https://www.youtube.com/watch?v=-ZFlmL_BsXE
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 2
https://www.youtube.com/watch?v=dv4mUjmuRRU
Main points addressed in the video
Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.
The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.
Prebiotic RNA and DNA synthesis
1. No prebiotic mechanism is known to select:
- Right-handed configurations of RNA and DNA
- The right backbone sugar
- How to get size complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions
2. Bringing all the parts together and joining them in the right position
- Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
- Prebiotic glycosidic bond formation between nucleosides and the base
- Prebiotic phosphodiester bond formation
- Fine-tuning of the strength of the hydrogen base pairing forces
3. The instability, degradation, and asphalt problem
- Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.
4. The energy problem
- Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.
5. The minimal nucleotide quantity problem.
- The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.
6. The Water Paradox
- The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.
7.The transition problem from prebiotic to biochemical synthesis
- Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.
Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!
The origin of the RNA and DNA molecule is an origin of life problem, not evolution.
Steve Benner, one of the world’s leading authorities on abiogenesis: The “origins problem” CANNOT be solved.
Graham Cairns-Smith: The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109). 'The odds are enormous against its being coincidence. No figures could express them.'
RNA & DNA: It's prebiotic synthesis: Impossible !!
https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 1
https://www.youtube.com/watch?v=-ZFlmL_BsXE
RNA & DNA: It's prebiotic synthesis: Impossible !! Part 2
https://www.youtube.com/watch?v=dv4mUjmuRRU
Main points addressed in the video
Synthesis of nitrogenous bases in prebiotic environments
- High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.
- Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
- The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
- Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
- Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: Synthesis problems of the Pentose 5 carbon sugar ring
The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction. Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.
The phosphate group
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.
Prebiotic RNA and DNA synthesis
1. No prebiotic mechanism is known to select:
- Right-handed configurations of RNA and DNA
- The right backbone sugar
- How to get size complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions
2. Bringing all the parts together and joining them in the right position
- Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
- Prebiotic glycosidic bond formation between nucleosides and the base
- Prebiotic phosphodiester bond formation
- Fine-tuning of the strength of the hydrogen base pairing forces
3. The instability, degradation, and asphalt problem
- Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.
4. The energy problem
- Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.
5. The minimal nucleotide quantity problem.
- The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.
6. The Water Paradox
- The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.
7.The transition problem from prebiotic to biochemical synthesis
- Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.
Unguided prebiotic synthesis of RNA and DNA: an unsolved riddle!
The origin of the RNA and DNA molecule is an origin of life problem, not evolution.
Steve Benner, one of the world’s leading authorities on abiogenesis: The “origins problem” CANNOT be solved.
Graham Cairns-Smith: The odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth would be a huge number, represented approximately by a 1 followed by 109 zeros ( 10^109). 'The odds are enormous against its being coincidence. No figures could express them.'


James Watson at left and Francis Crick discovered the structure of the DNA (deoxyribonucleic acid) molecule in 1953. DNA are the molecules which make up the “alphabet” which specifies biological heredity. DNA are the molecules which store the blueprint of life, and as such, hold a central indispensable position.
The RNA polymerase machine complex transcribes the instructional information stored in DNA into RNA. RNA is built of (almost) the same four-letter alphabet as DNA. It is more fragile, and as such, it could also be an information carrier, but less adequate long term.
Who wants to find answers about how life started, needs to find compelling explanations about how RNA and DNA first emerged on earth. In all known living beings, genetic information flows from DNA to RNA to proteins

Their work on the structure of DNA was performed with some access to the X-ray crystallography of Maurice Wilkins and Rosalind Franklin at King's College London. Combining all of this work led to the deduction that DNA exists as a double helix. This information was critical for their further progress. They obtained this information as part of a report by Franklin to the Medical Research Council.
The report was by no means secret, but it put the critical data on the parameters of the helix (base spacing, helical repeat, number of units per turn of the helix, and diameter of the helix) in the hands of two who had contributed none of those data.
With this information, they could begin to build realistic models. The big problem was where to put the purine and pyrimidine bases. Details of the diffraction pattern indicated two strands, and indicated that the relatively massive phosphate ribose backbones must be on the outside, leaving the bases in the center of the double helix.

Crick, Watson and Wilkins shared the 1962 Nobel Prize for Physiology or Medicine, Franklin having died of cancer in 1958.

Four major classes of organic molecules are found in living cells. All forms of life have organic molecules and macromolecules that fall into these four broad categories, based on their chemical and biological properties: carbohydrates, lipids, proteins, and nucleic acids.

