur in their synthesis. On early Earth, sulfur predominantly existed in oxidized forms like sulfate (SO₄²⁻), which are not readily incorporated into organic molecules. For these amino acids to form, sulfur must be available in a reduced and reactive form, such as hydrogen sulfide (H₂S). However, the reduction of sulfur compounds under prebiotic conditions is a challenging process, further complicating the availability of necessary organosulfur precursors.

3. Stability of Ammonia
Photochemical Dissociation: Ammonia (NH₃) is a critical nitrogen source for amino acid synthesis. However, ammonia is highly susceptible to photochemical dissociation, especially under the ultraviolet radiation prevalent on early Earth. This dissociation breaks ammonia into nitrogen and hydrogen, reducing its availability. The short lifetime of ammonia in such an environment poses a significant hurdle, as it would need to be continually replenished through nitrogen fixation processes, which, as previously discussed, are inefficient and sporadic.

Implications for Prebiotic Chemistry
The challenges in ensuring a steady and sufficient supply of fixed nitrogen and carbon, reduced sulfur compounds, and stable ammonia significantly hinder the prebiotic synthesis of amino acids. The sporadic and inefficient nature of abiotic nitrogen fixation, the difficulty in reducing sulfur compounds, and the rapid photochemical decomposition of ammonia collectively pose formidable obstacles.

Specific Requirements for Amino Acid Synthesis
For amino acids to form naturally under prebiotic conditions, the following requirements must be met:

1. Consistent Source of Fixed Nitrogen and Carbon
2. Availability of Reduced Sulfur Compounds
3. Continuous Replenishment of Ammonia to Counteract Photodecomposition
4. Localized Concentration of Precursors to Facilitate Reactions
5. Environmental Conditions Favoring the Stability and Reactivity of Precursors

Contradictions and Challenges
Meeting these requirements simultaneously is highly challenging, if not contradictory. For example, the conditions needed to protect ammonia from photodecomposition (e.g., shaded environments) may not coincide with those required for efficient nitrogen and sulfur reduction processes (e.g., high-energy environments). Additionally, the sporadic nature of abiotic nitrogen fixation means that consistent precursor availability is unlikely, further complicating the synthesis of amino acids. The availability of precursors for amino acid synthesis under prebiotic conditions presents significant challenges to naturalistic origin-of-life models. Addressing these challenges requires a deeper understanding of early Earth chemistry and the development of plausible scenarios where these precursors could reliably accumulate and react. Future discussions should focus on identifying and testing specific environmental conditions that could overcome these barriers, guiding experimental and theoretical research in the field of prebiotic chemistry.

2.2 Challenges of Prebiotic Peptide Bond Formation

The challenges of prebiotic peptide bond formation are multifaceted, as highlighted by recent empirical data and simulations ^[4]. The thermodynamic and kinetic barriers present significant hurdles, with equilibrium concentrations of even short peptides like nonapeptides calculated to be exceedingly low under prebiotic conditions ^[5]. These findings critically challenge current origin-of-life models that rely on the spontaneous formation of polypeptides in aqueous environments, especially considering the rapid racemization of amino acids that impedes the formation of homochiral peptides essential for functional biology ^[5]. To naturally form peptide bonds, numerous simultaneous requirements must be met, including high amino acid concentrations, energetically favorable conditions, homochirality, selective activation, catalytic surfaces, protection from hydrolysis, sequential polymerization, stable intermediate structures, environmental stability, and efficient concentration mechanisms ^[6]. However, many of these requirements are contradictory or mutually exclusive under prebiotic conditions, posing significant challenges to the spontaneous formation of functional peptides essential for the emergence of life ^[7].

1. Quantitative Findings Challenging Conventional Theories
A critical examination of the formation of peptide bonds reveals significant thermodynamic and kinetic barriers. Recent empirical data and computer simulations illustrate these challenges starkly. For instance, the equilibrium concentration of a nonapeptide (nine amino acids long) such as glycine ([Gly]₉) in water at temperatures between 25°C and 37°C is calculated to be less than 10^-50 M. This implies that under prebiotic conditions, not even a single molecule of [Gly]₉ would likely exist, let alone the much larger polypeptides required for primitive life forms.