Nucleotides are essential to cellular metabolism, and nucleic acids are the molecules of genetic information storage and expression.
General description of the structure of the RNA and DNA molecule
DNA is the molecule of life, which contains the blueprint, or instructions to make for example proteins that perform most life functions.

Nucleotides are building blocks for DNA and RNA. The two classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA molecules store genetic information coded in the sequence of their building blocks.
DNA can be considered as a modified form of RNA since the ribose sugar in RNA is transformed into deoxyribose in DNA at the 5 prime positions ( see the red circle in the picture above ), and the uracil base is methylated into thymidine ( More about this, later). The structural difference between these sugars is that ribonucleic acid contains a hydroxyl (-OH) group, whereas deoxyribonucleic acid contains only a hydrogen atom in the place of this hydroxyl group.

Nucleotides which contain deoxyribonucleic acid are known as deoxyribonucleotides. Those containing ribonucleic acid are known as ribonucleotides. Thus, the sugar molecule determines whether a nucleotide forms part of a DNA molecule or a RNA molecule.
These molecules consist of three components: a phosphate, a ribose sugar, and a nitrogenous (nitrogen-containing) ring compound that behaves as a base. The nucleotide is the repeating structural unit of both DNA and RNA.
The picture shows the repeating unit of nucleotides found in DNA and RNA. DNA and RNA contain deoxyribose and ribose respectively as its sugar and the bases attached. The locations of the attachment sites of the base and phosphate to the sugar molecule are important to the nucleotide’s function, and how prebiotic events supposedly came up with the right configuration is one of the unsolved riddles.
The nitrogenous base


Nucleotide bases appear in two forms: A single-ring nitrogenous base, called a pyrimidine, and a double-ringed base, called a purine.

High-energy precursors to produce purines and pyrimidines would have had to be produced in a sufficiently concentrated form. There is no known prebiotic route to this.
Scientists have failed to produce cytosine in spark-discharge experiments, nor has cytosine been recovered from meteorites or extraterrestrial sources. The deamination of cytosine and its destruction by other processes such as photochemical reactions place severe constraints on prebiotic cytosine syntheses.
The origin of guanine bases has proven to be a particular challenge. While the other three bases of RNA could be created by heating a simple precursor compound in the presence of certain naturally occurring catalysts, guanine had not been observed as a product of the same reactions.
Adenine synthesis requires unreasonable Hydrogen cyanide concentrations. Adenine deaminates 37°C with a half-life of 80 years. Therefore, adenine would never accumulate in any kind of "prebiotic soup." The adenine-uracil interaction is weak and nonspecific, and, therefore, would never be expected to function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup."
Uracil has also a half-life of only 12 years at 100◦C. For nucleobases to accumulate in prebiotic environments, they must be synthesized at rates that exceed their decomposition.
Ribose: The Pentose 5 carbon sugar ring of RNA and DNA

DNA has the ribose sugar in RNA transformed into deoxyribose in DNA at the 2 prime positions. A base is attached to the 1 prime carbon atom, and a phosphate group is attached at the 5 prime positions. Compared with ribose, deoxyribose lacks a single oxygen atom at the 2 prime positions; the prefix deoxy- (meaning without oxygen) refers to this missing atom.

The pentose sugar is a 5-carbon monosaccharide. These form two groups: aldopentoses and ketopentoses. The pentose sugars found in nucleotides are aldopentoses. Deoxyribose and ribose are two of these sugars. A DNA strand is formed when the nitrogenous bases are joined by hydrogen bonds, and the phosphates of one group are joined to the pentose sugars of the next group with a phosphodiester bond.
Ribose is a monosaccharide containing five carbon atoms. d-ribose is present as the six different forms. The β-d-furanose form is extensively used in biological systems as a component of RNA. The best-studied mechanism relevant to the prebiotic synthesis of ribose is the formose reaction.
Several problems have been recognized for the ribose synthesis via the formose reaction. The formose reaction is very complex. It depends on the presence of a suitable inorganic catalyst. Ribose is merely an intermediate product among a broad suite of compounds including sugars with more or fewer carbons.