2. Implications for Current Scientific Models
These findings pose a critical challenge to the current origin-of-life (OoL) models, which often rely on the spontaneous formation of polypeptides in aqueous environments. The extremely low equilibrium concentrations of even short peptides significantly undermine the plausibility of these models. Furthermore, the rapid racemization of amino acids under natural conditions exacerbates the problem, as it would prevent the formation of homochiral peptides necessary for functional biology.

3. Specific Requirements for Naturalistic Peptide Formation
For peptide bond formation to occur naturally under prebiotic conditions, the following requirements must be met simultaneously:

1. High Concentration of Amino Acids: A sufficiently high concentration of amino acids must be present in a localized area.
2. Energetically Favorable Conditions: The environment must provide the necessary energy to drive peptide bond formation despite the unfavorable equilibrium.
3. Homochirality: Only L-amino acids should be incorporated into peptides to avoid racemization.
4. Selective Activation: Amino acids must be selectively activated to form peptide bonds without undesired side reactions.
5. Catalytic Surfaces: The presence of catalytic surfaces or minerals to facilitate peptide bond formation.
6. Protection from Hydrolysis: Peptides must be protected from hydrolysis, which is thermodynamically favored in aqueous environments.
7. Sequential Polymerization: Amino acids must polymerize in a specific sequence to form functional peptides.
8. Stable Intermediate Structures: Intermediate peptide structures must be stable enough to avoid decomposition.
9. Environmental Stability: The prebiotic environment must remain stable over time to allow for these processes to occur.
10. Efficient Concentration Mechanisms: Mechanisms to concentrate and localize reactants and products must be in place.

4. Contradictions and Mutually Exclusive Conditions
Many of these requirements are mutually exclusive or contradictory under prebiotic conditions. For example, the need for high temperatures to drive peptide formation (Requirement #2) conflicts with the necessity to prevent racemization (Requirement #3), as higher temperatures accelerate racemization rates. Similarly, the need for an aqueous environment to provide a medium for reactions (Requirement #1) contradicts the requirement to protect peptides from hydrolysis (Requirement #6).

5. Illustrative Examples
Hydrothermal Vents: While hydrothermal vents provide the high temperatures and mineral surfaces that could facilitate peptide bond formation, the harsh conditions also lead to rapid hydrolysis and racemization of peptides.
Drying Lagoon Hypothesis: The theory that peptides could form in drying lagoons where water evaporates and concentrates amino acids faces the challenge of maintaining homochirality and preventing hydrolysis during subsequent wet-dry cycles.

6. Critical Examination of Current Theories
Current naturalistic explanations for peptide bond formation under prebiotic conditions face significant challenges. The quantitative data indicating extremely low peptide concentrations, coupled with the rapid racemization of amino acids, strongly suggest that these processes are highly improbable without additional, yet-to-be-discovered mechanisms. The simultaneous fulfillment of all necessary conditions under naturalistic scenarios appears implausible given our current understanding.

Conclusion
To structure further discussions on this topic, it is essential to:

1. Focus on Specific Mechanisms: Investigate specific, plausible mechanisms that could overcome these challenges.
2. Interdisciplinary Approaches: Encourage interdisciplinary research combining chemistry, biology, and geoscience to explore novel solutions.
3. Critical Evaluation of Assumptions: Reevaluate the assumptions underlying current models in light of empirical data.
4. Explore Alternative Scenarios: Consider alternative scenarios or environments that might provide the necessary conditions for peptide formation.
5. Incremental Advances: Aim for incremental advances in understanding rather than comprehensive theories, given the complexity of the problem.

By addressing these points, the scientific community can better navigate the significant hurdles associated with the prebiotic formation of amino acids and peptides, moving closer to unraveling the origins of life.