The reality of the formose reaction is that it descends into an inextricable mixture. The vast array of sugars produced is overwhelming and the intrinsic lack of selectivity for ribose is its undoing. Ultimately, the formose reaction produces a disastrously complex mixture of linear and branched aldo and keto-sugars in the racemic forms.
The consequences of such uncontrolled reactivity is that ribose is formed in less than 1% yield among a plethora of isomers and homologs. The instability of ribose prevents its accumulation and requires it to undergo extremely rapid onward conversion to ribonucleosides before the free sugar is lost to rapid degradation.
There are no further alternatives: Either chance "choose" by lucky random events the five-membered ring ribofuranose backbone for DNA and RNA, or it was a choice by intelligence with specific purposes. What makes more sense?
This reaction requires a high concentration of Formaldehyde, which, however, readily undergoes a variety of reactions in aqueous solutions. Another problem is that ribose is unstable and rapidly decomposes in water.
Furthermore, as Stanley Miller and his colleagues recently reported, "ribose and other sugars have surprisingly short half-lives for decomposition at neutral pH, making it very unlikely that sugars were available as prebiotic reagents."

Leslie Orgel concludes: Some progress has been made in the search for an efficient and specific prebiotic synthesis of ribose and its phosphates. However, in every scenario, there are still a number of obstacles to the completion of a synthesis that yields significant amounts of sufficiently pure ribose in a form that could readily be incorporated into nucleotides.

There have been a wide variety of attempts and proposals to try to solve the riddle, but up to date, without success. The article in Science magazine from 2016 admits: Ribose is the central molecular subunit in RNA, but the prebiotic origin of ribose remains unknown.
And a recent research paper from 2018 reports: Even if some progress has been made to understand the ribose formation under prebiotic conditions, each suggested route presents obstacles, limiting ribose yield and purity necessary to form nucleotides. A selective pathway has yet to be elucidated.
The third component of a nucleotide is a phosphate group

Phosphorus is the third essential element making part of the structures of DNA and RNA. It is perfect to form a stable backbone for the DNA molecule. Phosphates can form two phosphodiester bonds with two sugars at the same time and connect two nucleotides. Phosphorus is difficult to dissolve, and that would be a problem both in an aquatic as-as well on a terrestrial environment.
Phosphoesters form the backbone of DNA molecules. A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds.

Phosphodiester bonds are central to all life on Earth as they make up the backbone of the strands of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon atom of one sugar molecule and the 5' carbon atom of another, deoxyribose in DNA and ribose in RNA. Strong covalent bonds form between the phosphate group and two ribose 5-carbon rings over two ester bonds.
On prebiotic earth, however, there would have been no way to activate phosphate somehow, in order to promote the energy dispendious reaction.
That adds up to the fact that concentrations on earth are very low. So far, no geochemical process that led to abiotic production of polyphosphates in high yield on the Earth has been discovered.
The phosphate is connected to ribose which is connected to the nitrogenous base. Each of the 3 parts of nucleotides must be just right in size, form, and must fit together. The bonds must have the right forces in order to form the spiral form DNA molecule. And there would have to be enough units concentrated at the same place on prebiotic earth of the four bases in order to be able to form a self-replicating RNA molecule if the RNA world is supposed to be true.

A nucleotide is differentiated from a nucleoside by one phosphate group. Accordingly, a nucleotide can also be a nucleoside monophosphate. If more phosphates bond to the nucleotide (nucleoside monophosphate) it can become a nucleoside diphosphate (if two phosphates bond), or a nucleoside triphosphate (if three phosphates bond), such as adenosine triphosphate (ATP).

Adenosine triphosphate, or ATP, is the energy currency in the cell, a crucial component of respiration and photosynthesis, amongst other processes.
The base, sugar, and phosphate need to be joined together correctly - involving two endothermic condensation reactions involved in joining the nucleotides, which means it has to absorb energy from its surroundings. In other words, compared with polymerization to make proteins, nucleotides are even harder to synthesize and easier to destroy; in fact, to date, there are no reports of nucleotides arising from inorganic compounds in primaeval soup experiments.
Prebiotic RNA and DNA synthesis