2.3  Quantity and Concentration: Challenges in Prebiotic Amino Acid Availability

The challenges in prebiotic amino acid availability, as outlined in recent scientific literature, highlight the significant quantitative and qualitative obstacles faced by current abiogenesis models. Computational models suggest the need for concentrations in the millimolar range, far exceeding known prebiotic synthesis capabilities ^[10]. Experimental studies indicate low yields in peptide formation, necessitating initial amino acid concentrations orders of magnitude higher than achievable through current methods ^[8]. The absence of eight "never-observed" proteinogenic amino acids in prebiotic synthesis experiments raises fundamental questions about the completeness of origin-of-life models ^[11]. Proposed concentration mechanisms like thermophoresis or mineral surface adsorption face challenges in selectivity and efficiency, emphasizing the complexity of achieving the required molecular densities for polymerization ^[9]. Addressing these quantitative and qualitative requirements is crucial for advancing our understanding of the origin of life and refining abiogenesis hypotheses.

Quantitative Challenges
Recent computational models suggest that the formation of even the simplest self-replicating systems would require a minimum of 10^9 to 10^12 amino acid molecules (Lancet et al., 2018). This translates to local concentrations in the millimolar range, far exceeding those achievable through known prebiotic synthesis routes. Furthermore, studies on mineral-catalyzed peptide formation indicate that yields rarely exceed 1% under optimal laboratory conditions (Lambert, 2008), implying that initial amino acid concentrations would need to be orders of magnitude higher to compensate for inefficient polymerization.

Implications for Current Models
These quantitative constraints severely limit the plausibility of "primordial soup" hypotheses. Most prebiotic synthesis experiments produce amino acids in micromolar concentrations at best, falling short of the required levels by several orders of magnitude. This discrepancy undermines the assumption that simple chemical processes could lead to the spontaneous emergence of complex biomolecules.

Requirements for Natural Occurrence
For the prebiotic synthesis and concentration of amino acids to occur naturally, the following conditions must be simultaneously met:

1. Presence of all 20 proteinogenic amino acids in sufficient quantities
2. Protection mechanisms against UV radiation and hydrolysis
3. Chirality selection to produce only L-amino acids
4. Concentration mechanisms to achieve millimolar levels
5. Absence of interfering molecules that could disrupt synthesis or polymerization
6. Stable pH and temperature conditions conducive to amino acid stability
7. Energy sources for synthesis and concentration processes
8. Selective surfaces or environments for amino acid accumulation
9. Mechanisms to prevent the preferential concentration of simpler, competing molecules
10. Pathways for the synthesis of the eight "never-observed" proteinogenic amino acids

These requirements must coexist in a prebiotic environment, presenting a formidable challenge to naturalistic explanations. Several of these conditions are mutually exclusive or contradictory. For instance, the energy sources required for synthesis (point 7) often lead to the breakdown of complex molecules, conflicting with the need for protection mechanisms (point 2).

The "never-observed" amino acids present a particular challenge. Despite decades of prebiotic chemistry research, eight of the 20 proteinogenic amino acids have never been synthesized under plausible prebiotic conditions (Cleaves, 2010). These include arginine, lysine, histidine, tryptophan, methionine, asparagine, glutamine, and phenylalanine. Their absence in prebiotic synthesis experiments raises fundamental questions about the completeness of current origin-of-life models.

Moreover, the concentration problem extends beyond mere quantity. Amino acids would need to accumulate at specific assembly sites to facilitate polymerization. Proposed mechanisms like thermophoresis or mineral surface adsorption face significant limitations in selectivity and efficiency (Baaske et al., 2007). The quantitative and qualitative requirements for prebiotic amino acid availability present substantial challenges to current naturalistic explanations for the origin of life. Future discussions on this topic should focus on:

1. Developing more realistic models that account for the quantitative constraints highlighted here.
2. Exploring novel prebiotic synthesis pathways for the "never-observed" amino acids.
3. Investigating plausible concentration mechanisms that can achieve the required molecular densities.
4. Addressing the mutual exclusivity of certain required conditions in prebiotic scenarios.
5. Critically examine the assumptions underlying current abiogenesis hypotheses in light of these quantitative challenges.