What must be explained, is the origin and prebiotic making of nucleotides, that is adenine, guanine, cytosine, uracil and thymine and the transition to enzymatic biosynthesis of these.
The emergence in the 1980s of the RNA world as a major theory for the origin of life led to increased attention on the prebiotic synthesis of simple RNA and RNA-like molecules. RNA is a complex, polymeric structure. But its prebiotic synthesis faces many problems, of which we will give a closer look just to a few.
1. Selecting the right components
1a. Selecting right-handed configurations of RNA and DNA
1b. Selecting the right backbone sugar
1c. Size Complementarity of the nucleotide bases to form a DNA strand and strands of the DNA molecule running in the opposite directions
2. Bringing all the parts together and joining them in the right position Attach the nucleic bases to the ribose and in a repetitive manner at the same, correct place, and the backbone being a repetitive homopolymer
2a. Glycosidic bond formation between nucleosides and the base
2b. Prebiotic phosphodiester bond formation
2c. Fine-tuning of the strength of the hydrogen base pairing forces
3. The instability, degradation, and asphalt problem Bonds that are thermodynamically unstable in water, and overall intrinsic instability. RNA’s nucleotide building blocks degrade at warm temperatures in time periods ranging from nineteen days to twelve years. These extremely short survival rates for the four RNA nucleotide building blocks suggest why life’s origin would have to be virtually instantaneous—all the necessary RNA molecules would have to be assembled before any of the nucleotide building blocks decayed.
4. The energy problem: Doing things costs energy. There has to be a ready source of energy to produce RNA. In modern cells, energy is consumed to make RNA.
5. The minimal nucleotide quantity problem. The prebiotic conditions would have had to be right for reactions to give perceptible yields of bases that could pair with each other.
6. The Water Paradox: The hydrolytic deamination of DNA and RNA nucleobases is rapid and irreversible, as is the base-catalyzed cleavage of RNA in water. This leads to a paradox: RNA requires water to do its job, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place.
7 .The transition problem from prebiotic to biochemical synthesis Even if all this in a freaky accident occurred by random events, that still says nothing about the huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network, where complex biosynthesis pathways produce nucleotides in modern cells.
1. Selecting the right components
1a. Selecting right-handed configurations of RNA and DNA
Once the three components would have been synthesized prebiotically, they would have had to be separated from the confusing jumble of similar molecules nearby, and they would have had to become sufficiently concentrated in order to move to the next steps, to join them to form nucleosides, and nucleotides.

At a chemical level, a deep bias permeates all of biology. The molecules that make up DNA and other nucleic acids such as RNA have an inherent “handedness.” These molecules can exist in two mirror-image forms, but only the right-handed version is found in living organisms. Handedness serves an essential function in living beings; many of the chemical reactions that drive our cells only work with molecules of the correct handedness.
DNA takes on this form for a variety of reasons, all of which have to do with intermolecular forces. The phosphate/ribose backbone of DNA is hydrophilic (water-loving), so it orients itself outward toward the solvent, while the relatively hydrophobic bases bury themselves inside.
Additionally, the geometry of the deoxyribose-phosphate linkage allows for just the right pitch, or distance between strands in the helix, a pitch that nicely accommodates base pairing. Lots of things come together to create the beautiful right-handed double-helix structure.
Production of a mixture of d- and l-sugars produces nucelotides that do not fit together properly, producing a very open, weak structure that cannot survive to replicate, catalyze, or synthesize other biological molecules.

In DNA the atoms C1', C3', and C4' of the sugar moiety are chiral, while in RNA the presence of an additional OH group renders also C2' of the ribose chiral

A biological system exclusively uses d-ribose, whereas abiotic experiments synthesize both right- and lefthanded-ribose in equal amounts. But the pre-biological building blocks of life didn’t exhibit such an overwhelming bias. Some were left-handed and some right. So how did right-handed RNA emerge from a mix of molecules?
Some kind of symmetry-breaking process leading to enantioenriched biomonomers would have had to exist. But none is known.

Gerald Joyce wrote a science paper which was published in Nature magazine, in 1984. His findings, published in Nature in 1984, suggested that in order for life to emerge, something first had to crack the symmetry between left-handed and right-handed molecules, an event biochemists call “breaking the mirror.”
Since then, scientists have largely focused their search for the origin of life’s handedness in the prebiotic worlds of physics and chemistry, not biology - but with no success. So what is the cop-out ?

Pure chance !! Luck did the job. That is the only thinkable explanation. How could that be a satisfying answer in face of the immense odds?

But then, the same author, Christian de Duve, Nobel prize winner in physiology or medicine, dismisses instant creation as " heuristically sterile". A sterile discovery ?? in other words, a discovery lacking evidence?

In his following book, Genetics of Original Sin, he then extended a bit further, and exposed what he meant by "heuristically sterile".

It is conceivable that the molecules were short enough for all possible sequences, or almost, to be realized (by way of their genes) and submitted to natural selection. So, this is the way de Duve thought that Intelligent Design could be dismissed. This coming from a Nobel prize winner in medicine is nothing short than shocking, to say the least.
De Duve dismissed intelligent design and replaced it with natural selection. Without providing a shred of evidence. But based on pure guesswork and speculation.
Last edited by Admin on Thu Jul 02, 2020 11:47 am; edited 143 times in total